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The PROTOCOL trial aims to investigate the prevalence, clinical impact, and management of Lumen apposing metal stent (LAMS) occlusion-related complications in patients with acute pancreatitis. The trial also aims to determine the effect of discontinuing proton pump inhibitor (PPI) therapy on LAMS occlusion. The study includes an expert survey and a multicentric retrospective cohort study involving European centers with expertise in endoscopic pancreatology. Preliminary results from the expert survey and the retrospective cohort study are presented, with a total of 62 European interventional endoscopists participating in the survey and 443 cases entered into the electronic case report form. The PROTOCOL trial is the largest trial to date investigating the potential association between LAMS occlusion and PPI intake. [Extracted from the article]

Purpose: Post-COVID-19 condition (PCC) poses a substantial burden to affected individuals, health care systems, and society as a whole. We examined factors associated with recovery from PCC, focusing on the vaccination status prior to infection and the virus variant., Methods: Our analyses are based on the population-based cohort study for digital health research in Germany (DigiHero). Respondents who reported a SARS-CoV-2 infection and COVID-related symptoms ≥ 12 weeks post-infection were classified as having PCC. Those with ongoing PCC were followed-up in six-month intervals based on their date of infection. We used a Cox model for interval-censored data to analyze PCC recovery., Results: Among the 4,529 respondents with PCC included in our analyses, about 26%, 19%, 36%, and 44% of those infected during dominance of the SARS-CoV-2 wildtype, Alpha, Delta, and Omicron variant had recovered one year after infection, respectively. When stratifying by virus variant, vaccination was not associated with a faster recovery. Conversely, those infected with Omicron (HR = 2.20; 95%CI: 1.96-2.48) or Delta (HR = 1.69; 95%CI: 1.43-2.01) recovered faster than those infected with the SARS-CoV-2 wildtype or Alpha strain., Conclusion: Although the recovery from PCC is faster for the newer virus variants, still a substantial fraction of those who developed PCC after an infection with the Omicron variant report prolonged persistence of symptoms., Competing Interests: Declarations Ethics approval and consent to participate The responsible Ethics Committee of the Martin Luther University Halle-Wittenverg provided ethical approval (Registration number 2020-076). Informed consent was obtained from all participants. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-I) are markers of bone metabolism. We examined the effect of vitamin D3 supplementation on these markers and their relationship with growth and bone parameters in 12-month-old infants. In a randomized, double-blinded, Vitamin D intervention in infants (VIDI) study, 987 infants received daily vitamin D3 supplementation of 10 μg (Group-10) or 30 μg (Group-30) from age 2 weeks to 24 months. We conducted a secondary analysis of the original VIDI trial. At 12 months of age, P1NP (n=812) and CTX-I (n=786) concentrations were analyzed, and anthropometrics and total bone mineral content, volumetric bone mineral density, cross-sectional area and polar moment of inertia of tibia were measured by peripheral quantitative computed tomography. Growth rate in weight and length was calculated from birth to 12 months. Vitamin D dose did not influence mean (SD) levels of CTX-I (group-10: 0.90 (0.31); group-30: 0.89 (0.31) (p<0.53). Mean difference of P1NP (CI 95%) comparing group-10 with group-30 was 35 (-103, 33) ng/ml (p=0.31) in boys and -63 (-4, 130) ng/ml (p=0.064) in girls, respectively. In group-10 girls had higher mean (SD) value of P1NP (1509 (362) ng/mL) than boys (1407 (297) ng/mL) (p=0.003); no sex differences were observed in group-30 (girls: 1446 (359); boys: 1442 (359), p=0.91) or CTX-I. P1NP associated positively with growth rate in length (B (CI 95%] 0.0003 (0.0001, 0.001), p=0.022) in the whole cohort, but not in subgroups divided by intervention group nor sex, adjusted for birth size and parental heights and corrected for multiple testing. P1NP associated positively with growth rate in weight (0.01 (0.0003, 0.01), p<0.001). An inverse association was observed between CTX-I and length (cm) in the whole cohort (-0.90 (-1.40, -0.40), p=0.005) and in group-30 (-1.05 (-1.72, -0.39), p=0.011). Further, CTX-I associated negatively with weight (SDS) in the whole cohort (-0.33 (-0.55, -0.12), p=0.015) and growth rate in weight (-0.43 (-0.66, -0.20), p=0.005), persisting in group-30 and in boys, but not in group-10 or in girls. Neither marker was associated with bone parameters.The observed sex difference in P1NP might suggest that higher vitamin D dose resulted in a small decrease in bone collagen matrix formation in girls but not in boys. P1NP and CTX-I associate with growth and body size, but not with bone mineralization in infancy.

