Detailed Characteristics of Post-discharge Mortality in Acute Pancreatitis.

BACKGROUND & AIMS: The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95% to 98%. However, there is growing evidence that patients discharged after AP may be at risk of serious morbidity and mortality. Here, we aimed to investigate the risk, causes, and predictors of the most severe consequence of the post-AP period: mortality. METHODS: A total of 2613 well-characterized patients from 25 centers were included and followed by the Hungarian Pancreatic Study Group between 2012 and 2021. A general and a hospital-based population was used as the control group. RESULTS: After an AP episode, patients have an approximately threefold higher incidence rate of mortality than the general population (0.0404 vs 0.0130 person-years). First-year mortality after discharge was almost double than in-hospital mortality (5.5% vs 3.5%), with 3.0% occurring in the first 90-day period. Age, comorbidities, and severity were the most significant independent risk factors for death following AP. Furthermore, multivariate analysis identified creatinine, glucose, and pleural fluid on admission as independent risk factors associated with post-discharge mortality. In the first 90-day period, cardiac failure and AP-related sepsis were among the main causes of death following discharge, and cancer-related cachexia and non-AP-related infection were the key causes in the later phase. CONCLUSION: Almost as many patients in our cohort died in the first 90-day period after discharge as during their hospital stay. Evaluation of cardiovascular status, follow-up of local complications, and cachexia-preventing oncological care should be an essential part of post-AP patient care. Future study protocols in AP must include at least a 90-day follow-up period after discharge.

Selective intraoperative cholangiography should be considered over routine intraoperative cholangiography during cholecystectomy: a systematic review and meta-analysis.

BACKGROUND: Decades of debate surround the use of intraoperative cholangiography (IOC) during cholecystectomy. To the present day, the role of IOC is controversial as regards decreasing the rate of bile duct injury (BDI). We aimed to review and analyse the available literature on the benefits of IOC during cholecystectomy. METHODS: A systematic literature search was performed until 19 October 2020 in five databases using the following search keys: cholangiogra* and cholecystectomy. The primary outcomes were BDI and retained stone rate. To investigate the differences between the groups (routine IOC vs selective IOC and IOC vs no IOC), we calculated weighted mean differences (WMD) for continuous outcomes and relative risks (RR) for dichotomous outcomes, with 95% confidence intervals (CI). RESULTS: Of the 19,863 articles, 38 were selected and 32 were included in the quantitative synthesis. Routine IOC showed no superiority compared to selective IOC in decreasing BDI (RR = 0.91, 95% CI 0.66; 1.24). Comparing IOC and no IOC, no statistically significant differences were found in the case of BDI, retained stone rate, readmission rate, and length of hospital stay. We found an increased risk of conversion rate to open surgery in the no IOC group (RR = 0.64, CI 0.51; 0.78). The operation time was significantly longer in the IOC group compared to the no IOC group (WMD = 11.25 min, 95% CI 6.57; 15.93). CONCLUSION: Our findings suggest that IOC may not be indicated in every case, however, the evidence is very uncertain. Further good quality research is required to address this question.

Combined use of indomethacin and hydration is the best conservative approach for post-ERCP pancreatitis prevention: A network meta-analysis.

OBJECTIVES: Post-ERCP pancreatitis (PEP) is a life-threatening complication. Given the lack of a causative treatment for pancreatitis, it is of vital importance to minimize this risk of PEP. Multi-target preventive therapy may be the best choice for PEP prevention as disease development is multifactorial. AIM: We aimed to assess the efficacy of a combination of indomethacin and hydration - type and amount - for PEP prevention via a network meta-analysis. METHODS: Through a systematic search in three databases, we searched all randomized controlled trials involving hydration and indomethacin and ranked the PEP preventive efficacy with a Bayesian network meta-analysis using the PRISMA for Network Meta-Analyses (PRISMA-NMA) guideline. The RoB2 tool was used for risk of bias assessment, surface under the cumulative ranking curve (SUCRA) for ranking and PROSPERO for the study protocol [reg. no. CRD42018112698]. We used risk ratios (RR) for dichotomous data with 95% credible intervals (95% CrI). RESULTS: The quantitative analysis included 7559 patients from 24 randomized controlled trials. Based on the SUCRA values, a combination of lactated Ringer's and indomethacin is more effective than single therapy with a 94% certainty. The percent relative risk ratios estimate preventive efficacy 70-99% higher for combinations than single therapies. Aggressive hydration with indomethacin (SUCRA 100%) is also significantly more effective than all other interventions (percent relative effect 94.3-98.1%). CONCLUSIONS: A one-hit-on-each-target therapeutic approach is recommended in PEP prevention with an easily accessible combination of indomethacin and aggressive hydration for all average and high-risk patients without contraindication.

