The effect of adding pancreatin to standard otilinium bromide and simethicone treatment in type 2 diabetes mellitus patients with irritable bowel syndrome.

This study aimed to assess the impact of adding pancreatin (a pancreatic enzyme derivative) to standard treatment on patients diagnosed with Irritable Bowel Syndrome (IBS) and Type 2 Diabetes Mellitus (T2DM). IBS and T2DM frequently coexist, leading to significant gastrointestinal symptoms and a decrease in quality of life. Gastrointestinal symptoms arising in T2DM patients present challenges in management for both clinicians and patients. Standard treatments may not fully address these symptoms. Recent studies suggest that pancreatic enzyme replacement therapy may offer additional benefits. This study investigates whether adding pancreatin to standard treatment can improve gastrointestinal outcomes in this patient population. Conducted as a prospective observational study, the research involved patients diagnosed with IBS according to Rome IV criteria and having concomitant T2DM. The patients were divided into two groups: one receiving standard dual treatment (otilinium bromide + simethicone) and the other receiving a triple therapy including a pancreatin derivative in addition to the standard treatment. Various clinical scores and measurements, including Visual Analog Scale (VAS), Bristol Stool Chart (BSC), Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS), and Irritable Bowel Syndrome Quality of Life Instrument (IBS-QOL), were assessed before and after treatment. The study comprised 121 patients, with a median age of 41 years (interquartile range [IQR] 38-48), of whom approximately 70.2% were female. Fifty-eight patients (47.9%) received dual therapy, while sixty-three patients (52.1%) received triple therapy. Before treatment, both groups exhibited similar pre-treatment Bristol stool scale results: normal (39.7% and 49.2%) and constipation (37.9% and 31.7%) in the dual and triple therapy subgroups, respectively (p > 0.05). Post-treatment, the triple therapy group showed a significantly higher proportion of normal cases on the Bristol stool scale (82.5%) compared to the dual therapy group (44.8%) (p < 0.001). After treatment, the triple therapy group demonstrated statistically significant improvements in VAS score (p < 0.001), IBS-SSS (p < 0.001), and IBS-QOL (p < 0.001) compared to the dual therapy group. There were no significant differences between groups in BMI, HbA1c levels, duration of diabetes, or diabetes treatment at baseline (p > 0.05 for all parameters). The findings suggest that adding pancreatin to standard therapies significantly enhanced the quality of life for patients with both IBS and T2DM, demonstrating improvements across various symptom measurements and indicating the potential benefits of this supplementary therapy in managing gastrointestinal symptoms in this population. Further studies are warranted to explore its broader clinical implications and mechanisms of action.

Optimization of Exocrine Pancreatic Insufficiency in Pancreatic Adenocarcinoma Patients.

BACKGROUND/OBJECTIVES: This study explores the optimization of exocrine pancreatic insufficiency (EPI) management in pancreatic adenocarcinoma patients, focusing on the scientific advancements and technological interventions available to improve patient outcomes, including oral pancreatic enzyme replacement therapy (PERT) and immobilized lipase cartridge (RELiZORB®). This was a prospective Institutional Review Board (IRB)-approved study from October 2019 through to August 2021 at the Louisville Medical Center in collaboration with Norton Healthcare and the University of Louisville Division of Surgical Oncology. Patients with a diagnosis of pancreatic adenocarcinoma (Stage 2 or 3) who underwent oncologic surgical resection were included in this study. METHODS: Patients were contacted at pre-defined intervals (prior to surgery, before hospital discharge, and 2, 4, 6, and 12 weeks after surgery) to complete nutrition evaluation, EPI assessment, and quality of life questionnaires to identify the severity and frequency of gastrointestinal (GI) symptoms. RESULTS: EPI symptoms were reported in 28 of the 35 total patients studied (80%). Jejunostomy tubes were placed during oncologic surgery in 25 of the 35 total patients studied (71%), and 12 of the 25 patients with a jejunostomy tube utilized enzyme cartridges to manage EPI symptoms while on supplemental tube feeding (48%). EPI symptoms were reported in 8 of the 10 patients without a feeding tube (80%), and their EPI symptoms were managed with PERT alone. EPI interventions, both oral PERT and immobilized cartridges, were associated with a decrease in EPI symptoms after surgery and improved quality of life (QOL). CONCLUSIONS: Overall, early optimization of EPI is crucial to enhance overall patient care, return to oncology therapy after surgery, and improve quality of life in pancreatic adenocarcinoma patients.

