Cardiovascular risk factors in coeliac disease (ARCTIC): a protocol of multicentre series of studies.

INTRODUCTION: There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD and on a gluten-free diet in a Hungarian cohort of patients with CD. METHODS AND ANALYSIS: This study consists of two case-control studies and a prospective cohort study, involving newly diagnosed and treated patients with CD with age and sex-matched non-CD control subjects with an allocation ratio of 1:1. CD-related symptoms, quality of life, quality of the diet and CV risk will be assessed with questionnaires. Our primary outcomes are body composition parameters, which will be estimated with InBody 770 device. Secondary outcomes are CV-risk related metabolic parameters (eg, serum lipids, haemoglobin A1c, homeostatic model assessment index, liver enzymes, homocysteine, interleukin 6, galectin-3) and enteral hormones (leptin, ghrelin, adiponectin) measured from venous blood samples for all participants. Fatty liver disease will be assessed by transabdominal ultrasonography. In statistical analysis, descriptive and comparative statistics will be performed. With this study, we aim to draw attention to the often neglected metabolic and CV aspect of the management of CD. Findings may help to identify parameters to be optimised and reassessed during follow-up in patients with CD. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05530070.

Acquired Hemophilia A after SARS-CoV-2 Infection: A Case Report and an Updated Systematic Review.

The role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been implicated in the pathogenesis of acquired hemophilia A (AHA). The aim of this study is to report our case and to summarize clinical studies on de novo AHA after SARS-CoV-2 infection. We performed a systematic search on the association of SARS-CoV-2 with AHA in four medical databases up to 28 May 2023. Eligible studies should include de novo AHA patients who had SARS-CoV-2 infection before or concomitant with the diagnosis of AHA. Findings were synthesized narratively. In addition, we report the case of a 62-year-old female patient, who presented to our clinic with left flank pain 2 weeks after SARS-CoV-2 infection. Clinical investigations confirmed AHA and imaging studies revealed retroperitoneal bleeding. Her hemostasis was successfully secured with bypassing agents; however, despite immunosuppressive therapy, high inhibitor titer persisted. In the systematic review, we identified only 12 relevant cases with a questionable cause-effect relationship between SARS-CoV-2 infection and AHA. Based on the qualitative analysis of the relevant publications, current clinical evidence is insufficient to support a cause-effect relationship. The analysis of data from ongoing AHA registries can serve further evidence.

Clinicopathological analysis of diffuse large B-cell lymphoma using molecular biomarkers: a retrospective analysis from 7 Hungarian centers.

Background: The clinical and genetic heterogeneity of diffuse large B-cell lymphoma (DLBCL) presents distinct challenges in predicting response to therapy and overall prognosis. The main objective of this study was to assess the application of the immunohistochemistry- and interphase fluorescence in situ hybridization (FISH)-based molecular markers in the diagnosis of DLBCL and its prognostic value in patients treated with rituximab-based immunochemotherapy. Methods: This is a multicenter, retrospective study, which analyzed data from 7 Hungarian hematology centers. Eligible patients were adults, had a histologically confirmed diagnosis of DLBCL, were treated with rituximab-based immunochemotherapy in the first line, and had available clinicopathological data including International Prognostic Index (IPI). On the specimens, immunohistochemistry and FISH methods were performed. Germinal center B-cell like (GCB) and non-GCB subtypes were classified by the Hans algorithm. Outcomes included overall survival (OS), event-free survival (EFS), and EFS at 2 years (EFS24). For survival analysis, we used Kaplan-Meier curves with the log-rank test and multivariate Cox regression. Results: A total of 247 DLBCL cases were included. Cases were positive for MYC, BCL2, BCL6, and MUM1 expression in 52.1%, 66.2%, 72.6%, and 77.8%, respectively. BCL6 translocation, BCL2 gene copy number (GCN) gain, IGH::MYC translocation, MYC GCN gain, IGH::BCL2 translocation, and BCL6 GCN gain were detected in 21.4%, 14.1%, 7.3%, 1.8%, 7.3%, and 0.9%, respectively. At a median follow-up of 52 months, 140 patients (56.7%) had disease progression or relapse. The Kaplan-Meier estimate for EFS24 was 56.2% (CI: 50.4-62.8%). In univariate analysis, only IPI and BCL6 expression were significant predictors of both OS and EFS, whereas MUM1 predicted EFS only. In multivariate analysis, the IPI score was a significant independent negative, whereas MIB-1 and BCL6 protein expressions were significant independent positive predictors of both OS and EFS. Conclusion: In our study, we found that only IPI, BCL6 protein expression and MIB-1 protein expression are independent predictors of survival outcomes in DLBCL. We did not find any difference in survival by GCB vs. non-GCB subtypes. These findings may improve prognostication in DLBCL and can contribute to designing further research in the area.

