Metabolic-associated fatty liver disease is associated with acute pancreatitis with more severe course: Post hoc analysis of a prospectively collected international registry.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP. METHODS: We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis. RESULTS: MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant. CONCLUSIONS: MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP.

A consensus document on definition and diagnostic criteria for orthorexia nervosa.

PURPOSE: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with "correct" eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. METHODS: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A-Definition, Clinical Aspects, Duration; B-Consequences; C-Onset; D-Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. RESULTS: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. CONCLUSIONS: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. LEVEL OF EVIDENCE: Level V: opinions of expert committees.

Infection risk related to gastrointestinal endoscopic procedures during the SARS-CoV-2 pandemic / Tápcsatornai endoszkópos eljárásokkal összefüggo infekciós kockázat a SARS-CoV-2-járvány idején

Introduction: COVID­19 significantly affects endoscopic labs' workflow. Endoscopic examinations are considered high-risk for virus transmission. Objectives: To determine impact of COVID­19 pandemic on Hungarian endoscopic labs' workflow and on infection risk of endoscopic staff. Method: A nation-wide, cross-sectional online questionnaire was sent to heads of endoscopic labs in Hungary. The average number (with 95% confidence intervals) of upper and lower gastrointestinal endoscopies performed in 2020 was compared to that in 2019. The number of SARS-CoV-2-infected endoscopic staff members and the source of infection was also investigated. Results: Completion rate was 30% (33/111). Neither the number of upper (1.593 [743­1.514] vs. 1.129 [1.020­2.166], p = 0.053), nor that of lower gastrointestinal endoscopies (1.181 [823­1.538] vs. 871 [591­1.150], p = 0.072) decreased in 2020, but both upper and lower gastrointestinal endoscopies' number decreased by 80% during peak phases. Separate examination room was available in 12% of institutes. Appropriate quality personal protective equipment (PPE) was available during the first and second peak phase in 70% and 82%, respectively. Infection risk stratification by questionnaire and PCR testing was routinely performed in 85% and 42%, respectively. Employee number decreased by 33% and 26% for physicians, and by 19% and 21% for assistants during peak phases, mainly due to age restrictions and COVID care assignments. 32% of assistants and 41% of physicians were infected (associated with inappropriate PPE use in 16% and 18%, respectively). Conclusion: Peak phases' restrictions increase endoscopic workload afterwards. Despite PPE availability, 15% of employees' COVID infection resulted from inappropriate PPE use in pre-vaccination era.

Screening and treatment of hepatitis C virus in prisons: 10 years of experience / A hepatitis C-vírus szurésének és kezelésének 10 éves tapasztalata a börtönökben

Introduction and objective: Two-thirds of patients with hepatitis C virus (HCV) infection are unaware of their infection in the European Union. The WHO aims to reduce the number of new cases of chronic hepatitis by 90% by 2030. The proportion of people infected with HCV in prisons can be up to ten times higher compared to the general population. This article is a summary of the results of the HCV screening carried out in the Hungarian prisons between 2007 and 2017. Method: Screening of anti-HCV antibodies has been performed on a voluntary basis followed by HCV PCR and genotyping in positive cases. After obtaining written informed consent from the patients, treatment was started. Treatments were performed under the guidance of hepatologists in collaboration with prison medical staff. Results: HCV screening programs and treatments are in place in 84% of Hungarian prisons. A total of 25 384 patients underwent anti-HCV screening. Anti-HCV positive result was detected in 6.6% and HCV PCR positivity was confirmed in 3.8% of the screened inmates. 55.2% patients from the HCV PCR positive population were put on treatment. Only 143 patients received full treatment, while 162 (42.6%) treatments were terminated prematurely, and the duration of treatment was unknown in 75 patients. Based on the results available on the 24th week after the end of treatment, sustained virologic response rate was 88%. Discussion: Education of patients and collaboration between hepatologists and prison medical staff play an important role in the successful result of treatment. Conclusion: Our experience demonstrates that the test and treat principle is feasible and effective at microeliminating HCV in prisons.

Early prediction of acute necrotizing pancreatitis by artificial intelligence: a prospective cohort-analysis of 2387 cases.