Hydrophobic solid lipid-based microparticles for the protection of gastric-sensitive hydrophilic active biomolecules for oral administration in the treatment of EPI.

Exocrine Pancreatic Insufficiency (EPI), induced by conditions such as cystic fibrosis, chronic pancreatitis, and Crohn's disease, is a frequently overlooked and underdiagnosed gastrointestinal disorder. It leads to inadequate intestinal digestion due to insufficient secretion of pancreatic juice, resulting in discomfort, pain, and ultimately severe malnutrition. Despite numerous treatments proving ineffective over the past three decades, a strictly hydrophobic solid lipid formulation, administered orally, is proposed in this study to restore digestive function. This technology relies on the hydrophobic nature of the matrix to physically protect the hydrophilic active principle from the gastric environment while enabling its immediate release in the duodenum by targeting the amphiphilic nature of bile salts. Results demonstrate that this formulation effectively protects an acid-sensitive active ingredient during gastric passage (Simulated Gastric Fluid or SGF), facilitating its rapid release upon entering an artificial duodenal environment (Simulated Intestinal Fluid or SIF). Furthermore, it has been demonstrated that the preservation of a protein-based active ingredient extends beyond its primary protein structure to include its functional aspects, such as enzymatic activity. This drug delivery technology could enable the protection of hydrophilic active biomolecules, such as pancreatin, which are sensitive to gastric acidity, while promoting their immediate release upon contact with bile salts in the proximal duodenum, with the ultimate goal of correcting the digestive defect induced by EPI.

Exocrine pancreatic insufficiency in a child with STEC-HUS: a forgotten complication.

BACKGROUND: Exocrine pancreatic insufficiency (EPI) is an extremely rare complication of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) and, to our knowledge, only one patient has been reported to have received pancreatic enzyme replacement therapy (PERT). Furthermore, STEC-HUS is not usually included among EPI causes. CASE DIAGNOSIS/TREATMENT: We report a 4-year-old girl with STEC-HUS who required dialysis and 4 days after admission developed acute pancreatitis (ACPAN) and diabetes mellitus (DM). Amylase and lipase normalized 15 days later but on the 73rd day of admission, she presented abdominal discomfort, bloating, and bulky and malodorous stools with a low fecal elastase-1 level (FE-1) of 15.74 µg/g confirming EPI diagnosis. She received 3 months of PERT until normalization of FE-1 levels. CONCLUSIONS: In children with STEC-HUS with ACPAN or DM, a high index of suspicion for EPI is required, since its symptoms are often mild, nonspecific, or delayed. In addition, STEC-HUS should be further recognized as a cause of secondary EPI.

Clinical Efficacy and Safety of Treatments for Exocrine Pancreatic Insufficiency: A Systematic Literature Review.

INTRODUCTION: Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI. METHODS: A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria. RESULTS: We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated. CONCLUSIONS: This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.

Prevalence of Pancreatic Steatosis and Its Associated Factors in Turkey: A Nation-Wide Multicenter Study.