Understanding the potential adverse effects of the COVID-19-pandemic on mental health remains a challenge for public health. Differentiation between potential consequences of actual infection with SARS-CoV-2 and the subjective burden of the pandemic due to measures and restrictions to daily life still remains elusive. Therefore, we investigated the differential association between infection with SARS-Cov-2 and subjective burden of the pandemic in a study cohort of 7601 participants from the German population-based cohort for digital health research (DigiHero), who were recruited between March 4th and April 25th 2022. Data was collected using the online survey tool LimeSurvey® between March and October 2022 in consecutive surveys, which included questionnaires on infection status and symptoms following COVID-19 as well as retrospective assessment of the subjective burden of the pandemic. We observed an association of a past SARS-CoV-2 infection on deteriorated mental health related symptoms, whereas no association or interaction with burden of the pandemic occurred. The association was driven by participants with persistent symptoms 12 weeks after infection. On a symptom specific level, neuropsychiatric symptoms such as exhaustion and fatigue, concentration deficits and problems with memory function were the primary drivers of the association with small effect sizes between 0.048 and 0.062 η p 2 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Stress can detrimentally affect physical and mental health, especially during childhood. During this critical period, parental bonds can foster resilience or amplify stress. This study explored whether mothers' everyday stress can act as a source of childhood stress, affecting children's executive functioning. 76 healthy mother-child dyads participated, with mothers assigned to a stress-inducing or stress-free condition. Children observed their mothers and were subsequently tested for cognitive flexibility and working memory. Subjective stress, heart rate, and cortisol were measured repeatedly in mothers and children, alongside everyday stress perceptions. Linear mixed models showed that children's acute stress response was associated with impaired cognitive flexibility. Maternal stress, both acute and past-month, was a better predictor of children's cognitive performance than children's own stress. Quadratic relationships indicated the highest error rates at very low and high maternal stress. We found no evidence that children's working memory was impaired by their own or their mothers' stress. Although expected covariations of acute or prolonged stress between mothers and children were not observed, an interaction between maternal past-month stress and acute stress condition provided insights into adaptive mechanisms in children. These findings underscore the significant impact of maternal stress on children's executive functioning, illustrating how parental experiences shape children's everyday outcomes., (© 2024. The Author(s).)

European Union (EU) regulations on in vitro diagnostics (IVD) and on serious cross-border threats to health provide for the establishment of European Reference Laboratories (EURLs) and their harmonization and cooperation with National Reference Laboratories (NRLs). While the EURLs under the IVD Regulation will be operational by 1 October 2024, the EURLs under the Regulation on serious cross-border threats to health will be operational by January 2025. Although NRLs may have been operating for a long time on the basis of national legislation, they should now cooperate with each other and with EURLs in a network of centers of excellence for the authorization and post-market surveillance of IVDs and for the epidemiological surveillance and control of communicable diseases. The term "reference laboratory" has long been used colloquially to refer to many kinds of laboratories, regardless of their tasks, competencies, responsibilities and designation. A literature search and analysis confirmed this by showing that a considerable proportion of scientific publications in 2024 use the term "reference laboratory" inappropriately. In order to clarify the roles and functioning of EURLs and NRLs, we have evaluated the relevant current EU provisions and compared the findings with those of reference laboratories designated by other organizations, calibration (reference) laboratories and referral laboratories, which are simply referred to as "reference laboratories". With the forthcoming implementation of the EU regulations, at least the goals of providing safe and high-quality IVDs and adequate public health surveillance for communicable diseases appear to be achievable., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: In a representative survey conducted in Germany, normative values for the German short version of the RS-13 resilience scale were updated and compared with the data from a previous representative survey conducted in 2001., Methods: In a representative study conducted by the social science research institute USUMA GmbH in 2021, people aged 16 to 95 years (N=2,505) were randomly selected and interviewed by telephone. Data were compared to representative data collected in 2001 (N=2,045), and the influence of demographic variables on resilience was examined., Results: The internal consistency of the RS-13 was α=0.92. Current norm data of the RS-13, differentiated by gender and age, were generated. Access to these data is provided by an online tool, which can be used for the norm-oriented interpretation of individual resilience values (http://rs13.shinyapps.io/RS13). In the current 2021 sample, the mean resilience score was significantly higher than in 2001 (d=0.28, 