Objectives To evaluate the risk of symptomatic venous thromboembolism (VTE) recurrence at 3 months in relation to treatment duration, according to baseline risk factor profiles, in patients with superficial vein thrombosis (SVT) treated with intermediate dose of tinzaparin. Methods We performed a pooled analysis on individual data from two prospective studies designed to assess the efficacy and safety of tinzaparin in intermediate dose (131 IU/kg) in patients with SVT. Treatment duration was at the treating physician’s discretion. All patients were followed up for at least 3 months. Results A total of 956 patients (65% female, mean age 58.7 ± 13.7 years) were included. The median treatment duration was 30 days (range, 3–200 days). History of deep vein thrombosis (DVT), location of SVT above the knee, and palpable induration were the only independent factors associated with prolonged treatment duration. During follow-up, 95.9% of patients were event free. Outcomes-related adverse events occurred in 39 (4.1%) patients and their median duration of treatment was 33 days (range, 7–200 days). Recurrent VTE events occurred in 33 patients, including 22 cases of SVT recurrence, 8 cases of DVT, and 1 case of pulmonary embolism. The median time to the event was 29 (6–113) days. Recurrent thromboembolic events were not related to treatment duration as occurred in 17 patients (51.5%) treated up to 30 days and in 16 patients (48.8%) received prolong treatment ( p = .46). Length of thrombus at the index event was significantly associated with higher risk for VTE recurrence. Conclusions Intermediate dose of tinzaparin for 30 days is an effective and safe treatment for SVT. The risk of recurrent VTE events may be higher in patients with greater amount of thrombus at index event.
Background The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. Methods This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson’s Chi-squared and continuous variables by Mann–Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the “full” matching method. Results Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. Conclusions In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021). Graphical abstract
Background Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with Alberta Stroke Program Early CT Score (ASPECTS) 0–5 has not yet proven safe and effective by clinical trials. Objectives The aim of the study was to assess whether EVT in AIS patients presenting with low ASPECTS is beneficial. Design Systematic review and meta-analysis of available studies in accordance with the PRISMA statement. Data sources and Methods We have searched MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 28 May 2022 with the aim to calculate (1) modified Rankin scale (mRS) score 0–3 at 3 months, (2) mRS score 0–2 at 3 months, (3) symptomatic intracranial hemorrhage (sICH), and (3) mortality at 3 months. Results Overall, 24 eligible studies were included in the meta-analysis, comprising a total of 2539 AIS patients with ASPECTS 0–5 treated with EVT. The pooled proportion of EVT-treated patients achieving mRS 0–3 at 3 months was calculated at 38.4%. The pooled proportion of EVT-treated patients achieving mRS 0–2 at 3 months was 25.7%. Regarding safety outcomes, sICH occurred in 12.8% of patients. The 3-month pooled mortality was 30%. In pairwise meta-analysis, patients treated with EVT had a higher likelihood of achieving mRS 0–3 at 3 months compared with patients treated with best medical therapy (BMT, OR: 2.41). sICH occurred more frequently in EVT-treated patients compared with the BMT-treated patients (OR: 2.30). Mortality at 3 months was not different between the two treatment groups (OR: 0.71). Conclusion EVT may be beneficial for AIS patients with low baseline ASPECTS despite an increased risk for sICH. Further data from randomized-controlled clinical trials are needed to elucidate the role of EVT in this subgroup of AIS patients. Registration The protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO; Registration Number: CRD42022334417.
The clinical manifestations of proximal (extracranial) internal carotid artery occlusions (pICAOs) may range from asymptomatic to acute, large, and devastating ischemic strokes. The etiology and pathophysiology of the occlusion, intracranial collateral status and patient’s premorbid status are among the factors determining the clinical presentation and outcome of pICAOs. Rapid and accurate diagnosis is crucial and may be assisted by the combination of carotid and transcranial duplex sonography, or a computed tomography/magnetic resonance angiography (CTA/MRA). It should be noted that with either imaging modalities, the discrimination of a pseudo-occlusion of the extracranial internal carotid artery (ICA) from a true pICAO may not be straightforward. In the absence of randomized data, the management of acute, symptomatic pICAOs remains individualized and relies largely on expert opinion. Administration of intravenous thrombolysis is reasonable and probably beneficial in the settings of acute ischemic stroke with early presentation. Unfortunately, rates of recanalization are rather low and acute interventional reperfusion therapies emerge as a potentially powerful therapeutic option for patients with persistent and severe symptoms. However, none of the pivotal clinical trials on mechanical thrombectomy for acute ischemic stroke randomized patients with isolated extracranial large vessel occlusions. On the contrary, several lines of evidence from non-randomized studies have shown that acute carotid endarterectomy, or endovascular thrombectomy/stenting of the ICA are feasible and safe, and pοtentially beneficial. The heterogeneity in the pathophysiology and clinical presentation of acute pICAOs renders patient selection for an acute interventional treatment a complicated decision-making process. The present narrative review will outline the pathophysiology, clinical presentation, diagnostic challenges, and possible treatment options for pICAOs.