BACKGROUND/AIMS:  Pancreatic steatosis (PS) is a pathology associated with metabolic syndrome (MS), endocrin and exocrine disfunctions of the pancreas, and fatty liver. The data on the frequency of PS are very limited. We aimed to evaluate the frequency of PS detected by transabdominal ultrasonography (TAU) in gastroenterology clinics located in different geographical regions of Turkey and the factors associated with it. MATERIALS AND METHODS:  Volunteers were evaluated by TAU for PS and hepatosteatosis (HS), and its degree. Pancreatic stiffness was evaluated by ultrasonographic shear wave elastography (SWE). All demographic, physical, and biochemical parametres were measured. RESULTS:  A total of 1700 volunteers from 14 centers throughout Turkey were included in the study. Mean age was 48.03 ± 20.86 years (56.9% female). Prevalance of PS was detected in 68.9%. In the PS group, age, body mass index (BMI), waist circumference, systolic blood pressure, fasting blood glucose (FBG), lipid levels, insulin resistance, diabetes mellitus, hypertension, MS frequency, and pancreatic SWE score were increasing, and fecal elastase level was decreasing in correlation with the degree of PS. The frequency of HS was 55.5%. Hepatosteatosis [odds ratio (OR): 9.472], increased age (OR: 1.02), and BMI (OR: 1.089) were independent risk factors for the occurrence of PS. Lean-PS rate was 11.8%. The lean-PS group was predominantly female and younger than non-lean PS. Also it has lower blood pressure, FBG, liver enzymes, lipid levels, and HS rates. CONCLUSION:  The frequency of PS was found 68.9% in Turkey. Its relationship was determined with age, BMI, HS, MS (and its components), pancreatic stiffness, and fecal elastase level.

Pancreas and pancreatitis: Exocrine pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI) is highly prevalent among individuals with cystic fibrosis (CF). Individuals diagnosed with EPI are often labeled as having "pancreas insufficient cystic fibrosis (PI-CF)" while those with normal exocrine function are labeled as "pancreas sufficient CF (PS-CF)." This diagnosis of EPI relies on clinical and laboratory features and management involves consumption of pancreas enzyme replacement therapy. In this review, we discuss the nuances of diagnosis and management of EPI in CF. We also present emerging evidence on the effects of CFTR modulating agents on the management of EPI, and speculate that these medications may lead to greater heterogeneity in management of EPI in CF moving forward.

Preanalytical and analytical factors affecting elastase quantitation in stool.

Exocrine pancreatic insufficiency (EPI) is a condition caused by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption of nutrients. Clinical manifestations of EPI may include steatorrhea, weight loss, diarrhea, and abdominal pain. Although direct testing is the most sensitive and specific for EPI, these tests are invasive, time consuming, expensive, and not well standardized. Fecal elastase (FE-1) has been shown to be an indirect marker of the exocrine secretory capacity of the pancreas and has become the most commonly employed indirect test for diagnosis of EPI. Measurement of fecal elastase consists of two main phases, a preanalytical phase and analytical phase. The preanalytical phase involves stool collection, storage and handling. The second phase is the analytical phase, which includes the actual assay processes and products used to produce a result. For FE-1 this includes sample extraction and measurement on an immunoassay. Each step in the process can influence the result and contribute to heterogeneity in FE-1 measurement, potentially impacting clinical diagnosis and management. Thus, this paper provides an overview of the preanalytical and analytical factors that can affect measurement and interpretation of FE-1 results.

A review of proton pump inhibitor use in cystic fibrosis and considerations for deprescribing.

Use of proton-pump inhibitors (PPIs) is common among people with cystic fibrosis (pwCF) both for the management of suspected GERD, as well as pancreatic enzyme replacement therapy augmentation. Despite their use, limited data exist to demonstrate a clinically significant impact of PPIs on key endpoints in pwCF. Furthermore, the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy may modify the need for use. These notions, coupled with the potential for adverse outcomes associated with long-term PPI use in pwCF, should facilitate re-evaluation of long-term PPI use in pwCF and promote potential deprescribing. Despite limited data on PPI deprescribing in pwCF, it intuitively mirrors the existing guidance in adults in the general population, but with added consideration given to tapering strategy, and monitoring for CF-specific outcomes such as nutritional and respiratory status. The development of a monitoring and re-initiation plan is key to reducing deprescribing inertia. This review aims to summarize the evidence that details the concern for long-term use of PPIs and provide CF clinicians with rationale and guidance on how to approach deprescribing in their practice.