Pancreatic necrosis is a consistent prognostic factor in acute pancreatitis (AP). However, the clinical scores currently in use are either too complicated or require data that are unavailable on admission or lack sufficient predictive value. We therefore aimed to develop a tool to aid in necrosis prediction. The XGBoost machine learning algorithm processed data from 2387 patients with AP. The confidence of the model was estimated by a bootstrapping method and interpreted via the 10th and the 90th percentiles of the prediction scores. Shapley Additive exPlanations (SHAP) values were calculated to quantify the contribution of each variable provided. Finally, the model was implemented as an online application using the Streamlit Python-based framework. The XGBoost classifier provided an AUC value of 0.757. Glucose, C-reactive protein, alkaline phosphatase, gender and total white blood cell count have the most impact on prediction based on the SHAP values. The relationship between the size of the training dataset and model performance shows that prediction performance can be improved. This study combines necrosis prediction and artificial intelligence. The predictive potential of this model is comparable to the current clinical scoring systems and has several advantages over them.

The applicability of the Eating Disorder Inventory in pregnancy.

PURPOSE: The aim of our study was validating Eating Disorder Inventory (EDI) among pregnant women, who are vulnerable to eating disorders (EDs). METHODS: In 2012-2013, 1146 women (aged 18-47 years) completed a questionnaire including EDI during the first 3 days after delivery. We checked factorial validity of three diagnostic subscales of EDI with confirmative factor analysis and internal validity by Cronbach's alpha and item-total correlation. We also tested discriminative validity by comparing average of the three subscale of EDI in case of ED and non-ED groups. RESULTS: When applying the EDI to pregnant women, it seems necessary to exclude five items on three diagnostic subscales: on the Drive for Thinness subscale, 4 items remain (out of 7); on the Bulimia subscale, 6 items remain (out of 7); the Body Dissatisfaction subscale decreases from 9 to 8 items. Cronbach's alpha and item-total correlation values meet the requirements defined by Garner et al. The internal consistency of the EDI has proved to be appropriate, indicating that it is a reliable screening tool. CONCLUSIONS: Thinking, attitudes, and behaviors connected to eating, along with the relation to altering body weight change during pregnancy. Vomiting usually accompanies pregnancy; body weight gain within wide limits is also regarded as normal during pregnancy. These behaviors and changes are not feasible to use for measuring ED symptoms. These aspects cannot be neglected when screening eating disorders in pregnant women. LEVEL OF EVIDENCE: Level IV evidence obtained from multiple time series with or without an intervention.

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality.

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.

Initial Renal Function (eGFR) Is a Prognostic Marker of Severe Acute Pancreatitis: A Cohort-Analysis of 1,224 Prospectively Collected Cases.

Background: Acute pancreatitis (AP) is a life-threatening disease. We aimed to explore the prognostic relevance of renal function based on estimated glomerular filtration rate (eGFR). Methods: A prospective registry of AP patients was established by the Hungarian Pancreatic Study Group. Data of 1,224 consecutive patients were collected between 2012 and 2017. Patients were divided into 3 groups according to their eGFR measured within 24 h of hospitalization: normal renal function: >90 mL/min, mild to moderate renal functional impairment: 30-90 mL/min and severe renal dysfunction: <30 mL/min. Associations of eGFR with outcome (survival, length of hospitalization, AP severity, blood glucose), inflammatory markers (erythrocyte sedimentation rate, white blood cell count), anemia and organ failure (heart, kidney, liver) were analyzed. Results: Death, longer hospitalization and severe AP, but not the cause of AP, were significantly associated with lower eGFR. The inflammatory markers (CRP, WBC count) but not anemia (Hb, Htk) were closely associated with severe renal dysfunction. Renal function was associated with heart and renal failure but not with other complications of AP such as respiratory failure, local pancreatic complications, diabetes or peptic ulcer. eGFR was not associated with liver damage (ALAT, γ-GT) or liver function (serum bilirubin) although biliary complications, alcohol and metabolic syndrome were the most common etiologies of AP. Conclusions: Our study suggests a useful prognostic value of initial eGFR in AP patients. Even mild eGFR reduction predicted mortality, severity of AP and the length of hospitalization. Thus, precise evaluation of renal function should be considered for assessing AP severity and outcome.

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.

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model.

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

Family aggregation analysis shows a possible heritable background of equine grass sickness (dysautonomia) in a Hungarian stud population.