GReek-AntiPlatElet Atrial Fibrillation (GRAPE-AF) registry is a multicenter, observational, non-interventional study of AF patients undergoing PCI. Primary endpoint included clinically significant bleeding rate at 12 months between different antithrombotic regimens prescribed at discharge; secondary endpoints included major adverse cardiovascular events (MACEs) as well as net adverse clinical events (NACEs).A total of 647 patients were analyzed. The majority (92.9%) were discharged on NOACs with only 7.1% receiving VKA. A little over half of patients (50.4%) received triple antithrombotic therapy (TAT) - mostly (62.9%) for ≤ 1 month - while the rest (49.6%) received dual antithrombotic therapy (DAT). Clinically significant bleeding risk was similar between TAT and DAT (HR = 1.08; 95% CI = 0.66 - 1.78), though among TAT-receiving patients, the risk was lower in those receiving TAT for ≤ 1 month (HR = 0.50; 95% CI = 0.25 - 0.99). Anticoagulant choice (NOAC vs VKA) did not significantly affect bleeding rates (P=0.258). Age, heart failure, leukemia/myelodysplasia and acute coronary syndrome were associated with increased bleeding rates. Risk of MACEs and NACEs was similar between ΤAT and DAT (HR = 1.73; 95% CI = 0.95 - 3.18, P = 0.075 and HR = 1.39; 95% CI = 0.93 - 2.08, P=0.106, respectively).In conclusion, clinically significant bleeding and ischemic rates were similar between DAT and TAT, although TAT >1 month was associated with higher bleeding risk.
Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients’ tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC.
Background: A number of studies report small airways involvement in patients with systemic sclerosis (SSc). Furthermore, small airways dysfunction is increasingly recognized in patients with interstitial lung disease (ILD) of idiopathic or autoimmune etiology. The objectives of this study were to evaluate small airways function in SSc patients with ILD and explore the effect of treatment on small airways function by using conventional and contemporary pulmonary function tests (PFTs). Methods: This single-center, prospective, observational study included a total of 35 SSc patients, with and without ILD based on HRCT scan, evaluated by a special radiologist blindly. Clinical data were collected from all patients who were also assessed for HRCT findings of small airways disease. Small airways function was assessed by classic spirometry, measurement of diffusing capacity for carbon monoxide, body plethysmography, single breath nitrogen washout (N2SBW) and impulse oscillometry (IOS). The prevalence of small airways dysfunction according to R5–R20, phase III slopeN2SBW and CV/VC methodologies was calculated in the total SSc population. Pulmonary function tests were compared between: (a) SSc-ILD and non-ILD patients and (b) two time points (baseline and follow up visit) in a subset of SSc-ILD patients who received treatment for ILD and were re-evaluated at a follow up visit after 12 months. Results: Phase III slopeN2SBW and R5–R20 showed the highest diagnostic performance for detecting small airways dysfunction among SSc patients (61 and 37.5%, respectively). Twenty three SSc patients were found with ILD and 14 of them had a 12-month follow up visit. SSc-ILD patients compared to those without ILD exhibited increased phase III slopeN2SBW ≥120% (p = 0.04), R5–R20 ≥0.07 kPa/L/s (p = 0.025), airway resistance (Raw) (p = 0.011), and special airway resistance (sRaw) (p = 0.02), and decreased specific airway conductance (sGaw) (p = 0.022), suggesting impaired small airways function in the SSc-ILD group. Radiographic features of SAD on HRCT were observed in 22% of SSc-ILD patients and in none of SSc-non-ILD patients. Comparison of PFTs between baseline and follow-up visit after 12 months in the 14 SSc-ILD treated patients, showed improvement of phase III slopeN2SBW (p = 0.034), R5–R20 (p = 0.035) and Raw (p = 0.044) but not sRaw and sGaw parameters. Conclusion: Phase III slopeN2SBW and R5–R20 may reveal small airways dysfunction in SSc associated ILD before structural damage and may be partially improved in a subset of patients receiving treatment for ILD.
The so-called “smoking paradox”, conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS–STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.
