Background and aim The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. Methods Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Results Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. Conclusion Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication. • KEY MESSAGES • Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication. • Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication. • Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.
Psychological factors affect chronic pain and may lead to inactivity after total knee arthroplasty (TKA). This study aimed to determine whether using an activity diary for early postoperative rehabilitation after TKA reduced pain and improved physical functioning and psychological factors. In this non-randomized controlled trial (intervention group: n = 140; control group: n = 150), postoperative rehabilitation with physical and occupational therapy was performed for both groups, and self-monitoring using an activity diary one week postoperatively was implemented for the intervention group. The outcome variables were the numerical rating scale of pain, Timed Up & Go Test score, timed 10 m walk test score, the Pain Catastrophizing Scale (PCS), and the Pain Self-Efficacy Questionnaire (PSEQ). The data were analyzed using ANOVA with post hoc tests. Time-by-group interactions were obtained for PCS and PSEQ (p < .05), which were both more favorable in the intervention group. The intervention group showed greater improvement in PCS and PSEQ four weeks postoperatively, compared with the control group (p < .05). However, no significant results were observed for neither physical performance measures assessed. These results indicated that including an activity diary increased postoperative rehabilitation effectiveness, improved pain catastrophizing and pain self-efficacy. An activity diary is an effective and feasible addition to postoperative care for TKA patients.
Purpose Foot progression angle is a key factor for biomechanical knee load, which is associated with noncontact anterior cruciate ligament (ACL) injury during sports-specific tasks. The purpose of the present study was to assess the biomechanics of trunk, pelvis, and lower extremities during a cutting maneuver under different foot progression angles. Methods Nineteen male collegiate athletes (ages 18–24) participated in the present study. Cutting motion was analyzed using eight infrared cameras (250 Hz), two force plates (1250 Hz), and 44 reflective markers. Subjects performed 45-degree side cutting maneuvers under three foot progression angles, including 20 degrees (toe-out: TO), 0 degrees (neutral: TN), and − 20 degrees (toe-in: TI). Peak values of each biomechanical parameters in trunk, pelvis, hip, and knee within a first 40% stance phase and each parameter at the timing of the peak vertical ground reaction force were assessed. A statistical analysis was performed to compare data among the three-foot progression angles using the Friedman test. Results Peak angles of knee abduction, tibial internal rotation, hip internal rotation, and hip adduction were significantly greater for TI position than for TO position ( p < 0.01). Peak moments of knee abduction and tibial internal rotation under TI position were also significantly larger than TO position ( p < 0.01). Moreover, greater peak pelvis-trunk rotation was found for TI position than for TN and TO positions ( p < 0.01). Conclusion From the present study, TI position could lead to an increased risk of ACL injury during a pre-planned cut maneuver, compared to TO position.
Background Multiple deep organ abscesses associated with Staphylococcus aureus bloodstream infection (SAB) have a high mortality rate, requiring rapid removal or drainage of infective foci with long-term appropriate antimicrobial therapy. Cases in which infective foci cannot be completely removed are challenging for their management. Case presentation A 77-year-old man developed multiple deep organ abscesses associated with SAB. The left anterior chest subcutaneous abscess continued into the right anterior mediastinum and had extensively destroyed the sternum. Necrotizing fasciitis was observed in the bilateral feet. The anterior mediastinum abscess was drained percutaneously, and the chest wall abscess was incised cautiously without causing an external pneumothorax. On the next day, right-sided pyothorax had developed, requiring pleural drainage. On the third day, debridement of anterior chest wall abscess followed by concurrent thoracoscopic pleural curettage and debridement of bilateral feet were performed. Thorough sternal debridement was not performed, considering the risk of respiratory failure due to the sternal defects. On the 24th day, sternum debridement and incisional drainage of sciatic rectus fossa abscess, which had been present since the time of admission, were performed to control persistent infection. The caudal half of the sternal body was resected, leaving the costal cartilage attachments. The general condition further improved without postoperative respiratory failure after the second surgery, leading to a transfer to the general ward on the 43rd day. Conclusions We successfully treated the severe multiple deep organ abscesses, including a mediastinum abscess with sternum destruction, by repeated removal of the infective foci while avoiding respiratory failure due to excessive debridement of the anterior chest wall, including the sternum.