Prevalence of exocrine pancreatic insufficiency at 12 months after acute pancreatitis: a prospective, multicentre, longitudinal cohort study.

Background: Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort. Methods: In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 µg/g; severe FE-1 level ≤100 µg/g; mild FE-1 101-200 µg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398. Findings: EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%). Interpretation: EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening. Funding: This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc.

Vitamin D in blood serum and chronic pancreatitis.

Patients with chronic pancreatitis are at risk of developing malabsorption and malnutrition. Exocrine pancreatic insufficiency is accompanied by decreased serum micronutrient levels and low vitamin D levels are a frequent finding in up to 60-80% of patients. The aim of our prospective study was to investigate vitamin D in the blood serum of subjects with chronic pancreatitis with the possibility of influencing the reduced vitamin D levels with supplementation therapy. MATERIAL AND METHODOLOGY: Fifty patients with chronic pancreatitis and 20 subjects in the control group without gastrointestinal tract diseases, including pancreatic disease, were examined. The vitamin D level in blood serum was determined. The results were evaluated according to the age distribution of subjects with pancreatic disease and according to gender. Patients with low vitamin D levels were treated for 24 weeks with a dose of 1.500.000 IU of vitamin D3 per day, and then blood serum vitamin D levels were determined. RESULTS: In people with chronic pancreatitis, vitamin D levels were statistically significantly reduced compared to the control group. There was no statistically significant relationship of vitamin D with gender and age. Supplementation with vitamin D3 achieved an adjustment of vitamin D level to the level of the control group. CONCLUSION: Blood serum vitamin D levels are significantly reduced in people with chronic pancreatitis. Its correction by oral vitamin D supplementation was effective. Whether this adjustment of levels will be effective also in terms of e.g. beneficial effect on fibrogenesis will require further representative studies, because the limitation of the interpretation of the results of our study is the smaller number of subjects with chronic pancreatitis (Tab. 4, Ref. 29).

Developing the EPI Symptom Questionnaire (EPI-SQ): a qualitative study to understand the symptom experience of patients with exocrine pancreatic insufficiency (EPI).

BACKGROUND: Symptom assessment is the key factor in determining disease status and optimal management of exocrine pancreatic insufficiency (EPI). There is a need for a standardized patient-reported outcome (PRO) questionnaire to assess symptoms in patients diagnosed with EPI. The purpose of this qualitative study was to increase understanding of the EPI symptom experience from the patients' perspective, and to develop and evaluate the content validity of the EPI Symptom Questionnaire (EPI-SQ) in US patients with EPI. METHODS: Concept elicitation interviews (Phase I) were conducted to understand the symptom experience in patients with a clinical diagnosis of EPI (i.e., fecal pancreatic elastase value of ≤ 200 mcg/g based on most recent value) due to chronic pancreatitis or pancreatectomy. The EPI-SQ was developed based on the data extracted from Phase I interviews and feedback from clinical experts. Next, separate cognitive interviews (Phase II) were conducted to evaluate participants' understanding of the instructions, items, response scales, and recall periods of the instrument. RESULTS: During Phase I interviews (n = 21), 19 participants (90%) reported abdominal pain as the most frequent EPI symptom and lifestyle changes were the most frequently endorsed impacts (n = 18; 86%). Phase II results indicated that all participants (n = 7) felt the 12-item EPI-SQ was relevant to their symptom experience and that they understood the items, instructions, and response options as intended. CONCLUSION: The qualitative data from this study support the content validity of the EPI-SQ in measuring EPI symptom severity in US patient populations diagnosed with EPI.

