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Acute Pancreatitis: A Review
Abstract
Importance:
In the United States, acute pancreatitis is one of the leading causes of hospital admission from gastrointestinal diseases, with approximately 300 000 emergency department visits each year. Outcomes from acute pancreatitis are influenced by risk stratification, fluid and nutritional management, and follow-up care and risk-reduction strategies, which are the subject of this review.
Observations:
MEDLINE was searched via PubMed as was the Cochrane databases for English-language studies published between January 2009 and August 2020 for current recommendations for predictive scoring tools, fluid management and nutrition, and follow-up and risk-reduction strategies for acute pancreatitis. Several scoring systems, such as the Bedside Index of Severity in Acute Pancreatitis (BISAP) and the Acute Physiology and Chronic Health Evaluation (APACHE) II tools, have good predictive capabilities for disease severity (mild, moderately severe, and severe per the revised Atlanta classification) and mortality, but no one tool works well for all forms of acute pancreatitis. Early and aggressive fluid resuscitation and early enteral nutrition are associated with lower rates of mortality and infectious complications, yet the optimal type and rate of fluid resuscitation have yet to be determined. The underlying etiology of acute pancreatitis should be sought in all patients, and risk-reduction strategies, such as cholecystectomy and alcohol cessation counseling, should be used during and after hospitalization for acute pancreatitis.
Conclusions and relevance:
Acute pancreatitis is a complex disease that varies in severity and course. Prompt diagnosis and stratification of severity influence proper management. Scoring systems are useful adjuncts but should not supersede clinical judgment. Fluid management and nutrition are very important aspects of care for acute pancreatitis.
... Acute pancreatitis (AP) is one of the most common gastrointestinal diagnoses for inpatient admissions [1]. While alcohol and gallstones are the most common etiologies of AP, several medications can cause inflammation of the pancreas [2]. Drug-induced AP is a rare but important condition, making up less than 5% of all AP cases [2]. ...
... While alcohol and gallstones are the most common etiologies of AP, several medications can cause inflammation of the pancreas [2]. Drug-induced AP is a rare but important condition, making up less than 5% of all AP cases [2]. The most common medications resulting in drug-induced AP are azathioprine, sulfonamides, and diuretics such as furosemide and hydrochlorothiazide [3]. ...
... The most common medications resulting in drug-induced AP are azathioprine, sulfonamides, and diuretics such as furosemide and hydrochlorothiazide [3]. Pancreatic complications of AP include pseudocyst, a fluid sac forming outside of the pancreas, and pancreatic necrosis, which is tissue death of the organ [2]. Systemic complications include acute kidney injury and acute respiratory distress syndrome [2]. ...
... Acute pancreatitis (AP) is the most common cause of hospitalization with a gastrointestinal condition, which loads heavy burdens on the current healthcare system, and the incidence of AP is increasing annually both in the USA and worldwide [8]. Despite the generally mild clinical course observed in the majority of cases, a noteworthy one-fifth of AP patients develop severe systemic inflammation, leading to persistent organ failures and an associated mortality rate of approximately 20% [8]. ...
... Acute pancreatitis (AP) is the most common cause of hospitalization with a gastrointestinal condition, which loads heavy burdens on the current healthcare system, and the incidence of AP is increasing annually both in the USA and worldwide [8]. Despite the generally mild clinical course observed in the majority of cases, a noteworthy one-fifth of AP patients develop severe systemic inflammation, leading to persistent organ failures and an associated mortality rate of approximately 20% [8]. The rising prevalence of AP, occurring against the backdrop of relatively stable human genetics, hints at the involvement of non-genetic factors-specifically, environmental factors-in the pathogenesis of AP. ...
... Differential analysis of species level suggests that Escherichia coli abundance was increased while Akkermansia muciniphila was decreased in MSAP/SAP group compared with that in MAP group (Fig. 7l). Moreover, Akkermansia muciniphila abundance showed a negative correlation with the bedside index for severity in AP (BISAP) score [8] (Fig. 7m) and C-reactive protein (CRP) (Fig. 7o). Based on the presence or absence of Systemic Inflammatory Response Syndrome (SIRS) in AP, the cases were divided into SIRS and non-SIRS groups, compared to the non-SIRS group, the abundance of AKK was significantly reduced in the SIRS group (Additional file 1: Fig. S9f ). ...
Objective
Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation.
Design
C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota’s role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBPδ knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed.
Results
CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBPδ, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients.
Conclusions
This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation.
AK6FXV6th3dPv1KrtCUVtcVideo Abstract
... Severe acute pancreatitis (SAP) is one of the most critical illnesses in the digestive system 1 . Globally, its incidence varies depending on regional and population factors, but it has generally exhibited an increasing trend in recent years 1,2 . Pathologically, SAP is characterized by pancreatic hemorrhage and necrosis, which often trigger systemic inflammatory response syndrome and multiple organ failure (MOF) 3,4 . ...
... Previous basic studies have demonstrated that pancreatic tissue damage in early SAP activates both the immune system and pro-inflammatory responses. Concurrently, the systemic release of inflammatory mediators (e.g., cytokines and chemokines) contributes to remote organ injury and dysfunction via circulatory dissemination 2,7,8 . Furthermore, clinical evidence indicates that the incidence of OF in SAP patients with ANC exceeds 30% [9][10][11] . ...
This study aims to analyze the risk factors requiring early intervention in severe acute pancreatitis (SAP) patients with persistent organ failure and evaluate the clinical outcomes following treatment. This was a retrospective observational study. Inverse probability treatment weighting using propensity score methods was employed to balance baseline characteristics. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with early intervention. Smooth curve fitting was applied to explore potential relationships between variables and intervention timing. Threshold effect analysis was conducted to identify the optimal inflection point in nonlinear relationship. A total of 310 patients were included in this study. Compared to the standard treatment group (n = 162), the early intervention group (n = 148) had a higher proportion of multiple organ failure (77.1% vs. 63.6%, P = 0.021) and higher mortality (27.7% vs. 16.0%, P = 0.013), but early intervention was not significantly associated with adverse outcome (OR 1.52, 95% CI 0.71–3.26, P = 0.283). Risk factors associated with early intervention included computed tomography severity index, SOFA score, intra-abdominal pressure (IAP), and remifentanil equivalents. Among these, the SOFA score showed a negative linear relationship with intervention timing, while distinct threshold effects were observed between IAP, remifentanil equivalents, and intervention timing. One week after intervention, most patients showed improved organ function, along with reduced requirements for sedation and analgesia, as well as decreased C-reactive protein level levels and IAP (all P < 0.05). SAP patients requiring early intervention tended to have higher disease severity. Although early intervention can improve short-term organ function, reduce IAP, and lower analgesic requirements, its impact on reducing mortality remains uncertain.
... Acute pancreatitis (AP) is characterized by a broad spectrum of clinical courses. [1][2][3] Most cases of AP are usually self-limiting and can be treated conservatively; however, some patients may develop shock followed by multiorgan failure and thus death. 2 Inflammation in AP can result in peripancreatic fluid collections (PFCs). [4][5][6] According to the 2012 Revised Atlanta Classification guidelines, PFCs may develop into pseudocysts or walled-off necroses (WONs) 4 weeks after the onset of pancreatitis. 1 Among patients with AP, the rates of pseudocyst and WON incidence are approximately 5%-16% and 20%, respectively. ...
... [1][2][3] Most cases of AP are usually self-limiting and can be treated conservatively; however, some patients may develop shock followed by multiorgan failure and thus death. 2 Inflammation in AP can result in peripancreatic fluid collections (PFCs). [4][5][6] According to the 2012 Revised Atlanta Classification guidelines, PFCs may develop into pseudocysts or walled-off necroses (WONs) 4 weeks after the onset of pancreatitis. 1 Among patients with AP, the rates of pseudocyst and WON incidence are approximately 5%-16% and 20%, respectively. ...
Acute pancreatitis exhibits varying degrees of severity and may lead to complications such as peripancreatic fluid collections, which can develop into pseudo-cysts or walled-off necrosis. Interventions are necessary in cases of organ failure, bleeding, or infection. For endoscopic drainage, biomedical researchers have optimized stents such as double pigtail plastic stents (DPSs), modified fully covered self-expanding stents (mFCSEMSs), or lumen-apposing metallic stents (LAMSs). However, the most suitable type of stent for this purpose remains to be determined. Thus, we conducted the present systematic review and network meta-analysis of randomized controlled trials (RCTs) to compare efficacy and safety among various stents for the drainage of necrotic collection from necrotizing pancreatitis. PubMed, Embase, and Cochrane Library were comprehensively searched for RCTs (published before January 7, 2024) comparing various stents used for draining acute pancreatitis-associated peripan-creatic fluid collections. In addition, we manually searched the reference lists of the included RCTs as well as relevant review articles and clinical guidelines. The primary study outcome was clinical success, and the secondary outcomes were technical success and adverse events. This study included four RCTs (a total of 200 patients). A direct meta-analysis indicated no significant difference in the rate of clinical success between LAMSs and DPSs (risk ratio [RR]: 1.02; 95% confidence interval [CI]: 0.89-1.16) or between DPSs and mFCSEMSs
... Regarding the etiology, gallstones are the paramount cause and must be ruled-out before assuming other causes [5], representing about 40-50% of cases, and alcohol-related represent 20-30% [6]. Although, a mnemonic to recall other etiologies is: "I GET SMASHED": Idiopathic, Gallstones, Ethanol, Trauma, Steroids, Mumps (and other microorganisms: Mycoplasma spp., Cytomegalovirus, Epstein-Barr, Mycobacterium avium complex, Human Immunodeficiency Virus, Legionella spp. or Ascaris), Autoinmune, Scorpion and Snake venom, Hypertriglyceridemia and Hypercalcemia, Endoscopic retrograde cholangiopancreatography (ERCP) and Drugs (more than 500) [7,8]. ...
... To establish the etiologic cause, clinical context, anamnesis, and physical examination must be the priority [8,9]. Even though, as previously mentioned, the biliary cause must be excluded. ...
To expose the global importance of this disease, in 2012, an American study determined an estimated and annual cost of 2,6 billion dollars for inpatient costs as well as being the most common gastrointestinal cause for hospitalization
... Treatment of patients with acute pancreatic injuries of inflammatory genesis -acute pancreatitis, especially with its destructive forms, remains a complex and time-consuming problem of modern medicine confirmed by progressive increasing of incidence and high mortality rates together with frequencies of purulent-septic and other complications [10]. This current situation is apparently explained by this form of pancreatic damage pathogenesis complexity, by disease rapid progression to necrotic form development with quick and maximal mortality, by lack of early diagnosis and complications development [10,14]. ...
... Treatment of patients with acute pancreatic injuries of inflammatory genesis -acute pancreatitis, especially with its destructive forms, remains a complex and time-consuming problem of modern medicine confirmed by progressive increasing of incidence and high mortality rates together with frequencies of purulent-septic and other complications [10]. This current situation is apparently explained by this form of pancreatic damage pathogenesis complexity, by disease rapid progression to necrotic form development with quick and maximal mortality, by lack of early diagnosis and complications development [10,14]. ...
... Most patients with AP develop mild to moderate upper abdominal pain accompanied by vomiting, tachycardia, fever, leukocytosis, and increased pancreatic enzyme levels [1]. This disease is self-limited in the majority of patients and resolves within 1 week [2,3]. Approximately 20 % of patients develop moderate or severe acute pancreatitis (SAP). ...
... Approximately 20 % of patients develop moderate or severe acute pancreatitis (SAP). The incidence of SAP is approximately 20 %, which can be associated with organ failure and complications such as pancreatic necrosis and abscess, leading to septicemia, increased organ failure, and even death [2,3]. ...
Severe acute pancreatitis (SAP) is associated with metabolic disorders, hypocalcemia, and multiple organ failure. The objective of this study was to investigate changes in thyroid ultrastructure and function in rats with SAP and to provide a theoretical basis for the clinical treatment of thyroid injury in patients with SAP. 64 male SPF Wistar rats were randomly divided into the SAP group and the control group. Pancreatic enzymatic indicators and thyroid hormones were detected, pathology scores were evaluated, and morphological changes were observed under light microscopy and transmission electron microscopy (TEM) in both groups. The serum levels of triiodothyronine (T3), tetraiodothyronine (T4) and Ca2+ were significantly lower in the SAP group than in the control group (P<0.05), whereas the level of calcitonin (CT) was significantly higher than that in the control group (P<0.05). The thyroid structure (pathology and electron microscopy) of the SAP rats was seriously damaged and worsened over time. SAP can cause thyroid injury through a variety of mechanisms, which can also retroact to pancreatitis to aggravate the inflammatory response. This study may have theoretical significance for basic research on SAP.
... Acute pancreatitis (AP), a common condition of the digestive system, has been exhibiting a rising trend of incidence globally at a rate of 3.07% per year, posing a significant burden on individuals and society [1]. Although 80% of AP patients have mild self-limited disease, 20% of patients develop pancreatic necrosis and infected pancreatic necrosis (IPN), which have significantly increased mortality [2]. In addition, approximately 20% AP patients have a risk of recurrence, and as the frequency of AP attacks increases, the risk of pancreatic ductal adenocarcinoma (PDAC) also rises [3,4]. ...
This systematic review aims to comprehensively assess the epidemiology and identify risk factors associated with the severity and recurrence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP). A search of PubMed, Web of Science, and Cochrane databases was conducted to identify all relevant randomized controlled trials (RCTs), prospective, or retrospective cohort studies on HTG-AP. Data related to epidemiology and risk factors for severity and recurrence of HTG-AP were extracted and analyzed. Seventy-seven studies met the inclusion criteria, comprising 1 RCT, 21 prospective studies, and 55 retrospective studies. A total of 56,617 acute pancreatitis (AP) patients were included, of which 19.99% were diagnosed with HTG-AP (n = 11,315). Compared to non-HTG-AP patients, HTG-AP patients were more likely to be male (68.7% vs. 57.3%) and younger (mean age 41.47 ± 4.32 vs. 50.25 ± 7.70 years). HTG-AP patients exhibited higher mortality rates (up to 20% vs. 15.2%), increased severity (8.3% to 100% vs. 3.8% to 47.2%), and higher recurrence rates (up to 64.8% vs. 23.3%). Analysis of temporal trends from 2002 to 2023 showed a range of HTG-AP prevalence in overall AP patients from 1.6% to 47.6%, with a slight upward trend that was not statistically significant (P = 0.1081). Regional analysis indicated relatively stable prevalence in North America (P = 0.5787), Europe (P = 0.0881), other regions (P = 0.738), while prevalence in China showed a significant increase (P = 0.0119). Thirteen studies investigated risk factors affecting HTG-AP severity, with elevated serum triglyceride (TG) levels associated with increased risk of complications such as pancreatic necrosis, systemic inflammatory response syndrome (SIRS), shock, and multi-organ failure. Additional factors including high neutrophil-to-lymphocyte ratio (NLR), elevated levels of amylase and C-reactive protein (CRP), hypocalcemia, and hypoalbuminemia were also implicated in HTG-AP severity. Smoking history, poor lipid control (TG > 3.1 mmol/L), or recurrent hypertriglyceridemia during follow-up were identified as potential predictors of HTG-AP recurrence. Our findings indicate a stable global prevalence of HTG-AP within AP patients, but a notable increase in China, possibly attributed to socio-economic and dietary factors.