Pevonedistat, the first small-molecule inhibitor of NEDD8-activating enzyme, has demonstrated clinical activity in Western patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). We report findings from a phase 1/1b study in East Asian patients with AML or MDS, conducted to evaluate the safety/tolerability and characterize the pharmacokinetics of pevonedistat, alone or in combination with azacitidine, in this population, and determine the recommended phase 2/3 dose for pevonedistat plus azacitidine. Twenty-three adult patients with very high/high/intermediate-risk AML or MDS were enrolled in Japan, South Korea and Taiwan. All 23 patients experienced at least one grade ≥ 3 treatment-emergent adverse event. One patient in the combination cohort reported a dose-limiting toxicity. Eighteen patients discontinued treatment; in nine patients, discontinuation was due to progressive disease. Three patients died on study of causes considered unrelated to study drugs. Pevonedistat exhibited linear pharmacokinetics over the dose range of 10–44 mg/m ² , with minimal accumulation following multiple-dose administration. An objective response was achieved by 5/11 (45%) response-evaluable patients in the pevonedistat plus azacitidine arm (all with AML), and 0 in the single-agent pevonedistat arm. This study showed that the pharmacokinetic and safety profiles of pevonedistat plus azacitidine in East Asian patients were similar to those observed in Western patients as previously reported. The recommended Phase 2/3 dose (RP2/3D) of pevonedistat was determined to be 20 mg/m ² for co-administration with azacitidine 75 mg/m ² in Phase 2/3 studies, which was identical to the RP2/3D established in Western patients. Trial registration : clinicaltrials.gov: NCT02782468 25 May 2016. https://clinicaltrials.gov/ct2/show/NCT02782468
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder with an increased incidence of tumors, such as basal cell carcinomas and medulloblastomas. The PTCH1 gene, responsible for NBCCS, suppresses the hedgehog signaling pathway, which is recognized as one of the important pathways in tumorigenesis and, thus, is a therapeutic target in cancer. In the present study, we generated PTCH1 −/− induced pluripotent stem cells (iPSCs) from NBCCS patient-derived iPSCs ( PTCH1 +/− ) by gene editing. The proliferation of PTCH1 −/− iPSCs was accelerated due to the activation of the hedgehog signaling pathway. When PTCH1 −/− iPSCs were subcutaneously injected into immunodeficient mice, the resulting teratomas almost exclusively contained immature ectodermal lineage cells expressing medulloblastoma markers, and the percentages of the area occupied by medulloblastoma-like tissue were larger in PTCH1 −/− teratomas than in PTCH1 +/− teratomas. In contrast, in PTCH1 +/+ teratomas, medulloblastoma-like tissue positive for all of these medulloblastoma markers was not observed. The present results indicate the importance of PTCH1 in medulloblastoma formation and the suitability of these gene-edited iPSCs and PTCH1 −/− teratomas as models for the formation of tumors, such as medulloblastomas and Hh-related tumors.
