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We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents. Saline or fecal suspensions with a standardized dose range of bacterial colony-forming units (CFUs) were injected intraperitoneally into Sprague–Dawley rats. The qualitative composition of the initial inoculum and the ascites was analyzed separately by MALDI-TOF mass spectrometry. Invasive monitoring was conducted in separate anesthetized groups (n = 12–13/group) after 12, 24, 48 and 72 h to determine rat-specific organ failure assessment (ROFA) scores. Death and ROFA scores peaked at 24 h. At this time, 20% mortality occurred in animals receiving a monomicrobial E. coli suspension, and ROFA scores were significantly higher in the monomicrobial subgroup than in the polymicrobial one (median 6.5; 5.0–7.0 and 5.0; 4.75–5.0, respectively). ROFA scores dropped after 48 h, accompanied by a steady decrease in ascites CFUs and a shift towards intra-abdominal monomicrobial E. coli cultures. Furthermore, we found a relationship between ascites CFUs and the evolving change in ROFA scores throughout the study. Hence, quantitatively identical bacterial loads with mono- or polymicrobial dominance lead to a different degree of sepsis severity and divergent outcomes. Initial and intraperitoneal microbiological testing should be used to improve translational research success.

Sepsis is accompanied by a less-known mismatch between hemodynamics and mitochondrial respiration. We aimed to characterize the relationship and time dependency of microcirculatory and mitochondrial functions in a rodent model of intraabdominal sepsis. Fecal peritonitis was induced in rats, and multi-organ failure (MOF) was evaluated 12, 16, 20, 24 or 28 h later (n = 8/group, each) using rat-specific organ failure assessment (ROFA) scores. Ileal microcirculation (proportion of perfused microvessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI)) was monitored by intravital video microscopy, and mitochondrial respiration (OxPhos) and outer membrane (mtOM) damage were measured with high-resolution respirometry. MOF progression was evidenced by increased ROFA scores; microcirculatory parameters followed a parallel time course from the 16th to 28th h. Mitochondrial dysfunction commenced with a 4-h time lag with signs of mtOM damage, which correlated significantly with PPV, while no correlation was found between HI and OxPhos. High diagnostic value was demonstrated for PPV, mtOM damage and lactate levels for predicting MOF. Our findings indicate insufficient splanchnic microcirculation to be a possible predictor for MOF that develops before the start of mitochondrial dysfunction. The adequate subcellular compensatory capacity suggests the presence of mitochondrial subpopulations with differing sensitivity to septic insults.

Background Colonic involvement due to endometriosis is a rare condition with a nonspecific clinical presentation. In rare instances, it may undergo malignant transformation, mimicking primary colorectal carcinoma and complicating clinical decision-making. Case presentation We present two cases illustrating the diverse clinical manifestations of colonic endometriosis. In Case 1, a female patient underwent appendectomy for abdominal pain, but further evaluation revealed full-thickness endometriosis of the sigmoid colon, causing subtotal occlusion. In Case 2, sigmoid endometriosis was discovered during endoscopic evaluation prompted by positive occult fecal blood testing. Histopathological analysis revealed malignant transformation to endometrioid adenocarcinoma. In both cases, definitive treatment was achieved via laparoscopic sigmoid resection, highlighting the role of laparoscopic surgery in managing such conditions. Conclusions The potential for malignant transformation of colonic endometriosis and its tendency to mimic colorectal carcinoma underscore the importance of proper tissue sampling methods and histopathological confirmation. A high index of suspicion and appropriate surgical intervention are key to effective management.

Background Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. Methods The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit‐learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross‐validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross‐validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). Results The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy‐to‐use web application in the Streamlit Python‐based framework (http://easy‐app.org/). Conclusions The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model. The EASY prediction score is a practical tool for identifying patients at a greater risk for severe acute pancreatitis shortly after hospital admission. The explanation of the impact of features on the prediction helps physicians understand the decision of the machine learning model. The easy‐to‐use web application is available for clinicians and contributes to the improvement of the model.