... Studies indicate that around 80% of patients develop mild to moderate symptoms, while 20% experience severe pancreatitis with a 20% mortality rate. It can be quite challenging to anticipate disease progression at an early stage and the management of complications not only increases patient suffering but also consumes more medical resources [5,6]. Thus, effective assessment of AP severity is essential in early phase and timely intervention measures are of critical importance in reducing mortality in AP. ...
Objective
Blood urea nitrogen to albumin ratio (BAR) has served as a predictive marker for patients in the Intensive Care Unit (ICU), and has been studied in patients with sepsis, post-cardiac surgery, severe COVID-19, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This objective indicator has demonstrated capability in prognostic prediction.However, research on the prognostic value of BAR in acute pancreatitis (AP) patients are scarce,the goal was to explore the relationship between BAR and total mortality in AP admitted to ICU.
Methods
A Retrospective analysis was performed utilizing the Medical Information Market for Intensive Care (MIMIC IV) database. Patients with AP admitted to ICU were included and grouped based on BAR. Univariate and multivariate Cox regression analysis were utilized to explore the relationship between BAR and total mortality. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was applied to assess the predictive value of BAR. Cumulative hazard risk accumulation curve verified BAR’s predictive capability for short- and long-term mortality. Heterogeneity between different subgroups was excluded by subgroup analysis.
Results
Total 514 AP patients were divided into high-BAR (BAR ≥ 7.62) and low-BAR group (BAR < 7.62). The duration of ICU stay was significantly extended in the high BAR group. In the Cox proportional hazard model, whether adjusting for confounding factors or not, the high BAR was an independent risk factor for total mortality. AUC for BAR was 0.78 (95% C1: 0.72–0.84) at 28 days and 0.70 (95%: Cl: 0.64–0.75) at 360 days.
Conclusion
BAR is an objective and independent predictor of both short- and long-term total mortality in AP patients. A prompt, efficient, and uncomplicated assessment of the severity and prognosis, which facilitates ICU doctors to develop treatment plans for poor patient outcomes.
... Acute pancreatitis (AP) is a sterile inflammation, being a local immune inflammatory reaction caused by the early activation of pancreatic enzymes and subsequent autodigestion of the pancreas [1][2][3][4][5]. Most cases of AP are mild and can heal spontaneously, but still 10-20% of cases can progress to severe acute pancreatitis (SAP), with obvious pancreatic tissue necrosis, excessive activation of immune cells, and a large release of inflammatory mediators, triggering a systemic inflammatory reaction and leading to multiple organ failure and even death of patients [6,7]. ...
Background:
Acute pancreatitis (AP) is a sterile inflammation, and 10-20% of cases can progress to severe acute pancreatitis (SAP), which seriously threatens human life and health. Neutrophils and their extracellular traps (NETs) play an important role in the progression of AP. However, the immunodynamic factors between the excessive infiltration of neutrophils during the occurrence of AP have not been fully elucidated.
Methods:
Adult male C57BL/6 J mice were selected. An AP model was induced by cerulein, and a control group was set up. Single-cell sequencing technology was used to reveal the cell atlas of AP pancreatitis tissue. In vivo, the model mice were treated with anti-Ly6G antibody, DNase I, SC75741, PX-478, and SRT3109 respectively. In vitro, human pancreatic stellate cells were treated with hypoxia, H2O2, NAC, and JSH-2, and co-cultured with neutrophils in Transwell chambers. The severity of inflammation was evaluated, and the molecular mechanism by which fibroblasts exacerbate AP was revealed through techniques such as cell colony formation assay, cell migration assay, cell transfection, immunofluorescence, flow cytometry, Western blot, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and co-immunoprecipitation (co-IP).
Results:
The study showed that the elimination of neutrophils and NETs could significantly improve AP. Single-cell RNA sequencing (scRNA-seq) indicated that both neutrophils and fibroblasts in pancreatic tissue exhibited heterogeneity during AP. Among them, neutrophils highly expressed CXCR2, and fibroblasts highly expressed CXCL1. Further experimental results demonstrated that the infiltration of neutrophils in the early stage of AP was related to the activation of fibroblasts. The activation of fibroblasts depended on the nuclear factor kappa B (NF-κB) signaling pathway induced by hypoxia. NF-κB enhanced the activation of pancreatic stellate cells (PSCs) and the secretion of CXCL1 by directly promoting the transcription of HIF-1α and indirectly inhibiting PHD2, resulting in the accumulation of HIF-1α protein. The NF-κB-HIF-1α signal promoted the secretion of CXCL1 by fibroblasts through glycolysis and induced the infiltration of neutrophils. Finally, blocking the NF-κB-HIF-1α-CXCL1 signaling axis in vivo reduced the infiltration of neutrophils and improved AP.
Conclusions:
This study, for the first time, demonstrated that activation of fibroblasts is one of the immunological driving factors for neutrophil infiltration and elucidated that glycolysis driven by the NF-κB-HIF-1α pathway is the intrinsic molecular mechanism by which fibroblasts secrete CXCL1 to chemotactically attract neutrophils. This finding provides a highly promising target for the treatment of AP.
... Acute pancreatitis is a sudden inflammatory condition of the pancreas, primarily characterized by pancreatic tissue oedema, inflammatory response, and enzyme-mediated cellular necrosis (Mederos et al., 2021). Clinically, patients typically present with acute upper abdominal pain, nausea, vomiting, and markedly elevated serum amylase levels (Lee and Papachristou, 2019). ...
Astragaloside IV (C41H68O14, AS-IV) is a naturally occurring saponin isolated from the root of Astragalus membranaceus, a widely used traditional Chinese botanical drug in medicine. In recent years, AS-IV has attracted considerable attention for its hepatoprotective properties, which are attributed to its low toxicity as well as its anti-inflammatory, antioxidant and antitumour effects. Numerous preclinical studies have demonstrated its potential in the prevention and treatment of various liver diseases, including multifactorial liver injury, metabolic-associated fatty liver disease, liver fibrosis and liver cancer. Given the promising hepatoprotective potential of AS-IV and the growing interest in its research, this review provides a comprehensive summary of the current state of research on the hepatoprotective effects of AS-IV, based on literature available in databases such as CNKI, PubMed, ScienceDirect, Google Scholar and Web of Science. The hepatoprotective mechanisms of AS-IV are multifaceted, encompassing the inhibition of inflammatory responses, reduction of oxidative stress, improvement of insulin and leptin resistance, modulation of the gut microbiota, suppression of hepatocellular carcinoma cell proliferation and induction of tumour cell apoptosis. Notably, key molecular pathways involved in these effects include Nrf2/HO-1, NF-κB, NLRP3/Caspase-1, JNK/c-Jun/AP-1, PPARα/FSP1 and Akt/GSK-3β/β-catenin. Toxicity studies indicate that AS-IV has a high level of safety. In addition, this review discusses the sources, physicochemical properties, and current challenges in the development and clinical application of AS-IV, providing valuable insights into its potential as a hepatoprotective agent in the pharmaceutical and nutraceutical industries.
... Acute pancreatitis (AP) is a common digestive system disease characterized by acute onset, rapid progression, and severe clinical course (Horwitz and Birk, 2024). The global incidence is approximately 13-45 cases per 100,000 people annually (Mederos et al., 2021), with an increasing trend (Petrov and Yadav, 2019). About 20%-30% of AP patients develop severe acute pancreatitis (SAP) and/or necrotizing pancreatitis, which pose significant treatment challenges, incur high costs, and have poor prognoses, with mortality rates of 36%-50% (Portelli and Jones, 2017;Gao et al., 2021). ...
Objective
Tetramethylpyrazine (TMPZ), an active alkaloid derived from traditional Chinese medicine, has shown anti-inflammatory and anti-pyroptotic properties. However, its role in acute pancreatitis (AP)-induced pyroptosis remains unclear. This study aims to investigate the effects of TMPZ on AP-induced pyroptosis and its potential mechanisms.
Materials and methods
A cerulein-induced AP rat model was used to evaluate TMPZ’s protective effects in vivo, and its mechanisms were explored using AR42J cells in vitro. Pancreatic injury was assessed by hematoxylin-eosin staining, TUNEL assay, and serum biochemistry. Transmission electron microscopy, immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction (RT-qPCR) were conducted to examine pyroptosis and related signaling pathways. Cytotoxicity and apoptosis were measured by CCK-8, LDH assays, and Hoechst 33342/PI staining. The role of NRF2 in TMPZ’s effects was further evaluated using NRF2 siRNA.
Results
TMPZ alleviated pancreatic histopathological damage, reduced apoptosis, and decreased serum amylase levels and pro-inflammatory cytokines (IL-1β, IL-18). TMPZ also suppressed pyroptosis by inhibiting NLRP3 inflammasome activation and downregulating pyroptosis-related proteins (NLRP3,caspase-1, ASC, GSDMD) while upregulating NRF2 and HO-1 expression. NRF2 siRNA attenuated TMPZ’s anti-inflammatory and pyroptosis-inhibitory effects, confirming the involvement of the NRF2 pathway.
Conclusion
TMPZ mitigates AP-induced inflammation and injury by modulating pyroptosis via the NRF2 signaling pathway. These findings suggest TMPZ’s therapeutic potential for AP.
... Pancreas COX-2-Is was associated with reduction of SAP occurrence and OF durationIn the ITT population, the duration of OF in the COX-2-Is group was significantly shorter than that of the placebo group (median 4 days (IQR 1-8) in the COX-2-Is group versus 7 days(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) in the placebo group; p<0.001; table 2;figure 2). The occurrence of SAP (OF >48 hours) was 61.5% in the COX-2-Is group and 77.6% in the placebo group (p=0.001; ...
Background
There is no effective drug treatment for the organ failure (OF) caused by severe acute pancreatitis (SAP).
Objective
We aimed to evaluate the efficacy of cyclooxygenase-2 inhibitors (COX-2-Is) on the treatment of SAP and its safety.
Design
In this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18–75 years, <1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥7 or modified Marshall Score ≥2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group. SAP occurrence, duration of OF, local complications, clinical outcomes and serum inflammatory mediators were measured.
Results
Compared with the placebo group, SAP occurrence was reduced by 20.7% (77.6% vs 61.5%, p=0.001) and the persistent OF duration in SAP was shortened by 2 days (p<0.001) after COX-2-Is treatment. For patients enrolled within or after 48 hours from symptom onset, SAP occurrence was reduced by 23.8% (p=0.001) and 8.5% (p=0.202), and the persistent OF duration in SAP was shortened by 3 days (p=0.001) and 2 days (p=0.010) after COX-2-Is treatment, respectively. The occurrence of local complications in the COX-2-Is group was significantly lower than those in the placebo group, 33.7% vs 49.1%, p=0.004. The serum levels of inflammatory mediators and 30-day mortality (from 8.6% to 3.4%) were significantly reduced after COX-2-Is treatment, p<0.05. The incidence of adverse events was similar between the two treatment groups.
Conclusion
Parecoxib sequential with imrecoxib was effective and well tolerated in reducing the occurrence and duration of SAP and local complications through suppression of systemic inflammatory response, leading to decreased morbidity.
... Effective risk stratification is crucial in identifying patients at higher risk of mortality early in the clinical course of AP (5). Timely and accurate assessment enables clinicians to allocate critical care resources appropriately, ensuring that patients with life-threatening complications receive immediate attention (6). ...
Objective
Effective early diagnosis and timely intervention in acute pancreatitis (AP) are essential for improving patient outcomes. This study aims to evaluate the clinical utility of the neutrophil CD64 index (nCD64) in stratifying patients with SAP and assessing mortality risk.
Methods
A total of 302 AP patients were enrolled and divided into a training cohort (n = 226) and a validation cohort (n = 76). Venous blood samples were collected within 24 hours of admission, and the nCD64 index was measured via flow cytometry. Other clinical parameters, including C-reactive protein (CRP) and procalcitonin (PCT), were also recorded. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic value of the nCD64 index and its capacity to predict mortality risk.
Results
ROC curve analysis identified a cutoff value of 1.45 for the nCD64 index. Patients with nCD64 > 1.45 had significantly higher risks of complications, including systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and death. Over 65% of patients with acute pancreatitis (AP) can be effectively risk-stratified at a low cost, and it has been demonstrated that AP patients with an nCD64 value ≤ 1.45 have an extremely low mortality rate (no mortality in present training and validation cohort). Kaplan-Meier survival analysis revealed a significant survival difference between high-risk (nCD64 > 1.45) and low-risk groups (p < 0.001).
Conclusion
The nCD64 index is an effective tool for early identification of SAP patients, allowing for the classification of over 65% of cases as low-risk for mortality.
... Acute pancreatitis (AP) is a globally prevalent gastrointestinal disease characterized by the premature activation of a variety of digestive enzymes, leading to self-digestion by the pancreas; most patients with AP experience abdominal pain as the first symptom (1). AP imposes a heavy burden on the healthcare system, with a reported annual incidence of approximately 34 cases per 100,000 people and an associated mortality rate of approximately 1-5% (2). ...
Background
Although blood urea nitrogen and albumin alone are well-known clinical indicators, combining them as the blood urea nitrogen-to-albumin ratio (BAR) may provide additional prognostic information because they reflect the complex interplay between renal function, nutritional status, and systemic inflammation—all of which are key factors in the pathogenesis of acute pancreatitis (AP). Therefore, the objective of this study was to investigate the relationships between BAR and short- and long-term all-cause mortality (ACM) in patients with AP and to assess the prognostic significance of the BAR in AP.
Methods
This retrospective investigation utilized information extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV, Version 2.2) database. BAR was calculated using the BUN/ALB ratio obtained from the first measurement within 24 h of admission. R software was used to identify the optimal threshold for the BAR. The Kaplan–Meier (K–M) analysis was performed to compare mortality between the two groups. Multivariate Cox proportional hazards regression models and restricted cubic splines (RCS) were used to evaluate the association between BAR and 14-day, 28-day, 90-day, and 1-year ACM. The receiver operating characteristic curves were used to investigate the predictive ability, sensitivity, specificity, and area under the curve (AUC) of the BAR for short- and long-term mortality in AP patients. Subgroup analysis was performed to illustrate the reliability of our findings.
Results
This study comprised a total of 569 patients. The R software determined the optimal threshold for the BAR to be 16.92. The K–M analysis indicated a notable rise in ACM in patients with higher BAR (all log-rank p < 0.001). Cox proportional hazard regression models revealed independent associations between higher BAR and ACM before and after adjusting for confounding variables at days 14, 28, 90, and 1 year. The RCS analysis revealed J-shaped correlations between the BAR and short- and long-term ACM. The AUCs of the BAR for predicting ACM at days 14, 28, 90, and 1 year were 73.23, 76.14, 73.49, and 71.00%, respectively, which were superior to those of BUN, ALB, creatinine, Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation-II. Subgroup analyses revealed no significant interaction between BAR and the vast majority of subgroups.