Platelet function testing (PFT) could be a useful clinical tool to guide individualized antithrombotic treatment in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). We aimed to investigate platelet reactivity (PR) in the context of a contemporary registry. “Real-world” data were retrieved from a nationwide, multicenter, observational study of AF patients on oral anticoagulants (OAC) undergoing PCI. Patients treated with a P2Y12 inhibitor, namely clopidogrel or ticagrelor, as part of double or triple antithrombotic therapy, were submitted to PFT before discharge and were followed up for 12 months. Out of 101 patients included in the study, 66 were submitted to PFT while on clopidogrel and 35 while on ticagrelor; PR was 162.9 ± 68 PRU and 46.02 ± 46 PRU, respectively (P < 0.001). High on-treatment PR (HTPR) was observed in 15 patients under clopidogrel (22.7%); 7 of them escalated to ticagrelor. Low on-treatment PR (LTPR) was found in 9 clopidogrel and 28 ticagrelor-treated patients (13.6% vs. 80%, P < 0.001), of whom only 1 de-escalated to clopidogrel. PR did not differ by OAC regimen. PFT results had no impact on aspirin prescription at discharge, while failed to predict significant bleeding events at follow up. Ticagrelor administration led to lower PR and lower incidence of HTPR in comparison with clopidogrel. Physicians’ behavior in response to knowledge of a patient’s PR was variable. Further studies are required to elucidate the role of PFT as a tool to guide individualized antithrombotic treatment in this clinical scenario.
Background Immune-checkpoint inhibition (ICI) only benefits a subgroup of patients with head and neck squamous cell carcinoma (HNSCC). Several molecular and cellular components of the tumor microenvironment (TME) have been hypothesized to drive either response or resistance. Here, spatially defined whole transcriptome data were analysed in search of associations of compartment-specific gene-signatures with HNSCC immunotherapy outcomes Methods Pre-treatment biopsy samples from 50 immunotherapy-treated recurrent or metastatic HNSCC patients as well as 12 matched post-treatment biopsies obtained after 4 weeks of treatment, constructed in tissue microarray format (YTMA496), were included in the study. The GeoMx Human Whole Transcriptome Atlas (NanoString Technologies) assay was performed on samples to allow RNA quantification of 18,677 protein encoding genes, using in situ hybridization, in three molecularly defined tissue compartments; tumor (CK), leukocyte (CD45), macrophage (CD68). Differentially expressed genes (DEGs) (P<0.05) between pre- and post-treatment biopsies in each of the tissue compartments were identified. Next, these DEGs were used as a ‘biological’ filter for the initial 18,677 gene set and analysed using LASSO logistic regression models with the aim to obtain pre-treatment gene expression signatures for best overall response (RECIST 1.1.). The performance of each compartment signature was evaluated using the receiver operating characteristic (ROC) curve and AUCs were calculated for Best Overall Response (BOR) to ICI. Genes comprising the highest performing signature were investigated for correlations with immune cell genes extracted from the ‘Single Cell RNA-Seq HNSCC’ (CIBERSORTx) gene matrix. Results A six-gene signature (DDX4, COL17A1, HBA1, MMP1, GPNMB, TTN) in the CD45 compartment presented the highest AUC (0.83), followed by signatures in the CK and CD68 compartments (AUC: 0.72 and 0.68, respectively). Cross-testing of the CD45 signature in the other two compartments, as well as in a third, artificially generated ‘pseudo-bulk’ compartment (all compartments combined), showed poor performance, indicating spatial specificity. Interestingly, the CD45 signature included three extracellular-matrix protein-encoding genes (MMP1, COL17A1, TTN), all associated with resistance (negative coefficients in the BOR model) to ICI. Fibroblast and dendritic cell populations, characterized using the CIBERSORTx gene matrix, were the immune phenotypes most closely associated with the CD45 signature. Conclusions Our results indicate that CD45 molecular tissue compartment gene expression demonstrates increased association with ICI resistance in HNSCC. Extracellular matrix genes rather than immune-cell related genes dominated the CD45 compartment signature, highlighting the importance of non-immune stromal components within the TME and the importance of the use of spatial information in the understanding of ICI resistance. Acknowledgements This study was funded by Yale Head and Neck SPORE. Ethics Approval This study was approved by Yale Human Investigation IRB protocol ID 9505008219.
The Hippo pathway regulates and contributes to several hallmarks of prostate cancer (PCa). Although the elucidation of YAP function in PCa is in its infancy, emerging studies have shed light on the role of aberrant Hippo pathway signaling in PCa development and progression. YAP overexpression and nuclear localization has been linked to poor prognosis and resistance to treatment, highlighting a therapeutic potential that may suggest innovative strategies to treat cancer. This review aimed to summarize available data on the biological function of the dysregulated Hippo pathway in PCa and identify knowledge gaps that need to be addressed for optimizing the development of YAP-targeted treatment strategies in patients likely to benefit.