95% CI [0.22-0.34]). Age was significantly negatively associated with resilience, education and net household income showed a significant negative correlation., Discussion: The RS-13 has good psychometric properties. Providing updated normative values of the RS-13 is justified due to the significantly higher scores in 2021 compared to 2001. The updated normative values allow for the comparison of future data with those of the German general population. In addition, the online tool can be used for the norm-oriented interpretation of individual resilience scores as part of diagnostic procedures., Conclusion: The RS-13 is a reliable, valid and economical instrument for assessing resilience in its theoretical understanding of a stable personality trait. Future studies investigating resilience should consider age, education and income as relevant influencing variables., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The dolichyl-diphosphooligosaccharide-protein glycosyltransferase non-catalytic subunit (DDOST) is a key component of the oligosaccharyltransferase complex catalyzing N-linked glycosylation in the endoplasmic reticulum lumen. DDOST is associated with several cancers and congenital disorders of glycosylation. However, its role in pancreatic cancer remains elusive, despite its enriched pancreatic expression. Using quantitative mass spectrometry, we identify 30 differentially expressed proteins and phosphopeptides (DEPs) after DDOST knockdown in the pancreatic ductal adenocarcinoma (PDAC) cell line PA-TU-8988T. We evaluated DDOST / DEP protein-protein interaction networks using STRING database, correlation of mRNA levels in pancreatic cancer TCGA data, and biological processes annotated to DEPs in Gene Ontology database. The inferred DDOST regulated phenotypes were experimentally verified in two PDAC cell lines, PA-TU-8988T and BXPC-3. We found decreased proliferation and cell viability after DDOST knockdown, whereas ER-stress, ROS-formation and apoptosis were increased. In conclusion, our results support an oncogenic role of DDOST in PDAC by intercepting cell stress events and thereby reducing apoptosis. As such, DDOST might be a potential biomarker and therapeutic target for PDAC., (© 2024. The Author(s).)

Necrotizing pancreatitis with superinfection of necrotic tissue is associated with a high rate of complications and mortality. The step-up approach is a well-established treatment strategy for necrotizing pancreatitis, emphasizing minimally invasive and endoscopic interventions before considering surgical options. Minimally invasive strategies often involve percutaneous drainage of collections, which carries the risk of persisting cutaneous pancreatic fistulas. Since there is currently no guidance for managing this scenario, we present a novel treatment approach that utilized tissue glue to occlude a persisting and clinically compromising percutaneous fistula. In addition, we summarize the current knowledge in the treatment of percutaneous pancreatic fistulas and provide a potential therapeutic algorithm for further evaluation., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Purpose: We investigated the protection offered by vaccinations and previous infections for the household transmission of Omicron variant of SARS-CoV-2., Methods: 34,666 participants of the German DigiHero cohort study with two or more household members were invited to a prospective household transmission study between June and December 2022. In case of a positive SARS-CoV-2 test in a household, symptom diaries were completed for at least 14 days. Dry blood spots (DBS) were taken from all household members at the beginning and six to eight weeks later. DBS were analyzed for SARS-CoV-2 antibodies., Results: 1191 individuals from 457 households participated. The risk of acquiring a SARS-CoV-2 infection decreased with higher S-titer levels at the time of exposure (from 80% at titer of 0 binding antibody units (BAU)/ml to 20% at titer of 3000 BAU/ml) and increased linearly with the time since vaccination/previous infection (20% for less than one month to 80% at one year). Transmission probability was also reduced when the symptoms of the primary case were mild and if preventive measures were implemented., Conclusion: Vaccinations/previous infections offer a high protection against infection with the Omicron variant for a few months only, supporting the notion of seasonal circulation of the virus., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.

Objectives: In winter of 2022/2023 SARS-CoV-2 had developed into one of many seasonal respiratory pathogens, causing an additional burden of acute respiratory infections (ARIs). Although testing was still widely used, many positive tests were not reported for the official statistics. Using data from a population-based cohort, we aimed to investigate the contribution of SARS-CoV-2 to the burden of ARI., Methods: Over 70,000 participants of the German population-based DigiHero study were invited to a questionnaire about the number and time point of ARI and SARS-CoV-2 test results in winter 2022/2023. We calculated the incidence of non-severe acute respiratory syndrome (SARS) ARI, the additional contribution of SARS-CoV-2, and extrapolated the age-specific estimates to obtain the total burden of SARS-CoV-2 in Germany., Results: For the winter of 2022/2023, 37,708 participants reported 54,813 ARIs, including 9358 SARS-CoV-2 infections. This translated into a cumulative incidence of 145 infections/100 persons for all ARIs, 120 infections/100 persons for non-SARS ARI, and 25 infections/100 persons for SARS ARI (+21%)., Conclusions: Our estimate for ARI related to SARS-CoV-2 is consistent with the difference in all ARI