Common calcium-sensing receptor (CASR) gene variants do not modify risk for chronic pancreatitis in a Hungarian cohort.

The calcium-sensing receptor (CASR) is expressed in the pancreas where it might regulate calcium concentrations in pancreatic secretions. Two independent studies reported conflicting results claiming that commonly occurring missense variants of the CASR gene are risk factors for chronic pancreatitis (CP). Here, we attempted to replicate the association between CASR variants and CP. We analyzed 337 patients and 840 controls from the Hungarian National Pancreas Registry either by direct sequencing of exon 7 and the flanking noncoding regions or by TaqMan SNP genotyping assays. We identified two common missense variants, c.2956G>T (p.A986S), and c.2968A>G (p.R990G), three low-frequency variants, c.3031C>G (p.Q1011E), c.2610G>A (p.E870=) and c.∗60T>A, and 8 rare variants including the novel variant c.1895G>A (p.G632D). When allelic or genotype distributions were considered, none of the CASR variants associated with CP. Subgroup analysis of nonalcoholic versus alcoholic patients revealed no disease association either. Our results demonstrate that common CASR variants do not modify the risk for CP and should not be considered as genetic risk factors in the clinical setting.

ERCP is more challenging in cases of acute biliary pancreatitis than in acute cholangitis - Analysis of the Hungarian ERCP registry data.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an important therapeutic modality in acute biliary pancreatitis (ABP) cases with cholangitis or ongoing common bile duct obstruction. Theoretically, inflammation of the surrounding tissues would result in a more difficult procedure. No previous studies examined this hypothesis. OBJECTIVES: ABP and acute cholangitis (AC) without ABP cases were compared to assess difficulty of ERCP. METHODS: The rate of successful biliary access, advanced cannulation method, adverse events, cannulation and fluoroscopy time were compared in 240 ABP cases and 250 AC cases without ABP. Previous papillotomy, altered gastroduodenal anatomy, and cases with biliary stricture were excluded. RESULTS: Significantly more pancreatic guidewire manipulation (adjusted odds ratio (aOR) 1.921 [1.241-2.974]) and prophylactic pancreatic stent use (aOR 4.687 [2.415-9.098]) were seen in the ABP than in AC group. Average cannulation time in the ABP patients (248 vs. 185 s; p = 0.043) were longer than in AC cases. No difference was found between biliary cannulation and adverse events rates. CONCLUSION: ERCP in ABP cases seem to be more challenging than in AC. Difficult biliary access is more frequent in the ABP cases which warrants the involvement of an experienced endoscopist.

Early occurrence of pseudocysts in acute pancreatitis - A multicenter international cohort analysis of 2275 cases.

BACKGROUND: Pseudocysts being the most frequent local complications of acute pancreatitis (AP) have substantial effect on the disease course, hospitalization and quality of life of the patient. Our study aimed to understand the effects of pre-existing (OLD-P) and newly developed (NEW-P) pseudocysts on AP. METHODS: Data were extracted from the Acute Pancreatitis Registry organized by the Hungarian Pancreatic Study Group (HPSG). 2275 of 2461 patients had uploaded information concerning pancreatic morphology assessed by imaging technique. Patients were divided into "no pseudocyst" (NO-P) group, "old pseudocyst" (OLD-P) group, or "newly developed pseudocyst" (NEW-P) groups. RESULTS: The median time of new pseudocyst development was nine days from hospital admission and eleven days from the beginning of the abdominal pain. More NEW-P cases were severe (15.9% vs 4.7% in the NO-P group p < 0.001), with longer length of hospitalization (LoH) (median: 14 days versus 8 days, p < 0.001), and were associated with several changed laboratory parameters. OLD-P was associated with male gender (72.2% vs. 56.1%, p = 0.0014), alcoholic etiology (35.2% vs. 19.8% in the NO-P group), longer hospitalization (median: 10 days, p < 0.001), a previous episode of AP (p < 0.001), pre-existing diagnosis of chronic pancreatitis (CP) (p < 0.001), current smoking (p < 0.001), and increased alcohol consumption (unit/week) (p = 0.014). CONCLUSION: Most of the new pseudocysts develop within two weeks. Newly developing pseudocysts are associated with a more severe disease course and increased length of hospitalization. Pre-existing pseudocysts are associated with higher alcohol consumption and smoking. Because CP is more frequently associated with a pre-existing pseudocyst, these patients need closer attention after AP.