Objective: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement. Methods: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase (rhAC) in vitro. Results: The six new patients showed the hallmark features of SMA-PME, with variable initial symptom and age of onset. Five of six patients carried at least one of the recurrent SMA-PME variants observed in two specific codons of ASAH1. A review of 30 total cases revealed that patients who were homozygous for the most common c.125C > T variant presented in the first decade of life with limb-girdle weakness as the initial symptom. Sensorineural hearing loss was associated with the c.456A > C variant. Leukocyte acid ceramidase activity varied from 4.1%-13.1% of controls. Ceramide species in fibroblasts were detected and total cellular ceramide content was elevated by 2 to 9-fold compared to controls. Treatment with rhAC normalized ceramide profiles in cultured fibroblasts to control levels within 48 h. Interpretation: This study details the genotype-phenotype correlations observed in SMA-PME and shows the impact of rhAC to correct the abnormal cellular ceramide profile in cells.
Aims: Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF). Methods and results: We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome. Conclusions: Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.
Background/aim: Utilizing an experimental animal model, we investigated the correlation between aromatase inhibitors (AIs) (anastrozole and letrozole) and Calprotectin levels. AIs have demonstrated superior efficacy when used as adjuvant endocrine therapy or monotherapy for postmenopausal patients with hormone receptor (HR)-positive early-stage breast cancer, although various side effects have been recorded. Materials and methods: Fifty-five adult female Wistar rats were randomized and assigned into four groups. The control group received no intervention. The other three groups were subjected to ovariectomy, and serum Calprotectin levels were measured at baseline, 2, and 4 months. In addition, glucose, total cholesterol, very low-density lipoprotein- (VLDL-) cholesterol, low-density lipoprotein (LDL-) cholesterol, high-density lipoprotein- (HDL-) cholesterol, and triglyceride levels were measured. Histological analysis of liver tissue was carried out following rats' euthanasia. Results: Aromatase inhibitors (anastrozole and letrozole) affect calprotectin levels in ovariectomized rats. Calprotectin, a marker of inflammation, was found to be affected by the use of the inhibitors. Conclusion: The potential of hepatotoxicity can be examined by assessing the elevation of inflammation markers such as Calprotectin, which is an indicator that should be strictly taken into consideration when administering aromatase inhibitors as treatment.
Brodalumab's clinical efficacy and favourable safety profile have been demonstrated during controlled clinical trials, but real‐world data remain scarce. BrIDGE, an ongoing 104‐week, observational, prospective, multicentre study conducted in Greece, enrolled moderate‐to‐severe plaque psoriasis patients, with Body Surface Area (BSA)>10 or Psoriasis Area Severity Index score (PASI)>10 and Dermatology Life Quality Index (DLQI)>10, based on European consensus, initiating brodalumab treatment as per routine clinical practice. This interim analysis includes evaluations 12‐16 weeks following treatment initiation. Key efficacy endpoints included proportion of patients achieving static Physician's Global Assessment (sPGA) score of “clear/almost clear” (0/1) and a reduction ≥75%, 90%, 100% from baseline in PASI (PASI75, PASI90, PASI100) at week 12‐16. Other endpoints included time to achieve PASI100, changes in self‐reported DLQI and Psoriasis Symptom Inventory (PSI) at week 12‐16. From 200 patients (mean age 51.4 years, 70% male, mean disease duration 13.8 years) enrolled, 72.8% achieved sPGA of 0/1, whereas 70.2%, 47.5% and 32.0% achieved corresponding PASI75, PASI90 and PASI100 responses following 12‐16 weeks of brodalumab treatment, according to the “as‐observed” analysis. The mean time to achieve PASI100 was 13.7±1.2 weeks for the 32% who achieved PASI100. Concurrent decreases in mean DLQI and PSI were observed. Furthermore, 90% adherence to brodalumab was noted and 9 adverse events were reported. Brodalumab confers substantial clinical improvements short‐term as reflected by high levels of skin clearance in moderate‐to‐severe plaque psoriasis patients within 12‐16 weeks of treatment under everyday clinical conditions, followed by improvements in symptoms and quality of life and a favourable safety profile. This article is protected by copyright. All rights reserved.
Pain is the most common and fearsome symptom in cancer patients, particularly in the advanced stage of disease. In cancer pain management, the first option is represented by analgesic drugs, whereas surgery is rarely used. Prior to considering surgical intervention, less invasive locoregional procedures are available from the wide pain management arsenal. In this review article, comprehensive information about the most commonly used locoregional options available for treating cancer pain focusing on interventional radiology (neurolysis, augmentation techniques, and embolization) and interventional radiotherapy were provided, also highlighting the potential ways to increase the effectiveness of treatments.