Conclusion
This study revealed, for the first time, the unique prognostic value of BAR in ICU-managed AP patients. Higher levels of BAR were associated with higher short- and long-term ACM in ICU-managed AP patients.
... Severe AP (SAP) can lead to serious complications with a mortality of 10-30 [3]. AP is histopathologically characterized by damaged secretory acinar cells caused by primary or secondary factors, which activates trypsinogen to inappropriately release trypsin and further activates other digestive enzymes, thereby resulting in pancreatic autolysis in the parenchyma [4]. The pathophysiologic mechanisms of SAP are not yet fully understood. ...
Background
Assessing plasma volume is important in the management and treatment of severe acute pancreatitis (SAP). Although it is an easy and rapid method for estimating the plasma volume, the association between estimated plasma volume status (ePVS) and the prognosis of SAP remains elusive. This study was aimed at assessing the relationship of ePVS with the risk of 30-day all-cause mortality (ACM) in SAP patients.
Methods
This study collected clinical data on SAP patients in the ICU from the MIMIC-IV database. LASSO regression was used to screen for relevant covariates. The nonlinear relationship of ePVS with the risk of 30-day ACM was assessed utilizing the restricted cubic spline (RCS) analysis, and then their association was assessed by a multivariate Cox regression model. 30-day survival across different groups was compared by a Kaplan-Meier survival curve.
Results
This study included 1036 patients, with a 30-day survival rate of 86.8%. They were assigned to four groups by quartiles of ePVS. The Kaplan-Meier survival curve showed that the high ePVS group was at a higher risk of 30-day ACM (p = 0.007). Multivariate Cox regression analysis showed a positive association of ePVS as a continuous variable with the risk of 30-day ACM (HR = 1.09, 1.01–1.18, p = 0.035). The risk of 30-day ACM was higher in the Q4 group vs. the Q1 group with ePVS as a categorical variable (HR = 1.70, 95% CI: 1.03–2.80, p = 0.039). RCS analysis showed a linear relationship of ePVS with the risk of 30-day ACM (p = 0.606), with a cut-off value of 6.23 dL/g. Subgroup analysis revealed significant associations between the two within specific subgroups, but ePVS did not interact with any of the subgroup variables.
Conclusion
Our findings showed a significant association of high ePVS values with an increased risk of 30-day ACM. This study helps to identify high-risk patients early and guide the development of personalized treatment strategies.
... Annually, it accounts for over 288,220 hospital admissions and contributes to costs exceeding $2.2 billion in the United States alone (1). The clinical presentations of AP range from mild, self-limiting conditions to severe cases characterized by multiorgan failure, systemic inflammatory response syndrome, and the need for admission to an intensive care unit (ICU) to provide close monitoring and aggressive treatment (2,3). Assessing the prognosis of critically ill patients with AP remains a significant challenge in both clinical and scientific contexts. ...
Background
Acute pancreatitis (AP) is associated with significant global mortality and morbidity. Frailty, which can be assessed through clinical indicators and life history, is known to impact adverse outcomes across different medical conditions. The frailty index derived from laboratory tests (FI-Lab) is a novel approach to the quantification of frailty. This study sought to investigate the relationship between the FI-Lab and mortality among critically ill patients with AP.
Methods
We utilized data on patients diagnosed with AP from the Medical Information Mart for Intensive Care-IV database. The FI-Lab was calculated using a specific set of laboratory parameters indicative of physiological disturbances. The primary outcomes examined were 30-day and 90-day mortality rates. Multivariate Cox regression was used for the statistical analysis, with adjustments for age, gender, Acute Physiology and Chronic Health Evaluation II scores, and other variables. Propensity matching scores were used to ensure the robustness of our findings.
Results
A total of 1,116 AP patients were included in the analysis (mean age = 58.4 years; 57.9% male). Each 0.1 increment of FI-Lab was found to increase the risks of 30-day and 90-day mortality by 30% (hazard ratio (HR) = 1.30, p < 0.001 for both). The propensity score matching (PSM) analysis validated these results. The FI-Lab demonstrated an association with acute kidney injury and the requirement for continuous renal replacement therapy. However, these associations were not significant after the PSM analysis.
Conclusion
An elevated FI-Lab was associated with higher mortality rates among critically ill AP patients. Randomized controlled trials are needed to confirm these findings and to explore their clinical implications.
... Currently, the treatment of pancreatitis mainly includes intravenous fluid resuscitation, analgesia, enteral nutrition and organ support 28 . Recently, great progress has been made in the etiology, diagnosis, and treatment of complications of pancreatitis 29 . With the progress of clinical nutrition, critical care medicine and endoscopic technology, the treatment of pancreatitis is moving toward standardization. ...
To analyze the global burden of pancreatitis in women of childbearing age (WCBA) at the global, regional and national levels from 1990 to 2021. Data for pancreatitis incidence and deaths in females aged 15 to 49 years were downloaded from the Global Burden of Disease 2021 database. Estimated annual percentage changes (EAPCs) were calculated to describe the temporal trends. In 2021, the global numbers of incident cases and deaths of pancreatitis in the WCBA were 505,012 (409,536 to 627,684) and 7,002 (5,647 to 8,857), respectively. From 1990 to 2021, the global incidence and death rates of pancreatitis in the WCBA showed downward trends, with EAPCs of -0.15 (-0.21 to -0.09) and − 0.42 (-0.58 to -0.26), respectively. The most significant decreases in incidence and death rates were observed among females aged 40 to 44 years. Eastern Europe had the highest incidence and death rates in 2021. Countries with high socio-demographic index (SDI) showed the highest incidence rate, while showed greatest decrease in incidence during the past 32 years. The global pancreatitis incidence and death in WCBA has decreased since 1990, but the incidence is still high in countries with high-SDI. More efficient public health measures are needed to reduce the burden of pancreatitis.
... Most cases of AP are self-limited and resolve spontaneously with a favorable clinical recovery. However, the remaining approximately 20%-30% of patients may develop severe forms of AP and serious local and/or systemic complications with deterioration [6]. Severe cases may deteriorate rapidly for a brief period of time in the early stages of disease, resulting in systemic inflammatory response syndrome and even multiple organ dysfunction syndrome [7]. ...
BACKGROUND
Acute pancreatitis (AP) is an emergency gastrointestinal disease that requires immediate diagnosis and urgent clinical treatment. An accurate assessment and precise staging of severity are essential in initial intensive therapy.
AIM
To explore the prognostic value of inflammatory markers and several scoring systems [Acute Physiology and Chronic Health Evaluation II, the bedside index of severity in AP (BISAP), Ranson’s score, the computed tomography severity index (CTSI) and sequential organ failure assessment] in severity stratification of early-phase AP.
METHODS
A total of 463 patients with AP admitted to our hospital between 1 January 2021 and 30 June 2024 were retrospectively enrolled in this study. Inflammation marker and scoring system levels were calculated and compared between different severity groups. Relationships between severity and several predictors were evaluated using univariate and multivariate logistic regression models. Predictive ability was estimated using receiver operating characteristic curves.
RESULTS
Of the 463 patients, 50 (10.80%) were classified as having severe AP (SAP). The results revealed that the white cell count significantly increased, whereas the prognostic nutritional index measured within 48 hours (PNI48) and calcium (Ca2+) were decreased as the severity of AP increased (P < 0.001). According to multivariate logistic regression, C-reactive protein measured within 48 hours (CRP48), Ca2+ levels, and PNI48 were independent risk factors for predicting SAP. The area under the curve (AUC) values for the CRP48, Ca2+, PNI48, Acute Physiology and Chronic Health Evaluation II, sequential organ failure assessment, BISAP, CTSI, and Ranson scores for the prediction of SAP were 0.802, 0.736, 0.871, 0.799, 0.783, 0.895, 0.931 and 0.914, respectively. The AUC for the combined CRP48 + Ca2+ + PNI48 model was 0.892. The combination of PNI48 and Ranson achieved an AUC of 0.936.
CONCLUSION
Independent risk factors for developing SAP include CRP48, Ca2+, and PNI48. CTSI, BISAP, and the combination of PNI48 and the Ranson score can act as reliable predictors of SAP.
... AP is one of the leading causes of gastrointestinal system related causes in hospitalized patients and the incidence is increasing worldwide [14]. The disease course is variable, ranging from mild disease to organ failure and death [15]. Gallstones are the leading cause of AP worldwide. ...
Background
Acute pancreatitis (AP) is a complex disorder with gallstones being the most common underlying cause. Anatomical variations of gallbladder, cystic duct (CD), common bile duct and main pancreatic duct and their courses and interactions with each other have been studied and shown to be related to development of AP in various studies. With this study, we aimed to investigate the relationship between biliopancreatic tree anatomy and acute gallstone pancreatitis.
Materials and methods
157 gallstone related AP patients and 75 control group patients were enrolled in the study. The level at which cystic duct opened to common bile duct (as in proximal-mid-distal 1/3) and type of cystic duct course and opening (parallel to CBD, perpendicular to CBD, straight anatomy, tortuous anatomy) were evaluated from MRCP scans. Additionally, diameters of main pancreatic duct, common bile duct and angles between main pancreatic duct-common bile duct and cystic duct-common bile duct were calculated.
Results
All investigated parameters except CD opening angle were statistically significantly different between two groups. MPD opening angle was more acute in the control group. Parallel and tortuous CD was more common in the patient group. Patients with acute gallstone pancreatitis were more likely to have CD opening to the second and third parts of CBD.
Conclusion
Anatomy of the biliopancreatic tree and its variations are related to acute gallstone pancreatitis. Several proposed mechanism are thought to play role in this phenomenon but future prospective studies are required to reveal more on the topic.
... Pancreatitis is a common disease of the digestive system, which is classified as acute pancreatitis and chronic pancreatitis [1,2]. Being subordinate to pancreatitis, acute pancreatitis is one of the leading causes of hospitalization and huge medical expenses for gastrointestinal disorders [2,3], which can result in persistent organ failure, exacerbation of co-morbid disease or local complications such as peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected) [4]. A metaanalysis suggested that over the last 50 years, the overall incidence of acute pancreatitis increased by 3.07% per year [1], and in 2016 the global pooled incidence of acute pancreatitis is 34 cases per 100,000 general population per year [5], contributing to an increasing burden on health care systems world around. ...
Background
As one of the leading causes of hospitalization and huge medical expenses for gastrointestinal disorders, morbidity and mortality of acute pancreatitis continue to rise globally. Short videos are an important medium for population to achieve information about acute pancreatitis. We aimed to evaluate the content and quality of acute pancreatitis-related videos on TikTok and YouTube.
Method
A search was performed on the TikTok and YouTube platforms using the keyword “Acute pancreatitis”. The sources of the videos were categorized as academic institutions, national institutions, physicians, healthcare professionals other than physicians, health information websites and others. The Journal of American Medical Association (JAMA), Global Quality Scale (GQS), and modified DISCERN scores were used to assess the quality of the included videos.
Result
A total of 75 TikTok videos and 79 YouTube videos were included and analyzed. Regarding modified DISCERN scale, the videos from national institutions scored highest on TikTok (p = 0.020). As for YouTube, healthcare professionals other than physicians had the highest averaged score judged by GQS score and JAMA score (p = 0.016 for JAMA score, p = 0.020 for GQS score). The duration of the videos on TikTok are significantly shorter than that on YouTube (71.5 vs. 361, respectively; p < 0.01). The length of the video was associated with higher JAMA score and DISCERN score (p < 0.01, r = 0.635 and 0.207, respectively).
Conclusion
According to TikTok and YouTube, basic information about acute pancreatitis was the main presentation of the videos. We recommend that video producers extend the length of their videos appropriately to flesh out the content, and national institutions, physicians, and healthcare professionals other than physicians are all great resource of getting to know the acute pancreatitis better for viewers.
... Acute pancreatitis (AP) is a common acute abdominal disease, the incidence of which is increasing year by year, and the prognosis of patients with severe disease is poor [1,2]. The pathological features of AP are edema and necrosis of acinar cells, as well as inflammatory cell infiltration of pancreatic tissue and hemorrhage, and so on. ...
Early acute pancreatitis is an acute inflammatory disease that involves multiple modes of cell death, including apoptosis, necrotic apoptosis, and pyroptosis in its disease process. PANoptosis, a type of cell death that includes pyroptosis, apoptosis, and necroptosis, has had an important role in a variety of infectious and inflammatory diseases in recent years. To judge the relationship between PANoptosis and AP, we first analyzed the data from pancreatic transcriptome data by bioinformatics techniques, and we found the enrichment of PANoptosis pathway in AP. Next, we screened the genes and identified differentially expressed genes (DEGs) associated with AP and PANoptosis. Finally, we found that Zbp1 may have a major role in the process of PANoptosis. For this purpose, we constructed AP models in mice and in vitro cell line 266-6 and intervened by inhibiting Zbp1. The final results showed that the PANoptosis in mice was significantly suppressed after inhibition of Zbp1. In conclusion, inflammatory injury in AP can be significantly improved by inhibiting Zbp1- PANoptosome-mediated PANoptosis.
... 1 The disease can progress from a mild, self-limiting condition to severe multi-organ failure, potentially leading to death. 2 Therefore, early identification and accurate assessment of the severity of AP are crucial for improving patient prognosis. Current clinical methods for assessing the prognosis of acute pancreatitis (AP) include the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system, the Ranson scoring system, and the Computed Tomography Severity Index (CTSI). ...
Objective
To analyze the differences in Harmless Acute Pancreatitis Score (HAPS), serum Calcium/Calmodulin-dependent Protein Kinase II (CaMK II) expression, and prognosis among patients with acute pancreatitis (AP) of varying disease severities.
Methods
A retrospective analysis was conducted on the clinical data of 103 patients with acute pancreatitis (AP) treated at our hospital between April 2022 and April 2024. According to the revised Atlanta classification and the International Consensus on Definitions (2012), patients were divided into Group A (59 cases, mild cases) and Group B (44 cases, severe cases). The HAPS score was calculated using relevant examination data obtained upon admission. Fasting venous blood samples (5 mL) were collected from all subjects on the morning of the second day after admission, and serum CaMK II expression levels were measured using a double-antibody sandwich method. Patients were followed up for three months from the date of admission to record local complications, systemic complications, and mortality. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of HAPS scores and serum CaMK II levels for mild AP and patient prognosis.
Results
HAPS scores and serum CaMK II levels were assessed at admission. Severe cases showed significantly higher HAPS and CaMK II levels vs mild (P<0.05). ROC analysis demonstrated combined detection (AUC=0.902) outperformed individual markers (HAPS=0.827; CaMK II=0.773) in predicting mild AP. Both biomarkers progressively increased with complication severity (local < systemic < death, P<0.05), showing predictive value (AUC>0.6) for prognosis.