Background Glomus tumors (GTs) are mesenchymal neoplasms that are typically benign. Gastric GTs are uncommon and occur mainly in the upper gastrointestinal tract. Malignant gastric GTs are extremely rare, constituting less than 1% of gastric tumors. Because their features are similar to those of other tumors found in the same gastrointestinal region, such as stromal tumors, leiomyomas, lymphomas, and lipomas, the diagnosis is challenging. Case Presentation A 52-year-old male patient presented with fatigue and melena. The initial endoscopic examination did not locate any source of bleeding. Six months later, pan-gastroscopy, performed due to progressive microcytic anemia, revealed a 40 × 30 mm polypoid lesion with deep ulcerations; histopathological analysis confirmed that it was a gastric GT with expression of alpha-actin and cadherin 17 and a Ki-67 index of 20%. The patient delayed surgical therapy until his symptoms worsened. Laparoscopic sleeve resection revealed a 65 × 45 × 25 mm tumor, and secondary immunohistochemical analysis revealed extensive spread into the mucosa and subserosa. Focally, the tumor bulged into some large veins. Genetic examination with RNA isolation further supported the histopathological diagnosis of gastric GT with uncertain malignant potential. Conclusions This case underscores the diagnostic challenges posed by gastric GTs because they are rare and their clinical features are similar to those of other gastric tumors. Thorough histopathological and molecular analysis is essential for an accurate diagnosis. Surgical intervention remains the primary therapeutic approach. This case also emphasizes the need for long-term follow-up due to the potential for recurrence and malignancy.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for the minimally invasive management of biliary and pancreatic disorders. Under certain indications, performing ERCP without delay during the weekend can be important for improving outcomes. Objectives: To compare the outcomes of ERCP performed on weekends and holidays with those of regular weekday ERCPs. Design: Propensity score match analysis of the data from the Hungarian ERCP Registry. Methods: A total of 116 ERCPs were performed during weekends or holidays, and 3144 during weekday working hours. The analyses were performed on 1:2 propensity-matched groups (116 weekend and 232 weekday cases). Results: Weekend ERCPs were mostly performed for acute cholangitis and acute biliary pancreatitis (70% of cases), whereas in the weekday group, only 32% of cases were performed for these indications. No significant difference was found between weekday and weekend ERCPs in terms of the rates of successful (91.38% vs 93.1%, p = 0.565) and difficult (33.62% vs 36.64%, p = 0.511) biliary cannulations. We found no significant differences in the number of adverse events (bleeding, post-ERCP pancreatitis, and 30-day mortality) in ERCPs performed during weekends or weekdays. Moreover, no significant differences in the aforementioned outcomes were detected between the propensity-matched groups. Conclusion: In this propensity-matched study, no significant differences were found in the outcomes of weekend and weekday ERCPs.

The number of patients with high bleeding risk (HBR) and high thromboembolic risk (HTR) is increasing. Gastrointestinal bleeding (GIH), acute coronary syndrome (ACS), and pulmonary embolism (PE) are representative conditions due to HBR/HTR. Although these disorders are located at opposite ends of the same disease spectrum, this does not mean a patient with HBR cannot have a concomitant HTR. The clinical manifestation of these two risks mostly results in critically ill patients for whom management means a huge challenge. We have numerous well-structured guidelines about treating GIH, ACS, or PE, but the literature and recommendations about the concomitant onset of these diseases are limited. Expert recommendations suggest an integrative, comprehensive assessment of patient and intervention-related factors to decide on the antithrombotic regimen with the best clinical benefit by assessing thrombotic and bleeding risks. In general, if thrombotic factors predominate, a longer duration, more aggressive antithrombotic regimen should be planned, and if bleeding susceptibility is higher, a shorter duration, de-escalated regimen should be pursued. In this study, we aimed to explore the clinical dilemmas involved by presenting two cases with delicate management.

