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The Oncologist Dec 2023Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk...
BACKGROUND
Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI.
PATIENTS AND METHODS
A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start.
RESULTS
Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01).
CONCLUSION
ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.
Topics: Humans; Pancrelipase; Immune Checkpoint Inhibitors; Steatorrhea; Retrospective Studies; Case-Control Studies; Acute Disease; Pancreatitis; Exocrine Pancreatic Insufficiency; Hyperglycemia; Weight Loss
PubMed: 37285223
DOI: 10.1093/oncolo/oyad150 -
International Journal of Pharmaceutics Jan 2023The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as...
In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model.
The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as negative control, and Creon® 10,000 U as market reference) were evaluated using an in vitro simulation of the stomach and upper intestinal tract with an acidic duodenal incubation (pH 4.5 for the first 10 min, pH 6 for the remaining 17 min) to simulate exocrine pancreatic insufficiency. Caffeine was a marker of capsule dissolution, and tributyrin to butyrate conversion measured pancrelipase activity. All capsules were filled with pancrelipase; the NGE, VCE, VCE/VCE, and HGC capsules also contained 50 mg caffeine. Caffeine was released first from the HGC capsule, followed by the VCE, NGE, and VCE/VCE capsules. Pancrelipase activity followed this trend and demonstrated a similar activity level over time for the NGE, VCE/VCE, and Creon® capsules. The HGC formulation confirmed gastric degradation of unprotected pancrelipase. NGE capsules provided similar protection to the simple fill formulation as observed for the complex formulation of the Creon® capsule in a setting with increased pepsin activity and may hasten the time needed to go from formula development to first-in-human studies for pH sensitive drugs or those requiring small intestine targeting.
Topics: Humans; Pancrelipase; Capsules; Caffeine; Gastrointestinal Agents; Exocrine Pancreatic Insufficiency; Duodenum; Gelatin
PubMed: 36442722
DOI: 10.1016/j.ijpharm.2022.122441 -
The American Journal of Case Reports Aug 2022BACKGROUND Major findings of myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome is a rare...
BACKGROUND Major findings of myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome is a rare genetic condition caused by a gain-of-function mutation in the SAMD9 gene. It acts as a growth repressor expressed in the endothelial cells. Pathogenic variants in the SAMD9 gene lead to profound growth-restricting activity intrinsic to the protein, which further reduces cellular proliferation and instigates this growth-limiting condition. Gastrointestinal features include chronic diarrhea, severe diaper rash, and colonic dilatation. Until now, there has been no description of exocrine pancreatic insufficiency as a possible cause of enteropathy in MIRAGE syndrome. CASE REPORT We report a case of MIRAGE syndrome affecting multiple systems in an infant who had severe enteropathy which responded well to porcine-derived pancreatic enzyme supplements despite normal pancreatic fecal elastase level. The infant is being followed up by multidisciplinary teams in our outpatient department. CONCLUSIONS Porcine-derived pancreatic enzyme is beneficial in enteropathy due to MIRAGE syndrome and is worth considering.
Topics: Adrenal Insufficiency; Animals; Endothelial Cells; Feces; Humans; Intracellular Signaling Peptides and Proteins; Pancreatic Elastase; Pancrelipase; Swine
PubMed: 35994417
DOI: 10.12659/AJCR.937057 -
Animal Nutrition (Zhongguo Xu Mu Shou... Jun 2021The objective of this study was to investigate the effects of natural capsicum extract (NCE, containing 2% natural capsaicin, the rest is carrier) replacing...
Natural capsicum extract replacing chlortetracycline enhances performance via improving digestive enzyme activities, antioxidant capacity, anti-inflammatory function, and gut health in weaned pigs.