Conclusion
HAPS scores and CaMK II expression levels in AP patients show a gradual increase with the severity of the disease, and both can serve as predictive indicators of disease severity and prognosis in AP patients. Moreover, combined detection of these indicators has a higher predictive efficiency than single-item detection.
... The PUD data among WCBA analyzed in this study were derived from the 2021 GBD Study using the GBD Outcomes Tool, which provides a comprehensive scientific assessment of published, publicly available, and contributory incidence, prevalence, and mortality data for 369 diseases, injuries, and impairments, as well as 88 risk factors across 21 GBD regions and 204 countries and territories (14). As defined by the World Health Organization (WHO), WCBA refers to individuals aged 15-49 years (15). To summarize the age distribution of the burden of PUD in WCBA, patients were categorized into 7 groups: 15-19 years, 20-24 years, 25-29 years, 30-34 years, 35-39 years, 40-44 years, 45-49 years. ...
Background
Peptic ulcer disease (PUD) constitutes a significant global health concern, particularly in women of childbearing age (WCBA), who face elevated risks of severe pregnancy-associated complications. This investigation aimed to map the temporal dynamics and forecast the future incidence of PUD in this demographic to inform targeted prevention and control initiatives.
Methods
This analysis drew on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, extracting data on PUD incidence and mortality across seven age groups (15–49 years) in WCBA. Age-standardized incidence and mortality rates were calculated using the direct method of age standardization. Temporal trends from 1992 to 2021 were analyzed using joinpoint regression. The study further employed age-period-cohort analysis to discriminate the effects of these variables on incidence and mortality, and frontier analysis to evaluate potential reductions in burden by country based on developmental status. Nordpred modeling was used to project epidemiological trends up to 2044.
Results
In 2021, the global age-standardized incidence rates (ASIR) and death rates (ASDR) for PUD among WCBA were 24.18 per 100,000 (95% CI: 14.72–36.38) and 0.54 per 100,000 (95% CI: 0.42–0.66), respectively. The highest incidence rates were observed in Oceania, while the greatest mortality rates were recorded in South Asia. Over the period from 1992 to 2021, global age-standardized mortality rates showed a significant decline. Conversely, after an initial drop, age-standardized incidence rates began to rise, with considerable regional and country-specific variation. This increase was particularly marked in regions with high Socio-demographic Index (SDI). Frontier analyses indicate that countries or regions in the middle SDI quintiles possess significant untapped potential to enhance both access to and quality of healthcare. Despite predictions of declining age-standardized incidence and mortality rates, total case numbers are expected to continue rising modestly through 2044.
Conclusions
The study underscores substantial global disparities in PUD trends in WCBA, with increasing case numbers and regional inequalities. The findings highlight the need for focused attention on high SDI regions and older WCBA cohorts to refine disease management and prevention strategies, aiding in the mitigation of PUD's public health impact.
... The activation of digestive enzymes within the pancreas is commonly hypothesized as a primary trigger, 6 and several factors-including alcohol consumption, a high-fat diet, cholelithiasis, certain medications, and genetic predispositions-are known to correlate with the onset of AP. 23 The disease typically presents with symptoms such as intense abdominal pain, nausea, and vomiting, and in severe cases, it can lead to multiple organ dysfunction syndrome and even mortality. 24 Currently, the therapeutic approach to AP is primarily supportive and symptomatic, with surgical intervention required in more severe cases. 25 A comprehensive study of AP is thus crucial for advancing our understanding of its pathogenesis, refining diagnostic approaches, and improving treatment outcomes. ...
Background
Acute pancreatitis (AP) is a common disease of acute abdominal pain, the incidence of which is increasing annually, but its pathogenesis remains incompletely understood.
Methods
Gene expression profiles of AP were obtained from the Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes (DEGs) and perform functional analysis. The diagnostic value of HLA-DR-related genes was assessed by receiver operating characteristic (ROC) curves. Monocyte infiltration abundance in AP and normal groups was analyzed by Cibersort method, and the correlation between HLA-DR-related genes and monocyte abundance was analyzed. The modules highly correlated with HLA-DR-related genes were clarified by WGCNA modeling, and the core genes regulating HLA-DR were obtained by using LASSO regression. Finally, potential drugs targeting the above genes were analyzed by Enrichr database.
Result
A Total of 3 HLA-DR-related genes (HLA-DRA, HLA-DRB1, and HLA-DRB5) were identified, which were negatively correlated with the severity of AP and had excellent disease diagnostic value (AUC = 0.761, 0.761, and 0.718), were were positively correlated with monocyte abundance. We identified 110 genes that positively regulate HLA-DR and 130 genes that negatively regulate HLA-DR. LASSO regression identified UCP2, GK, and SAMHD1 as the core nodes of the regulated genes. Compared with the normal group, UCP2 and SAMHD1 were reduced in AP, and the opposite was true for GK, and SAMHD1 had better sensitivity and specificity in diagnosing AP. Drug sensitivity analysis predicted 12 drugs acting on HLA-DRA, HLA-DRB1, and HLA-DRB5 and 8 drugs acting on UCP2, GK, and SAMHD1.
Conclusion
We identified 3 HLA-DR-related genes (HLA-DRA, HLA-DRB1, and HLA-DRB5) and 3 coregulatory nodes (UCP2, GK, and SAMHD1), which were associated with AP severity and monocyte abundance. Based on these genes, we predicted 20 potential therapeutic agents for AP.
... AP remains a great financial burden on gastroenterology services around world 4 . Crohn's disease (CD) is an inflammatory bowel disease characterized by alternative periods of relapse and remission and can cause extra-intestinal manifestations and also iatrogenic complications 5 . ...
Background: Acute pancreatitis is a medical condition defined by an inflamed pancreas that comes with certain signs and symptoms. This disease has a wide range of etiologies and possible clinical presentations. In the last decade, it has become increasingly popular to write about it in the specialized literature, as it was thrust into the limelight. Even though they have a low prevalence, Crohn's disease and tumor necrosis factor-alpha that might affect the progression of the inflammatory disorder. Despite the huge therapeutic progress in the past few years, we should not forget about the physiopathology behind these complex medical situations. Case presentation: We present the case of a 64-year-old female, known with a medical history of Crohn's disease under therapy with 5-aminosalicylic acid (5-ASA) therapy and Infliximab, who presented herself to the emergency room, with diffuse abdominal pain in the epigastrium and left hypochondrium, nausea, and alteration of general condition. After careful investigation, the patient was diagnosed with acute pancreatitis, and a CT scan was performed, showing a space-occupying mass located in the caudal pancreatic region and revealed the suspicion of a pancreatic neoplasm. Further investigation (Endoscopic Ultrasound with aspiration puncture) established the presence of a cyst in the caudal region of the pancreas. To highlight the complex situation of the medical condition of our patient, in addition, she has insulin-dependent type 2 diabetes, type 2 obesity and elevated TNF-alpha levels.
... Epidemiological studies indicated a global rise in hospital admissions due to acute pancreatitis, with hundreds of thousands of cases occurring annually [2]. Despite advances in intensive care and supportive therapies, severe acute pancreatitis leaded to critical complications in up to 25% of patients, including multi-organ dysfunction syndrome and pancreatic necrosis, with a mortality rate as high as 20% [3]. The management of this disease often involves various therapeutic strategies, including the use of anticoagulants [4]. ...
Objective
Acute pancreatitis is a critical condition in the intensive care unit (ICU), often complicated by systemic issues, which may benefit from heparin therapy due to its anti-inflammatory and anticoagulant properties. However, the optimal duration of heparin therapy remained unclear. This retrospective study aimed to evaluate the association between heparin therapy duration and mortality outcomes in patients diagnosed with acute pancreatitis.
Method
This retrospective study utilized data from the Medical Information Mart for Intensive Care (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD), including 1705 patients diagnosed with acute pancreatitis between 2008 and 2019. Restricted cubic splines (RCS) were employed to analyze the non-linear relationship between heparin therapy duration and 30-day and 90-day mortality. Patients were categorized into four groups based on quartiles: < 4 days, 4–7 days, 8–14 days, and > 14 days, using characteristics identified in the RCS curves, with 4–7 days as the reference. Cox multivariate regression and Kaplan-Meier analysis assessed the association between these groups and mortality, with 30-day mortality as the primary outcome and 90-day mortality as the secondary outcome.
Result
The relationship between heparin therapy duration and mortality at 30 and 90 days in patients with acute pancreatitis exhibited a J-shaped curve, with the lowest mortality observed around 7 days for both 30-day and 90-day mortality. Heparin therapy durations less than 4 days were significantly associated with higher 30-day mortality (HR: 2.57, 95% CI: 1.53–4.30) and increased 90-day mortality (HR: 1.57, 95% CI: 1.07–2.32), with mortality stabilizing beyond 7 days of therapy. Subgroup analysis stratified by severity consistently supported these findings.
Conclusion
In critically ill patients with acute pancreatitis, heparin therapy lasting less than 4 days was associated with increased 30-day and 90-day mortality, whereas the lowest mortality was observed among patients receiving heparin therapy for approximately 7 days.
This overview delves into the comprehensive management of acute pancreatitis, covering procedures like percutaneous catheter drainage, necrosectomy, endoscopic retrograde cholangiopancreatography (ERCP), and ultrasonography-guided endoscopic cyst gastrostomy. Tailoring interventions to specific patient needs is emphasized, with considerations for special populations such as pregnant individuals and children. The conclusion underscores the importance of judicious procedure selection and ongoing monitoring for optimal outcomes.
Severe acute pancreatitis (SAP) is an acute abdominal disease with extremely high mortality; autophagy‐dependent ferroptosis plays a crucial role in acute pancreatitis. However, the specific underlying mechanism remains unclear. To investigate the role of nuclear receptor coactivator 4 (NCOA4) in SAP and the mechanism by which tetrandrine influences it. Experimental SAP models were established using L‐arginine (L‐Arg) induction to observe changes in NCOA4 expression. Knockout and overexpression experiments of NCOA4 were conducted to assess the impact on SAP. Additionally, in vitro cell experiments were performed to verify these findings. Furthermore, the impact of N‐glycosylation of NCOA4 on its function, particularly its binding ability with ferritin heavy chain 1 (FTH1), was studied. Finally, the effects of tetrandrine on N‐glycosylation of NCOA4, the binding between NCOA4 and FTH1, and the progression of SAP were analyzed. NCOA4 expression was significantly upregulated in SAP. Knockout of NCOA4 improved the phenotype of SAP, whereas its overexpression exacerbated SAP. This was also confirmed in vitro. N‐glycosylation of NCOA4 is crucial for its binding with FTH1, which in turn affects ferroptosis. Tetrandrine targets the N‐glycosylation of NCOA4, weakening the interaction between NCOA4 and FTH1, thereby inhibiting the progression of SAP. This study demonstrates that tetrandrine targets the N‐glycosylation of NCOA4, inhibiting autophagy‐dependent ferroptosis mediated by its binding to FTH1 and thus ameliorates SAP. This finding provides us with a novel therapeutic approach for SAP and offers a new perspective on understanding the mechanism of action of tetrandrine in SAP.
Background
Acute pancreatitis (AP) is the most common disease in emergency and intensive care units; early mortality predictions and intervention are crucial for improving patient prognosis. We investigated the association of serum phosphate with mortality among AP patients using a large public database.
Methods
This was a retrospective study. All AP patients in the MIMIC-IV database were included. Based on the tertiles of serum phosphate, all AP patients were divided into 3 groups. Two generalized additive models were performed to explore the association of serum phosphate with in-hospital and 30-day mortality. Kaplan-Meier analysis was introduced for survival probability.
Results
A total of 1088 AP patients admitted to the ICU were included. The mortalities of in-hospital (n=137) and 30-day (n=118) were 12.59% and 10.85%, respectively. The median levels of serum phosphate in the survivor and the non-survivor groups were 3.20 and 3.90 mg/dL, respectively ( P <0.001). After adjusting for all potential confounders, with 1 mg/dL increment in serum phosphate, the risk of in-hospital and 30-day mortality increased by 20% (HR=1.20, 95% CI: 1.00–1.44, P =0.0443) and 25% (HR=1.25, 95% CI: 1.03–1.52, P =0.0214), respectively. The areas under the ROC curve (AUC) of serum phosphate for predicting in-hospital and 30-day mortality were 0.650 (95% CI: 0.599–0.701) and 0.659 (95% CI: 0.605–0.714), respectively. The cutoff values of serum phosphate were 3.65 and 4.35 mg/dL, respectively.
Conclusions
A linear positive relationship was found between serum phosphate and in-hospital and 30-day mortality in AP. Serum phosphate was associated with in-hospital and 30-day mortality in AP. Our results could be used for screening out those AP patients with a higher risk of worse outcomes.
BACKGROUND
This study was motivated by the increased prevalence of pancreatitis, along with the considerable morbidity and socioeconomic impact caused by its severe complications. It is essential to understand pancreatitis’ association with systemic arterial disease.
METHODS
The Mendelian randomization (MR) method was used to analyze the single-nucleotide polymorphism data related to common arterial diseases in individuals with pancreatitis from the FinnGen and Genetic Consortium for Alcohol and Nicotine use databases. Causality was primarily evaluated using the inverse variance weighted method. In addition, multivariable MR (MVMR) analysis was performed to account for potential interference from alcohol-related phenotypes. Sensitivity analysis was conducted to validate the robustness of the results.
RESULTS
This study examined the relationship between four types of pancreatitis (acute pancreatitis [AP], alcohol-induced acute pancreatitis [AAP], chronic pancreatitis [CP], and alcohol-induced CP [ACP]), as well as 17 different arterial diseases. Positive results were specifically found in vascular dementia, aneurysms, and isolated proteinuria. Initial univariable MR analysis indicated an increased risk of vascular dementia in individuals with CP and ACP, as well as a higher risk of vascular dementia (multiple infarctions) in those with all types of pancreatitis. Furthermore, individuals with all types of pancreatitis were also at a greater risk of developing some types of aneurysms. Cerebral aneurysms were associated with an increased risk of CP and ACP, while isolated proteinuria seemed to have a protective effect in individuals with all types of pancreatitis. Reverse MR analysis suggested a predominantly unidirectional causal relationship between pancreatitis and systemic arterial disease. Finally, MVMR analysis showed that there was no causal effect of pancreatitis on susceptibility to vascular dementia and vascular dementia (multiple infarctions) after adjusting for alcohol consumption.
CONCLUSION
This study revealed a strong link between pancreatitis and cerebral aneurysms and other aneurysms, as well as a protective effect against isolated proteinuria. Reverse MR suggested a one-way causal relationship between pancreatitis and arterial disease. The multivariable analysis indicated that even without alcohol consumption, pancreatitis still had a strong direct causal effect on vascular diseases.