Background Micropenis is treated preferably in infancy (≤ 2 yrs) or at the onset οf puberty, usually with 3 (2-4) monthly testosterone enanthate I. M. injections at the dose of 100 mg/m2. This short-term therapy may temporarily advance bone maturation but with a concomitant increase in height velocity and no apparent change in predicted adult height. Bone maturation depends on locally produced estrogens by aromatization. Third generation aromatase inhibitors (AIs) are used as an off-label treatment to improve predicted adult height (PAH) in boys as well as in girls, either as monotherapy or in combination with growth hormone and/or puberty inhibition. They induce reverse binding inhibiting the activity of aromatase (a cytochrome P450 enzyme), which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively, resulting in a substantial increase of the circulating testosterone concentrations. Aims To compare the traditional treatment of isolated - idiopathic - relative micropenis in boys with testosterone enanthate monotherapy to its combination with anastrozole 1 mg×1 p. o. Methods 164 boys with micropenis (stretched penile length ≤ -2 SD) received testosterone enanthate 100 mg/m2 I. M. /month either as monotherapy (n=63, mean age 10.8 yrs, group A) or in combination with anastrozole 1 mg/day (n=101, mean age 11 yrs, group B) for 3 months. Stretched penile length, bone maturation and auxological data were analyzed. All measurements were performed by the same examiner. The choice of therapeutic intervention was made randomly. Groups A and B did not differ in terms of age at intervention onset, bone age, target height or predicted adult height. They underwent a 6-month follow-up that included clinical examination, bone age X-ray evaluated by BoneXpert ver. 3.2. 0 (Visiana, Denmark), and laboratory tests at 8: 00hrs (LH, FSH, testosterone, estradiol, estrone), prior and under treatment. Results In both groups penile length normalized: for group A gain was +1.9 cm (+2. 08 SD) and for group B +2.24 cm (+2.3 SD), with group B attaining a greater length by +18% (p=0. 004) due to the higher testosterone concentrations attained by at least 50%. Group A presented a slight acceleration of height velocity with parallel advancement of their bone age maturation while group B with unchanged or lower estradiol and estrone concentrations maintained their height velocity with parallel movement of their bone age maturation. Conclusions Addition of anastrozole 1 mg/day p. o. in testosterone enanthate treatment for idiopathic-isolated-relative micropenis at the beginning of puberty significantly improves penile length by almost 20% while the tempo of height velocity and bone maturation continue their previous track. Presentation: No date and time listed
Background Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). Methods and results We retrospectively analyzed 790 AHF patients enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/ml) on admission more frequently had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] >150 ng/dl) and myocardial injury (≥ 20% increase in the peak high sensitivity cardiac troponin I [hs-cTnI] value compared to admission). They less frequently had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or HF rehospitalization and death alone at one-year. After multivariable adjustment, higher galectin-3 was only associated with death. Conclusions In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and predicted worse outcomes.
Rationale Septic patients admitted to the intensive care unit (ICU) suffer from immune dysregulation, potentially leading to a secondary sepsis episode. This study aims to (i) assess the secondary sepsis rate, (ii) compare the second with the first episodes in terms of demographics, clinical and laboratory characteristics, and outcomes, and iii) evaluate the outcome of secondary sepsis. Methods A single-center, retrospective study (2014–2017) was conducted in a Greek ICU, including consecutive cases of adult patients admitted to the ICU for at least 48 h with a principal admission diagnosis of sepsis and stayed for at least 48 h. We searched for a secondary episode of sepsis following the primary-one. We performed survival analyses with Cox proportional hazard, Fine-Gray, and multistate models. Results In this study, 121 patients that fulfilled the eligibility criteria were included. The secondary sepsis group included 28 (23.1 %) patients, with episode onset, median (interquartile range), 9.5 (7.7–16.2) days after ICU admission, who had less frequently had a medical admission diagnosis, a microbiologically confirmed first episode, and the C-reactive protein was lower. The overall ICU mortality of the cohort was 44.6 %. The group that developed secondary sepsis had higher mortality, but significance was lost in Cox regression [Hazard ratio (95 % CI) 0.59(0.31–1.16)]. However, after multistate modeling adjustment, the attributable mortality was estimated at 43.9 % (95 %CI ± 14.8 %). Conclusion Secondary sepsis was evident in a quarter of the study participants and may be associated with an increased risk of death.
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