between pre-pandemic years and 2022/2023. This additional burden should be considered, particularly, with respect to the implications for the work force., Competing Interests: Declarations of competing interest The authors have no competing interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gastrointestinal (GI) bleeding is one of the most common complications associated with the use of direct oral anticoagulants (DOAC). Clear algorithms exist for the emergency measures in (suspected) GI bleeding, including assessing the medication history regarding anti-platelet drugs and anticoagulants as well as simple coagulation tests during pre-endoscopic management. Platelet transfusions, fresh frozen plasma (FFP), or prothrombin complex concentrate (4F-PCC) are commonly used for optimizing the coagulation status. For severe bleeding under the thrombin inhibitor dabigatran, idarucizumab is available, and for bleeding under the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa is available as specific antidotes for DOAC antagonization. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures including emergency endoscopy. Antagonization of oral anticoagulants should be considered for severe gastrointestinal bleeding in the following situations: (1) refractory hemorrhagic shock, (2) endoscopically unstoppable bleeding, or (3) nonavoidable delays until emergency endoscopy for life-threatening bleeding. After successful (endoscopic) hemostasis, anticoagulation (DOACs, vitamin K antagonist, heparin) should be resumed timely (i.e. usually within a week), taking into account individual bleeding and thromboembolic risk., Competing Interests: Dieses Manuskript fasst die wesentlichen Diskussionspunkte eines interdisziplinären Expertentreffens im Juli 2022 mit Vertreter*innen aus der Gastroenterologie, Intensivmedizin und Hämostaseologie zusammen, in dem die Bedeutung und mögliche Einsatzgebiete von spezifischen Antidots zur Antagonisierung der neuen/direkten orale Antikoagulantien (DOAK) bei schweren und lebensbedrohlichen gastrointestinalen (GI)-Blutungen diskutiert und herausgearbeitet wurde. Dieses Expertentreffen wurde durch die Fa. AstraZeneca (damals Alexion) finanziell unterstützt., (Thieme. All rights reserved.)

Biomass-derived oligo- and polysaccharides may act as elicitors, i.e., bioactive molecules that trigger plant immune responses. This is particularly important to increase the resistance of plants to abiotic and biotic stresses. In this study, cellulose nanofibrils (CNF) gels were obtained by TEMPO-mediated oxidation of unbleached and bleached kraft pulps. The molecular structures were characterized with ESI and MALDI MS. Analysis of the fine sequences was achieved by MS and MS/MS of the water-soluble oligosaccharides obtained by acid hydrolysis of the CNF gels. The analysis revealed the presence of two families: one corresponding to homoglucuronic acid sequences and the other composed by alternating glucose and glucuronic acid units. The CNF gels, alone or with the addition of the water-soluble oligosaccharides, were tested on Chili pepper (Capsicum annuum). Based on the characterization of the gene expression with Next Generation Sequencing (NGS) of the C. annuum's total messenger RNA, the differences in growth of the C. annuum seeds correlated well with the downregulation of the pathways regulating photosynthesis. A downregulation of the response to abiotic factors was detected, suggesting that these gels would improve the resistance of the C. annuum plants to abiotic stress due to, e.g., water deprivation and cold temperatures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens., Methods: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP., Results: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose., Conclusions: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Low-grade systemic inflammation measured as high sensitivity C-reactive protein (hs-CRP) has been associated with non-communicable disease risk. We assessed whether prenatal inflammation and early-childhood vitamin D are associated with inflammation until age 6-8., Methods: We analyzed blood hs-CRP and 25-hydroxy vitamin D [25(OH)D] in pregnancy, at birth from umbilical cord blood (UCB), from offspring at ages 1, 2, and 6-8 years in the Vitamin D Intervention in Infants (VIDI) study. VIDI was a randomized-controlled trial of vitamin D supplementation of 10 μg/day or 30 μg/day from age 2 weeks until 2 years in 975 infants recruited in 2013-14, with follow-up at age 6-8 in 2019-21 (n = 283)., Results: Pregnancy hs-CRP was associated with UCB hs-CRP (r = 0.18, p < 0.001) but not independently with childhood hs-CRP (Estimate [95% CI] 0.04 [<-0.00, 0.09]). Higher UCB hs-CRP was associated independently with higher hs-CRP until 6-8 years (0.20 [0.12, 0.29]). Infant vitamin D dose had no effect on longitudinal hs-CRP (6-8 years, 0.11 [-0.04, 0.25]). Childhood 25(OH)D were associated positively with hs-CRP until age 6-8 (0.01 [>0.00, 0.01])., Conclusion: Our results indicate that in children, inflammation, assessed by hs-CRP, persists from birth until 6-8 years. We observed positive associations between 25(OH)D and hs-CRP in vitamin D-sufficient children., Impact: High sensitivity C-reactive protein (hs-CRP) concentrations tract from birth to age 8 years Our novel finding suggests a long-lasting pro-inflammatory phenotype in the child Higher vitamin D concentration - but not dose - is associated with higher childhood hs-CRP Chronic disease risk related to inflammation may in part originate from the prenatal period or early childhood Further studies are needed to investigate the effects of inflammation on long-term clinical health outcomes., (© 2024. The Author(s).)

