Infectious etiology and indicators of malabsorption or intestinal injury in childhood diarrhea. / Etiología infecciosa e indicadores de malabsorción o daño intestinal en diarrea infantil

INTRODUCTION: The multifactorial etiology of gastroenteritis emphasizes the need for different laboratory methods to identify or exclude infectious agents and evaluate the severity of diarrheal disease. OBJECTIVE: To diagnose the infectious etiology in diarrheic children and to evaluate some fecal markers associated with intestinal integrity. MATERIALS AND METHODS: The study group comprised 45 children with diarrheal disease, tested for enteropathogens and malabsorption markers, and 76 children whose feces were used for fat evaluation by the traditional and acid steatocrit tests. RESULTS: We observed acute diarrhea in 80% of the children and persistent diarrhea in 20%. Of the diarrheic individuals analyzed, 40% were positive for enteropathogens, with rotavirus (13.3%) and Giardia duodenalis (11.1%) the most frequently diagnosed. Among the infected patients, occult blood was more evident in those carrying pathogenic bacteria (40%) and enteroviruses (40%), while steatorrhea was observed in infections by the protozoa G. duodenalis (35.7%). Children with diarrhea excreted significantly more lipids in feces than non-diarrheic children, as determined by the traditional (p<0.0003) and acid steatocrit (p<0.0001) methods. Moreover, the acid steatocrit method detected 16.7% more fecal fat than the traditional method. CONCLUSIONS: Childhood diarrhea can lead to increasingly severe nutrient deficiencies. Steatorrhea is the hallmark of malabsorption, and a stool test, such as the acid steatocrit, can be routinely used as a laboratory tool for the semi-quantitative evaluation of fat malabsorption in diarrheic children.

Introducción. La etiología multifactorial de la gastroenteritis enfatiza la necesidad de usar diferentes métodos de laboratorio para identificar o excluir agentes infecciosos y evaluar la gravedad de la enfermedad diarreica. Objetivo. Diagnosticar la etiología infecciosa de la diarrea en niños y evaluar algunos marcadores fecales asociados con la integridad intestinal. Materiales y métodos. Se estudiaron 45 niños con enfermedad diarreica, en los cuales se evaluaron la presencia de enteropatógenos y los marcadores de malabsorción. Se analizaron las muestras fecales de 76 niños, mediante las pruebas de esteatocrito tradicional y esteatocrito ácido, para la cuantificación de la grasa. Resultados. Se observó diarrea aguda en el 80 % de los niños y diarrea persistente en el 20 %. De los individuos con diarrea, el 40 % fue positivo para enteropatógenos; los más diagnosticados fueron rotavirus (13,3 %) y Giardia duodenalis (11,1 %). Entre los pacientes infectados, la sangre oculta fue más evidente en aquellos portadores de bacterias patógenas (40 %) o enterovirus (40%), mientras que la esteatorrea se observó en infecciones por el protozoo G. duodenalis (35,7 %). Los niños con diarrea excretaron significativamente más lípidos en las heces que aquellos sin diarrea, según lo determinado por los métodos de esteatocrito tradicional (p<0,0003) y esteatocrito ácido (p<0,0001). Conclusiones. La diarrea infantil puede provocar deficiencias graves de nutrientes. La esteatorrea es distintiva de la malabsorción intestinal y puede detectarse mediante la estimación del esteatocrito ácido. Esta prueba podría utilizarse de forma rutinaria como una herramienta de laboratorio para la evaluación semicuantitativa de la malabsorción de grasas en niños con diarrea.

Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

Prospective Monitoring of Small Intestinal Bacterial Overgrowth After Gastric Bypass: Clinical, Biological, and Gas Chromatographic Aspects.