Equine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since its first description over a century ago, several factors, such as the phenotype, intestinal microbiome, environment, management and climate, have been supposed to be associated with the increased risk of dysautonomia. In this retrospective study, we examined the possible involvement of genetic factors. Medical and pedigree datasets regarding 1,233 horses with 49 affected animals born during a 23-year period were used in the analysis. Among the descendants of some stallions, the proportion of animals diagnosed with dysautonomia was unexpectedly high. Among males, the odds of dysautonomia were found to be higher, albeit not significantly, than among females. Significant familial clustering (genealogical index of familiality, P = 0.001) was observed among the affected animals. Further subgroups were identified with significant (P < 0.001) aggregation among close relatives using kinship-based methods. Our analysis, along with the slightly higher disease frequency in males, suggests that dysautonomia may have a genetic causal factor with an X-linked recessive inheritance pattern. This is the first study providing ancestry data and suggesting a heritable component in the likely multifactorial aetiology of the disease.

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.

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.

Multiple Hits in Acute Pancreatitis: Components of Metabolic Syndrome Synergize Each Other's Deteriorating Effects.

INTRODUCTION: The incidence of acute pancreatitis (AP) and the prevalence of metabolic syndrome (MetS) are growing worldwide. Several studies have confirmed that obesity (OB), hyperlipidemia (HL), or diabetes mellitus (DM) can increase severity, mortality, and complications in AP. However, there is no comprehensive information on the independent or joint effect of MetS components on the outcome of AP. Our aims were (1) to understand whether the components of MetS have an independent effect on the outcome of AP and (2) to examine the joint effect of their combinations. METHODS: From 2012 to 2017, 1435 AP cases from 28 centers were included in the prospective AP Registry. Patient groups were formed retrospectively based on the presence of OB, HL, DM, and hypertension (HT). The primary endpoints were mortality, severity, complications of AP, and length of hospital stay. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: 1257 patients (55.7 ± 17.0 years) were included in the analysis. The presence of OB was an independent predictive factor for renal failure [OR: 2.98 (CI: 1.33-6.66)] and obese patients spent a longer time in hospital compared to non-obese patients (12.1 vs. 10.4 days, p = 0.008). HT increased the risk of severe AP [OR: 3.41 (CI: 1.39-8.37)], renal failure [OR: 7.46 (CI: 1.61-34.49)], and the length of hospitalization (11.8 vs. 10.5 days, p = 0.020). HL increased the risk of local complications [OR: 1.51 (CI: 1.10-2.07)], renal failure [OR: 6.4 (CI: 1.93-21.17)], and the incidence of newly diagnosed DM [OR: 2.55 (CI: 1.26-5.19)]. No relation was found between the presence of DM and the outcome of AP. 906 cases (mean age ± SD: 56.9 ± 16.7 years) had data on all four components of MetS available. The presence of two, three, or four MetS factors increased the incidence of an unfavorable outcome compared to patients with no MetS factors. CONCLUSION: OB, HT, and HL are independent risk factors for a number of complications. HT is an independent risk factor for severity as well. Components of MetS strongly synergize each other's detrimental effect. It is important to search for and follow up on the components of MetS in AP.

A Multicenter, International Cohort Analysis of 1435 Cases to Support Clinical Trial Design in Acute Pancreatitis.

BACKGROUND: C-reactive protein level (CRP) and white blood cell count (WBC) have been variably used in clinical trials on acute pancreatitis (AP). We assessed their potential role. METHODS: First, we investigated studies which have used CRP or WBC, to describe their current role in trials on AP. Second, we extracted the data of 1435 episodes of AP from our registry. CRP and WBC on admission, within 24 h from the onset of pain and their highest values were analyzed. Descriptive statistical tools as Kruskal-Wallis, Mann-Whitney U, Levene's F tests, Receiver Operating Characteristic (ROC) curve analysis and AUC (Area Under the Curve) with 95% confidence interval (CI) were performed. RESULTS: Our literature review showed extreme variability of CRP used as an inclusion criterion or as a primary outcome or both in past and current trials on AP. In our cohort, CRP levels on admission poorly predicted mortality and severe cases of AP; AUC: 0.669 (CI:0.569-0.770); AUC:0.681 (CI: 0.601-0.761), respectively. CRP levels measured within 24 h from the onset of pain failed to predict mortality or severity; AUC: 0.741 (CI:0.627-0.854); AUC:0.690 (CI:0.586-0.793), respectively. The highest CRP during hospitalization had equally poor predictive accuracy for mortality and severity AUC:0.656 (CI:0.544-0.768); AUC:0.705 (CI:0.640-0.769) respectively. CRP within 24 h from the onset of pain used as an inclusion criterion markedly increased the combined event rate of mortality and severe AP (13% for CRP > 25 mg/l and 28% for CRP > 200 mg/l). CONCLUSION: CRP within 24 h from the onset of pain as an inclusion criterion elevates event rates and reduces the number of patients required in trials on AP.