This study aimed to compare different pancreatic enzyme preparations (PEPs) available in Germany regarding particle geometry and size, and to evaluate enzyme activity under physiologically relevant conditions in vitro. Pancreatic endocrine insufficiency is characterized by deficiency of pancreatic enzymes resulting in maldigestion. It is orally treated by pancreatic enzyme replacement therapy. The formulations differ in their physical properties and enzyme release behavior, potentially resulting in inconsistent dosages and poor interchangeability of products. A total of 25 products were analyzed for particle size and number of particles per capsule. Enzyme activities of lipase, amylase, and protease were measured by digestion of olive oil emulsion, starch, and casein, respectively. To analyze enzyme release, gastric environments were simulated by incubating PEPs at pH 1, 4, or 5. Duodenal conditions were simulated by subsequent incubation at pH 6. Regarding physical properties and enzyme release kinetics, considerable differences between different PEPs were found. Furthermore, compared to the label claim, excess lipase activity was observed for most products, reaching up to 148%. These in vitro results suggest poor interchangeability of PEPs, potentially explained by physical and release characteristics. Physicians and patients should be aware of the potential gap between label claims and the real-life performance of different PEPs.

65 million people worldwide are estimated to suffer from long-term symptoms after their SARS-CoV-2 infection (Long COVID). However, there is still little information about the early recovery among those who initially developed Long COVID, i.e. had symptoms 4-12 weeks after infection but no symptoms after 12 weeks. We aimed to identify associated factors with this early recovery. We used data from SARS-CoV-2-infected individuals from the DigiHero study. Participants provided information about their SARS-CoV-2 infections and symptoms at the time of infection, 4-12 weeks, and more than 12 weeks post-infection. We performed multivariable logistic regression to identify factors associated with early recovery from Long COVID and principal component analysis (PCA) to identify groups among symptoms. 5098 participants reported symptoms at 4-12 weeks after their SARS-CoV-2 infection, of which 2441 (48%) reported no symptoms after 12 weeks. Men, younger participants, individuals with mild course of acute infection, individuals infected with the Omicron variant, and individuals who did not seek medical care in the 4-12 week period after infection had a higher chance of early recovery. In the PCA, we identified four distinct symptom groups. Our results indicate differential risk of continuing symptoms among individuals who developed Long COVID. The identified risk factors are similar to those for the development of Long COVID, so people with these characteristics are at higher risk not only for developing Long COVID, but also for longer persistence of symptoms. Those who sought medical help were also more likely to have persistent symptoms., (© 2024. The Author(s).)

Introduction: This study explores how chronic pancreatitis (CP) relates to subclinical cognitive impairment (SCI) and its prevalence, characteristics, risk factors, and effects on patients' quality of life (QoL) and physical performance., Methods: Patients with fulfilled CP criteria in imaging were prospectively enrolled. Overt encephalopathy, neurodegenerative disorders, decompensated cirrhosis, and sepsis were exclusion criteria. All patients underwent psychometric testing and assessment of health-related QoL, such as mobility and strength. SCI was diagnosed when at least 1 test of the psychometric test battery was pathological., Results: Seventy-one patients were enrolled. The etiology was toxic (alcohol/smoking) in most (49%) of the cases. SCI was prevalent in 41% of the patients while 25% had only 1 and 16% had 2 or more pathological tests. Patients with SCI exhibited diminished overall QoL scores ( P = 0.048), primarily affecting physical functionality ( P < 0.001). This was reaffirmed in mobility tests, where patients with SCI were slower in the timed up-and-go test ( P = 0.008) and showed increased prevalence of abnormal chair rising tests ( P = 0.004). Among all variables analyzed, only alcohol abuse was an independent risk factor of SCI (odds ratio 3.46; P = 0.02) in a multivariable regression model together with the variables age, sex, education, and compensated cirrhosis. Despite SCI affecting global QoL, sleep disturbance seemed to be the strongest variable independently associated with impaired QoL (odds ratio 9.9; P = 0.001)., Discussion: The largest study to the subject to date shows that SCI is common in patients with CP and is linked to significant morbidity. These findings suggest the need for addressing modifiable risk factors in patients with CP to improve outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied., Methods: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test., Results: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months)., Conclusions: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla., Competing Interests: Disclosure The following authors disclosed financial relationships: M. Bruno: honoraria from Boston Scientific for lectures and research support. E. Wedi and A. Schmidt: honoraria from Ovesco for lectures and research support. M. Hollenbach: honoraria from Fujifilm for lectures and expert panel. All of the other authors disclosed no financial relationships., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Although evidence for benefits of psychotherapy is substantial, less is known about potential harm. Therefore, we systematically summarized randomized controlled trials (RCTs) to compile evidence-based data on the frequency and characteristics of adverse events (AEs) of psychotherapy. Method: This systematic review of result publications is based on a review of harm consideration in psychotherapy study protocols. Results: On the basis of 115 study protocols, 85 RCTs with 126 psychotherapy and 61 control conditions were eligible for inclusion. The sample consisted of 14,420 participants with the most common mental disorders. Harmful events, e.g., AEs, number of individuals with symptom deterioration, were explicitly reported in 60% of the studies. Conceptualization, recording, and reporting of AEs were heterogeneous. For most reported AEs, the association to study treatment remained unclear. Conclusions: Because the AE recording approaches of the individual studies differed substantially, results could only be compared to a limited extent. Consistent with other findings, this review demonstrates that AEs can be expected to affect more than one in ten participants. Serious AEs occurred more than in one in 21 participants in psychotherapy RCTs. To allow a balanced risk/benefit evaluation of psychotherapy, systematic harm monitoring and reporting should become standard in psychotherapy RCTs.