Dose optimization of pancreatic enzyme replacement therapy is essential to mitigate muscle loss in patients with advanced pancreatic cancer and exocrine pancreatic insufficiency.

BACKGROUND & AIMS: Exocrine pancreatic insufficiency (EPI) contributes to malnutrition, marked by muscle loss during chemotherapy for advanced pancreatic cancer (aPC). Pancreatic enzyme replacement therapy (PERT) is recommended for patients with EPI; however, it's efficacy for attenuating muscle loss has not been demonstrated. We aimed to delineate the impact of PERT dose on muscle loss using a 7-year population-based cohort with aPC who were provided PERT at the discretion of their oncologist or dietitian according to clinical indications of EPI. METHODS: All patients treated with chemotherapy for aPC from 2013 to 2019 in Alberta, Canada (population ∼4.3 million) were included if they had computed tomography (CT) scans both prior to and 12 ± 4 weeks after chemotherapy initiation. Change in muscle area (cm2) was measured at 3rd lumbar level on repeated CT scans. Muscle loss was defined by measurement error (loss >2.3 cm2). Clinical and pharmaceutical data were retrieved from provincial registries. For patients who were dispensed PERT -8 to +6 weeks from chemo start (PERT users), estimated dose consumed per day was calculated as: (total dose dispensed) / (days, first to last dispensation). PERT users were categorized as high dose or low dose users according to the median estimated dose consumed. Non-users were classified as No PERT. Association between PERT use and muscle loss was analyzed with multivariable logistic regression. RESULTS: Among 210 patients, 81 (39%) were PERT users. Median estimated dose consumed per day of 75 000 USP lipase units defined the cutoff between low dose and high dose uses. There were no significant differences in baseline characteristics between high dose and low dose groups. Muscle loss was more prevalent among low dose compared to both high dose and No PERT groups (88% vs. 58% and 67%, p < 0.05). In the multivariable model predicting muscle loss, low dose PERT was independently associated with greater odds of muscle loss (OR 5.4, p = 0.004) vs. high dose, independent of tumour response, disease stage, and chemotherapy regimen. CONCLUSION: In patients with clinical indications of EPI during chemotherapy for aPC, low doses of PERT were insufficient to prevent muscle loss. Patients with EPI consuming higher doses of PERT had similar odds of muscle maintenance to patients without clinical indications of EPI. Provider education for optimal PERT dosing in patients with EPI should be prioritized, and resources must be allocated to support dose titration.

Pancreatic enzyme replacement therapy and resource utilization in patients with chronic pancreatitis in a US healthcare system: a retrospective study.

OBJECTIVE: To assess the association between pancreatic enzyme replacement therapy (PERT) and resource utilization among patients with chronic pancreatitis (CP) in a large Midwestern US healthcare system. METHODS: This retrospective cohort study used electronic medical record data. Eligible patients (N = 2445) were aged ≥18 years and diagnosed with non-cystic fibrosis CP between January 2005 and December 2018, with ≥6 months' follow-up; study initiation was first encounter with the healthcare system. Patients in the PERT group were prescribed PERT at ≥1 encounter; patients in the non-PERT group were not prescribed PERT at any encounter. RESULTS: In total, 62,899 encounters were reviewed (PERT, n = 22,935; non-PERT, n = 39,964). More patients in the PERT group were younger, male, White, married/partnered and with private insurance than those in the non-PERT group. They also received longer care and had more overall encounters, fewer outpatient and day surgery/24-hour observation encounters, and more inpatient encounters. Emergency room encounters were similar between groups. Average cost by encounter was similar between groups ($225 and $213, respectively). CONCLUSIONS: Despite similar average costs per encounter, the groups had very different encounter types. More inferential research on PERT use among patients with CP is needed, particularly regarding resource utilization and long-term outcomes.

Clinical and Analytical Comparison of Monoclonal and Polyclonal Immunoassays for Fecal Pancreatic Elastase.