Glucose levels show independent and dose-dependent association with worsening acute pancreatitis outcomes: Post-hoc analysis of a prospective, international cohort of 2250 acute pancreatitis cases.

BACKGROUND: Metabolic risk factors, such as obesity, hypertension, and hyperlipidemia are independent risk factors for the development of various complications in acute pancreatitis (AP). Hypertriglyceridemia dose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role of hyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet. METHODS: We analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1) glycosylated hemoglobin (HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binary logistic regression accounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables. RESULTS: Both on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p < 0.001 in both), mortality (p < 0.001), LOH (p < 0.001), maximal CRP (p < 0.001), systemic (p < 0.001) and local complications (p < 0.001). Patients with peak glucose >7 mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasing HbA1c with increasing LOH (p < 0.001), severity and local complications. CONCLUSIONS: On-admission and peak in-hospital glucose are independently and dose-dependently associated with increasing AP severity and mortality. In-hospital laboratory control of glucose and adequate treatment of hyperglycemia are crucial in the management of AP.

Genome-wide association study identifies an early onset pancreatic cancer risk locus.

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 × 10-4 ). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.

Endoscopic and surgical drainage for pancreatic fluid collections are better than percutaneous drainage: Meta-analysis.

BACKGROUND: Pancreatic pseudocyst (PP) and walled-off necrosis can be managed endoscopically, percutaneously or surgically, but with diverse efficacy. AIMS & METHODS: A comprehensive literature search was carried out from inception to December 2018, to identify articles which compared at least two of the three kinds of treatment modalities, regarding the mortality, clinical success, recurrence, complications, cost and length of hospitalisation (LOH). RESULTS: The outcomes of endoscopic (ED) and percutaneous drainage (PD) were comparable in six articles. The clinical success of endoscopic intervention was better considering any types of fluid collections (OR = 3.36; 95% confidence interval (CI) 1.48, 7.63; p = 0.004). ED was preferable regarding recurrence of PP (OR = 0.23; 95% CI 0.08, 0.66; p = 0.006). Fifteen articles compared surgical intervention with ED. Significant difference was found in postoperative LOH (WMD (days) = -4.61; 95%CI -7.89, -1.33; p = 0.006) and total LOH (WMD (days) = -3.67; 95%CI -5.00, -2.34; p < 0.001) which favored endoscopy, but ED had lower rate of clinical success (OR = 0.54; 95% CI 0.35, 0.85; p = 0.007) and higher rate of recurrence (OR = 1.80; 95% CI 1.16, 2.79; p = 0.009) in the treatment of PP. Eleven studies compared surgical and percutaneous intervention. PD resulted in higher rate of recurrence (OR = 4.91; 95% CI 1.82, 13.22; p = 0.002) and lower rate of clinical success (OR = 0.13; 95% CI 0.07, 0.22, p < 0.001). CONCLUSION: Both endoscopy and surgery are preferable over percutaneous intervention, furthermore endoscopic treatment is associated with shorter hospitalisation than surgery.

EarLy Elimination of Fatty Acids iN hypertriglyceridemia-induced acuTe pancreatitis (ELEFANT trial): Protocol of an open-label, multicenter, adaptive randomized clinical trial.

INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease, with no specific pharmacological treatment. However, concerning some etiologies, early specific intervention (such as ERCP in biliary AP) has proven to be remarkably beneficial. Hypertriglyceridemia (HTG) induces severe pancreatic damage by several direct (cellular damage) and indirect (deterioration of microcirculation) mechanisms. Published data suggest that early removal of triglycerides (TGs) and toxic free fatty acids (FFAs) may be advantageous; however, high-quality evidence is still missing in the literature. METHODS: Design: ELEFANT is a randomized controlled, multicenter, international trial testing the concept that early elimination of TGs and FFAs from the blood is beneficial in HTG-AP. The study will be performed with the adaptive "drop-the-loser" design, which supports the possibility of dropping the inferior treatment arm, based on the results of the interim analysis. Patients with HTG-AP defined by TG level over 11.3 mmol/l (1000 mg/dL) are randomized into three groups: (A) patients who undergo plasmapheresis and receive aggressive fluid resuscitation; (B) patients who receive insulin and heparin treatment with aggressive fluid resuscitation; and (C) patients with aggressive fluid resuscitation. Please note that all intervention must be started within 48 h from the onset of abdominal pain. Exclusion criteria are designed logically to decrease the possibility of any distorting effects of other diseases. The composite primary endpoint will include both severity and mortality. RESULTS: Our null hypothesis is that early elimination of HTG and FFAs reduces the risk of mortality and severity of AP. Sample size calculation suggests that 495 patients will need to be enrolled in order to confirm or reject the hypothesis with a 10% dropout, 80% power and 95% significance level. The general safety and quality checks required for high-quality evidence will be adhered to. The study will be organized between February 2020 and December 2025. CONCLUSION: Our study would provide the first direct evidence for or against early intervention in HTG-induced AP.

Development of disturbance of consciousness is associated with increased severity in acute pancreatitis.

BACKGROUND: Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP. METHODS: From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analyzed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used. RESULTS: From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p < 0.001), higher mortality (14.9% vs. 1.7%, p < 0.001), and a longer length of hospitalization (LOH) (Me = 11; IQR: 8-17 days vs. Me = 9; IQR: 6-13 days, p = 0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p < 0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p = 0.119). CONCLUSION: DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (<1.7 mmol/l, 1.7-2.19 mmol/l, 2.2-5.59 mmol/l, 5.6-11.29 mmol/l, 11.3-22.59 mmol/l, ≥22.6 mmol/l). RESULTS: Hypertriglyceridemia (≥1.7 mmol/l) presented in 30.6% of the patients and was significantly and dose-dependently associated with younger age and male gender. In 7.7% of AP cases, hypertriglyceridemia was considered as a causative etiological factor (≥11.3 mmol/l); however, 43.6% of these cases were associated with other etiologies (alcohol and biliary). Hypertriglyceridemia was significantly and dose-dependently related to obesity and diabetes. The rates of local complications and organ failure and maximum CRP level were significantly and dose-dependently raised by hypertriglyceridemia. Triglyceride above 11.3 mmol/l was linked to a significantly higher incidence of moderately severe AP and longer hospital stay, whereas triglyceride over 22.6 mmol/l was significantly associated with severe AP as well. CONCLUSION: Hypertriglyceridemia dose-dependently aggravates the severity and related complications of AP. Diagnostic workup for hypertriglyceridemia requires better awareness regardless of the etiology of AP.

A Cross-Sectional Survey on the Transitional Care of Adolescents with Inflammatory Bowel Disease in Hungary.

PURPOSE: Since little is known about transitional care practices of adolescents with inflammatory bowel diseases (IBD) in Central-Eastern Europe, we aimed to investigate the currently applied transition practices in Hungary. DESIGN AND METHODS: A nationwide, multicentre survey was conducted with the invitation of 41 pediatric and adult IBD centres in February 2019.We developed a 34-item questionnaire, which included single- and multiple-choice questions related to the current clinical practice of IBD transition. RESULTS: The overall response rate was 31.7% (13/41); answers came predominantly from tertiary centres. Only 15.4% of the respondent centres followed international IBD guidelines. The majority of the IBD centres provided transition support; however, responses revealed a marked heterogeneity of these services. Joint visits were held only in 54% of the clinics. Gastroenterologists and next of kin are not provided education regarding transition across most centres (85 and 92%). Although adolescents received age-specific education, transition readiness was not measured. More IBD nurses and dietitians were employed in adult centres than in pediatric ones. CONCLUSIONS: The current survey revealed critical gaps in the Hungarian IBD transition practices. As the beneficial effects of structured IBD transition programmes are recognized in Hungary, there is a growing need for the introduction of new, more effective transition practices. PRACTICE IMPLICATIONS: Our results can serve as a basis for planning more effective transition strategies.