Competing Interests: The authors declare that they have no conflict of interest.

Background: Genetic predisposition is crucial in the pathogenesis of early-onset chronic pancreatitis (CP). So far, several genetic alterations have been identified as risk factors, predominantly in genes encoding digestive enzymes. However, many early-onset CP cases have no identified underlying cause. Chymotrypsins are a family of serine proteases that can cleave trypsinogen and lead to its degradation. Because genetic alterations in the chymotrypsins CTRC, CTRB1, and CTRB2 are associated with CP, we genetically and functionally investigated chymotrypsin-like protease (CTRL) as a potential risk factor., Methods: We screened 1005 non-alcoholic CP patients and 1594 controls for CTRL variants by exome sequencing. We performed Western blots and activity assays to analyse secretion and proteolytic activity. We measured BiP mRNA expression to investigate the potential impact of identified alterations on endoplasmic reticulum (ER) stress., Results: We identified 13 heterozygous non-synonymous CTRL variants: five exclusively in patients and three only in controls. Functionality was unchanged in 6/13 variants. Four alterations showed normal secretion but reduced (p.G20S, p.G56S, p.G61S) or abolished (p.S208F) activity. Another three variants (p.C201Y, p.G215R and p.C220G) were not secreted and already showed reduced or no activity intracellularly. However, intracellular retention did not lead to ER stress., Conclusion: We identified several CTRL variants, some showing potent effects on protease function and secretion. We observed these effects in variants found in patients and controls, and CTRL loss-of-function variants were not significantly more common in patients than controls. Therefore, CTRL is unlikely to play a relevant role in the development of CP., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Parameters to adapt individual treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) are urgently needed. The present study aimed to evaluate body composition parameters as predictors of overall survival (OS) in PDAC patients., Methods: Measurements of body composition parameters were performed on computed tomography scans at diagnosis. Height-standardized and Body Mass Index- and sex-adjusted regression formulas deriving cut-offs from a healthy population were used. The Kaplan-Meier method with the log-rank test was performed for survival analysis. Independent prognostic factors were identified with uni- and multivariable Cox regression analyses., Results: In total, 354 patients were analyzed. In a multivariable Cox model, besides tumor stage and resection status, only myosteatosis (HR 1.53; 95% CI 1.10-2.14, p = 0.01) was an independent prognostic factor of OS among body composition parameters. Subgroup analyses revealed that the prognostic impact of myosteatosis was higher in patients ≤68 years of age, with advanced tumor stages and patients without curative intended resection., Conclusions: The analysis of one of the largest Caucasian cohorts to date, demonstrated myosteatosis to be an independent prognostic factor of OS in PDAC. To improve outcomes, prospective trials aiming to investigate the utility of an early assessment of myosteatosis with subsequent intervention by dieticians, sports medicine physicians, and physiotherapists are warranted., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Purpose: It is known that contact of nucleus pulposus with the dorsal root ganglion may induce changes in nerve conduction and pain behavior. It has also been suggested that the behavioristic changes are caused by changes in voltage-gated ion channels, which in turn have been upregulated by TNF. Such upregulations have previously been shown for NaV 1.8 and NaV 1.9. In this investigation, we expanded the number of studied ion channels after the application of nucleus pulposus or TNF., Methods: Following removal of the left L4-5 fact joint, a disc puncture was performed and the dorsal root ganglion was exposed to nucleus pulposus (n = 5) and TNF (n = 5). Operated rats without disc puncture served as sham (n = 5) and 5 non-operated (naïve) rats were included. After 24 h, the DRGs were harvested and analyzed by quantitative PCR on validated pre-spotted primer plates displaying genes for 90 voltage-gated ion channels., Results: It was evident that the changes in operated animals were separate from the naïve rats. It was also apparent that gene expression changes in rats with nucleus pulposus or TNF application showed similar trends and were also separated from sham-operated animals., Conclusion: The application of nucleus pulposus and TNF onto the DRG in rats induces comparable changes in gene expression of several ion channels. Since the changes induced by TNF and NP are similar, one might also suspect that TNF mediates the NP-induced changes. However, such a mechanism needs further investigation., Competing Interests: No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript., (© 2023 The Authors.)