The objective of this study was to investigate the effects of natural capsicum extract (NCE, containing 2% natural capsaicin, the rest is carrier) replacing chlortetracycline (CTC) on performance, digestive enzyme activities, antioxidant capacity, inflammatory cytokines, and gut health in weaned pigs. A total of 108 weaned pigs (Duroc × [Landrace × Yorkshire], initial body weight = 8.68 ± 1.34 kg; weaned on d 28) were randomly allotted into 3 treatments with 6 replicate pens per treatment (3 barrows and 3 gilts per pen). The treatments include a corn-soybean meal basal diet as a control group (CON), a CTC group (basal diet + CTC at 75 mg/kg), and a NCE group (basal diet + NEC at 80 mg/kg). Compared with CON and CTC, NCE had increased ( < 0.05) average daily gain in phase 2 (d 15 to 28) and overall (d 1 to 28), and higher ( < 0.05) apparent total tract digestibility of gross energy, dry matter, crude protein, and organic matter in phase 1 (d 1 to 14). These pigs also had increased ( < 0.05) pancrelipase activity in pancreas, α-amylase, lipase and protease activities in the jejunal mucosa, and lipase activity in the ileal mucosa on d 28. Moreover, NCE had increased ( < 0.05) the contents of growth hormone, β-endorphin, 5-hydroxytryptamine, total antioxidant capacity, total superoxide dismutase, catalase, and IL-10, as well as decreased ( < 0.05) contents of malondialdehyde, tumor nuclear factor-α, interferon-γ, and interleukin-6 in serum on d 28 compared with CON and CTC. NCE showed higher ( < 0.05) propionic acid, butyric acid and total volatile fatty acids (VFA) contents, and increased ( < 0.05) relative abundance of in colon, as well as higher ( < 0.05) propionic acid and total volatile fatty acids in cecum on d 28 compared with CON. In conclusion, NCE replacing CTC could enhance performance via improving digestive enzyme activities, antioxidant capacity, anti-inflammatory function, gut VFA composition and microbiota community in weaned pigs, and it could be used as a potential target for the development of feed additives.
PubMed: 34258418
DOI: 10.1016/j.aninu.2020.12.004 -
Physiological Reports Apr 2022Viral infections are linked to the progression of inflammatory reactions and oxidative stress that play pivotal roles in systemic diseases. To confirm this phenomenon,...
Viral infections are linked to the progression of inflammatory reactions and oxidative stress that play pivotal roles in systemic diseases. To confirm this phenomenon, in the present study, TNF-α level and oxidative stress markers were examined in the liver, kidney, and pancreas of HTLV1-infected male BALB/c mice. To this end, twenty BALB/c mice were divided into HTLV1-infected mice that were inoculated with 1-million HTLV1-infected cells (MT-2), and the control groups. Two months after inoculation, the peripheral blood, mesenteric lymph nodes, liver, kidney, and pancreas were collected after deep anesthetization of mice (ketamine, 30 mg/kg). The extracted DNA of mesenteric lymph nodes was obtained to quantify proviral load (PVL) using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of lipid peroxidation, total thiol (SH), nitric oxide (NO), TNF-α, catalase (CAT), and superoxide dismutase (SOD) activities were examined in the liver, kidney, and pancreases. Furthermore, histopathological changes in the liver and kidney were evaluated. In liver tissue, the levels of MDA, TNF-α, and blood cell infiltration were significantly increased, and the levels of CAT and SOD were significantly decreased. In the kidney, a reduction in SOD, CAT, and total SH and an increase in MDA and NO were observed. In the pancreas, CAT activity, total SH, and SOD were decreased, and the levels of MDA and NO were enhanced. In terms of TNF-α production, it has been shown that the level of this inflammatory cytokine was increased in the liver, kidney, and pancreas. The HTLV1 may have a role in inducing inflammatory reactions and oxidative stress pathways in the tissues.
Topics: Animals; Kidney; Liver; Male; Mice; Mice, Inbred BALB C; Oxidative Stress; Pancreas; Pancrelipase; Superoxide Dismutase
PubMed: 35373925
DOI: 10.14814/phy2.15243 -
Medical Oncology (Northwood, London,... Apr 2022To evaluate omega-3 fatty acid-rich enteral nutrient effects in patients with unresectable or recurrent biliary tract or pancreatic cancers during chemotherapy. Enteric...
