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Background/aim: Severity of microlithiasis- and sludge-induced pancreatitis in comparison to gallstone-induced pancreatitis has never been studied for a lack of definition., Materials and Methods: In this retrospective cohort study, 263 patients with acute biliary pancreatitis treated at a tertiary care center from 2005 to 2021 were stratified according to the recent consensus definition for microlithiasis and sludge. The gallstone-pancreatitis cohort was compared to microlithiasis, sludge, and suspected stone passage pancreatitis cohorts in terms of pancreatitis outcome, liver function, and endosonography/endoscopic retrograde cholangiopancreatography results using one-way analysis of variance and χ 2 test. Multinomial logistic regression analysis was performed to correct for bias., Results: Microlithiasis- and sludge-induced pancreatitis, classified according to the revised Atlanta classification, did not present with a milder course than gallstone-induced pancreatitis ( P = 0.62). Microlithiasis and sludge showed an increase in bilirubin on the day of admission to hospital, which was not significantly different from gallstone-induced pancreatitis ( P = 0.36). The likelihood of detecting biliary disease on endosonography resulting in bile duct clearance was highest on the day of admission and day 1, respectively., Conclusions: Microlithiasis and sludge induce gallstone-equivalent impaired liver function tests and induce pancreatitis with similar severity compared with gallstone-induced acute biliary pancreatitis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care., (© 2023. The Author(s).)

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

Background and Aims: Non-thyroidal illness syndrome (NTIS) is frequent in critically ill patients and associated with adverse outcomes. We aimed to characterize the evolution of NTIS in patients with acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF), since NTIS is not well described in these newly defined syndromes., Methods: Thyroid hormones (TH) were quantified at baseline in consecutive patients with cirrhosis. In addition, 76 inflammatory mediators were quantified by proximity extension analysis assay in a subgroup of patients. Associations between TH, cirrhosis stage, mortality and inflammation were assessed., Results: Overall, 437 patients were included, of whom 165 (37.8%), 211 (48.3%), and 61 (14%) had compensated cirrhosis (CC), AD, and ACLF. FT 3 concentrations were lower in AD versus CC, and further decreased in ACLF. Importantly, NTIS was present in 83 (39.3%) patients with AD and in 44 (72.1%) patients with ACLF (P<0.001). Yet, TSH and TSH-based indexes (TSH/FT 3 -ratio, thyroid index) showed an U-shaped evolution during progression of cirrhosis, suggesting a partially preserved responsiveness of the hypothalamus and pituitary in AD. Infections were associated with lower FT 3 concentrations in AD, but not in ACLF. Low FT 3 concentrations correlated significantly with 90-day mortality. Both, AD/ACLF and NTIS, were associated with signatures of inflammatory mediators, which were partially non-overlapping., Conclusion: NTIS is frequent already in AD and therefore precedes critically illness in a subgroup of patients with decompensated cirrhosis. This might constitute a new paradigm of TH signaling in cirrhosis, offering opportunities to explore preventive effects of TH in AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Langer, Bauschen, Guckenbiehl, Klauss, Lutz, Denk, Zwanziger, Moeller and Lange.)

A fraction of COVID-19 patients progress to a severe disease manifestation with respiratory failure and the necessity of mechanical ventilation. Identifying patients at risk is critical for optimised care and early therapeutic interventions. We investigated the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding relative to disease severity.We analysed nasopharyngeal and tracheal shedding of SARS-CoV-2 in 92 patients with diagnosed COVID-19. Upon admission, standardised nasopharyngeal swab or sputum samples were collected. If patients were mechanically ventilated, endotracheal aspirate samples were additionally obtained. Viral shedding was quantified by real-time PCR detection of SARS-CoV-2 RNA.45% (41 out of 92) of COVID-19 patients had a severe disease course with the need for mechanical ventilation (severe group). At week 1, the initial viral shedding determined from nasopharyngeal swabs showed no significant difference between nonsevere and severe cases. At week 2, a difference could be observed as the viral shedding remained elevated in severely ill patients. A time-course of C-reactive protein, interleukin-6 and procalcitonin revealed an even more protracted inflammatory response following the delayed drop of virus shedding load in severely ill patients. A significant proportion (47.8%) of patients showed evidence of prolonged viral shedding (>17 days), which was associated with severe disease courses (73.2%).We report that viral shedding does not differ significantly between severe and nonsevere COVID-19 cases upon admission to the hospital. Elevated SARS-CoV-2 shedding in the second week of hospitalisation, a systemic inflammatory reaction peaking between the second and third week, and prolonged viral shedding are associated with a more severe disease course., Competing Interests: Conflict of interest: D. Munker has nothing to disclose. Conflict of interest: A. Osterman has nothing to disclose. Conflict of interest: H. Stubbe has nothing to disclose. Conflict of interest: M. Muenchhoff has nothing to disclose. Conflict of interest: T. Veit has nothing to disclose. Conflict of interest: T. Weinberger has nothing to disclose. Conflict of interest: M. Barnikel has nothing to disclose. Conflict of interest: J-N. Mumm has nothing to disclose. Conflict of interest: K. Milger has nothing to disclose. Conflict of interest: E. Khatamzas has nothing to disclose. Conflict of interest: S. Klauss has nothing to disclose. Conflict of interest: C. Scherer has nothing to disclose. Conflict of interest: J.C. Hellmuth has nothing to disclose. Conflict of interest: C. Giessen-Jung has nothing to disclose. Conflict of interest: M. Zoller has nothing to disclose. Conflict of interest: T. Herold has nothing to disclose. Conflict of interest: S. Stecher has nothing to disclose. Conflict of interest: E.N. De Toni has nothing to disclose. Conflict of interest: C. Schulz has nothing to disclose. Conflict of interest: N. Kneidinger has nothing to disclose. Conflict of interest: O.T. Keppler has nothing to disclose. Conflict of interest: J. Behr has nothing to disclose. Conflict of interest: J. Mayerle has nothing to disclose. Conflict of interest: S. Munker has nothing to disclose., (Copyright ©ERS 2021.)