The inhalation anesthetic sevoflurane reversibly suppresses Period2 (Per2) mRNA expression in the suprachiasmatic nucleus (SCN). However, a discrepancy exists in phase shifting of the Per2 expression rhythm between sevoflurane application in rats (in vivo application) and explants (ex vivo application). This investigation aimed to resolve this issue. First, tissues from the SCN, choroid plexus in the lateral ventricle (CP-LV), and choroid plexus in the fourth ventricle (CP–4V), which are robust circadian oscillators, and pineal gland (PG) tissue, which is a circadian influencer, were prepared from Per2::dLuc transgenic rats. Significant phase responses of bioluminescence rhythms for different preparation times were monitored in the four tissue explant types. Second, tissue explants were prepared from anesthetized rats immediately after sevoflurane treatment, and bioluminescence rhythms were compared with those from non-anesthetized rats at various preparation times. Regarding bioluminescence rhythm phases, in vivo application of sevoflurane induced phase shifts in CP-LV, CP-4V, and PG explants according to the times that rats were administered anesthesia and the explants were prepared. Phase shifts in these peripheral explants were withdrawn due to the recovery period after the anesthetic treatment, which suggests that peripheral tissues require the assistance of related tissues or organs to correct phase shifts. In contrast, no phase shifts were observed in SCN explants. These results indicated that SCN explants can independently correct bioluminescence rhythm phase. The bioluminescence intensity of explants was also decreased after in vivo sevoflurane application. The suppressive effects on SCN explants were withdrawn due to a recovery day after the anesthetic treatment. In contrast, the suppressive effects on the bioluminescence intensities of CP-LV, CP-4V, and PG explants remained at 30 days after anesthesia administration. These results suggest that anesthetic suppression is imprinted within the peripheral tissues.
Cardiorenal syndrome (CRS) is the leading cause of death associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, the underlying mechanisms of CRS are still poorly understood. Here, we studied a CKD model of unilateral ureteral obstruction (UUO) and observed pathological cardiac fibrosis and lymphangiogenesis in 180-day old UUO rats, in which inflammatory injury plays a major role. In addition, treatment of UUO rats with eplerenone, a mineralocorticoid receptor blocker (MRB), significantly reduced cardiac lymphangiogenesis and fibrosis. In conclusion, our experimental results showed that cardiac lymphangiogenesis in long-term UUO rats may be involved in the formation of cardiac fibrosis and that eplerenone can alleviate lymphangiogenesis and cardiac fibrosis by inhibiting inflammation.
Background The number of studies on the characteristics of patients with stroke who would benefit from robot-assisted upper limb rehabilitation is limited, and there are no clear criteria for determining which individuals should receive such treatment. The current study aimed to develop a clinical prediction rule using machine learning to identify the characteristics of patients with stroke who can the achieve minimal clinically important difference of the Fugl-Meyer Upper Extremity Evaluation (FMA-UE) after single-joint hybrid assistive limb (HAL-SJ) rehabilitation. Methods This study included 71 patients with subacute stroke who received HAL-SJ rehabilitation. The chi-square automatic interaction detector (CHAID) model was applied to predict improvement in upper limb motor function. Based the analysis using CHAID, age, sex, days from stroke onset to the initiation of HAL-SJ rehabilitation, and upper limb motor and cognitive functions were used as independent variables. Improvement in upper limb motor function was determined based on the minimal clinically important difference of the FMA-UE, which was used as a dependent variable. Results According to the CHAID model, the FMA-UE score during the initiation of HAL-SJ rehabilitation was the most significant predictive factor for patients who are likely to respond to the intervention. Interestingly, this therapy was more effective in patients with moderate upper limb motor dysfunction and early initiation of HAL-SJ rehabilitation. The accuracy of the CHAID model was 0.89 (95% confidence interval: 0.81–0.96). Conclusion We developed a clinical prediction rule for identifying the characteristics of patients with stroke whose upper limb motor function can improve with HAL-SJ rehabilitation.