Body Mass Index during Gluten-Free Diet in Patients with Celiac Disease.

The association of clinical variables with body mass index (BMI) and changes experienced during a gluten-free diet (GFD) in celiac disease (CD) is not well established. In this retrospective cohort study, we aimed to investigate factors aligned with baseline and a follow-up regarding BMI in CD cases diagnosed at the University of Pécs (Hungary). Data were collected regarding gender, age, clinical presentation, histology, serology, extraintestinal manifestations, and BMI upon diagnosis and during follow-up. To compare variables with baseline BMI and BMI changes in short-, intermediate-, and long-term periods, we applied univariate analyses. A total of 192 CD patients were included. Males had significantly higher mean BMI when compared with females at diagnosis (22.9 ± 4.1 vs. 21.4 ± 4.3 kg/m2, p = 0.041) and during follow-up (p = 0.031, p = 0.029, and p = 0.033 for short-, intermediate-, and long-term follow-ups, respectively). Non-classical CD patients experienced higher mean BMI at diagnosis (22.9 ± 4.0 vs. 20.7 ± 4.4 kg/m2, p < 0.001) and following long-term follow-up (24.5 ± 3.2 vs. 22.6 ± 3.4 kg/m2, p = 0.039) than classical patients. In conclusion, although the mean BMI remained in the normal range, it increased significantly during follow-up, even at the short-term follow-up. This change was characteristic for non-classical cases and males on the long-term follow-ups.

Clinical Presentation Is Dependent on Age and Calendar Year of Diagnosis in Celiac Disease: A Hungarian Cross-Sectional Study.

International trends indicate that celiac disease (CeD) is becoming more common, while the clinical presentation of CeD tends to change. We aimed to investigate factors associated with the clinical presentation of CeD. We reviewed all CeD cases diagnosed at our tertiary center, University of Pécs (Hungary), between 1992 and 2019. We collected data of verified CeD patients on clinical presentations (classified by the Oslo Classification), the age at and calendar year of diagnosis, and sex, serology and histology at diagnosis. To assess the associations of baseline variables with clinical presentations, we applied univariate and multivariate (binary logistic regression) statistics. A total of 738 CeD patients were eligible for inclusion. In the univariate analysis, patients with classical CeD were more common in the latest calendar period (p < 0.001) and tended to be older (p = 0.056), but we failed to observe a significant association between the clinical presentation and sex, serology or histology at diagnosis. In the multivariate analysis, only age at diagnosis and calendar year were independently associated with clinical presentations (OR = 1.02, CI: 1.01-1.04 and OR = 0.93, CI: 0.89-0.98, respectively). Our findings confirmed that classical CeD is independently associated with age at diagnosis and calendar year of diagnosis of CeD, whereas other parameters were not significantly associated with clinical presentations.

Quality-of-life outcomes with endoscopic and microscopic type I tympanoplasty-a prospective cohort study.

PURPOSE: Endoscopic type I tympanoplasty was originally introduced in the 1990s and the extensive spread of this practice can be easily observed. The conventional technique performed involves the repair of a tympanic membrane perforation and is defined as microscopic type I tympanoplasty. The aim of this study is the comparison of quality-of-life (QoL) outcomes with endoscopic to that with microscopic type I tympanoplasty. METHODS: All patients, or in the case of children with the aid of a parent, were asked to complete a novel QoL questionnaire drafted by our study group. The analysis was performed with descriptive statistics-mean, SD and relative frequency-and with a mixed model (generalized least squares fit). A two-sided p value of < 0.05 was regarded as statistically significant. RESULTS: A total of 83 patients completed the questionnaire, 38 in the endoscopic group and 45 in the microscopic group. Every question represented a different. A statistically significant result was found in favor of the endoscopic approach regarding average hospitalization rate (p = 0.003) and cosmetic outcomes (p = 0.015). No statistically significant difference was otherwise observed between the groups. CONCLUSIONS: Based on our prospective cohort study, the QoL outcomes of endoscopic type I tympanoplasty in terms of postoperative pain, headache, nausea, vomiting, dizziness, taste disorder and hearing were comparable to the microscopic type I tympanoplasty. In regard to cosmetics, an increase in desirable results was achieved in the endoscopic group, particularly the average hospitalization rate proved to be statistically significantly lower than in the microscopic group.

