Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA

The risk of postoperative respiratory complications following adenotonsillar surgery in children with or without obstructive sleep apnea: A systematic review and meta-analysis

Obstructive sleep apnoea (OSA) appears in 2-5% of children, with first-line treatment being adenotonsillar (AT) surgery. Our aim was to examine the risk of postoperative respiratory complications (PoRCs) in non-OSA and the different OSA severity (mild, moderate, severe) groups.We conducted a systematic review and meta-analysis of studies comparing PoRCs following AT surgery in children with and without OSA.19 observational studies were identified with the same search key used in MEDLINE, Embase and CENTRAL. The connection between PoRCs, the presence and severity of OSA, and additional comorbidities were examined. Odds ratios (OR) were calculated with 95% confidence intervals (CI).We found that PoRCs appeared more frequently in moderate (p=0.048, OR: 1.79, CI (1.004, 3.194)) and severe OSA (p=0.002, OR: 4.06, CI (1.68, 9.81)) compared to non-OSA patients. No significant difference was detected in the appearance of major complications (p=0.200, OR: 2.14, CI (0.67, 6.86)) comparing OSA and non-OSA populations. No significant difference was observed in comorbidities (p=0.669, OR: 1.29, CI (0.40, 4.14)) or in the distribution of PoRCs (p=0.904, OR: 0.94, CI (0.36, 2.45)) between the two groups.Uniform guidelines and a revision of postoperative monitoring are called for, since children with moderate and severe OSA are more likely to develop PoRCs following AT surgery based on our results, but no significant difference was found in mild OSA. Furthermore, the presence of OSA only is not associated with an increased risk of developing major complications. This article is protected by copyright. All rights reserved

Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma—a systematic review and meta-analysis

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive versus negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR=2.81, CI:1.31-6,00, I2=88.7%, p<0.001), and progression (UHR=3.33, CI: 2.33-4.77, I2=0, p=0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR=5.55, CI: 3.24-9.49, I2=0, p=0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR=2.51, CI: 0.55-11.43, I2=90.3%, p<0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR=4.08, CI: 2.16-7.69, I2=46.9%, p=0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use

HLA-DQ2 homozygosis increases tTGA levels at diagnosis but does not influence the clinical phenotype of celiac disease: a multicenter study

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Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19 : a systematic review and meta-analysis

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention

Pancreatic family history does not predict disease progression but connotes alcohol consumption in adolescents and young adults with acute pancreatitis: Analysis of an international cohort of 2,335 patients

In pediatric acute pancreatitis (AP), a family history of pancreatic diseases is prognostic for earlier onset of recurrent AP (ARP) and chronic pancreatitis (CP). No evidence supports the same association in adult-onset pancreatitis. Age-specific reasons for familial aggregation are also unclear. We aimed to examine the prognostic role of pancreatic family history for ARP/CP and observe possible underlying mechanisms.We conducted a secondary analysis of the Hungarian Pancreatic Study Group's (HPSG) multicenter, international, prospective registry of patients with AP, both children and adults. We compared the positive family history and the negative family history of pancreatic diseases, in different age groups, and analyzed trends of accompanying factors. Chi-square and Fisher exact tests were used.We found a higher rate of ARP/CP in the positive pancreatic family history group (33.7 vs. 25.9%, p = 0.018), peaking at 6-17 years. Idiopathic AP peaked in childhood in the positive family history group (75% 0-5 years) and was consistently 20-35% in the negative group. A higher rate of alcohol consumption/smoking was found in the positive groups at 12-17 years (62.5 vs. 15.8%, p = 0.013) and 18-29 years (90.9 vs. 58.1%, p = 0.049). The prevalence of diabetes and hyperlipidemia steadily rose with age in both groups.Positive family history most likely signifies genetic background in early childhood. During adolescence and early adulthood, alcohol consumption and smoking emerge-clinicians should be aware and turn to intervention in such cases. Contrary to current viewpoints, positive pancreatic family history is not a prognostic factor for ARP and CP in adults, so it should not be regarded that way

Metabolic-Associated Fatty Liver Disease is associated with Acute Pancreatitis with More Severe Course: Post hoc Analysis of a Prospectively Collected International Registry

Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP.We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis.MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant.MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP

Invalidity of Tokyo guidelines in acute biliary pancreatitis : A multicenter cohort analysis of 944 pancreatitis cases

There is a noteworthy overlap between the clinical picture of biliary acute pancreatitis (AP) and the 2018 Tokyo guidelines currently used for the diagnosis of cholangitis (AC) and cholecystitis (CC). This can lead to significant antibiotic and endoscopic retrograde cholangiopancreatography (ERCP) overuse.We aimed to assess the on-admission prevalence of AC/CC according to the 2018 Tokyo guidelines (TG18) in a cohort of biliary AP patients, and its association with antibiotic use, ERCP and clinically relevant endpoints.We conducted a secondary analysis of the Hungarian Pancreatic Study Group's prospective multicenter registry of 2195 AP cases. We grouped and compared biliary cases (n = 944) based on the on-admission fulfillment of definite AC/CC according to TG18. Aside from antibiotic use, we evaluated mortality, AC/CC/AP severity, ERCP performance and length of hospitalization. We also conducted a literature review discussing each criteria of the TG18 in the context of AP.27.8% of biliary AP cases fulfilled TG18 for both AC and CC, 22.5% for CC only and 20.8% for AC only. Antibiotic use was high (77.4%). About 2/3 of the AC/CC cases were mild, around 10% severe. Mortality was below 1% in mild and moderate AC/CC patients, but considerably higher in severe cases (12.8% and 21.2% in AC and CC). ERCP was performed in 89.3% of AC cases, common bile duct stones were found in 41.1%.Around 70% of biliary AP patients fulfilled the TG18 for AC/CC, associated with a high rate of antibiotic use. Mortality in presumed mild or moderate AC/CC is low. Each of the laboratory and clinical criteria are commonly fulfilled in biliary AP, single imaging findings are also unspecific-AP specific diagnostic criteria are needed, as the prevalence of AC/CC are likely greatly overestimated. Randomized trials testing antibiotic use are also warranted