Background: Pain due to pancreatic cancer/PCa or chronic pancreatitis/CP, is notoriously resistant to the strongest pain medications. Here, we aimed at deciphering the specific molecular mediators of pain at surgical-stage pancreatic disease and to discover novel translational targets., Methods: We performed a systematic, quantitative analysis of the neurotransmitter/neuroenzmye profile within intrapancreatic nerves of CP and PCa patients. Ex vivo neuronal cultures treated with human pancreatic extracts, conditional genetically engineered knockout mouse models of PCa and CP, and the cerulein-induced CP model were employed to explore the therapeutic potential of the identified targets., Findings: We identified a unique enrichment of neuronal nitric-oxide-synthase (nNOS) in the pancreatic nerves of CP patients with increasing pain severity. Employment of ex vivo neuronal cultures treated with pancreatic tissue extracts of CP patients, and brain-derived-neurotrophic-factor-deficient (BDNF +/- ) mice revealed neuronal enrichment of nNOS to be a consequence of BDNF loss in the progressively destroyed pancreatic tissue. Mechanistically, nNOS upregulation in sensory neurons was induced by tryptase secreted from perineural mast cells. In a head-to-head comparison of several genetically induced, painless mouse models of PCa (KPC, KC mice) or CP (Ptf1a-Cre;Atg5 fl/fl ) against the hypersecretion/cerulein-induced, painful CP mouse model, we show that a similar nNOS enrichment is present in the painful cerulein-CP model, but absent in painless genetic models. Consequently, mice afflicted with painful cerulein-induced CP could be significantly relieved upon treatment with the specific nNOS inhibitor NPLA., Interpretation: We propose nNOS inhibition as a novel strategy to treat the unbearable pain in CP. FUND: Deutsche Forschungsgemeinschaft/DFG (DE2428/3-1 and 3-2)., (Copyright © 2019. Published by Elsevier B.V.)

Chronic pancreatitis (CP) is an utmost complex disease that is pathogenetically linked to pancreas-intrinsic ( e.g., duct obstruction), environmental-toxic ( e.g., alcohol, smoking), and genetic factors. Studying such a complex disease naturally requires validated experimental models. In the past 2 decades, the various animal models of CP usually addressed either the pancreas-intrinsic ( e.g., the caerulein model), the environmental-toxic ( e.g., diet-induced models), or the genetic component of CP. As such, these models were far from mirroring CP in its full spectrum, and the correct choice of models was vital for valid scientific conclusions on CP. The quest for mechanistic, genetic models gave rise to models based on gene modification and transgene insertion, such as the PRSS1 and the IL-1β/IL-1β models. Recently, we witnessed the development of highly exciting models that rely on the importance of autophagy in CP, that is, the murine pancreas-specific Atg5 and LAMP2 knockout models. Today, critical comparison of these several models is more important than ever for guiding research on CP in an efficient direction. The present review outlines the characteristics of the new genetic models in comparison with the well-known classic models for CP, notes the caveats in the choice of models, and also indicates novel directions for model development.-Klauss, S., Schorn, S., Teller, S., Steenfadt, H., Friess, H., Ceyhan, G. O., Demir, I. K. Genetically induced vs. classical animal models of chronic pancreatitis: a critical comparison.