Background: Fixed‐ratio combinations (FRCs) provide an alternative to intensified conservative insulin treatments (ICTs); however, therapy simplification in patients with high total daily insulin dose (TDD) or high HbA 1c is a debated issue; additionally, its influence on target organ damage (TOD) is less known. Methods: Data were retrospectively collected from patients with Type 2 diabetes, including 58 patients who continued ICT and 104 patients who underwent therapy simplification between January 1, 2017, and January 1, 2023. Patient characteristics and therapy details are at baseline and 3, 6, 12, and 24 months after FRC initiation. Results: HbA 1c significantly decreased in both groups (−0.9% [−1.6%, −0.5%] with ICT vs. −1.3% [−2.1%, −0.3%] with FRC), whereas body weight significantly decreased only after simplification (−1 kg [−4, 1] vs. −5 kg [−7, −2]). Diabetes duration was not associated with therapy efficacy. Significant HbA 1c reduction and FRC dose elevation occurred earlier in patients with an initial HbA 1c > 8.0 % than in those with an initial HbA 1c < 8.0 % . FRC dose was significantly higher at 3 months in patients with a TDD of > 60 U/day than in those with lower TDD. Relative risk reduction with therapy simplification was 72.1%, 50.6%, 32.3%, and 59.7% for hypoglycemia, renal function decline, microalbuminuria, and macrovascular complications, respectively. Risk of retinopathy, neuropathy, and chronic kidney disease did not significantly change with FRCs. Discussion: FRCs are safe and as effective as ICT even in patients with high initial HbA 1c , high TDD, or long diabetes duration. A protective role of FRCs in diabetic ASCVD has been proven, but their protective role in CKD was not observed. Conclusions: The significant improvements in glycemic and weight control, as well as in TODs, suggest that therapy simplification may represent a more favorable approach compared to the continuation of previous ICT even in patients characterized by high baseline TDD and HbA 1c levels.

Background/Objectives: Difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) poses significant challenges and increases the risk of adverse events. Pancreatic guidewire (PGW)-assisted techniques offer potential solutions, but real-world comparative data are limited. Methods: This cohort study of prospectively collected data analyzed 234 ERCP cases from the Hungarian ERCP Registry, focusing on three PGW-assisted methods: transpancreatic sphincterotomy (TPS), double-guidewire technique (DGW), and prophylactic pancreatic stent-assisted cannulation (PPS-C). Results: TPS demonstrated the highest primary cannulation success rate (83.1%), significantly outperforming DGW (67.7%) and PPS-C (67.6%) (p < 0.001). With salvage methods, cannulation success was high across all groups. Post-ERCP pancreatitis rates were low (5.0% TPS, 5.6% DGW, 3.9% PPS-C), but prophylactic measures (pancreatic stents, indomethacin) were underutilized. Conclusions: Our findings suggest that TPS is a safe and effective alternative for difficult biliary cannulation in ERCP. Routine considerations of post-ERCP pancreatitis prophylaxis (prophylactic pancreatic stents and non-steroidal suppositories) are recommended in all PGW-assisted cannulations to minimize complications.

Sepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threatening consequences. Since the results of organ-protective treatments cannot always be transferred from laboratory models into human therapies, increasing the translational potential of preclinical settings is an important goal. Our aim was to develop a standardized research protocol, where the progression of sepsis-related events can be characterized reproducibly in model experiments within clinically-relevant time frames. Peritonitis was induced in anesthetized minipigs injected intraperitoneally with autofeces inoculum ( = 27) or with saline (sham operation; = 9). The microbial colony-forming units (CFUs) in the inoculum were retrospectively determined. After awakening, clinically relevant supportive therapies were conducted. Nineteen inoculated animals developed sepsis without a fulminant reaction. Sixteen hours later, these animals were re-anesthetized for invasive monitoring. Blood samples were taken to detect plasma TNF-α, IL-10, big endothelin (bET), high mobility group box protein1 (HMGB1) levels and blood gases, and sublingual microcirculatory measurements were conducted. Hemodynamic, respiratory, coagulation, liver and kidney dysfunctions were detected to characterize the septic status with a pig-specific Sequential Organ Failure Assessment (pSOFA) score and its simplified version (respiratory, cardiovascular and renal failure) between 16 and 24 h of the experiments. Despite the standardized sepsis induction, the animals could be clustered into two distinct levels of severity: a sepsis ( = 10; median pSOFA score = 2) and a septic shock ( = 9; median pSOFA score = 8) subgroup at 18 h of the experiments, when the decreased systemic vascular resistance, increased DO and VO , and markedly increased ExO demonstrated a compensated hyperdynamic state. Septic animals showed severity-dependent scores for organ failure with reduced microcirculation despite the adequate oxygen dynamics. Sepsis severity characterized later with pSOFA scores was in correlation with the germ count in the induction inoculum ( = 0.664) and CFUs in hemocultures ( = 0.876). Early changes in plasma levels of TNF-α, bET and HMGB1 were all related to the late-onset organ dysfunctions characterized by pSOFA scores. This microbiologically-monitored, large animal model of intraabdominal sepsis is suitable for clinically-relevant investigations. The methodology combines the advantages of conscious and anesthetized studies, and mimics human sepsis and septic shock closely with the possibility of numerical quantification of host responses.