Effects of an enteral nutrient-rich therapy with omega-3 fatty acids in patients with unresectable or recurrent biliary tract cancer or pancreatic cancer during chemotherapy: a case-control study.
To evaluate omega-3 fatty acid-rich enteral nutrient effects in patients with unresectable or recurrent biliary tract or pancreatic cancers during chemotherapy. Enteric nutritional supplements containing omega-3 fatty acids (Racol) was administered to aforementioned patients with cancers during chemotherapy. The skeletal muscle mass and blood test data were obtained pre-administration and 28 and 56 days after. Patients with pancreatic cancer were administered the digestive enzyme supplement pancrelipase (LipaCreon) 28 days after the start of Racol administration. The number of chemotherapies skipped due to neutropenia was recorded for 2 months before and after enteral nutrient initiation. In all 39 patients, the skeletal muscle mass increased on day 56 versus baseline (median 17.3 kg vs. 14.8 kg, p < 0.01), number of chemotherapies skipped decreased (mean: 0.65 times/month vs. 1.3 times/month, p = 0.03), and retinol-binding protein (mean: 2.56 mg/dL vs. 2.42 mg/dL, p = 0.05) increased. Patients with pancreatic cancer showed increased blood eicosapentaenoic acid concentration on day 56 versus baseline (median: 48.1 μg/mL vs. 37.0 μg/mL, p = 0.04) and increased skeletal muscle mass (median 16.8 kg vs. 14.4 kg, p = 0.006). Baseline median neutrophil count increased significantly from 2200/μL at baseline to 2500/μL (p = 0.04). Patients with biliary tract cancer during chemotherapy also exhibited increased skeletal muscle mass following omega-3 supplementation (median 17.3 kg vs. 15.8 kg, p = 0.01). In patients undergoing chemotherapy for unresectable or post-recurrence pancreatic and biliary tract cancers, high-omega-3 fatty acid nutrition therapy use improved skeletal muscle maintenance and chemotherapy dosing intensity.
Topics: Biliary Tract Neoplasms; Case-Control Studies; Fatty Acids, Omega-3; Gastrointestinal Neoplasms; Humans; Nutrients; Pancreatic Neoplasms
PubMed: 35478069
DOI: 10.1007/s12032-021-01625-4 -
Frontiers in Microbiology 2023The airways of people with cystic fibrosis () often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of...
The airways of people with cystic fibrosis () often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of providing a wealth of insight, this cataloguing tells us little about how the organisms interact with one another in the airways. However, such relationships can be inferred using the theoretical framework of the Lotka-Volterra (LV) model. In the current work, we use a generalized Lotka-Volterra model to interrogate the nationwide data collected and curated by the UK Registry. This longitudinal dataset (covering the period 2008-2020) contains annual depositions that record the presence/absence of microbial taxa in each patient, their medication, and their genotype. Specifically, we wanted to identify trends in ecological relationships between the microbiota at a nationwide level, and whether these are potentially affected by medication. Our results show that some medications have a distinct influence on the microbial interactome, especially those that potentially influence the "gut-lung axis" or mucus viscosity. In particular, we found that patients treated with a combination of antimicrobial agents (targeting the airway microbiota), digestive enzymes (assisting in the assimilation of dietary fats and carbohydrates), and DNase (to reduce mucus viscosity) displayed a distinctly different airway interactome compared with patients treated separately with these medications.
PubMed: 37323900
DOI: 10.3389/fmicb.2023.1178131 -
Case Reports in Oncology 2023We report the case of a 66-year-old woman who presented with diarrhea and weight loss approximately 14 months after unrelated allogeneic bone marrow transplantation for...