La inflamación del páncreas, llamada pancreatitis, es un motivo de consulta común, y es uno de los más representativos cuando el dolor abdominal es el motivo de consulta para acudir a una sala de emergencia; representa un alto costo para todo el sistema de salud, pues solo uno de cada tres pacientes cursa con pancreatitis moderada a grave, con un aumento significativo de morbimortalidad y tasa de complicaciones. Actualmente, las principales etiologías incluyen causas obstructivas de origen biliar o no biliar por reflujo y ausencia de flujo de enzimas al intestino que se activan en el parénquima degradándolo, el alcoholismo y la hipertrigliceridemia son mecanismos relacionados con la toxicidad celular luego del metabolismo de estas moléculas. La pancreatitis inducida por fármacos es una afección rara relacionada con antibióticos, analgésicos y antidepresivos. El deferasirox es un quelante del hierro especialmente utilizado en pacientes que necesitan múltiples transfusiones para evitar la sobrecarga de hierro. Ha sido poco correlacionado con el desarrollo de pancreatitis, aunque existen datos que podrían corroborarla; adicionalmente la farmacéutica responsable de su producción incluye esta entidad como una posible complicación en los aspectos técnicos. Este artículo presenta el caso de una paciente de 71 años de edad que desarrolló pancreatitis moderada a grave sin complicaciones importantes. Los médicos descartaron las causas más frecuentes de pancreatitis, por lo que concluyeron que el agente desencadenante fue el quelante del hierro deferasirox.
Objective
This study aimed to compare computed tomography (CT)/magnetic resonance imaging (MRI) characteristics of acute pancreatitis (AP) between patients with cholecystectomy and non-cholecystectomy and to validate the effect of prior cholecystectomy on the severity of subsequent pancreatitis.
Methods
This retrospective study included 384 inpatients with AP at our hospital from January 1, 2020 to December 31, 2023. Based on their history of cholecystectomy, the patients were split into cholecystectomy and non-cholecystectomy groups. propensity score matching was applied, considering age and sex, in a 1:3 ratio. Demographic, clinical, laboratory, and CT/MRI parameters of each group were analyzed.
Results
There were 200 (52.1%) males and 184 (47.9%) females, with a mean age of 53.55 ± 13.86 years (range: 18–98 y). Ninety-six patients were in the cholecystectomy group that had previously undergone cholecystectomy, and 288 in the non-cholecystectomy group. Creatinine and C-reactive protein levels were lower in the patients with cholecystectomy than in patients with non-cholecystectomy ( P 1 = 0.001, P 2 = 0.049). In the prevalence of biliary pancreatitis, the cholecystectomy patients are 27.1%, whereas the non-cholecystectomy patients are 45.8% ( P = 0.005). The non-cholecystectomy patients had a significantly higher mean CT/MRI severity index score (3.57 ± 1.72 points) than the cholecystectomy group (3.00 ± 1.58 points; P < 0.001). Regarding local complications, In the groups that underwent cholecystectomy and those that did not, the prevalence of acute peripancreatic fluid collection was 40.4% and 21.9%, respectively. ( P < 0.001).
Conclusions
AP following cholecystectomy exhibits unique imaging characteristics. Cholecystectomy reduces the severity and acute peripancreatic fluid collection rate of subsequent pancreatitis on CT/MRI.
INTRODUÇÃO: A coledocolitíase é uma doença caracterizada pela presença de cálculos no ducto biliar comum. O objetivo do estudo foi analisar o perfil clínico e epidemiológico de pacientes diagnosticados com essa patologia atendidos em um hospital de alta complexidade do sul de Santa Catarina entre os anos de 2018 e 2022. MÉTODOS: Foram avaliados os prontuários de 121 pacientes com coledocolitíase submetidos à colangiopancreatografia retrógrada endoscópica (CPRE). Os dados analisados foram: idade, sexo, raça, índice de massa corporal, comorbidades, manifestações clínicas, diagnóstico, tipo de tratamento e presença de divertículo periampular. RESULTADOS: Foi observado que 62% dos pacientes eram do sexo feminino e a média de idade foi de 56,5 anos. Notou-se que 38,8% dos indivíduos possuíam sobrepeso e 27,3% obesidade. Ademais, as manifestações clínicas apresentadas por 58,7% dos indivíduos foram dor abdominal associada à icterícia, e o método diagnóstico mais utilizado foi colangiografia por ressonância magnética (76,0%). Ainda, o tratamento recorrido foi a CPRE, que em 55,4% dos pacientes foi feita isolada e em 39,7% foi associada à cirurgia videolaparoscópica. Por fim, encontrou-se divertículo periampular presente em 9,9% dos pacientes. CONCLUSÃO: Esse estudo destacou a ocorrência de coledocolitíase em mulheres com sobrepeso e obesidade; também, mostrou-se condizente com a literatura acerca da presença de divertículos periampulares em pacientes com coledocolitíase.
Acute pancreatitis may require hospitalization and intensive care unit admission, and, therefore, it is crucial for critical care pharmacists to possess the ability to manage patients with this disease state. Effective treatment involves appropriate fluid resuscitation, pain control, nutritional support, and, in some cases, antimicrobial therapy. In severe cases, acute pancreatitis can progress to cause end-organ failure. Identifying the underlying cause of the disease is imperative to prevent both recurrence and development of chronic pancreatitis. This chapter offers pharmacists fundamental insights into understanding the causes, mechanisms, diagnosis, treatment, and post-hospitalization care for patients with acute pancreatitis.
BACKGROUND
Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis (AP). Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.
AIM
To explore the biological processes and mechanisms of intestinal injury associated with AP, and to find potential targets for early prevention or treatment of intestinal barrier injury.
METHODS
This study utilized single-cell RNA sequencing of the small intestine, alongside in vitro and in vivo experiments, to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.
RESULTS
Seventeen major cell types and 33232 cells were identified across all samples, including normal, AP1 (4x caerulein injections, animals sacrificed 2 h after the last injection), and AP2 (8x caerulein injections, animals sacrificed 4 h after the last injection). An average of 980 genes per cell was found in the normal intestine, compared to 927 in the AP1 intestine and 1382 in the AP2 intestine. B cells, dendritic cells, mast cells (MCs), and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine. Enterocytes, brush cells, enteroendocrine cells, and goblet cells maintained numbers similar to the normal intestine, while cytotoxic T cells and natural killer (NK) cells increased. Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities. Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities. Activated MCs, secreted chemokine (C-C motif) ligand 5 (CCL5), promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.
CONCLUSION
These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury, suggesting that CCL5 from MCs is a potential target for addressing dysfunction.
Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20% of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered.
Background/objectives:
The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis.
Methods:
Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests.
Results:
Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests.
Conclusions:
The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.
Background
Acute pancreatitis (AP) is a common and expensive condition. Improving quality of care in AP is vital to minimizing cost and improving patient outcomes. However, there has been little work accomplished toward developing and validating explicit quality indicators (QIs) in AP.
Aims
To define quality of care in patients with AP by developing explicit QIs using standardized techniques.
Methods
We used the UCLA/RAND Delphi panel approach to combine a comprehensive literature review with the collective judgment of experts to identify a defined set of process measures for AP.
Results
We produced 164 candidate QIs after a comprehensive literature review. After Delphi review, 75 had a median rating ≥ 7. We excluded 11 QIs where the disagreement index exceeded 1.0 and combined indicators overlapping in content to produce a final list of 22 QIs. Overall, 8 QIs related to diagnosis, prevention, or determination of etiology, 2 QIs focused on determination of severity, 3 QIs captured fluid resuscitation, 2 QIs measured nutrition, 1 QI use of antibiotics, and 6 QIs captured endoscopic or surgical management.
Conclusions
We have developed 22 QIs spanning the spectrum of AP management including diagnosis, risk stratification, and pharmacological and endoscopic therapy. These QIs will facilitate future quality improvement by practitioners and organizations who treat patients with AP and further identify areas that are amenable to improvement to enhance patient care. We anticipate that this QI set will represent the first step in determining a framework for demonstrating value in the care of patients with AP.
Aims:
To assess the severity of acute pancreatitis (AP) using computed tomography (CT) severity index (CTSI) and modified CT severity index (MCTSI), to correlate with clinical outcome measures, and to assess concordance with severity grading, as per the revised Atlanta classification (RAC).
Materials and methods:
In this prospective study approved by the Institutional Review Board (November 2014 to March 2016), sixty patients with AP (as per the RAC definition) underwent contrast-enhanced computed tomography (CECT) 5-11 days (median 6 days) after symptom onset. Two radiologists, blinded to clinical parameters, independently assessed CTSI and MCTSI (differences were resolved by consensus). Clinical outcome parameters included duration of stay in the hospital and intensive care unit (ICU), presence of persistent organ failure (OF), evidence of infection, need for intervention, and mortality.
Results:
We included 60 cases [36 males, age range 19-65 (mean 37) years]. As per the RAC, 26 patients had mild AP, 12 moderately severe, and 22 severe AP. According to CTSI and MCTSI, mild, moderate, and severe cases were 27 (45%), 19 (31.7%), 14 (23.3%) and 24 (40%), 10 (16.7%), 26 (43.3%), respectively. MCTSI was concordant with the RAC grading in 54 (90.0%), CTSI was concordant in 47 (78.3%), and both were concordant in 43 (71.7%) cases. Area under the receiver-operating characteristic (ROC) curves (AUROC) was compared by the Hanley and McNeil method. Both CTSI and MCTSI were significantly associated with outcome parameters (P < 0.001), except duration of ICU stay. Sensitivity, specificity, positive predictive value (PPV), and accuracy of CTSI for detecting moderate/severe disease were 97.1%, 100%, 100%, and 98.3% respectively, and of MCTSI were 100%, 92.3%, 94.4%, and 96.7% respectively.
Conclusion:
Both CTSI and MCTSI showed significant correlation with clinical outcome parameters, and good concordance with RAC grading of severity. MCTSI showed a higher sensitivity but lower specificity than CTSI in differentiating mild from moderate/severe AP.
Background We have established a multicenter international consortium to better understand
the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future
randomized clinical trials.
Methods Th e AP patient registry to examine novel therapies in clinical experience (APPRENTICE)
was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively
capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors,
severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes
of AP patients.
Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States,
5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP
patients. All data were entered into the REDCap (Research Electronic Data Capture) database
by participating centers and systematically reviewed by the coordinating site (University of
Pittsburgh). Th e approaches and methodology are described in detail, along with an interim
report on the demographic results.
Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout
the world, has demonstrated the feasibility of building a large, prospective, multicenter patient
registry to study AP. Analysis of the collected data may provide a greater understanding of AP and
APPRENTICE will serve as a future platform for randomized clinical trials.
Keywords Acute pancreatitis, international multicenter consortium, methodology, APPRENTICE
Background:
We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials.
Methods:
The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients.
Results:
Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results.
Conclusion:
APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.
Objective
The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP.
Design
Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group.
Patients
600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013.
Main Results
With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality.
Conclusions
Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP.
Background:
Early enteral feeding through a nasoenteric feeding tube is often used in patients with severe acute pancreatitis to prevent gut-derived infections, but evidence to support this strategy is limited. We conducted a multicenter, randomized trial comparing early nasoenteric tube feeding with an oral diet at 72 hours after presentation to the emergency department in patients with acute pancreatitis.
Methods:
We enrolled patients with acute pancreatitis who were at high risk for complications on the basis of an Acute Physiology and Chronic Health Evaluation II score of 8 or higher (on a scale of 0 to 71, with higher scores indicating more severe disease), an Imrie or modified Glasgow score of 3 or higher (on a scale of 0 to 8, with higher scores indicating more severe disease), or a serum C-reactive protein level of more than 150 mg per liter. Patients were randomly assigned to nasoenteric tube feeding within 24 hours after randomization (early group) or to an oral diet initiated 72 hours after presentation (on-demand group), with tube feeding provided if the oral diet was not tolerated. The primary end point was a composite of major infection (infected pancreatic necrosis, bacteremia, or pneumonia) or death during 6 months of follow-up.
Results:
A total of 208 patients were enrolled at 19 Dutch hospitals. The primary end point occurred in 30 of 101 patients (30%) in the early group and in 28 of 104 (27%) in the on-demand group (risk ratio, 1.07; 95% confidence interval, 0.79 to 1.44; P=0.76). There were no significant differences between the early group and the on-demand group in the rate of major infection (25% and 26%, respectively; P=0.87) or death (11% and 7%, respectively; P=0.33). In the on-demand group, 72 patients (69%) tolerated an oral diet and did not require tube feeding.
Conclusions:
This trial did not show the superiority of early nasoenteric tube feeding, as compared with an oral diet after 72 hours, in reducing the rate of infection or death in patients with acute pancreatitis at high risk for complications. (Funded by the Netherlands Organization for Health Research and Development and others; PYTHON Current Controlled Trials number, ISRCTN18170985.).
Background and objective The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the disease make a revision necessary.
Methods A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained.
Results The revised classification of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images.
Conclusions This international, web-based consensus provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.
To compare non-liquid and clear-liquid diets, and to assess whether the latter is the optimal treatment for mild acute pancreatitis.
The Cochrane Library, PUBMED, EMBASE, EBM review databases, Science Citation Index Expanded, and several Chinese databases were searched up to March 2011. Randomized controlled trials (RCTs) that compared non-liquid with clear-liquid diets in patients with mild acute pancreatitis were included. A meta-analysis was performed using available evidence from RCTs.
Three RCTs of adequate quality involving a total of 362 participants were included in the final analysis. Compared to liquid diet, non-liquid diet significantly decreased the length of hospitalization [mean difference (MD): 1.18, 95% CI: 0.82-1.55; P﹤0.00001] and total length of hospitalization (MD: 1.31, 95% CI: 0.45-2.17; P = 0.003). The subgroup analysis showed solid diet was more favorable than clear liquid diet in the length of hospitalization, with a pooled MD being -1.05 (95% CI: -1.43 to -0.66; P﹤0.00001). However, compared with clear liquid diet, both soft and solid diets did not show any significant differences for recurrence of pain after re-feeding, either alone [relative risk (RR): 0.95; 95% CI: 0.51-1.87; P = 0.88] and (RR: 1.22; 95% CI: 0.69-2.16; P = 0.49), respectively, or analyzed together as non-liquid diet (RR: 0.80; 95% CI: 0.47-1.36; P = 0.41).
The non-liquid soft or solid diet did not increase pain recurrence after re-feeding, compared with the clear-liquid diet. The non-liquid diet reduced hospitalization.
Identification of patients at risk for mortality early in the course of acute pancreatitis (AP) is an important step in improving outcome.
Using Classification and Regression Tree (CART) analysis, a clinical scoring system was developed for prediction of in-hospital mortality in AP. The scoring system was derived on data collected from 17,992 cases of AP from 212 hospitals in 2000-2001. The new scoring system was validated on data collected from 18,256 AP cases from 177 hospitals in 2004-2005. The accuracy of the scoring system for prediction of mortality was measured by the area under the receiver operating characteristic curve (AUC). The performance of the new scoring system was further validated by comparing its predictive accuracy with that of Acute Physiology and Chronic Health Examination (APACHE) II.