Intravenous ferric carboxymaltose versus oral ferrous sulfate replacement in elderly patients after acute non-variceal gastrointestinal bleeding (FIERCE): protocol of a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Acute gastrointestinal bleeding (GIB) is a life-threatening emergency with a critical economic burden. As a result of bleeding, anaemia often requires intravenous or oral iron supplementation. Elderly patients are even more prone to untoward outcomes after hospital discharge if iron supplementation is inefficient. There is a gap in current guidelines on which supplementation route clinicians should choose. We aim to investigate the effect of one dose of intravenous iron therapy versus 3-month oral iron administration on anaemia in an elderly population. METHODS AND ANALYSIS: The FIERCE study is an open-label, randomised controlled, two-armed trial. At least 48 hours after the acute non-variceal GIB treatment, patients will be recruited in participating centres. A random sequence generator will allocate the participants to group A (intravenous ferric carboxymaltose, 1000 mg) or group B (oral ferrous sulfate (FS), ca. 200 mg every day) with an allocation ratio of 1:1 on the day of the planned discharge from the hospital. Randomisation will be stratified for participating centres and the need for transfusion within the same hospitalisation before recruitment to the trial. Quality of life assessment, functional measurement and laboratory tests will be performed at baseline, 1 and 3 months±7 days after enrolment to the trial. The primary endpoint is a composite endpoint, including all-cause mortality, anaemia-associated unplanned emergency visit and anaemia-associated unplanned hospital admission within 3 months of enrolment in the trial. ETHICS AND DISSEMINATION: The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (46395-5/2021/EÜIG). We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. TRIAL REGISTRATION: The trial has been registered at ClinicalTrials.gov (NCT05060731).

Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events. METHODS: MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models. RESULTS: A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95-4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38-0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30-0.84, p < 0.01). CONCLUSIONS: Low platelet reactivity is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393).

Geno- and phenotypic characteristics and clinical outcomes of CACNA1C gene mutation associated Timothy syndrome, "cardiac only" Timothy syndrome and isolated long QT syndrome 8: A systematic review.

Background: Mutations in the CACNA1C gene-encoding for the major Ca2+ channel of the heart-may exhibit a variety of clinical manifestations. These include typical or atypical Timothy syndromes (TS) which are associated with multiple organ manifestations, and cardiac involvement in form of malignant arrhythmias, QTc prolongation, or AV block. "Cardiac only" Timothy syndrome (COTS) shows no extracardiac manifestation, whereas some CACNA1C gene mutations are associated with QTc prolongation alone (isolated long QT syndrome 8, LQT8). Methods: A systematic search of the literature reporting cases of CACNA1C gene mutation associated syndromes, including TS, COTS and isolated LQT8 via major databases published from 2004 through 2019 was performed. Detailed patient-level phenotypic and genotypic characteristics, as well as long-term outcome measures were collected and compared between pre-specified patient groups, defined both on phenotype and genotype. Results: A total of 59 TS, 6 COTS, and 20 isolated LQT8 index cases were identified. Apart of syndactyly or baldness, there were no major differences regarding clinical manifestations or outcome measures between TS subtypes, either defining TS subtypes on the genotype or based on the phenotype. Both subtypes were characterized by an extreme degree of QTc prolongation (median ≥600 ms) which were reflected in high major adverse cardiac event rate. On the other hand, there were marked differences between TS, COTS, and isolated LQT8. Timothy syndrome was characterized by a much earlier disease onset, much more pronounced QTc prolongation and much higher mortality rate than COTS or isolated LQT8. Similar differences were observed comparing CACNA1C exon 8/8A vs. non-exon 8/8A mutation carriers. TS showed a high degree of genetic homogeneity, as the p.Gly406Arg mutation either in exon 8 or exon 8A alone was responsible for 70% of the cases. Conclusions: Clinical phenotypes associated with mutations in the CACNA1C gene show important clinical differences. Timothy syndrome is associated with the most severe clinical phenotype and with the highest risk of morbidity and mortality. However, distinguishing TS subtypes, in any form, are not supported by our data. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020184737].

90Y-ibritumomab Tiuxetan in B-cell Non-Hodgkin Lymphomas: Real-world Data From the United Arab Emirates.