BACKGROUND AND AIMS: Obesity is a predisposing factor for small intestinal bacterial overgrowth (SIBO). The aim of this study was to prospectively evaluate the prevalence of SIBO as well as its clinical, biological, and nutritional aspects before and up to 24 months after a Roux-en-Y gastric bypass (RYGB) surgery. PATIENTS AND METHODS: Fifty-one patients (mean BMI 46.9 kg/m2, 66.7% women) requesting RYGB were included between 2016 and 2020. Each patient underwent a glucose breath test, a standardized interrogation on functional digestive signs, a dietary survey, a blood test, a fecalogram, and anthropometric data gathering. These investigations were carried out before surgery and at 1, 3, 6, 9, 12, 18, and 24 months after RYGB. RESULTS: Before surgery, we found a prevalence of 17.6% of SIBO (95% CI = [8.9%; 31.4%]). After RYGB, at the end of 24 months of follow-up, 89.5% of patients developed SIBO. Anal incontinence appeared to be very frequent after surgery, affecting 18.8% of our population 18 months after surgery. We observed positive steatorrhea after surgery with an average of 11.1 g of lipids/24 h despite a significant limitation of dietary lipids (p = 0.0282). CONCLUSION: Our study corroborates data in the literature on the prevalence of SIBO in severe obesity patients. For the first time, we observed the sudden appearance of SIBO after RYGB, with a correlation between exhaled hydrogen on a breath test and lipid malabsorption on the fecalogram. As a result, these patients develop fatty diarrhea, with frequent fecal incontinence.

Exocrine Pancreatic Insufficiency Induced by Immune Checkpoint Inhibitors.

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.

Utility of Fecal Elastase-1 to diagnose severe exocrine insufficiency in chronic pancreatitis: Real world experience.

INTRODUCTION: Quantitative fecal fat estimation is the gold standard test to diagnose steatorrhea (fecal fat >7 g/day) in chronic pancreatitis (CP), but cumbersome and inconvenient. So, fecal elastase-1 (FE) is proposed as a good alternative but the data on the diagnostic utility of FE to diagnose steatorrhea is variable. METHODS: This retrospective study included adult CP patients evaluated with both 24-h fecal-fat and FE tests within a 3-month period. The objective was to evaluate the diagnostic performance of FE to diagnose steatorrhea and to evaluate the FE progression over 9-month period. RESULTS: Among the 147 included patients, the frequency of steatorrhea (fecal fat >7 g/day) was 34%. The sensitivity, specificity, and negative likelihood ratio (LR) of FE was 90%, 28.9% and 0.35 at cut-off of <100 µg/g stool to diagnose steatorrhea; and 96%, 11.3% and 0.35 at cut-off of <200 µg/g stool, respectively. The optimal cut-off of FE was <20 on receiver operating characteristic curve (sensitivity 66%; specificity 69%; positive LR 2.14). There was no statistically significant variation in FE levels over 9 months interval among a hundred patients. CONCLUSION: Compared to FE ≥ 200 µg/g stool, FE ≥ 100 can used to exclude steatorrhea (better specificity and negative LR). FE < 20 alone cannot replace fecal fat estimation to confirm steatorrhea but to be interpreted with clinical features. Repeat FE testing for exocrine insufficiency progression can be done at least a year later.

Risk factors for developing hyperoxaluria in children with Crohn's disease.