BACKGROUND: Numerous immunoassays have been commercialized to determine pancreatic elastase (PE) in feces in screening for exocrine pancreatic insufficiency (EPI), but how the different assays compare to one another is controversial, especially in the context that all methods use the same cut-off values for interpreting the results obtained on the presence or absence of EPI or the degree of insufficiency if it is present. Our aim was to analytically verify a new method for determining PE, compare the results with a previous method, and verify the declared cut-off values for interpretation of the results. METHODS: PE in the stool was assayed using a previous monoclonal enzyme-linked immunosorbent assay ("ScheBo ELISA") and a new polyclonal particle-enhanced turbidimetric immunoassay ("Bühlmann PETIA"). The direct method comparison of two immunoassays was performed in 40 samples. Clinical comparisons were conducted against each other for the binary determination of "abnormal/normal" elastase levels and the three-way determination of "severe/moderate/no" EPI in 56 samples. The indirect comparison method used external quality assessment (EQA) data to compare the monoclonal and polyclonal immunoassays for PE, and additionally compare the monoclonal ScheBo ELISA to a monoclonal chemiluminescence immunoassay ("DiaSorin CLIA"). RESULTS: Precision in the series and intra-laboratory precision for Bühlmann PETIA met the manufacturer's specifications for the concentration range of limit/lower values and the range of normal values. The Bühlmann PETIA immunoassay on different analytical platforms yielded comparable results and nearly perfect agreement in the case of three-way classification (kappa = 0.89 with 95%CI from 0.79 to 1.00. ScheBo ELISA tends to generate higher values of pancreatic elastase than the Bühlmann PETIA; agreement between the methods was moderate in the case of binary classification (kappa = 0.43; 95% CI 0.25 to 0.62), and substantial in the case of three-way classification (kappa = 0.62; 95% CI 0.50 to 0.75). EQA data analysis showed a statistically significant difference between ScheBo ELISA and Bühlmann PETIA peer groups (p = 0.031), as well as the DiaSorin CLIA and ScheBo ELISA peer groups (p = 0.010). CONCLUSION: The ScheBo ELISA and Bühlmann PETIA do not appear to be commutable in the analytical and clinical context. Our data address a discordance between different mono- and polyclonal immunoassays for pancreatic elastase and the potential of misclassification using its universal cut-off values in screening suspected patients for exocrine pancreatic insufficiency.

Gastrointestinal side effects of somatostatin analogs in neuroendocrine tumors: a focused review.

Neuroendocrine tumors (NETs) are a group of well-differentiated heterogeneous neoplasms characterized by slow progression and distinct clinical and biological behavior. In the majority of patients with NET, first-line treatment is represented by somatostatin analogs (SSAs) that, despite being drugs with high tolerability (even at high doses) and providing to carcinoid symptoms control and anti-proliferative effects, may present some side effects, with potential impact on quality of life and nutritional status. The most frequent side effects are represented by gastrointestinal events in particular alterations in bowel habits (diarrhea and constipation), abdominal pain, exocrine pancreatic insufficiency, and cholelithiasis. Considering the relative rarity of NETs, literature about frequency and standard clinical management of adverse events SSA-related is still lacking and heterogeneous. The aim of this review is to arm gastroenterologists and other physicians treating NET patients with essential knowledge on the side effects of SSAs. By identifying and managing these adverse events early, healthcare professionals can offer optimal care, avert foreseeable complications, and ensure the best outcomes for patients. Without such early recognition, there is a risk of diminishing the patient's quality of life and their ability to sustain treatment over time.

Features of exocrine pancreatic insufficiency in patients with non-alcoholic fatty liver disease in combination with type 2 diabetes and COVID-19.