Lithium’s inhibitory effect on enzymes involved in sulfation process, such as inhibition of 3’(2’)-phosphoadenosine 5’-phosphate (PAP) phosphatase, is a possible mechanism of its therapeutic effect for bipolar disorder (BD). 3’-Phosphoadenosine 5’-phosphosulfate (PAPS) is translocated from cytosol to Golgi lumen by PAPS transporter 1 (PAPST1/SLC35B2), where it acts as a sulfa donor. Since SLC35B2 was previously recognized as a molecule that facilitates the release of D-serine, a co-agonist of N-methyl-D-aspartate type glutamate receptor, altered function of SLC35B2 might be associated with the pathophysiology of BD and schizophrenia (SCZ). We performed genetic association analyses of the SLC35B2 gene using Japanese cohorts with 366 BD cases and 370 controls and 2012 SCZ cases and 2170 controls. We then investigated expression of SLC35B2 mRNA in postmortem brains by QPCR using a Caucasian cohort with 33 BD and 34 SCZ cases and 34 controls and by in situ hybridization using a Caucasian cohort with 37 SCZ and 29 controls. We found significant associations between three SNPs (rs575034, rs1875324, and rs3832441) and BD, and significantly reduced SLC35B2 mRNA expression in postmortem dorsolateral prefrontal cortex (DLPFC) of BD. Moreover, we observed normalized SLC35B2 mRNA expression in BD subgroups who were medicated with lithium. While there was a significant association of SLC35B2 with SCZ (SNP rs2233437), its expression was not changed in SCZ. These findings indicate that SLC35B2 might be differentially involved in the pathophysiology of BD and SCZ by influencing the sulfation process and/or glutamate system in the central nervous system.
The Hybrid Assistive Limb (HAL) is used in training to improve walking ability for stroke patients; however, the quality of the evidence for its effects has not been fully critiqued to date. This study conducted a systematic review of randomized controlled trials to investigate the effectiveness of post-stroke gait training with the HAL. PubMed, the Cochrane Library, the Physiotherapy Evidence Database (PEDro), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for randomized controlled clinical trials evaluating the effect of HAL on gait training in stroke patients, published from the inception of each database until March 2021. Two authors screened the titles and abstracts of articles returned in the initial search and reviewed the full text of articles that met the selection criteria. The risk of bias was assessed using the PEDro scale. Of 273 articles retrieved from the databases, three met all inclusion criteria. One study showed that gait training using HAL improves independence in walking; however, the quality of this study was rated as 4 (medium quality). Other studies did not show improvement with HAL in walking independence. This review did not provide strong evidence to support the effectiveness of HAL in improving walking ability.
Background The effectiveness of combination therapy for COVID-19 pneumonia remains unclear. We evaluated favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia. Methods In this open-label phase 3 study, hospitalized adults who were positive for SARS-CoV-2 and had COVID-19 pneumonia were enrolled prior to official vaccination drive in Japan. Participants were randomly assigned to favipiravir monotherapy or favipiravir + camostat + ciclesonide combination therapy. The primary outcome was the length of hospitalization due to COVID-19 infection after study treatment. The hospitalization period was calculated from the time of admission to the time of patient discharge using the clinical management guide of COVID-19 for front-line healthcare workers developed by the Japanese Ministry of Health, Labour, and Welfare (Version 3). Cases were registered between November 11, 2020, and May 31, 2021. Japan Registry of Clinical Trials registration: jRCTs031200196. Findings Of 121 enrolled patients, 56 received monotherapy and 61 received combination therapy. Baseline characteristics were balanced between the groups. The median time of hospitalization was 10 days for the combination and 11 days for the monotherapy group. The median time to discharge was statistically significantly lower in the combination therapy vs monotherapy group (HR, 1·67 (95% CI 1·03–2·7; P = 0·035). The hospital discharge rate was statistically significantly higher in the combination therapy vs monotherapy group in patients with less severe COVID-19 infections and those who were ≤60 years. There were no significant differences in clinical findings between the groups at 4, 8, 11, 15, and 29 days. Adverse events were comparable between the groups. There were two deaths, with one in each group. Interpretation Combination oral favipiravir, camostat and, ciclesonide therapy could decrease the length of hospitalization stays without safety concerns in patients with moderate COVID-19 pneumonia. However, lack of hard clinical primary outcome is one of the major limitations of the study. Funding This research was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 20fk0108261h0001.