Background: Although routinely used, the benefit of surgically placed intraperitoneal drains after pancreas resection is still under debate. To assess the true impact of intraperitoneal drains in pancreas resection, a systematic review with meta-analysis was performed., Methods: For this, the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were conducted and Pubmed/Medline, Embase, Scopus and The Cochrane Library were screened for relevant studies., Results: 8 retrospective and 3 prospective studies were included in the systematic review. No difference was found between patients with or without intraperitoneal drains in mortality (Risk-ratio/RR 0.74, 95%-Confidence-interval/CI: 0.47-1.18, p = 0.20), in Grade B/C-postoperative pancreatic fistulas/POPF (RR 1.31, 95%-CI: 0.74-2.32, p = 0.35), in intraabdominal abscesses (RR 0.92, 95%-CI: 0.65-1.30, p = 0.64), in surgical site infection (RR 1.20, 95%-CI: 0.85-1.70, p = 0.30), in delayed gastric emptying (RR 1.11, 95%-CI: 0.65-1.90, p = 0.71), in postoperative haemorrhages (RR 0.92 95%-CI: 0.63-1.33, p = 0.65), in reoperations (RR 1.15, 95%-CI: 0.87-1.52, p = 0.33), or in radiological reinterventions (RR 0.95, 95%-CI: 0.69-1.31, p = 0.76). The risk for overall morbidity (RR 1.16, 95%-CI: 1.04-1.29, p = 0.008), of any POPF (RR 2.15, 95%-CI: 1.52-3.04, p < 0.0001) and of readmissions (RR 1.23, 95%-CI: 1.04-1.45, p = 0.01) was increased for patients with intraperitoneal drain compared to patients without following pancreatic resection., Conclusion: Regarding the controversial results of the recent prospective, randomized trials this meta-analysis revealed no difference in mortality but an increased risk for postoperative morbidity, POPF and readmissions of patients with intraperitoneal drains after pancreatic resection. Therefore, the indication for intraperitoneal drains should be critically weighed in patients undergoing pancreatic resections., (Copyright © 2018. Published by Elsevier B.V.)

Background: The SESAM 2 study was performed to estimate consultations of general practitioners. In the recent work we focused on the reasons for encounter of children and adolescents consulting the general practitioner., Methods: Cross-sectional study with general practices in Saxony (Germany) as setting. Two hundred and seventy of the 2510 (10.8%) Saxon general practitioners agreed to participate and recorded data of 8877 patients. Evaluation of the data was organized by the Saxon Society of General Medicine (SGAM). Cross-sectional data were collected during a one-year period. One day of the week (Monday till Friday) was chosen at random for recording. Data were documented from every tenth patient with personal contact to the practitioner using a standardized report form at either the morning or afternoon consulting hours., Main Outcome Measures: reasons for encounter, the investigations and treatments performed and also the results of the consultation. Unpublished but publicly available data from the Dutch Transition Project were also analysed., Results: Eight hundred and five of 8877 patients were aged under 20 years. The mean percentage of children and adolescents in the general practice consultation was 9.1%. The mean number of reasons for encounter per child patient was about 1.5 and did not differ between the age groups. Most consultations were due to respiratory, digestive, skin or general symptoms with typical seasonal variations regarding the most frequent reasons for encounter caused by infectious diseases., Conclusions: As there is limited access to pediatric specialists, German general practitioners have to deal with children quite frequently. The number of child reasons for encounter is manageable for the general practitioner with an increasing spectrum of reasons for encounter among adolescents. In agreement with other publications most of the young patients consult for respiratory or general symptoms, or require preventive immunization or injection., Keywords: Children; Adolescents; Reason for encounter; General practice; Primary care.

Background: The present study aimed to explore the consultation prevalence, differential diagnoses, and management of patients presenting with nausea or vomiting to their family doctors., Methods: Cross-sectional data were collected from randomly selected patients during the SESAM 2 study (October 1, 1999 to September 30, 2000). We contacted 2510 doctors; 270 (10.8%) of them participated in the study. Data were collected from randomly selected patients previously known to the general practitioner. Unpublished but publicly available data from the Dutch Transition Project were also analysed., Results: One hundred and sixty-nine of the total 8874 patients consulted their general practitioner for nausea/vomiting; 97 (57.4%) were female and 72 (42.6%) were male. Most patients suffering from nausea or vomiting in general practice were aged between 15 and 64 years. Nearly all patients were given a physical examination. Most diagnoses were made without further investigation, additional diagnostic procedures were found to be necessary in only 7 patients. Drugs were prescribed as the most frequent form of medical treatment, in 76.3% of cases. Non-infectious gastroenteritis or colitis was the most frequent diagnosis. Nausea or vomiting was associated with diarrhoea, fever, and abdominal pain. Headache, general weakness, and epigastric pain were also statistically significantly associated with nausea or vomiting., Conclusions: Many disorders cause nausea or vomiting. Although most of the patients were diagnosed with non-infectious gastroenteritis or colitis, the general practitioner also has to bear in mind that nausea and vomiting may be alarm symptoms. Medication was prescribed in most of the cases and there were only a few referrals to a specialist or hospital. Life-threatening disorders (appendicitis, bowel obstruction/ileus) were found in a few cases presenting with nausea or vomiting., Keywords: Nausea; Vomiting; General practice; Primary care.