Purpose: B-cell non-Hodgkin lymphomas (NHLs) are significant contributors to cancer-related mortality. In this single-arm, retrospective cohort study, we aimed to examine the outcomes of a radioimmunotherapeutic modality, 90Y-labeled ibritumomab tiuxetan (90YIT) in B-cell NHLs. Methods and Materials: We conducted this study based on data from the United Arab Emirates lymphoma registry. All patients with NHL subjected to 90YIT were eligible for inclusion. The country of research lacked a national autologous stem cell transplantation (ASCT) center, but many ASCT-eligible patients received 90YIT. We investigated overall survival (OS) and event-free survival (EFS), as well as safety outcomes. Results: Between 2004 and 2008, 54 of 111 patients with B-cell NHL received radioimmunotherapy. The therapy was applied as first-line treatment in 18 cases (33.3%) and second- or later-line treatment in 36 cases (66.7%). All patients were evaluable for response. The first-line group consisted mainly of follicular lymphoma cases, and 3 of 18 patients died (16.7%) during the follow-up (range, 22-67 months). Median OS was not reached. No progression occurred after treatment (median EFS, 36.5 months [Q1-Q3 range, 30.5-44 months]). The second- or later-line group consisted mainly of diffuse large B-cell lymphoma cases, and 3 of 36 patients died (8.3%) during the follow-up (range, 4-68 months). Median OS was not reached. One case of progression was registered (median EFS: 33 months [Q1-Q3 range, 30.5-44 months]). 90YIT had acceptable short- and long-term safety profiles. Conclusions: The findings suggest that patients with NHL may benefit from 90YIT as salvage treatment if ASCT is not available; however, this should be validated in randomized studies.

Preoperative Serum Carbohydrate Antigen 19-9 Levels Cannot Predict the Surgical Resectability of Pancreatic Cancer: A Meta-Analysis.

Background and Aims: Pancreatic ductal adenocarcinoma has one of the worst prognosis of all malignancies. This investigated the relationship between the preoperative serum carbohydrate antigen 19-9 and surgical resectability. Methods: A systematic search was performed in three databases (MEDLINE, EMBASE, and Web of Science) to compare the surgical resectability of pancreatic ductal adenocarcinoma in patients with high and low preoperative serum carbohydrate antigen 19-9 values. The receiving operating characteristic curves were constructed and the weighted mean differences for preoperative serum carbohydrate antigen 19-9 levels of resectable and unresectable groups of patients were calculated. The PROSPERO registration number is CRD42019132522. Results: Results showed that there was a significant difference in resectability between the low and high carbohydrate antigen 19-9 groups. Six out of the eight studies utilised receiver operating characteristic curves in order to find the cut-off preoperative carbohydrate antigen 19-9 levels marking unresectability. The overall result from the pooled area under curve values from the receiver operating characteristic curves was 0.794 (CI: 0.694-0.893), showing that the preoperative carbohydrate antigen 19-9 level is a "fair" marker of resectability. The result of the pooled weighted mean differences was 964 U/ml (p < 0.001) showing that there is a significant carbohydrate antigen 19-9 difference between the resectable and unresectable groups. Based on the results of the I-squared test, the result was 87.4%, accounting for "considerable" heterogeneity within the population. Conclusion: Carbohydrate antigen 19-9 is not a reliable marker of unresectability, it should not be used on its own in surgical decision-making.

Role of stereotactic body radiation in the enhancement of the quality of life in locally advanced pancreatic adenocarcinoma: a systematic review.

INTRODUCTION: Up to 30% of pancreatic cancer patients initially present locally advanced (LAPC). Stereotactic body radiation therapy (SBRT) may be an additional palliative treatment option when curative resection is no longer achievable. Our systematic review aimed to assess the effect of SBRT on the quality of life in LAPC. METHODS: We searched five databases until June 29th, 2021, for original articles that reported on SBRT for histologically proven LAPC in adults. Data were extracted on study characteristics, SBRT and additional therapy regimen, pain, biliary complications, nutrition, quality of life and other patient-reported outcomes. Statistical analyses were performed for population and survival data. RESULTS: 11 case series studies comprising 292 patients with a median age of 66 (range 34-89) years were included in the final analysis. The weighted average BED2;10 (radiation biologically effective dose, equivalent dose in 2 Gy fractions) was 54 Gy, delivered in 3 to 6 fractions. The individual studies used different scales and endpoints, not allowing a meta-analysis. Pain generally appeared to be improved by SBRT. SBRT significantly reduced jaundice. Local control was achieved in 71.7% of patients. Weight loss and nausea also tended to improve after SBRT. CONCLUSION: SBRT of locally advanced irresectable pancreatic cancer is a promising approach for achieving local control and improving the quality of life. However, randomized controlled trials with larger cohorts are needed to assess the value of SBRT in pancreatic cancer therapy.