- Tomoaki Tatsumi
- Yoko Takatsuna
- Toshiyuki Oshitari
- Shuichi Yamamoto
To compare the efficacy and safety of intravitreal aflibercept with three loading doses + pro re nata regimen combined with subthreshold laser application to that of IVA monotherapy on eyes with diabetic macular edema. This was a phase 4 clinical trial with a prospective, randomized, and parallel investigator-driven protocol. Patients with DME were randomly assigned to the IVA monotherapy group (n = 25) or the IVA + SL combination therapy group (n = 26). The main outcome measures were the number of IVA injections and the changes in the best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) at the final evaluation at 96 weeks. The mean number of IVA injections in the monotherapy group was 5.86 ± 2.43 and it was 6.05 ± 2.73 in the IVA + SL group at 96 weeks, and this difference was not significant (P = 0.83). The differences in the mean changes of the CRT (P = 0.17) and the BCVA (P = 0.31) were also not significant between the two groups throughout the follow-up period. We conclude that adjunct of SL to anti-VEGF therapy does not reduce the number of necessary intravitreal injections.
Rationale: Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. Objective: Based on our observation that lung fibroblasts express thromboxane-prostanoid receptor (TBXA2R) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. Methods: We identified TBXA2R expression in lungs of IPF patients and mice, and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. We utilized TBXA2R deficient mice and small molecule inhibitors to investigate TBXA2R signaling in preclinical lung fibrosis models. Measurements and main results: TBXA2R expression was up-regulated in fibroblasts in the lungs of IPF patients and in mouse lungs during experimental lung fibrosis. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, thereby suggesting an alternative ligand activates profibrotic TBXA2R signaling. In contrast to thromboxane, F2-isoprostanes (F2-IsoPs), which are nonezymatic products of arachidonic acid induced by reactive oxygen species (ROS), were persistently elevated during fibrosis. F2-IsoPs induced TBXA2R signaling in fibroblasts and mediated a myofibroblast activation profile due, at least in part, to potentiation of TGF-β signaling. In vivo treatment with the TBXA2R antagonist ifetroban reduced pro-fibrotic signaling in the lungs, protected mice from lung fibrosis in three pre-clinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution following bleomycin treatment. Conclusions: TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.
TCR ligation with an Ag presented on MHC molecules promotes T cell activation, leading to the selection, differentiation, and proliferation of T cells and cytokine production. These immunological events are optimally arranged to provide appropriate responses against a variety of pathogens. We here propose signal-transducing adaptor protein-2 (STAP-2) as a new positive regulator of TCR signaling. STAP-2-deficient T cells showed reduced, whereas STAP-2-overexpressing T cells showed enhanced, TCR-mediated signaling and downstream IL-2 production. For the mechanisms, STAP-2 associated with TCR-proximal CD3ζ immunoreceptor tyrosine activation motifs and phosphorylated LCK, resulting in enhancement of their binding after TCR stimulation. In parallel, STAP-2 expression is required for full activation of downstream TCR signaling. Importantly, STAP-2-deficient mice exhibited slight phenotypes of CD4+ T-cell-mediated inflammatory diseases, such as experimental autoimmune encephalomyelitis, whereas STAP-2-overexpressing transgenic mice showed severe phenotypes of these diseases. Together, STAP-2 is an adaptor protein to enhance TCR signaling; therefore, manipulating STAP-2 will have an ability to improve the treatment of patients with autoimmune diseases as well as the chimeric Ag receptor T cell therapy.