CART analysis identified five variables for prediction of in-hospital mortality. One point is assigned for the presence of each of the following during the first 24 h: blood urea nitrogen (BUN) >25 mg/dl; impaired mental status; systemic inflammatory response syndrome (SIRS); age >60 years; or the presence of a pleural effusion (BISAP). Mortality ranged from >20% in the highest risk group to <1% in the lowest risk group. In the validation cohort, the BISAP AUC was 0.82 (95% CI 0.79 to 0.84) versus APACHE II AUC of 0.83 (95% CI 0.80 to 0.85).
A new mortality-based prognostic scoring system for use in AP has been derived and validated. The BISAP is a simple and accurate method for the early identification of patients at increased risk for in-hospital mortality.
Several clinical guidelines exist for acute pancreatitis, with varying recommendations. The aim of this study was to determine the quality of guidelines for acute pancreatitis.
A literature search identified relevant guidelines, which were then reviewed to determine their document format and scope and the presence of endorsement by a professional body. The quality of guidelines was determined using the validated Grilli, Shaneyfelt, and AGREE instruments.
Twenty-one of the 30 guidelines analyzed were endorsed by professional bodies. Median quality scores were as follows: Grilli, 2; Shaneyfelt, 13; and AGREE, 50. Guideline quality did not improve over time. Guidelines endorsed by a professional body had higher scores than those without official endorsement. Guidelines with tables, a recommendations summary, evidence grading, and audit goals had significantly higher scores than guidelines lacking those features.
The many clinical guidelines for acute pancreatitis range widely in quality. Guidelines developed by professional bodies, and those with tables, a recommendations summary, evidence grading, and audit goals, are of higher quality. Further research is required to determine whether guideline quality alters clinical outcomes.
Our aim was to prospectively evaluate the ability of the bedside index for severity in acute pancreatitis (BISAP) score to predict mortality as well as intermediate markers of severity in a tertiary center.
The BISAP score was evaluated among 397 consecutive cases of acute pancreatitis admitted to our institution between June 2005 and December 2007. BISAP scores were calculated on all cases using data within 24 h of presentation. The ability of the BISAP score to predict mortality was evaluated using trend and discrimination analysis. The optimal cutoff score for mortality from the receiver operating curve was used to evaluate the development of organ failure, persistent organ failure, and pancreatic necrosis.
Among 397 cases, there were 14 (3.5%) deaths. There was a statistically significant trend for increasing mortality (P < 0.0001) with increasing BISAP score. The area under the receiver operating curve for mortality by BISAP score in the prospective cohort was 0.82 (95% confidence interval: 0.70, 0.95), which was similar to that of the previously published validation cohort. A BISAP score >or=3 was associated with an increased risk of developing organ failure (odds ratio=7.4, 95% confidence interval: 2.8, 19.5), persistent organ failure (odds ratio=12.7, 95% confidence interval: 4.7, 33.9), and pancreatic necrosis (odds ratio=3.8, 95% confidence interval: 1.8, 8.5).
The BISAP score represents a simple way to identify patients at risk of increased mortality and the development of intermediate markers of severity within 24 h of presentation. This risk stratification capability can be utilized to improve clinical care and facilitate enrollment in clinical trials.
Drug-induced acute pancreatitis (DIAP) is a rare entity that is often challenging for clinicians. The aim of our study was to provide updated DIAP classes considering the updated definition of acute pancreatitis (AP) and in light of new medications and new case reports. A MEDLINE search (1950–2018) of the English language literature was performed looking for all adult (≥17 years old) human case reports with medication/drug induced as the cause of AP. The included case reports were required to provide the name of the drug, and diagnosis of AP must have been strictly established based on the revised Atlanta Classification criteria. A total of 183 medications were found to be implicated in 577 DIAP cases. A total of 78 cases were excluded because of minimal details or lack of definite diagnosis of AP. Drug-induced AP is rare, and most drugs cause mild DIAP. Only 2 drugs are well described in the literature to explain causation rather than association (azathioprine and didanosine). Larger case-control studies and a formal standardized DIAP reporting system are essential to study the true potential of the DIAP-implicated drugs described in this review.
Introduction:
Early cholecystectomy shortly after admission for mild gallstone pancreatitis has been proposed based on observational data. We hypothesized that cholecystectomy within 24 hours of admission versus after clinical resolution of gallstone pancreatitis that is predicted to be mild results in decreased length-of-stay (LOS) without an increase in complications.
Methods:
Adults with predicted mild gallstone pancreatitis were randomized to cholecystectomy with cholangiogram within 24 hours of presentation (early group) versus after clinical resolution (control) based on abdominal exam and normalized laboratory values. Primary outcome was 30-day LOS including readmissions. Secondary outcomes were time to surgery, endoscopic retrograde cholangiopancreatography (ERCP) rates, and postoperative complications. Frequentist and Bayesian intention-to-treat analyses were performed.
Results:
Baseline characteristics were similar in the early (n = 49) and control (n = 48) groups. Early group had fewer ERCPs (15% vs 29%, P = 0.038), faster time to surgery (16 h vs 43 h, P < 0.005), and shorter 30-day LOS (50 h vs 77 h, RR 0.68 95% CI 0.65 - 0.71, P < 0.005). Complication rates were 6% in early group versus 2% in controls (P = 0.613), which included recurrence/progression of pancreatitis (2 early, 1 control) and a cystic duct stump leak (early). On Bayesian analysis, early cholecystectomy has a 99% probability of reducing 30-day LOS, 93% probability of decreasing ERCP use, and 72% probability of increasing complications.
Conclusion:
In patients with predicted mild gallstone pancreatitis, cholecystectomy within 24 hours of admission reduced rate of ERCPs, time to surgery, and 30-day length-of-stay. Minor complications may be increased with early cholecystectomy. Identification of patients with predicted mild gallstone pancreatitis in whom early cholecystectomy is safe warrants further investigation.
Objectives:
The aim of this study was to determine the recent trends of the rates of hospitalization, mortality of hospitalized patients, and associated health care utilization in patients with acute pancreatitis (AP).
Methods:
We identified adult patients with primary discharge diagnosis of AP from the National Inpatient Sample database. Patients with chronic pancreatitis and/or pancreatic cancer were excluded. Primary outcomes included age-adjusted incidence of AP and in-hospital mortality based on US standard population derived from the 2000 census data. Secondary outcomes were length of stay, inflation-adjusted hospital costs in 2014 US dollars, and procedural rates. Subgroup analysis included disease etiologies, age, race, sex, hospital region, hospital size, and institution type.
Results:
From 2001 to 2014, the rate of primary discharge diagnosis for AP increased from 65.38 to 81.88 per 100,000 US adults per year. In-hospital case fatality decreased from 1.68% to 0.69%. Mortality rate is higher in patients with AP who are older than 65 years (3.4%). Length of stay decreased, with a median of 3.8 days; cost per hospitalization decreased since 2007 from 6766 in 2014.
Conclusions:
The rate of hospitalization related to AP in the United States continues to increase. Mortality, length of stay, and cost per hospitalization decrease. The increase in volume of hospitalization might contribute to an overall increase in health care resource utilization.
Objective: To study the outcome of acute pancreatitis and risk factors for recurrent and chronic pancreatitis in a population based cohort of patients with first-time acute pancreatitis.
Methods: All patients with first-time acute pancreatitis from 2006–2015 in Iceland were retrospectively evaluated. Medical records were scrutinized and relevant data extracted.
Results: 1102 cases of first-time acute pancreatitis were identified: mean age 56yr, 46% female, 41% biliary, 21% alcohol, 26% idiopathic, 13% other causes, mean follow-up 4yr. 21% had ≥1 recurrent acute pancreatitis which was independently related to alcoholic (vs. biliary hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.51–3.46), male gender (HR 1.48, 95%CI 1.08–2.04), and smoking (HR 1.62, 95%CI 1.15–2.28). 3.7% developed chronic pancreatitis. Independent predictors were recurrent acute pancreatitis (HR 8.79, 95%CI 3.94–19.62), alcoholic (vs. biliary HR 9.16, 95%CI 2.71–30.9), local complications (HR 4.77, 95%CI 1.93–11.79), and organ-failure (HR 2.86, 95%CI 1.10–7.42).
Conclusions: Recurrent acute pancreatitis occurred in one-fifth of patients. Development of chronic pancreatitis was infrequent. Both recurrent acute pancreatitis and chronic pancreatitis were related to alcoholic acute pancreatitis, while recurrent acute pancreatitis was associated with smoking and male gender, and chronic pancreatitis to recurrent acute pancreatitis, organ-failure, and local complications.
Objectives:
We sought to examine temporal trends in incidence and outcomes of acute pancreatitis (AP) in hospitalized adult patients in the United States.
Methods:
Subjects were obtained from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database using International Classification of Diseases, Ninth Revision, Clinical Modification codes for the years 2002-2013. Incidence of AP, all-cause mortality, cost, and duration of hospitalization were assessed.
Results:
We identified 4,791,802 cases of AP. A significant increase in the incidence of AP was observed from 9.48 cases per 1000 hospitalizations in 2002 to 12.19 per 1000 hospitalizations in 2013 (P < 0.001). In-hospital mortality decreased from 2.99 cases per 100 cases in 2002 to 2.04 cases per 100 cases in 2013 (P < 0.001). Mean length of stay decreased from 6.99 (standard deviation [SD], 9.37) days in 2002 to 5.74 (SD, 7.94) days in 2013 (P < 0.001). Cost of hospitalization increased from 54,556) in 2002 to 106,205) in 2013 (P < 0.001).
Conclusions:
Hospital admissions for AP in adults increased significantly in the United States from 2002 to 2013. In-hospital all-cause mortality and mean length of stay significantly decreased. In contrast, total cost of hospitalization rose.
Background:
Gallstones and alcohol are currently the most frequent aetiologies of acute pancreatitis (AP). The aim of this study is to quantify these aetiologies worldwide, by geographic region and by diagnostic method.
Methods:
A systematic review of observational studies published from January 2006 to October 2017 was performed. The studies provided objective criteria for establishing the diagnosis and aetiology of AP for at least biliary and alcoholic causes. A random-effects meta-analysis was used to assess the frequency of biliary (ABP), alcoholic (AAP) and idiopathic AP (IAP) worldwide and to perform 6 subgroup analyses: 2 compared diagnostic methods for AP aetiology and the other 4 compared geographic regions.
Results:
Forty-six studies representing 2,341,007 patients of AP in 36 countries were included. The global estimate of proportion (95% CI) of aetiologies was 42 (39-44)% for ABP, 21 (17-25)% for AAP and 18 (15-22)% for IAP. In studies that used discharge code diagnoses and in those from the US, IAP was the most frequent aetiology. ABP was more frequent in Latin America than in other regions.
Conclusion:
Gallstones represent the main aetiology of AP globally, and this aetiology is twice as frequent as the second most common aetiology.
Background:
There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach.
Methods:
Twelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting.
Results:
The 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as 'strong' and plenary voting revealed 'strong agreement' for 34 (89%) recommendations.
Conclusions:
The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis.
Gallstones are the most common cause of acute pancreatitis in the United States.¹⁻⁵ The timing of cholecystectomy among patients with mild gallstone pancreatitis (GSP) remains controversial.¹⁻⁶ Many institutions delay laparoscopic cholecystectomy (LC) for mild GSP until normalization of laboratory values and resolution of abdominal pain, fearing early surgery may increase complications.¹,3
Background/Objectives
Aggressive fluid resuscitation is recommended for initial management of acute pancreatitis. However, there are few studies which focus on types of fluid therapy.
Methods
We performed a randomized controlled trial in patients with acute pancreatitis. The patients were randomized into two groups. Each group received Normal Saline solution (NSS) or Lactated Ringer's solution (LRS) through a goal-directed fluid resuscitation protocol. Systemic inflammatory response syndrome (SIRS) at 24 and 48 h, mortality, presence of local complications and inflammatory markers were measured.
Results
Forty-seven patients were included. Twenty-four patients (51%) received NSS and 23 patients received LRS. There was significant reduction in SIRS after 24 h among subjects who resuscitated with LRS compared with NSS (4.2% in NSS, 26.1% in LRS, P = 0.02). However, SIRS reduction at 48 h was not different between groups (33.4% in NSS, 26.1% in LRS, P = 0.88). Mortality was not different between NSS and LRS (4.2% in NSS, 0% in LRS, P = 1.00). CRP, ESR and procalcitonin increased at 24 h and 48 h after admission with no difference between the two groups. Local complications were 29.2% in NSS and 21.7% in LRS (P = 0.74). The median length of hospital stay was not significantly different in the two groups (5.5 days in NSS, 6 days in LRS, P = 0.915).
Conclusions
Lactated Ringer's solution was superior to NSS in SIRS reduction in acute pancreatitis only in the first 24 h. But SIRS at 48 h and mortality were not different between LRS and NSS.
Background & aims:
Epidemiologic analyses of acute and chronic pancreatitis (AP and CP) provide insight into causes and strategies for prevention, and affect allocation of resources to its study and treatment. We sought to determine current and accurate incidences of AP and CP, along with the prevalence of CP, in children and adults in the United States.
Methods:
We collected data from the Truven MarketScan Research Databases of commercial inpatient and outpatient insurance claims in the United States from 2007 through 2014 (patients 0-64 years old). We calculated the incidences of AP and CP, and prevalence of CP, based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Children were defined as 18 years or younger and adults as 19 to 64 years old.
Results:
The incidence of pediatric AP was stable from 2007 through 2014, remaining at 12.3/100,000 persons in 2014. Meanwhile the incidence for adult AP decreased from 123.7/100,000 persons in 2007 to 111.2/100,000 persons in 2014. The incidence of CP decreased over time in children (2.2/100,000 persons in 2007 to 1.9/100,000 persons in 2014) and adults (31.7/100,000 persons in 2007 to 24.7/100,000 persons in 2014). The prevalence of pediatric and adult CP was 5.8/100,000 persons and 91.9/100,000 persons, respectively in 2014. Incidences of AP and CP increased with age; we found little change in incidence during the first decade of life, but linear increases starting in the second decade.
Conclusions:
We performed a comprehensive epidemiologic analysis of privately insured non-elderly adults and children with AP and CP in the United States. Changes in gallstone formation, smoking, and alcohol consumption, along with advances in pancreatitis management, may be responsible for the stabilization and even decrease in the incidences of AP and CP.
Introduction:
Acute pancreatitis (AP) is the most common gastroenterology-related reason for hospital admission, and a major source of morbidity and mortality in the United States. This study examines the National Emergency Database Sample, a large national database, to analyze trends in emergency department (ED) utilization and costs, risk factors for hospital admission, and associated hospital costs and length of stay (LOS) in patients presenting with AP.
Methods:
The National Emergency Database Sample (2006 to 2012) was evaluated for trends in ED visits, ED charges, hospitalization rates, hospital charges, and hospital LOS in patients with primary diagnosis of AP (further subcategorized by age and etiology). A survey logistic-regression model was used to determine factors predictive of hospitalization.