BACKGROUND: For the purpose of a better understanding of enteric hyperoxaluria in Crohn's disease (CD) in children and adolescents, we investigated the occurrence and risk factors for development of hyperoxaluria in those patients. METHODS: Forty-five children with CD and another 45 controls were involved in this cross-sectional study. Urine samples were collected for measurement of spot urine calcium/creatinine (Ur Ca/Cr), oxalate/creatinine (Ur Ox/Cr), and citrate/creatinine (Ur Citr/Cr) ratios. Fecal samples were also collected to detect the oxalyl-CoA decarboxylase of Oxalobacter formigenes by PCR. Patients were classified into 2 groups: group A (with hyperoxaluria) and group B (with normal urine oxalate excretion). The disease extent was assessed, and the activity index was calculated. RESULTS: According to the activity index, 30 patients (66.7%) had mild disease and 13 patients (28.9%) had moderate disease. There was no significant difference in Ur Ox/Cr ratio regarding the disease activity index. O. formigenes was not detected in 91% of patients in group A while it was detected in all patients in group B (p < 0.001). By using logistic regression analysis, the overall model was statistically significant when compared to the null model, (χ2 (7) = 52.19, p < 0.001), steatorrhea (p = 0.004), frequent stools (p = 0.009), and O. formigenes (p < 0.001). CONCLUSION: Lack of intestinal colonization with O. formigenes, steatorrhea, and frequent stools are the main risk factors for development of enteric hyperoxaluria in CD patients. Identifying risk factors facilitates proper disease management in future studies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Historical note: Horace Dobell's report of cystic fibrosis in 1872.

In 1872, Horace Dobell, a respected Victorian physician, described the key features of cystic fibrosis, with pancreatic insufficiency, pulmonary disease, and familial recurrence, plus effective treatment of steatorrhea with a pancreatic extract, and was aware of the combination of digestive and pulmonary disease in the pediatric population! This antedated modern descriptions of the full disorder by over 60 years.

Clinical characteristics of smoking-related chronic pancreatitis.

Objective: The pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking. Design: Patients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively. Results: A total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM (P = 0.011) and PPC (P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls (P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea. Conclusion: The clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP.

Individualized pharmaceutical care for a patient after pancreaticoduodenectomy with trypsin replacement nutritional therapy: A case report.

RATIONALE: Optimal nutritional therapy for pancreaticoduodenectomy (PD) has been debated; however, little is known about key points of pancreatin enteric-coated capsule administration, a critical component of the PD treatment regimen. Patients often report elevations in tablet platoon and steatorrhea, and steatorrhea may adversely affect nutritional therapy for PD. Herein, we report a case of individualized pharmaceutical care for a patient after PD with trypsin replacement nutritional therapy. PATIENT CONCERNS AND DIAGNOSIS: After PD with trypsin replacement nutritional therapy, the patient developed acute steatorrhea. INTERVENTION: Individualized pharmaceutical care was provided by clinical pharmacists to address intolerance to pancreatin enteric-coated capsules following PD. OUTCOMES: The clinical pharmacist's integration into the patient's treatment plan enhanced pharmacotherapy optimization, especially through pharmacokinetic monitoring and interventions related to nutritional therapy. LESSON: Pharmaceutical care by clinical pharmacists aids in ensuring the safety and efficacy of drugs and nutritional treatment. Clinical pharmacists should be members of the nutrition support team.

[Clinical phenotypes and genotypic spectrum of cystic fibrosis with pancreatic insufficiency in children].

Objective: To investigate the clinical phenotypes and genotypic spectrum of exocrine pancreatic insufficiency in children with cystic fibrosis. Methods: This was a retrospective analysis of 12 children with cystic fibrosis who presented to Children's Hospital of Fudan University from December 2017 to December 2021. Clinical features, fecal elastase-1 level, genotype, diagnosis and treatment were systematically reviewed. Results: A total of 12 children, 7 males and 5 females, diagnosis aged 5.4 (2.0, 10.6) years, were recruited. Common clinical features included chronic cough in 12 cases, malnutrition in 7 cases, steatorrhea in 7 cases, bronchiectasis in 5 cases and electrolyte disturbance in 4 cases. Exocrine pancreatic insufficiency were diagnosed in 8 cases,the main clinical manifestations were steatorrhea in 7 cases, of which 5 cases started in infancy; 6 cases were complicated with malnutrition, including mild in 1 case, moderate in 2 cases and severe in 3 cases; 3 cases had abdominal distension; 2 cases had intermittent abdominal pain; 4 cases showed fatty infiltration or atrophy of pancreas and 3 cases showed no obvious abnormality by pancreatic magnetic resonance imaging or B-ultrasound. All 8 children were given pancreatic enzyme replacement therapy, follow-up visit of 2.3 (1.2,3.2) years. Diarrhea significantly improved in 6 cases, and 1 case was added omeprazole due to poor efficacy. A total of 20 variations of CFTR were detected in this study, of which 7 were novel (c.1373G>A,c.1810A>C,c.270delA,c.2475_2478dupCGAA,c.2489_c.2490insA, c.884delT and exon 1 deletion). Conclusions: There is a high proportion of exocrine pancreatic insufficiency in Chinese patients with cystic fibrosis. The main clinical manifestations are steatorrhea and malnutrition. Steatorrhea has often started from infancy. Pancreatic enzyme replacement therapy can significantly improve the symptoms of diarrhea and malnutrition.