OBJECTIVE: Aim: The aim of the research was to study the features of pancreatic exocrine insufficiency (EPI) in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM) at COVID-19. PATIENTS AND METHODS: Materials and Methods: 72 patients with NAFLD and COVID-19 were examined. The patients have been divided into two groups: group 1 included 42 patients with NAFLD and insulin resistance (IR); group 2 consisted of 30 patients with NAFLD in the combination with type 2 DM. EPI was detected by 13С-mixed triglyceride breath test (13С-MTBT) in all the patients. RESULTS: Results: The result of 13С-MTBT indicates EPI in the examined subjects of the 2 group. A significant decrease in the maximum concentration of 13СО2 between 150 and 210 min was also diagnosed in group 1 patients. research (up to 8.2 ± 0.9% - p < 0.05), however, the total concentration of 13СО2 at the end of 360 min. the study reached only 27.7 ± 1.1% (p < 0.05). CONCLUSION: Conclusions: Based on the results of laboratory-instrumental methods of research, patients with NAFLD and type 2 diabetes with COVID-19 were diagnosed with severe EPI. The results of 13С-MTBT in NAFLD and IR with COVID-19 indicate a decrease in the functional reserves of the pancreas and the formation of its EPI.

Johanson-Blizzard syndrome caused by novel UBR1 mutation in four Saudi patients.

Johanson-Blizzard syndrome (JBS) is a rare genetic disorder caused by Ubiquitin Protein Ligase E3 Component N-Recognin1 (UBR1) gene mutations. It is characterized by exocrine pancreatic insufficiency, craniofacial deformities, sensorineural hearing loss, and a broad variety of intellectual disabilities. The aim of our study is to report four pediatric cases (three of which are siblings, and the fourth patient is unrelated) that presented some features of JBS. The cases have been confirmed by genetic testing to have mutations in the UBR1 gene. This case series study was conducted retrospectively, giving a detailed description of the demographic and clinical information of these four cases, and reflecting our experience with this subset of patients. All these cases have been treated at the King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, and were identified by their clinical and laboratory markers that favor JBS. A novel homozygous missense mutation c.2075 T > C (p. lle692Thr) in exon 18 (UBR1: NM_174916.3) was identified and confirmed by Sanger sequencing in all our cases outlined in this paper. These presented cases illustrate the phenotypic variability and complexity of JBS and the importance of physical examination to reach a diagnosis. The identified novel mutation in this study broadens the spectrum of UBR1 mutations that contribute to JBS.

A review: Pancreatic enzymes in the treatment of chronic pancreatic insufficiency in companion animals.

The purpose of this review was to analyze the scientific literature on exocrine pancreatic insufficiency (EPI) in dogs and cats and our own research on porcine model to compare animal- and microbial-derived enzymes in the treatment of animals with this disease. Clinical signs of EPI occur when more than 85% of the pancreatic parenchyma is non-functional. EPI can be a consequence of various diseases. The insufficient activity or deficiency of pancreatic enzymes leads to impaired digestion and absorption, and consequently, to malnutrition. The primary treatment for enzyme insufficiency is pancreatic enzyme replacement therapy (PERT). PERT in animals with EPI is a lifetime therapy. Most commercially available products are of animal origin (processed pancreata obtained from a slaughter house) and contain lipases, alpha-amylase, and proteases. Enzymes of microbial and plant origin seem to be a promising alternative to animal-derived enzymes, but to date there are no registered preparations containing all enzymes simultaneously for use in clinical practice to treat EPI. Results from some previous studies have highlighted the "extra-digestive" functions of pancreatic enzymes, as well as the actions of pancreatic-like microbial enzymes. For example, trypsin activates protease-activated receptor and provokes maturation of enterocytes and enterostatin inhibits fat absorption. It has been postulated that intrapancreatic amylase is the main component of the acini-islet-acinar axis-the reflex which down regulates insulin release, while gut and blood amylase exhibit anti-incretin actions "per se." Additionally, high but still physiological blood amylase activity coincide with physiological glucose homeostasis and a lack of obesity.