Results:
A total of 2,193,830 ED visits were analyzed. There was a nonsignificant 5.5% (P=0.07) increase in incidence of ED visits for AP per 10,000 US adults from 2006 to 2012, largely driven by significant increases in ED visits for AP in the 18 to <45 age group (+9.2%; P=0.025), AP associated with alcohol (+15.9%; P=0.001), and AP associated with chronic pancreatitis (+59.5%; P=0.002). Visits for patients aged ≥65 decreased over the time period. Rates of admission and LOS decreased during the time period, while ED and inpatient costs increased (62.1%; P<0.001 and 7.9%; P=0.0011, respectively). Multiple factors were associated with increased risk of hospital admission from the ED, with the strongest predictors being morbid alcohol use [odds ratio (OR), 4.53; P<0.0001], advanced age (age>84 OR, 3.52; P<0.0001), and smoking (OR, 1.75; P<0.0001).
Conclusions:
Despite a relative stabilization in the overall incidence of ED visits for AP, continued increases in ED visits and associated costs appear to be driven by younger patients with alcohol-associated and acute on chronic pancreatitis. While rates of hospitalization and LOS are decreasing, associated inflation-adjusted costs are rising. In addition, identified risk factors for hospitalization, such as obesity, alcohol use, and increased age, should be explored in further study for potential use in predictive models and clinical improvement projects.
PurposeTo investigate whether computed tomography (CT)-based scoring systems obtained within 72 h of symptoms onset can predict disease course in acute pancreatitis. Methods
Between October 2007 and December 2015, 189 patients (age range 21–93 years) who underwent abdominopelvic CT for the diagnosis of acute pancreatitis were included in the study. Balthazar grade and original and modified versions of CT severity index (CTSI) measurements were carried out for each patient. ResultsThere were significant associations between each CT based scoring system and development of pancreatic and extrapancreatic complications (p < 0.001). A cutoff value of > 6 for CTSI and > 9 for the modified version of CTSI achieved a specificity of 98.7 and 99.2% for predicting pancreatic and extrapancreatic complications with areas under the curve (AUC) of 0.96 and 0.96, respectively. Balthazar grade of > C yielded a sensitivity of 98.4% for predicting pancreatic and extrapancreatic complications with an AUC of 0.95. The modified version of CTSI had the most significant association with pancreatic and extrapancreatic complications (HR: 3.22; p = 0.002, HR: 2.99, p = 0.003, respectively). Pancreatic necrosis was the only parameter significantly associated with mortality (HR: 5.83, p = 0.045). Conclusion
Early CT scan has an important role in prediction of complications and the management of acute pancreatitis.
Objectives:
The epidemiological trends contributing to increasing acute pancreatitis (AP) hospitalizations remain unknown. We sought to analyze etiological factors and outcomes of increasing AP hospitalizations.
Methods:
Utilizing the Nationwide Inpatient Sample, retrospective analyses of adult (≥18 years) inpatient admissions with a primary diagnosis of AP (N = 2,016,045) were performed. Patient hospitalizations from 2009 to 2012 were compared with those from 2002 to 2005.
Results:
Compared with 2002-2005, there was a 13.2% (P < 0.001) increase in AP admissions in 2009-2012. Multivariate analysis adjusted for "period," patient and hospital demographics, AP etiologies, and disease associations demonstrated an increase in the odds of associated chronic pancreatitis (CP) [2002-2005: odds ratio, (OR), 32.04; 95% confidence interval (CI), 30.51-33.64; 2009-2012: OR, 35.02; 95% CI, 33.94-36.14], whereas associated odds of gallstones (2002-2005: OR, 36.37; 95% CI, 35.32-37.46; 2009-2012: OR, 29.85; 95% CI, 29.09-30.64) decreased. Compared with 2002-2005, the AP-related mortality decreased in 2009-2012 (1.62%-0.79%, P < 0.001) and was lower in AP with associated CP (0.65%-0.26%; P < 0.001) compared with AP without CP.
Conclusion:
In the preceding decade, AP hospitalizations are increasing, but associated mortality is declining. Associated CP has emerged as a leading contributor for AP-related hospitalizations. Further research is needed to identify novel interventions to prevent disease progression of AP.
This review summarizes recent changes in the management of acute pancreatitis, encompassing fluid resuscitation, antibiotic use, nutritional support, and treatment of necrosis, and also addresses common misunderstandings and areas of controversy.
The 2012 revised Atlanta classification is an update of the original 1992 Atlanta classification, a standardized clinical and radiologic nomenclature for acute pancreatitis and associated complications based on research advances made over the past 2 decades. Acute pancreatitis is now divided into two distinct subtypes, necrotizing pancreatitis and interstitial edematous pancreatitis (IEP), based on the presence or absence of necrosis, respectively. The revised classification system also updates confusing and sometimes inaccurate terminology that was previously used to describe pancreatic and peripancreatic collections. As such, use of the terms acute pseudocyst and pancreatic abscess is now discouraged. Instead, four distinct collection subtypes are identified on the basis of the presence of pancreatic necrosis and time elapsed since the onset of pancreatitis. Acute peripancreatic fluid collections (APFCs) and pseudocysts occur in IEP and contain fluid only. Acute necrotic collections (ANCs) and walled-off necrosis (WON) occur only in patients with necrotizing pancreatitis and contain variable amounts of fluid and necrotic debris. APFCs and ANCs occur within 4 weeks of disease onset. After this time, APFCs or ANCs may either resolve or persist, developing a mature wall to become a pseudocyst or a WON, respectively. Any collection subtype may become infected and manifest as internal gas, though this occurs most commonly in necrotic collections. In this review, the authors present a practical image-rich guide to the revised Atlanta classification system, with the goal of fostering implementation of the revised system into radiology practice, thereby facilitating accurate communication among clinicians and reinforcing the radiologist's role as a key member of a multidisciplinary team in treating patients with acute pancreatitis. (©)RSNA, 2016.
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of nasogastric versus nasojejunal tube feeding for people with severe acute pancreatitis.
Background: Acute pancreatitis is a common and potentially lethal disease with increasing incidence. Severe cases are characterised by high mortality, and despite improvements in intensive care management, no specific treatment relevantly improves clinical outcomes of the disease. Meta-analyses suggest that enteral nutrition is more effective than conventional treatment consisting of discontinuation of oral intake with use of total parenteral nutrition. However, no systematic review has compared different enteral nutrition formulations for the treatment of patients with acute pancreatitis.
Objectives: To assess the beneficial and harmful effects of different enteral nutrition formulations in patients with acute pancreatitis.
Search methods: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Specialised Register of Clinical Trials, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 7), MEDLINE (from inception to 20 August 2013), EMBASE (from inception to 2013, week 33) and Science Citation Index–Expanded (from 1990 to August 2013); we conducted full-text searches and applied no restrictions by language or publication status.
Selection criteria: We considered randomised clinical trials assessing enteral nutrition in patients with acute pancreatitis. We allowed concomitant interventions if they were received equally by all treatment groups within a trial.
Data collection and analysis: Two review authors independently assessed trials for inclusion and extracted data. We performed the analysis using Review Manager 5 (Review Manager 2013) and both fixed-effect and random-effects models. We expressed results as risk ratios (RRs) for dichotomous data, and as mean differences (MDs) for continuous data, both with 95% confidence intervals (CIs). Analysis was based on an intention-to-treat principle.
Main results: We included 15 trials (1376 participants) in this review. We downgraded the quality of evidence for many of our outcomes on the basis of high risk of bias. Low-quality evidence suggests that immunonutrition decreases all-cause mortality (RR 0.49, 95% CI 0.29 to 0.80). The effect of immunonutrition on other outcomes from a subset of the included trials was uncertain. Subgrouping trials by type of enteral nutrition did not explain any variation in effect. We found mainly very low-quality evidence for the effects of probiotics on the main outcomes. One eligible trial in this comparison reported a higher rate of serious adverse events leading to increased organ failure and mortality due to low numbers of events and low risk of bias. When we excluded this study as a post hoc sensitivity analysis, risks of mortality (RR 0.30, 95% CI 0.10 to 0.84), organ failure (RR 0.74, 95% CI 0.59 to 0.92) and local septic complications (RR 0.40, 95% CI 0.22 to 0.72) were lower with probiotics. In one trial assessing immunonutrition with probiotics and fibres, no deaths occurred, but hospital stay was shorter with immunonutrition (MD -5.20 days, 95% CI -8.73 to -1.67). No deaths were reported following semi-elemental enteral nutrition (EN), and the effect on length of hospital stay was small (MD 0.30 days, 95% CI -0.82 to 1.42). Fibre-enriched formulations reduced the number of other local complications (RR 0.52, 95% CI 0.32 to 0.87) and length of hospital stay (MD -9.28 days, 95% CI -13.21 to -5.35) but did not significantly affect all-cause mortality (RR 0.23, 95% CI 0.03 to 1.84) and other outcomes. Very low-quality evidence from the subgroup of trials comparing EN versus no intervention showed a decrease in all-cause mortality with EN (RR 0.50, 95% CI 0.29 to 0.86).
Authors' conclusions: We found evidence of low or very low quality for the effects of immunonutrition on efficacy and safety outcomes. The role of supplementation of enteral nutrition with potential immunomodulatory agents remains in question, and further research is required in this area. Studies assessing probiotics yielded inconsistent and almost contrary results, especially regarding safety and adverse events, and their findings do not support the routine use of EN enriched with probiotics in routine clinical practice. However, further research should be carried out to try to determine the potential efficacy or harms of probiotics. Lack of trials reporting on other types of EN assessed and lack of firm evidence regarding their effects suggest that additional randomised clinical trials are needed. The quality of evidence for the effects of any kind of EN on mortality was low, and further studies are likely to have an impact on the finding of improved survival with EN versus no nutritional support. Evidence remains insufficient to support the use of a specific EN formulation.
Acute pancreatitis, an inflammatory disorder of the pancreas, is the leading cause of admission to hospital for gastrointestinal disorders in the USA and many other countries. Gallstones and alcohol misuse are long-established risk factors, but several new causes have emerged that, together with new aspects of pathophysiology, improve understanding of the disorder. As incidence (and admission rates) of acute pancreatitis increase, so does the demand for effective management. We review how to manage patients with acute pancreatitis, paying attention to diagnosis, differential diagnosis, complications, prognostic factors, treatment, and prevention of second attacks, and the possible transition from acute to chronic pancreatitis.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca(2+)) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca(2+) overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca(2+) signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca(2+) elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca(2+) from stores in the intracellular endoplasmic reticulum and/or increased Ca(2+) entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca(2+) by the sarco/endoplasmic reticulum Ca(2+)-activated ATPase and plasma membrane Ca(2+)-ATPase pumps, which contribute to Ca(2+) overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca(2+) signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca(2+) signals in the pathogenesis of pancreatitis.
Background
The gut is implicated in the pathogenesis of acute pancreatitis but there is discrepancy between individual studies regarding the prevalence of gut barrier dysfunction in patients with acute pancreatitis. The aim of this study was to determine the prevalence of gut barrier dysfunction in acute pancreatitis, the effect of different co-variables, and changes in gut barrier function associated with the use of various therapeutic modalities.MethodsA literature search was performed using PRISMA and MOOSE guidelines. Summary estimates were presented as pooled prevalence of gut barrier dysfunction and the associated 95 per cent c.i.ResultsA total of 44 prospective clinical studies were included in the systematic review, of which 18 studies were subjected to meta-analysis. The pooled prevalence of gut barrier dysfunction was 59 (95 per cent c.i. 48 to 70) per cent; the prevalence was not significantly affected by disease severity, timing of assessment after hospital admission or type of test used, but showed a statistically significant association with age. Overall, nine of 13 randomized clinical trials reported a significant improvement in gut barrier function following intervention compared with the control group, but only three of six studies that used standard enteral nutrition reported a statistically significant improvement in gut barrier function after intervention.Conclusion
Gut barrier dysfunction is present in three of five patients with acute pancreatitis, and the prevalence is affected by patient age but not by disease severity. Clinical studies are needed to evaluate the effect of enteral nutrition on gut function in acute pancreatitis.
Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI.
Importance:
Current guidelines recommend that patients with an initial episode of gallstone pancreatitis receive cholecystectomy. However, for various reasons, many patients do not.
Objective:
To determine the risk of developing recurrent gallstone pancreatitis in patients who never receive a cholecystectomy.
Design:
Retrospective cohort study using electronic medical records.
Setting:
Inpatient and outpatient.
Patients:
All patients in Kaiser Permanente Southern California with a primary diagnosis of acute gallstone pancreatitis hospitalized from January 1, 1995, through December 31, 2010, with no previous diagnosis of gallstone pancreatitis documented in the medical record.
Interventions:
Endoscopic retrograde cholangiopancreatography (ERCP) with or without sphincterotomy and/or stent placement, or no intervention.
Main outcomes and measures:
Recurrent acute pancreatitis.
Results:
A total of 1119 patients were identified. The median age at diagnosis was 63 years. Among the patients, 802 received no intervention and 317 received ERCP. After a median follow-up of 2.3 years, the overall risk of recurrent pancreatitis was 14.6%; it was 8.2% and 17.1% in patients who had ERCP and no intervention, respectively (P < .001). The median time to recurrence was 11.3 and 10.1 months in the patients who had ERCP and no intervention, respectively. Kaplan-Meier estimates of recurrence for 1, 2, and 5 years in the ERCP group were 5.2%, 7.4%, and 11.1%, compared with 11.3%, 16.1%, and 22.7% in the no-intervention group (hazard ratio = 0.45; 95% CI, 0.30-0.69; P < .001). Charlson Comorbidity Index and intensive care unit stay were independently associated with recurrence, whereas age, sex, and admission Ranson score were not associated.
Conclusions and relevance:
In patients who did not undergo cholecystectomy, the risk of recurrent pancreatitis is significant. Endoscopic retrograde cholangiopancreatography mitigates this risk and should be considered during initial hospitalization if cholecystectomy is not done.
Recently, the original Atlanta classification of 1992 was revised/updated by the Working Group using a web-based consultative process involving multiple international pancreatic societies. New understanding of the disease, its natural history, and objective description and classification of pancreatic and peripancreatic fluid collections make this new 2012 classification a potentially valuable means of international communication and interest. This revised classification identifies two phases of acute pancreatic-early (first week or two) and late (thereafter). Acute pancreatitis can be either edematous interstitial pancreatitis or necrotizing pancreatitis, the latter involving necrosis of the pancreatic parenchyma and peripancreatic tissues (most common), pancreatic parenchyma alone (least common), or just the peripancreatic tissues (~20%). Severity of the disease is categorized into three levels: mild, moderately severe, and severe. Mild acute pancreatitis lacks both organ failure (as classified by modified Marshal scoring system) and local or systemic complications. Moderately severe acute pancreatitis has transient organ failure (organ failure of <2 days), local complications, and/or exacerbation of co-existent disease. Severe acute pancreatitis is defined by the presence of persistent organ failure (organ failure that persists for ≥2 days). Local complications are defined by objective criteria based primarily on contrast-enhanced computed tomography; these local complications are classified as acute peripancreatic fluid collections (APFC), pseudocyst (which are very rare in acute pancreatitis), acute (pancreatic/peripancreatic) necrotic collection (ANC), and walled-off necrosis (WON). This classification will help the clinician to predict outcome of patients with acute pancreatitis and will allow comparison of patients and disease treatment/management across countries and practices.