Prevalence of Autoimmune-phenomena behind Chronic Gastritis of Unknown Origin, and their Role in the Poor Histological Outcome of the Stomach: A Single-centre, Retrospective Cross-sectional Study.

BACKGROUND AND AIMS: The underlying aetiology of chronic gastritis (CG) often remains unknown due to its underrated significance in clinical practice. However, the role of chronic inflammation of the stomach in the development of atrophy, intestinal metaplasia (IM) and eventually of gastric cancer is well documented. We aimed to explore the possible aetiological factors of CG, determine the prevalence of systemic autoimmune disorders in patients with CG of unknown aetiology, and clarify the role of autoantibodies in the development of precancerous lesions in the stomach. METHODS: This is a retrospective, cross-sectional study, conducted from January 2016 to January 2020, including data from 175 patients with CG. Exclusion criteria were: (1) acute gastritis; (2) reactive gastropathy; (3) gastric cancer; (4) subjects without any serology testing results; and (5) Helicobacter pylori positivity. The primary endpoint was a composite endpoint involving gastric atrophy and IM. RESULTS: Fifty-five per cent of patients with CG had autoantibodies. Systemic lupus erythematosus (SLE)-related antibodies were positive in most of the cases, including antinuclear antibody (ANA) positivity, which was found in 19.13% of the patients. Autoimmune positivity was shown to be associated with precancerous lesions in the stomach (p<0.001): IM, atrophy and IM with atrophy. Anti-parietal cell antibody positivity seems to be a significant risk factor for IM and IM with atrophy. Autoimmune thyroiditis-related antibodies and ANA positivity by itself were only associated with atrophy; SLE-related antibodies and inflammatory bowel diseases related antibodies (ASCA and ANCA) correlated either with IM or with atrophy. No significant relation was found between any other investigated autoimmune disease-related antibodies and precancerous lesions. CONCLUSIONS: Autoimmune positivity often underlies gastritis of unknown aetiology and predisposes to precancerous lesions in the stomach. These antibodies can serve as non-invasive markers for the of optimal timing of an endoscopic follow-up strategy. Furthermore, CG can be an early symptom of a systemic autoimmune disorder.

Efficacy of Treatments in Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults. AIM: We aimed to analyze the efficacy of the noninvasive and minimally invasive therapeutic options of NAION. METHODS: We performed a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to 10 June 2019 to identify the studies that report on the effect of different therapies on visual acuity (VA) and visual field (VF). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for these outcomes. The efficacy of steroids was investigated in quantitative, oxygen, steroid plus erythropoietin (EPO), levodopa/carbidopa, memantine, and heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) therapies and other therapeutic modalities in qualitative synthesis. RESULTS: Thirty-two studies were found to be eligible. We found that steroid therapy compared to control did not improve VA (p = 0.182, WMD = 0.14, 95% CI: -0.07, 0.35) or VF (p = 0.853, WMD = 0.16, 95% CI: -1.54, 1.86). Qualitative analysis could be performed for oxygen, steroid plus EPO, and HELP as well, however, none of them showed VA and VF benefit. Two individual studies found memantine and levodopa beneficial regarding VA. CONCLUSION: Our systematic review did not reveal any effective treatment. Further investigations are needed to find therapy for NAION.

Differential Diagnostic Challenges in the COVID-19 Pandemic: Renal Abscess After SARS-CoV-2 Infection in a Young Adolescent.