We report the case of a 66-year-old woman who presented with diarrhea and weight loss approximately 14 months after unrelated allogeneic bone marrow transplantation for acute myeloid leukemia. Her early post-transplant course was notable for mild acute skin graft-versus-host disease (GVHD) and biopsy-proven upper gastrointestinal (GI) acute GVHD, both of which resolved with treatment. She then developed weight loss and diarrhea treated with prednisolone for what was thought to be GI late acute GVHD. However, her diarrhea and weight loss persisted. Colonoscopy showed a grossly intact mucosa, and stool studies only confirmed steatorrhea. However, an atrophic pancreas was found on an abdominal computed tomography (CT) scan. Exocrine pancreatic enzymes, such as lipase and pancreatic amylase, were markedly decreased, yet pancreatic endocrine function remained intact. The patient's diarrhea and weight loss improved upon treatment with pancrelipase. Therefore, we suggest that her exocrine pancreatic insufficiency was likely partly caused by atypical chronic GVHD.
PubMed: 37900836
DOI: 10.1159/000533381 -
Journal of Human Nutrition and... Apr 2020Little is known about adults' experience of living with cystic fibrosis (CF) specifically in relation to the gut. However, their unique perspectives may be meaningful to...
BACKGROUND
Little is known about adults' experience of living with cystic fibrosis (CF) specifically in relation to the gut. However, their unique perspectives may be meaningful to children with CF and inform the understanding and practice of dietitians. The present study aimed to explore adults' lived experience of the CF gut and how they learnt to manage the gut as they were growing up.
METHODS
Semi-structured interviews were conducted with adult inpatients (n = 10). Interviews were audio-recorded, transcribed verbatim and accounts analysed using interpretative phenomenological analysis.
RESULTS
Three super-ordinate themes were identified: taking Creon, the learning process and this much I (now) know. Participants accounts of how CF affects the gut predominantly focused on taking Creon (pancreatin, Mylan). Various strategies were employed for coping with peer responses to taking Creon at school. Several participants reached adulthood before they understood and/or accepted that taking Creon consistently needed to be normal for them. Knowledge and understanding developed over time, with 'CF experience' and was shaped by family, CF care teams and other children with CF. All had unmet information needs when growing up. Having key explanations earlier, to make connections between eating, taking Creon, gaining weight and growth, did or would have helped most participants. Participants urged children to be assertive, ask questions and not only be involved in managing their diet and gut, but also begin to take control of this aspect of their CF.
CONCLUSIONS
Supporting development of knowledge, skills and confidence to manage diet and the gut needs to be integral to care throughout childhood.
Topics: Adult; Cystic Fibrosis; Diet; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Health Knowledge, Attitudes, Practice; Humans; Inpatients; Male; Pancrelipase; Qualitative Research
PubMed: 31763740
DOI: 10.1111/jhn.12703 -
Ecology and Evolution Sep 2023Fish feeding habit determines the digestive tract structure and intestinal microflora. However, the relationship between feeding habit, digestive intestinal morphology,...
Fish feeding habit determines the digestive tract structure and intestinal microflora. However, the relationship between feeding habit, digestive intestinal morphology, and microbial diversity of omnivorous, herbivorous, plankton feeder, and carnivorous fish from the same environment has not been compared. This study compared the digestive enzyme activities, intestinal morphology, and intestinal microflora of omnivorous (), herbivorous (), carnivorous (), and plankton feeder () fishes and predicted the potential functions of specific microflora on different nutrients. Twelve intestine samples were collected from each of the four fishes from Dianchi Lake. The composition and diversity of microbial communities were determined by using high-throughput sequencing of 16S rDNA. The results showed that the carnivorous fish () had higher trypsin and pancrelipase activities in the hepatopancreas and enteropeptidase in the intestine, but lower amylase activities in the intestine. The carnivorous fish intestine had more microvilli branches and complex structures than other fish species in the order carnivorous > herbivorous > plankton feeder > omnivorous. The intestinal microflora diversity was higher in the omnivorous fish and followed the order omnivorous > herbivorous > plankton feeder > carnivorous. species and species were the most dominant flora in the carnivorous and herbivorous fishes, respectively. species and species might help the host to digest protein, while species may help the host to digest cellulose. Taken together, feeding habit determines the digestive enzyme activities, intestinal tissue morphology, and differential colonization of fish intestinal flora. The knowledge obtained is useful in feed formulation and feeding practices for the studied fish species.
PubMed: 37706163
DOI: 10.1002/ece3.10499