Hypothesis Patients with mild gallstone pancreatitis may undergo an early laparoscopic cholecystectomy (LC) within 48 hours of hospital admission without awaiting the normalization of pancreatic and liver enzyme levels. This may decrease the hospital stay without increasing morbidity or mortality and may minimize the unnecessary use of endoscopic retrograde cholangiopancreatography.
Design A retrospective review.
Setting Two university-affiliated urban medical centers.
Patients A total of 303 patients with mild gallstone pancreatitis, of whom 117 underwent an early LC and 186 underwent a delayed LC.
Main Outcome Measures Hospital length of stay, morbidity and mortality rates, and the use of endoscopic retrograde cholangiopancreatography.
Results Similar hospital admission variables were observed in the early and delayed LC groups, although the delayed group was older (P = .006). The median hospital length of stay was significantly less for the early group than for the delayed group (3 vs 6 days; P < .001). There were no patients who died, and the complication rates were similar for both groups. However, the patients who underwent an early LC were less likely than patients who underwent a delayed LC to undergo endoscopic retrograde cholangiopancreatography (P = .02).
Conclusions An early LC may be safely performed for patients with mild gallstone pancreatitis, without concern for increased morbidity and mortality, resulting in shortened hospital stays and a decrease in the use of endoscopic retrograde cholangiopancreatography. The practice of delaying an LC until normalization of laboratory values appears to be unnecessary.
To determine the risk of recurrent biliary events in the period after mild biliary pancreatitis but before interval cholecystectomy and to determine the safety of cholecystectomy during the index admission.
Although current guidelines recommend performing cholecystectomy early after mild biliary pancreatitis, consensus on the definition of early (ie, during index admission or within the first weeks after hospital discharge) is lacking.
We performed a systematic search in PubMed, Embase, and Cochrane for studies published from January 1992 to July 2010. Included were cohort studies of patients with mild biliary pancreatitis reporting on the timing of cholecystectomy, number of readmissions for recurrent biliary events before cholecystectomy, operative complications (eg, bile duct injury, bleeding), and mortality. Study quality and risks of bias were assessed.
After screening 2413 studies, 8 cohort studies and 1 randomized trial describing 998 patients were included. Cholecystectomy was performed during index admission in 483 patients (48%) without any reported readmissions. Interval cholecystectomy was performed in 515 patients (52%) after 40 days (median; interquartile range: 19-58 days). Before interval cholecystectomy, 95 patients (18%) were readmitted for recurrent biliary events (0% vs 18%, P < 0.0001). These included recurrent biliary pancreatitis (n = 43, 8%), acute cholecystitis (n = 17), and biliary colics (n = 35). Patients who had an endoscopic retrograde cholangiopancreatography had fewer recurrent biliary events (10% vs 24%, P = 0.001), especially less recurrent biliary pancreatitis (1% vs 9%). There were no differences in operative complications, conversion rate (7%), and mortality (0%) between index and interval cholecystectomy. Because baseline characteristics were only reported in 26% of patients, study populations could not be compared.
Interval cholecystectomy after mild biliary pancreatitis is associated with a high risk of readmission for recurrent biliary events, especially recurrent biliary pancreatitis. Cholecystectomy during index admission for mild biliary pancreatitis appears safe, but selection bias could not be excluded.
An international working group has modified the Atlanta classification for acute pancreatitis to update the terminology and provide simple functional clinical and morphologic classifications. The modifications (a) address the clinical course and severity of disease, (b) divide acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis, (c) distinguish an early phase (1st week) and a late phase (after the 1st week), and (d) emphasize systemic inflammatory response syndrome and multisystem organ failure. In the 1st week, only clinical parameters are important for treatment planning. After the 1st week, morphologic criteria defined on the basis of computed tomographic findings are combined with clinical parameters to help determine care. This revised classification introduces new terminology for pancreatic fluid collections. Depending on presence or absence of necrosis, acute collections in the first 4 weeks are called acute necrotic collections or acute peripancreatic fluid collections. Once an enhancing capsule develops, persistent acute peripancreatic fluid collections are referred to as pseudocysts; and acute necrotic collections, as walled-off necroses. All can be sterile or infected. Terms such as pancreatic abscess and intrapancreatic pseudocyst have been abandoned. The goal is for radiologists, gastroenterologists, surgeons, and pathologists to use the revised classifications to standardize imaging terminology to facilitate treatment planning and enable precise comparison of results among different departments and institutions.
Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs.
Objective assessment of acute pancreatitis (AP) is critical to help guide resuscitation efforts. Herein we (1) validate serial blood urea nitrogen (BUN) measurement for early prediction of mortality and (2) develop an objective BUN-based approach to early assessment in AP.
We performed a secondary analysis of 3 prospective AP cohort studies: Brigham and Women's Hospital (BWH), June 2005 through May 2009; the Dutch Pancreatitis Study Group (DPSG), March 2004 through March 2007; and the University of Pittsburgh Medical Center (UPMC), June 2003 through September 2007. Meta-analysis and stratified multivariate logistic regression adjusted for age, sex, and creatinine levels were calculated to determine risk of mortality associated with elevated BUN level at admission and rise in BUN level at 24 hours. The accuracy of the BUN measurements was determined by area under the receiver operating characteristic curve (AUC) analysis compared with serum creatinine measurement and APACHE II score. A BUN-based assessment algorithm was derived on BWH data and validated on the DPSG and UPMC cohorts.
A total of 1043 AP cases were included in analysis. In pooled analysis, a BUN level of 20 mg/dL or higher was associated with an odds ratio (OR) of 4.6 (95% confidence interval [CI], 2.5-8.3) for mortality. Any rise in BUN level at 24 hours was associated with an OR of 4.3 (95% CI, 2.3-7.9) for death. Accuracy of serial BUN measurement (AUC, 0.82-0.91) was comparable to that of the APACHE II score (AUC, 0.72-0.92) in each of the cohorts. A BUN-based assessment algorithm identified patients at increased risk for mortality during the initial 24 hours of hospitalization.
We have confirmed the accuracy of BUN measurement for early prediction of mortality in AP and developed an algorithm that may assist physicians in their early resuscitation efforts.
Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP.
One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) < 35%, n = 56) or slow hemodilution (HCT > or = 35%, n = 59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined.
The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P < 0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4 +/- 1.9) days) compared with the slow hemodilution group ((10.2 +/- 2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P < 0.05).
Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.
We hypothesized that laparoscopic cholecystectomy performed within 48 hours of admission for mild gallstone pancreatitis, regardless of resolution of abdominal pain or abnormal laboratory values, would result in a shorter hospital stay.
Although there is consensus among surgeons that patients with gallstone pancreatitis should undergo cholecystectomy to prevent recurrence, the precise timing of laparoscopic cholecystectomy for mild disease remains controversial.
Consecutive patients with mild pancreatitis (Ranson score <or=3) were prospectively randomized to either an early laparoscopic cholecystectomy group (within 48 hours of admission) versus a control laparoscopic cholecystectomy group (performed after resolution of abdominal pain and normalizing trend of laboratory enzymes). The primary end point was hospital length of stay. Secondary end point was a composite of rates of conversion to an open procedure, perioperative complications, and need for endoscopic retrograde cholangiography. The study was designed to enroll 100 patients with an interim analysis after 50 patients.
At interim analysis, 50 patients were enrolled at a single university-affiliated public hospital. Of them, 25 patients were randomized to the early group and 25 patients to the control group. Patient age ranged from 18 to 74 years with a median duration of symptoms of 2 days upon presentation and a median Ranson score of 1. There were no baseline differences between the groups with regards to demographics, clinical presentation, or the presence of comorbidities. The hospital length of stay was shorter for the early cholecystectomy group (mean: 3.5 [95% CI, 2.7-4.3], median: 3 [IQR, 2-4]) compared with the control group (mean: 5.8 [95% CI, 3.8-7.9], median: 4 [IQR, 4-6] [P = 0.0016]). Six patients from the early group required endoscopic retrograde cholangiography, compared with 4 in the control group (P = 0.72). There was no statistically significant difference in the need for conversion to an open procedure or in perioperative complication rates between the 2 groups.
In mild gallstone pancreatitis, laparoscopic cholecystectomy performed within 48 hours of admission, regardless of the resolution of abdominal pain or laboratory abnormalities, results in a shorter hospital length of stay with no apparent impact on the technical difficulty of the procedure or perioperative complication rate.
Background:
Acute pancreatitis creates a catabolic stress state promoting a systemic inflammatory response and nutritional deterioration. Adequate supply of nutrients plays an important role in recovery. Total parenteral nutrition (TPN) has been standard practice for providing exogenous nutrients to patients with severe acute pancreatitis. However, recent data suggest that enteral nutrition (EN) is not only feasible, but safer and more effective.Therefore, we sought to update our systematic review to re-evaluate the level of evidence.
Objectives:
To compare the effect of TPN versus EN on mortality, morbidity and length of hospital stay in patients with acute pancreatitis.
Search strategy:
Trials were identified by computerized searches of The Cochrane Controlled Trials Register, MEDLINE, and EMBASE. Additional studies were identified by searching Scisearch, bibliographies of review articles and identified trials. The search was undertaken in August 2000 and updated in September 2002, October 2003, November 2004 and November 2008. No language restrictions were applied.
Selection criteria:
Randomized clinical trials comparing TPN to EN in patients with acute pancreatitis.
Data collection and analysis:
Two reviewers independently abstracted data and assessed trial quality. A standardized form was used to extract relevant data.
Main results:
Eight trials with a total of 348 participants were included. Comparing EN to TPN for acute pancreatitis, the relative risk (RR) for death was 0.50 (95% CI 0.28 to 0.91), for multiple organ failure (MOF) was 0.55 (95% CI 0.37 to 0.81), for systemic infection was 0.39 (95% CI 0.23 to 0.65), for operative interventions was 0.44 (95% CI 0.29 to 0.67), for local septic complications was 0.74 (95% CI 0.40 to 1.35), and for other local complications was 0.70 (95% CI 0.43 to 1.13). Mean length of hospital stay was reduced by 2.37 days in EN vs TPN groups (95% CI -7.18 to 2.44). Furthermore, a subgroup analysis for EN vs TPN in patients with severe acute pancreatitis showed a RR for death of 0.18 (95% CI 0.06 to 0.58) and a RR for MOF of 0.46 (95% CI 0.16 to 1.29).
Authors' conclusions:
In patients with acute pancreatitis, enteral nutrition significantly reduced mortality, multiple organ failure, systemic infections, and the need for operative interventions compared to those who received TPN. In addition, there was a trend towards a reduction in length of hospital stay. These data suggest that EN should be considered the standard of care for patients with acute pancreatitis requiring nutritional support.
Routine laboratory tests that reflect intravascular volume status can play an important role in the early assessment of acute pancreatitis (AP). The objective of this study was to evaluate accuracy of serial blood urea nitrogen (BUN) versus serial hemoglobin (Hgb) measurement for prediction of in-hospital mortality in AP.
We performed an observational cohort study on data from 69 US hospitals from January 2003 to December 2006. Repeated measures analysis was used to examine the relationship between early trends in BUN and Hgb with respect to mortality. Multivariate logistic regression was used to evaluate the impact of admission BUN, change in BUN, admission Hgb, and change in Hgb on mortality. Time-specific receiver operating characteristic curves and multivariable logistic regression compared accuracy of BUN, Hgb, and additional routine laboratory tests.
BUN levels were persistently higher among nonsurvivors than survivors during the first 48 hours of hospitalization (F-test; P < .0001). No such relationship existed for Hgb (F-test; P = .33). For every 5-mg/dl increase in BUN during the first 24 hours, the age- and gender-adjusted odds ratio for mortality increased by 2.2 (95% confidence limits, 1.8, 2.7). Of the 6 routine laboratory tests examined, BUN yielded the highest area under the concentration-time curve (AUC) for predicting mortality at admission (AUC = 0.79), 24 hours (AUC = 0.89), and 48 hours (AUC = 0.90). Combining admission BUN and change in BUN at 24 hours produced an AUC of 0.91 for mortality.
In a large, hospital-based cohort study, we identified serial BUN measurement as the most valuable single routine laboratory test for predicting mortality in AP.
In the long term, half of patients with their first alcohol-associated acute pancreatitis (AP) develop acute recurrence, alcohol consumption being the main risk factor. None of the recent national or international guidelines for treatment include recommendations aimed to decrease recurrences, possibly because of a lack of studies. This study investigated whether AP recurrences can be reduced.
One hundred and twenty patients admitted to a university hospital for their first alcohol-associated AP were randomized either to repeated intervention (n = 59) or initial intervention only (n = 61). The patients in the 2 groups did not differ. A registered nurse performed an intervention in both groups before discharge, after which it was repeated in the study group at 6-month intervals at the gastrointestinal outpatient clinic. Acute recurrences during the next 2 years were monitored.
There were 9 recurrent AP episodes in 5 patients in the repeated-intervention group compared with 20 episodes (P = .02) in 13 patients (P = .04) in the control group. The recurrence rates were similar during the first 6 months (4 vs 5 episodes), after which the repeated-intervention group had fewer recurrences than the control group (5 vs 15 episodes; P = .02).
The repeated visits at 6-month intervals at the gastrointestinal outpatient clinic, consisting of an intervention against alcohol consumption, appear to be better than the single standardized intervention alone during hospitalization in reducing the development of recurrent AP during a 2-year period.
One hundred and sixty-one consecutive patients with primary acute pancreatitis were admitted to a double-blind trial of intravenous Trasylol therapy as a supplement to a standard regimen of conservative management. The patients were subdivided into younger (less than 60 years) and older patients (aged 60 years and over), and subjects in each group were randomly allocated on a double-blind basis either to Trasylol therapy (starter 500 000 KIU and thereafter 200 000 q. i. d. for 5 days) or to placebo. There were 14 deaths (8.7 per cent), 7 in the Trasylol and 7 in the placebo group, and no significant difference was found in either the mortality or the major complications rate, either overall or within either age group.
All 14 patients who died met the objective criteria for severe acute pancreatitis determined by the presence of at least three of a possible nine factors during the first 48 h of admission. Severe acute pancreatitis was present in 37 per cent of patients, who were evenly distributed between the Trasylol and placebo groups. Neither in those patients with severe nor those with less severe acute pancreatitis was there any significant difference between the two therapeutic regimens. Supplementary intravenous Trasylol therapy at this dosage confers no advantage over standard conservative treatment in the management of patients with primary acute pancreatitis.