Exocrine pancreatic insufficiency after bariatric surgery.

BACKGROUND: Exocrine pancreatic insufficiency (EPI) is a known complication of upper gastrointestinal surgery and has recently been associated with bariatric surgery. Our objectives were to determine the incidence of EPI in patients who underwent bariatric surgery and to identify the type of bariatric procedure most associated with EPI. METHODS: This retrospective cohort analysis included patients age ≥18 years who underwent bariatric surgery at Mayo Clinic between 2010 and 2020. Patients with a history of other gastrointestinal or hepatobiliary resection, revision of bariatric surgery, EPI prior to surgery, and surgery greater than >10 years earlier were excluded from the study. Characteristics were compared between two groups based on type of bariatric surgery including Roux-en-Y gastric bypass (RYGB) or gastric sleeve (GS). Characteristics were also analyzed between patients with RYGB who developed post-operative steatorrhea and those who did not. RESULTS: Of 150 patients, 126 underwent RYGB while 24 patients had GS. Thirty-one (20.6%) patients developed post-operative steatorrhea and 14 (9.3%) were diagnosed with EPI. Mean pancreatic elastase level was 287 ± 156 mcg/g and fecal fat level 31 ± 22 g/d. There was a significantly higher proportion of post-operative steatorrhea in patients who underwent RYGB compared to gastric sleeve surgery (p = 0.029). CONCLUSION: The incidence of EPI after bariatric surgery in our cohort was 9.3%. Overall, patients who underwent RYGB had higher rates of EPI (10.3%) than those who had GS (4.2%). Clinicians should be aware of EPI as a cause for steatorrhea in patients who underwent bariatric surgery and consider treatment with enzyme replacement therapy.

Risk factor analysis and nomogram development for steatorrhea in idiopathic chronic pancreatitis.

OBJECTIVES: Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP). METHODS: ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed. RESULTS: There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P < 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P < 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes. CONCLUSIONS: We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.

Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study.

INTRODUCTION: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. METHODS: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. RESULTS: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. CONCLUSION: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Bile Acid Malabsorption in Patients with Neuroendocrine Tumors.

BACKGROUND: Chronic diarrhea in patients with neuroendocrine tumors (NET) may be caused by bioactive products of NET, bile acid malabsorption (BAM), ileal resection (IR) or steatorrhea. AIM: To quantitate BA and fat malabsorption in NET with diarrhea. METHODS: Part of evaluation in medical oncology clinical practice, 67 patients [42F, 25 M; median age 64.0 y (17.0 IQR)] with well-differentiated NET and diarrhea underwent clinically indicated measurements of 48-h fecal BA [(FBA), fecal weight (normal < 400 g/48 h), fecal fat (normal < 7 g/day) in n = 52] and fasting serum 7αC4 (marker of hepatic BA synthesis, n = 30) between 01/2018 and 11/2020. IR had been performed in 45 patients. BAM diagnosis was based on FBA criteria: elevated total FBA (> 2337 µmol/48 h) or > 10% primary FBA or combination > 4% primary FBA plus > 1000 µmol total FBA/48 h. We also measured fecal elastase (for pancreatic insufficiency) in 13 patients. RESULTS: BAM was present in 48/52 (92%) patients with NET. There were significant correlations between total FBA and 48-h fecal weight (Rs = 0.645, P < 0.001). Mean length of IR was 47 cm; in patients with IR < 25 cm, total FBA was elevated in 85% and primary FBA > 10% in 69%. In 22 patients with no IR, 13/15 tested (87%) had BAM. Among 6 patients with pancreatic NET and no IR, 80% had BAM. Fecal fat was ≥ 15 g/day in 18/42 (43%). In 4/17 (24%) with IR < 25 cm and 8/19 (42%) patients with IR > 25 cm fecal fat was 44.0 (40.5) and 38.0 (38.0)g/day, respectively. CONCLUSION: A majority of patients with NET and diarrhea had BAM, even with < 25 cm or no IR.