Purpose To investigate the relationship between subjective cyclofusion ranges and objective ocular torsion in normal participants according to age. Methods This cross-sectional study included 120 participants aged ≥ 20 years with no ocular diseases. The subjective cyclofusion ranges were measured centrifugally and centripetally in the direction of excyclotorsion and incyclotorsion, respectively, concurrently with rotational diplopia production by rotation using synoptophore. Disc fovea angle (DFA) was defined as the angle formed by two lines: a line passing through the center of the optic nerve papilla and fovea and a horizontal line passing through the center of gravity of the optic papilla using fundus photographs. Results The participants were aged 49.1 ± 17.7 years. The total cyclofusion centrifugal (sum of extorsion and intorsion) and centripetal ranges were 10.9 ± 2.2° and 7.2 ± 1.8°, respectively, both of which decreased in participants in their 60 s and 70 s (p < 0.01). The DFA was − 7.0 ± 3.4° in the right eye (− : excyclo, + : incyclo) and − 8.0 ± 3.2° in the left, which was associated with age (p < 0.001). The correlation between the DFA and centrifugal (r = − 0.13, p = 0.16) and centripetal (r = − 0.002, p = 0.99) cyclofusion ranges of extorsion was not significantly different. The centrifugal (r = 0.37, p < 0.001) and centripetal (r = 0.40, p < 0.001) cyclofusion ranges of intorsion were positively correlated. Conclusion Subjective cyclofusion ranges decreased in both extorsion and intorsion in the elderly. Objective ocular torsion showed excyclotorsion with age. When strabismus surgery is performed in elderly patients with torsional strabismus, the decrease in subjective cyclofusion ranges should be considered.
Purpose : Pathogenic genetic testing for Coronavirus disease 2019 (COVID-19) can detect viruses with high sensitivity, however there are several challenges. In the prevention, testing, and treatment of COVID-19, more effective, safer, and convenient methods are desired. We evaluated the possibility of monocyte distribution width (MDW) as an infection biomarker in COVID-19 testing. Methods : The efficacy of MDW as a screening test for COVID-19 was retrospectively assessed in 80 patients in the COVID-19 group and 232 patients in the Non-COVID-19 group (141 patients with acute respiratory infection, 19 patients with non-respiratory infection, 1 patient with viral infection, 11 patients who had received treatment for COVID-19, 1 patient in contact with COVID-19 patients, and 59 patients with non-infectious disease). Results : The median MDW in 80 patients in the COVID-19 group was 23.3 (17.2-33.6), and the median MDW in 232 patients in the Non-COVID-19 group was 19.0 (13.6-30.2) ( P < 0.001). When the COVID-19 group was identified using the MDW cut-off value of 21.3 from the Non-COVID-19 group, the area under the curve (AUC) was 0.844, and the sensitivity and specificity were 81.3% and 78.2%, respectively. Comparison of MDW by severity between the COVID-19 group and patients with acute respiratory infection in the Non-COVID-19 group showed that MDW was significantly higher in the COVID-19 group for all of mild, moderate I, and moderate II disease. Conclusions : MDW (cut-off value: 21.3) may be used as a screening test for COVID-19 in fever outpatients, etc.
Purpose: To establish the best treatment strategy for acute appendicitis. Methods: We collected data on 2142 appendectomies performed in 2017 and compared the backgrounds and surgical outcomes of patients who underwent early surgery (ES) (< 48 h) with those managed with non-ES (> 48 h). We performed a risk factor analysis to predict postoperative complications and subgroup analysis to propose a standard treatment strategy. Results: The incidence of postoperative complications was significantly higher in the ES group than in the non-ES group, and significantly lower in the laparoscopic surgery group than in the laparotomy group. Surgical outcomes, including the incidence of postoperative complications, were comparable after acute surgery (< 12 h) and subacute surgery (12-48 h), following antibiotic treatment. The risk factors for postoperative complications in the ES group were a higher age, history of abdominal surgery, perforation, high C-reactive protein level, histological evidence of gangrenous or perforated appendicitis, a long operation time, and intraoperative complications. The risk factors for postoperative complications in the non-ES group were perforation and unsuccessful conservative treatment. Conclusions: Non-early appendectomy is feasible for acute appendicitis but should be applied with care in patients with risk factors for postoperative complications or failure of pretreatment, including diabetes mellitus, abscess formation, and perforation.
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