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.

Outcomes and timing of endoscopic retrograde cholangiopancreatography for acute biliary pancreatitis.

BACKGROUND: Indication of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) is challenging. AIMS: In this retrospective study, we analyzed real-world data to understand the ERCP practice in ABP in Hungarian centers. METHODS: Clinical data on ABP patients (2013-2015) were extracted from our large multicentric database. Outcomes, quality indicators and the role of early timing of ERCP (<24 h from admission) were analyzed. RESULTS: There were 356 patients with ABP. ERCP was performed in 267 (75%). Performance indicators of ERCP proved to be suboptimal with a biliary cannulation rate of 84%. Successful vs unsuccessful cannulation of naïve papilla resulted in lower rates of local [22.9% vs 40.9%, (P = 0.012)] and systemic [4.9% vs 13.6%, (P = 0.042)] complications. Successful vs unsuccessful clearance resulted in lower rates of local complications [22.5% vs 40.8%, (P = 0.008)]. Successful cannulation and drainage correlated with less severe course of ABP [3.6% vs 15.9%, (P = 0.001) and 4.1% vs 12.2%, (P = 0.033)] respectively. A tendency of an increased rate of local complications was observed if ERCP was performed later [<24 h: 21.1% (35/166); between 24-48 h: 23.4% (11/47); >48h: 37.2% (16/43) (P = 0.088)]. CONCLUSION: Optimization of ERCP indication in ABP patients is critical as suboptimal ERCP practices in ABP without definitive stone detection are associated with poorer clinical outcomes.

Definition and diagnostic criteria for orthorexia nervosa: a narrative review of the literature.

AIM: In some cases, detrimental consequences on health are generated by self-imposed dietary rules intended to promote health. The pursuit of an "extreme dietary purity" due to an exaggerated focus on food may lead to a disordered eating behavior called "orthorexia nervosa" (ON). ON raises a growing interest, but at present there is no universally shared definition of ON, the diagnostic criteria are under debate, and the psychometric instruments used in the literature revealed some flaws. This narrative review of the literature aims at assessing state of the art in ON definition, diagnostic criteria and related psychometric instruments and provides research propositions and framework for future analysis. METHODS: The authors collected articles through a search into Pubmed/Medline, Scopus, Embase and Google Scholar (last access on 07 August 2018), using "orthorexia", "orthorexia nervosa" and "obsessive healthy eating" as search terms, and filled three tables including narrative articles (English), clinical trials (English), and articles in languages different from English. The data extrapolated from the revised studies were collected and compared. In particular, for each study, the diagnostic criteria considered, the specific psychometric instrument used, the results and the conclusions of the survey were analyzed. RESULTS: The terms employed by the different authors to define ON were fixation, obsession and concern/preoccupation. Several adjectives emphasized these expressions (e.g. exaggerated/excessive, unhealthy, compulsive, pathological, rigid, extreme, maniacal). The suitable food and the diet were defined in different ways. Most of the papers did not set the diagnostic criteria. In some cases, an attempt to use DSM (edition IV or 5) criteria for anorexia nervosa, or avoidant/restrictive food intake disorder, or body dysmorphic disorder, was done. Specific diagnostic criteria proposed by the authors were used in few studies. All these studies indicated as primary diagnostic criteria: (a) obsessional or pathological preoccupation with healthy nutrition; (b) emotional consequences (e.g. distress, anxieties) of non-adherence to self-imposed nutritional rules; (c) psychosocial impairments in relevant areas of life as well as malnutrition and weight loss. The ORTO-15 and the Orthorexia Self-Test developed by Bratman were the most used psychometric tools. CONCLUSIONS: The present review synopsizes the literature on the definition of ON, proposed diagnostic criteria and psychometric instruments used to assess ON attitudes and behaviors. This work represents a necessary starting point to allow a further progression of the studies on the possible new syndrome and to overcome the criticisms that have affected both research and clinical activity until now. LEVEL OF EVIDENCE: Level V, narrative review.