Objective: In this study, treatment- and disease-associated consequences of intensive care treatment of COVID-19 in patients and relatives were investigated and compared with data from the general population and sepsis patients. In addition, dyadic associations in symptoms of patients and relatives were analyzed., Methods: In a monocentric, prospective, non-controlled observational study, patients who underwent intensive care treatment due to Covid-19 disease at Jena University Hospital between November 2020 and March 2021 and their relatives were included. We assessed the long-term outcome between three and six months after discharge from the intensive care unit (ICU) using the Hospital Anxiety and Depression Scale, the Posttraumatic Stress Scale-14, the Multidimensional Fatigue Inventory-10, and the EQ-5D-5L., Results: Seventy-two patients (Mdn 64 years, 67% men) and 56 relatives (Mdn 60 years, 80% women, 80% partners) were included in the study. 39,4% of the patients reported clinically relevant anxiety symptoms, 38,8% depressive symptoms, and 45,1% PTSD symptoms, with most cases having abnormal scores in multiple symptom domains. Among relatives, a smaller proportion had clinically relevant scores (29,2%/15,3%/31,5%). Compared with the general population, Covid 19 patients reported significantly higher anxiety and fatigue scores and a reduced quality of life. In relatives, significantly higher anxiety scores for women and lower quality of life for men were found. Compared to ICU patients with severe sepsis, Covid-19 patients were found to have significantly higher PTSD symptoms and lower quality of life. Significant dyadic associations were found for anxiety and fatigue., Discussion: The results of this study on psychological symptoms after ICU treatment confirm findings from previous studies, but also indicate a stronger PTSD symptomatology, which can be explained by the increased traumatizing potential of isolation and protective measures during treatment. Compared to the general population, particularly elevated anxiety scores of the patients are noticeable, which can be explained by the possible risk of re-infection., Conclusion: Psychological long-term consequences of intensive care treatment of Covid-19 disease should be diagnosed and adequately addressed in the outpatient follow-up of affected individuals., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Endoscopic approaches in the treatment of transmural esophageal defects, either after esophageal resection or due to perforation, have demonstrated convincing feasibility. Surgical options are limited and associated with high morbidity and mortality rates. Currently, internal endoscopic drainage with pigtail stents, self-expanding metal stent (SEMS), or endoscopic vacuum therapy (EVT) are options for first-line treatment. Here, we report the outcome of the recently developed combination of SEMS and EVT using the endoscopic Microtech ® -VAC-Stent (EVS)., Methods: Between June and July 2022, three consecutive patients (one female and two males) with esophageal transmural defects were treated with the Microtech ® -VAC-Stent. Two patients suffered from an anastomotic leak after oncologic gastroesophageal surgery, and one patient presented with esophageal perforation due to Boerhaave syndrome., Results: Three consecutive patients were successfully treated with EVS. In one patient, one EVS treatment was sufficient, whereas the other two patients needed two and six EVS exchanges. Exchanges were scheduled every 7 days and no procedural adverse events were observed., Conclusion: In line with the former case series, EVS therapy is a promising new approach for the treatment of esophageal leaks. Exchange of the EVS seems feasible every 7 days reducing interventions for the individual patient. Prospective studies comparing EVS with other endoscopic therapies are needed to define the best therapeutic approach., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Context: Childhood hyperphosphatasemia is usually transient and may be associated with infections. It remains less well known how hyperphosphatasemia is related to growth and bone mineralization., Objective: We explored alkaline phosphatase (ALP) concentrations and prevalence of hyperphosphatasemia, and their association with vitamin D, growth, infections, and bone parameters in healthy children., Methods: The study was a secondary analysis of a vitamin D intervention trial. Participants received vitamin D3 10 or 30 µg daily from age 2 weeks to 2 years. Children with data on ALP at 12 and/or 24 months (n = 813, girls 51.9%) were included. Anthropometrics and bone parameters were measured at 12 and 24 months. Infections were recorded prospectively by the parents., Results: Boys had higher ALP than girls at 12 months (median [IQR] 287 [241-345] U/L vs 266 [218-341] U/L; P = .02). At 24 months concentrations were lower than at 12 months (240 [202-284]; P < .001) but without sex difference. The prevalence of hyperphosphatasemia (ALP > 1000 U/L) at 12 months was 5.3% and at 24 months 0.6%. Body size, growth rate, and bone mineral content associated positively with ALP, while vitamin D