BACKGROUND Prolonged fever in pediatric patients is often a diagnostic challenge. Clinicians tend to associate prolonged fever with COVID-19-related diseases in patients with a history of SARS-CoV-2 infection. Here we present a patient who was admitted with a clinical suspicion of multi-inflammatory syndrome in children (MIS-C) and was finally diagnosed with a renal abscess. CASE REPORT A 16-year-old girl with prolonged fever, bilateral non-purulent conjunctivitis, weight loss, muscle pain, general malaise, cough, and yellow sputum was admitted to Heim Pál National Pediatric Institute, Budapest, Hungary. She had proven SARS-CoV-2 infection 3 weeks prior to admission. Although inflammatory markers were elevated, repeated urine analyses, aerobic and anaerobic urine cultures, hemoculture, chest X-ray, and otorhinolaryngology examinations were negative. Based on clinical and laboratory criteria, the diagnosis of MIS-C was eventually ruled out. Abdominal ultrasound revealed a 17×20×15 mm simplex cyst at the edge of the parenchyma in the upper third of the left kidney. Magnetic resonance imaging was performed, showing a multi-compartment, septated, thick-walled parenchymal lesion of 50×40×52 mm in the upper pole of the right kidney, which showed signal characteristics of an abscess, and 20×16 mm and 8 mm lesions in the upper pole of the left kidney, which appeared to be cysts. After being unresponsive to intravenous wide-spectrum antibiotic therapy (meropenem 2 g tid for 5 days), surgical intervention was needed to remove the abscess. CONCLUSIONS This case demonstrates that during the COVID-19 pandemic, besides the obvious post-COVID etiology, other life-threatening conditions should be investigated in the first line.

Weight reduction added to CPAP decreases blood pressure and triglyceride level in OSA: Systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension and high cardiovascular risk. Continuous positive airway pressure (CPAP) fails to reduce cardiovascular risks consistently. Obesity and OSA show reciprocal association and they synergistically increase hypertension via different pathways. Our meta-analysis aimed to assess the cardiovascular benefits of combining weight loss (WL) with CPAP (vs. WL or CPAP alone) in OSA. Outcomes included systolic and diastolic blood pressure (BP) and blood lipid parameters. We explored Medline, Embase, Cochrane, and Scopus. Eight randomized controlled studies (2627 patients) were included. The combined therapy decreased systolic BP more than CPAP alone. Weighted mean difference (WMD) for CPAP + WL versus CPAP was -8.89 mmHg, 95% confidence interval (95% CI; -13.67 to -4.10, p < 0.001) for systolic BP. For diastolic BP, this decrease was not significant. In case of blood lipids, the combined treatment decreased triglyceride levels more than CPAP alone (WMD = -0.31, 95% CI -0.58 to -0.04, p = 0.027). On the other hand, addition of CPAP to WL failed to suppress BP further. The certainty of evidence according to GRADE was very low to moderate. In conclusion, our results showed that the addition of WL to CPAP significantly improved BP and blood lipid values in OSA. On the other hand, the addition of CPAP to WL could not significantly improve BP or blood lipid values. Review protocol: PROSPERO CRD42019138998.

Recurrent acute pancreatitis prevention by the elimination of alcohol and cigarette smoking (REAPPEAR): protocol of a randomised controlled trial and a cohort study.

BACKGROUND/OBJECTIVES: Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP. METHODS AND ANALYSIS: The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04647097.

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 vs 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.

Prognostic role of cell-free DNA biomarkers in pancreatic adenocarcinoma: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.

The EFFect of dietary fat content on the recurrence of pancreaTitis (EFFORT): Protocol of a multicenter randomized controlled trial.

BACKGROUND: Around 20% of patients with acute pancreatitis (AP) will develop acute recurrent pancreatitis (ARP) and 10% will progress to chronic pancreatitis. While interventions to avoid recurrences exist for the two most common causes - abstinence for alcoholic and cholecystectomy for biliary pancreatitis - the are no known preventive measures in idiopathic ARP. Though it is not included in any of the guidelines, a low-fat diet is often recommended. Our aim is to test dietary fat reduction's effect on AP recurrence in a randomized controlled setting, in order to provide high-quality evidence for the validity of such an intervention. METHODS, DESIGN: Participants with at least 2 episodes of AP in the preceding 2 years of which the last episode was idiopathic will be randomized to one of two diets with different fat contents: a 'reduced fat diet' (15% fat, 65% carbohydrate, 20% protein) and a 'standard healthy diet' (30% fat, 50% carbohydrate, 20% protein; based on WHO recommendations). Participants will be followed-up for 2 years (visits will be scheduled for months 3, 6, 12, 18 and 24) during which they will receive a repeated session of nutritional guidance, complete food frequency questionnaires and data on relapse, mortality, BMI, cardiovascular parameters and serum lipid values will be collected. DISCUSSION: This study will determine the effect of modifying the dietary fat content on AP recurrence, mortality, serum lipids and weight loss in idiopathic cases.