Outcomes of Patients With Inflammatory Bowel Diseases Switched From Maintenance Therapy With a Biosimilar to Remicade.

BACKGROUND & AIMS: There is evidence that it is safe and effective for patients with inflammatory bowel diseases (IBD) to switch from maintenance therapy with an original infliximab drug to a biosimilar, but little is known about outcomes of reverse switches and/or multiple switches. We aimed to evaluate the effects of a reverse switch (from a biosimilar to Remicade) in a real-life cohort. METHODS: We performed a prospective observational study of 174 unselected and consecutive patients with IBD (136 with Crohn's disease [CD] and 38 with ulcerative colitis [UC]) who received maintenance therapy with the biosimilar in Hungary. In September 2017, patients were switched from the biosimilar (CT-P13) to Remicade, due to reimbursement policies. In our cohort, 8% (n = 14) patients had been previously exposed to the originator Remicade. We collected clinical and biochemical information from patients at baseline (time of the switch) and 16 and 24 weeks thereafter. Clinical remission was defined as a Crohn's disease activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16. RESULTS: There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch (82.5% with CD and 82.9% with UC), at baseline (80.6% with CD and 81.6% with UC), at week 16 (77.5% with CD and 83.7% with UC), or at week 24 (CD 76.3% with CD and 84.9% with UC) (P = .60 among groups for patients with CD and P = .98 among groups for patients with UC). For all patients, mean serum trough levels of infliximab were 5.33 ± 4.70 µg/mL at baseline and 5.69 ± 4.94 µg/mL at week 16 (P = .71); we did not find significant differences in prevalence of anti-drug antibody at baseline (16.2%) compared with week 16 (16.9%) (P = .87). Four infusion reactions occurred, until week 24 of follow up. There was no difference in outcomes or trough or antidrug antibody levels between patients with or without previous exposure to Remicade. CONCLUSIONS: We collected data from a real-life cohort of patients with CD or UC who were switched from maintenance therapy with a biosimilar to Remicade or were treated with only Remicade. No significant changes were observed in remission, trough levels, or antidrug antibodies in patients switched from the biosimilar to Remicade. No new safety signals were detected.

Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations.

BACKGROUND: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis. METHODS: Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals. RESULTS: The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy. CONCLUSIONS: The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making.

Transpancreatic Sphincterotomy Is Effective and Safe in Expert Hands on the Short Term.

In cases of difficult biliary cannulation, transpancreatic sphincterotomy (TPS) can be an alternative approach of biliary access. However, its success and safety profile have not been studied in detail. A systematic review and meta-analysis were performed to study the overall cannulation success and adverse events of TPS. These outcomes were also compared to other advanced cannulation methods. A systematic literature search was conducted to find all relevant articles containing data on TPS. Successful biliary cannulation and complications rates [post-ERCP pancreatitis (PEP), bleeding, and perforation rates] were compared in the pooled analyses of prospective comparative studies. The overall outcomes were calculated involving all studies on TPS. TPS was superior compared to needle-knife precut papillotomy (NKPP) and the double-guidewire method (DGW) regarding cannulation success (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.37-3.93; and OR 2.72; 95% CI 1.30-5.69, respectively). The rate of PEP did not differ between TPS and NKPP or DGW; however, TPS (only retrospective studies were available for comparison) proved to be worse than needle-knife fistulotomy in this regard (OR 4.62; 95% CI 1.36-15.72). Bleeding and perforation rates were similar among these advanced techniques. There were no data about long-term consequences of TPS. The biliary cannulation rate of TPS is higher than that of the other advanced cannulation techniques, while the safety profile is similar to those. However, no long-term follow-up studies are available on the later consequences of TPS; therefore, such studies are strongly needed for its full evaluation.

Short-Course Antibiotic Treatment Is Not Inferior to a Long-Course One in Acute Cholangitis: A Systematic Review.