intervention had no effect. Infants with hyperphosphatasemia were smaller than infants with ALP ≤ 1000 U/L. Hyperphosphatasemia was not associated with previous infections., Conclusion: Approximately 5% of infants had hyperphosphatasemia at 12 months, but <1% at 24 months. ALP concentrations and hyperphosphatasemia were associated with sex, anthropometry, and bone mineralization. Infections did not contribute to hyperphosphatasemia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To commercialize a biomedical product as a medical device, reproducibility of production and time-stability are important parameters. Studies of reproducibility are lacking in the literature. Additionally, chemical pre-treatments of wood fibres to produce highly fibrillated cellulose nanofibrils (CNF) seem to be demanding in terms of production efficiency, being a bottleneck for industrial upscaling. In this study, we evaluated the effect of pH on the dewatering time and washing steps of 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO)-mediated oxidized wood fibres when applying 3.8 mmol NaClO/g cellulose. The results indicate that the method does not affect the carboxylation of the nanocelluloses, and levels of approximately 1390 μmol/g were obtained with good reproducibility. The washing time of a Low-pH sample was reduced to 1/5 of the time required for washing a Control sample. Additionally, the stability of the CNF samples was assessed over 10 months and changes were quantified, the most pronounced were the increase of potential residual fibre aggregates, reduction of viscosity and increase of carboxylic acid content. The cytotoxicity and skin irritation potential were not affected by the detected differences between the Control and Low-pH samples. Importantly, the antibacterial effect of the carboxylated CNFs against S. aureus and P. aeruginosa was confirmed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Healthcare workers (HCWs) are at a high risk of SARS-CoV-2 infection due to exposure to potentially infectious material, especially during aerosol-generating procedures (AGP). We aimed to investigate risk factors for SARS-CoV-2 infection among HCWs in medical disciplines with AGP., Methods: A nationwide questionnaire-based study in private practices and hospital settings was conducted between 12/16/2020 and 01/24/2021. Data on SARS-CoV-2 infections among HCWs and potential risk factors of infection were investigated., Results: 2070 healthcare facilities with 25113 employees were included in the study. The overall infection rate among HCWs was 4.7%. Multivariate analysis showed that regions with higher incidence rates had a significantly increased risk of infection. Furthermore, hospital setting and HCWs in gastrointestinal endoscopy (GIE) had more than double the risk of infection (OR 2.63; 95% CI 2.50-2.82, p<0.01 and OR 2.35; 95% CI 2.25-2.50, p<0.01). For medical facilities who treated confirmed SARS-CoV-2 cases, there was a tendency towards higher risk of infection (OR 1.39; 95% CI 1.11-1.63, p=0.068)., Conclusion: Both factors within and outside medical facilities appear to be associated with an increased risk of infection among HCWs. Therefore, GIE and healthcare delivery setting were related to increased infection rates. Regions with higher SARS-CoV-2 incidence rates were also significantly associated with increased risk of infection., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Chymotrypsin C (CTRC) is a digestive serine protease produced by the pancreas that regulates intrapancreatic trypsin activity and provides a defensive mechanism against chronic pancreatitis (CP). CTRC exerts its protective effect by promoting degradation of trypsinogen, the precursor to trypsin. Loss-of-function missense and microdeletion variants of CTRC are found in around 4% of CP cases and increase disease risk by approximately 3-7-fold. In addition, a commonly occurring synonymous CTRC variant c.180C>T (p.Gly60=) was reported to increase CP risk in various cohorts but a global analysis of its impact has been lacking. Here, we analyzed the frequency and effect size of variant c.180C>T in Hungarian and pan-European cohorts, and performed meta-analysis of the new and published genetic association data. When allele frequency was considered, meta-analysis revealed an overall frequency of 14.2% in patients and 8.7% in controls (allelic odds ratio (OR) 2.18, 95% confidence interval (CI) 1.72-2.75). When genotypes were examined, c.180TT homozygosity was observed in 3.9% of CP patients and in 1.2% of controls, and c.180CT heterozygosity was present in 22.9% of CP patients and in 15.5% of controls. Relative to the c.180CC genotype, the genotypic OR values were 5.29 (95% CI 2.63-10.64), and 1.94 (95% CI 1.57-2.38), respectively, indicating stronger CP risk in homozygous carriers. Finally, we obtained preliminary evidence that the variant is associated with reduced CTRC mRNA levels in the pancreas. Taken together, the results indicate that CTRC variant c.180C>T is a clinically relevant risk factor, and should be considered when genetic etiology of CP is investigated., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)