Staging exocrine pancreatic dysfunction.

Digestive capacity of the gastrointestinal tract, largely but not wholly, depends on exocrine pancreatic function to achieve near complete digestion and absorption of ingested food. Coefficient of fat absorption (CFA), the proportion of ingested fat absorbed (normal >93%), reflects digestive capacity. Exocrine pancreatic insufficiency (EPI) is the state of insufficient digestive capacity (CFA <93%) caused by severe loss of pancreatic exocrine function despite variable compensation by upregulation of extra-pancreatic lipolysis. Fecal elastase 1 (FE1) level is the most widely used, though imperfect, non-invasive test of pancreatic enzyme output. Decline in pancreas enzyme output, or pancreatic exocrine dysfunction (EPD), has a variable correlation with measurable decline in CFA. EPI results in steatorrhea, weight loss and nutrient deficiency, which are mitigated by pancreatic enzyme replacement therapy (PERT). We propose a staging system for EPD, based on measurement of fecal elastase (FE1) and, if necessary, CFA and serum fat-soluble vitamin levels. In Stage I (Mild) EPD, FE1 is 100-200 mcg/gm; if steatorrhea is present, non-pancreatic causes are likely. In Stage II (Moderate) EPD), FE1 is < 100 mcg/gm without clinical and/or laboratory evidence of steatorrhea. In Stage III, there are marked reductions in FE1 and CFA, but vitamin levels remain normal (Severe EPD or EPI without nutritional deficiency). In Stage IV all parameters are abnormal (Severe EPD or EPI with nutritional deficiency). EPD stages I and II are pancreas sufficient and PERT may not be the best or first approach in management of early-stage disease; it needs further study to determine clinical utility. The term EPI refers strictly to EPD Stages III and IV which should be treated with PERT, with Stage IV requiring micronutrient supplementation as well.

Biallelic deletion in a minimal CAPN15 intron in siblings with a recognizable syndrome of congenital malformations and developmental delay.

Calpainopathies constitute a heterogeneous group of disorders resulting from deficiencies in calpains, calcium-specific proteases that modulate substrates by limited proteolysis. Clinical manifestations depend on tissue-specific expression of the defective calpain and substrate specificity. CAPN15, encoding the Drosophila small optic lobes (sol) homolog, was recently found to cause various eye defects in individuals carrying bi-allelic missense variants. Here we report on two siblings with manifestations reminiscent of Johanson-Blizzard syndrome including failure to thrive, microcephaly, global developmental delay, dysmorphic features, endocrine abnormalities and congenital malformations, in addition to eye abnormalities. Exome sequencing identified a homozygous 47 base-pair deletion in a minimal intron of CAPN15, including the splice donor site. Sequencing of cDNA revealed single exon skipping, resulting in an out-of-frame deletion with a predicted premature termination codon. These findings expand the phenotypic spectrum associated with CAPN15 variants, and suggest that complete loss-of-function is associated with a recognizable syndrome of congenital malformations and developmental delay, overlapping Johanson-Blizzard syndrome and the recently observed brain defects in Capn15 knockout (KO) mice. Moreover, the data highlight the unique opportunity for indel detection in minimal introns.