AIMS: Our aim was to summarize the available literature on the effect of short- versus long-course antibiotic therapy on acute cholangitis. METHODS: A systematic review was performed according to the PRISMA Statement. We searched three databases for papers discussing the length of ABT in acute cholangitis. Long and short therapy groups were defined based on the most recent guideline available at the time of publication of the articles. Primary outcomes were the rate of recurrent cholangitis and mortality; secondary outcomes included length of hospitalization and the duration of fever after ERCP. Data were extracted on these outcomes and on general characteristics. A narrative synthesis was then provided based on collected data. RESULTS: Out of 692 articles produced by our search, four met our inclusion and exclusion criteria. These contained 205 acute cholangitis patients, with 137 and 68 patients receiving short and long antibiotic therapy, respectively. No significant difference was observed in any of the studies on the outcomes of mortality and duration of fever after ERCP between the two groups. One out of four studies found the rate of recurrent cholangitis to be significantly lower in the short antibiotic therapy group (0.0% vs. 13.3%, p = 0.036). Length of hospitalization was only compared in the same retrospective article, where it was found to be significantly shorter in the short-term antibiotic therapy group (with a median of 14 vs. 17.5 days, p < 0.001). CONCLUSIONS: Our review suggests short-course antibiotic therapy is non-inferior to long-course treatment; however, several limitations underline the need for well-designed randomized trials.

HLA-DQ2 homozygosis increases tTGA levels at diagnosis but does not influence the clinical phenotype of coeliac disease: A multicentre study.

BACKGROUND AND PURPOSE: Magnitude of gluten-specific T-cell responses in coeliac disease (CD) might be dependent on HLA-DQ2 gene dose. We aimed to investigate the effects of HLA-DQB1*02 allele dose on clinical outcomes. METHODS: We reviewed the charts of all coeliac patients attending to three Hungarian university clinics after 1997 and included those patients, who (a) were diagnosed with CD, (b) underwent high-resolution HLA typing and (c) were ≥18 years at the time of data collection. HLA typing was performed to determine DQB1*02 allele dose. Patients were divided into risk groups by DQB1*02 allele dose, as follows: high-, intermediate- and low-risk groups corresponded to a double, single and zero doses, respectively. We used ANOVA and Pearson's chi-squared test to explore association between HLA risk and clinical variables. RESULTS: A total of 727 coeliac patients attended the clinics but only 105 (14.4%) patients were eligible for inclusion. High, intermediate and low HLA risk patients comprised 35.3%, 52.3% and 12.3% of the study population, respectively. Double dose of HLA-DQB1*02 was more frequent in patient with high tTGA level (>10 times the upper limit of normal; p = 0.045). Gene dose was not associated with younger age at diagnosis (p = 0.549), gender (p = 0.739), more severe diagnostic histology (p = 0.318), more frequent classical presentation (p = 0.846), anaemia (p = 0.611), metabolic bone disease (p = 0.374), dermatitis herpetiformis (p = 0.381) and autoimmune diseases (p = 0.837). CONCLUSIONS: Our study shows a significant gene dose effect in terms of tTGA level at diagnosis, but no significant association between HLA-DQB1*02 allele dose and the clinical outcomes in CD.

Faecal microbiota transplantation for Clostridium difficile infection using a lyophilized inoculum from non-related donors: A case series involving 19 patients.

Faecal microbiota transplantation (FMT) has been reported to be effective in treating relapsing of refractory Clostridium difficile infections, although some practical barriers are limiting its widespread use. In this study, our objective was to evaluate the rate of resolution of diarrhea following administration of lyophilized and resolved FMT via a nasogastric (NG) tube. We recruited 19 patients suffered from laboratory-confirmed C. difficile infection. Each of them was treated by lyophilized and resolved inoculum through a NG tube. One participant succumbed following the procedure due to unrelated diseases. Out of 18 cases, 15 patients reportedly experienced a resolution of the symptoms. One patient was treated with another course of antibiotics, and two of the non-responders were successfully retreated with another course of FMT utilizing a lyophilized inoculum. Notably, no significant adverse activities were observed. In accordance to our clinical experiences, a patient will likely benefit from FMT treatment including lyophilized inoculum.