The pathophysiology of bile acid diarrhoea: differences in the colonic microbiome, metabolome and bile acids.

Bile acid diarrhoea (BAD) is a common disorder resulting from increased loss of bile acids (BAs), overlapping irritable bowel syndrome with diarrhoea (IBS-D). The gut microbiota metabolises primary BAs to secondary BAs, with differing impacts on metabolism and homeostasis. The aim of this study was to profile the microbiome, metabolic products and bile acids in BAD. Patients with BAD diagnosed by SeHCAT testing, were compared with other IBS-D patients, and healthy controls. Faecal 16S ribosomal RNA gene analysis was undertaken. Faecal short chain fatty acid (SCFA) and urinary volatile organic compounds (VOCs) were measured. BAs were quantified in serum and faeces. Faecal bacterial diversity was significantly reduced in patients with BAD. Several taxa were enriched compared to IBS-D. SCFA amounts differed in BAD, controls and IBS-D, with significantly more propionate in BAD. Separation of VOC profiles was evident, but the greatest discrimination was between IBS-D and controls. Unconjugated and primary BA in serum and faeces were significantly higher in BAD. The faecal percentage primary BA was inversely related to SeHCAT. BAD produces dysbiosis, with metabolite differences, including VOC, SCFA and primary BAs when compared to IBS-D. These findings provide new mechanistic insights into the pathophysiology of BAD.

Maldigestion Versus Malabsorption in the Elderly.

PURPOSE OF REVIEW: To evaluate recently published information about the frequency of maldigestion and malabsorption in older individuals, likely diagnoses causing these problems, and the diagnostic scheme when these diagnoses are being considered. RECENT FINDINGS: Although the prevalence of malnourishment and frank malnutrition may be increasing among older adults admitted to the hospital, this appears to be due to reduced food intake rather than maldigestion or malabsorption. The mechanisms of food digestion and absorption seem to be resilient, even in old age, but concurrent illness may produce malabsorption in older individuals. Illnesses that may be more common among the elderly include small intestinal bacterial overgrowth, exocrine pancreatic insufficiency, enteropathies, vascular disease, diabetes, and certain infections, such as Whipple's disease. In addition, older adults may have had previous surgeries or exposure to medicines which may induce malabsorption. The presentation of maldigestion and malabsorption in the elderly may be different than in younger individuals, and this may contribute to delayed recognition, diagnosis, and treatment. Diagnostic testing for maldigestion and malabsorption generally is similar to that used in younger patients. Maldigestion and malabsorption occur in older individuals and require a high level of suspicion, especially when weight loss, sarcopenia, or nutrient deficiencies are present.

Lessons from rodent gastric bypass model of enteric hyperoxaluria.

PURPOSE OF REVIEW: The aim of the article is to review studies on bone health and oxalate metabolism/therapeutics in the obese rodent model of Roux-en-Y gastric bypass (RYGB) and examine pathways to decrease procedural morbidity. RECENT FINDINGS: Compared with controls, RYGB rodents have up to 40-fold more fat in their stool (steatorrhea) which positively correlates to increased urinary oxalate. These unabsorbed intestinal fatty acids bind calcium and prevent gut calcium oxalate formation, increasing soluble luminal oxalate availability and absorption (enteric hyperoxaluria). When intraluminal fecal fat exceeded about 175 mg/24 h in our model, more paracellular and transcellular oxalate transport across the distal colon occurred. Increasing dietary calcium and colonization with Oxalobacter formigenes reduced hyperoxaluria, whereas vitamin B6 supplementation did not. RYGB animals, when severely calcium deficient, had bone mineral density loss that could not be rescued with vitamin D supplementation. SUMMARY: The findings of hyperoxaluria, steatorrhea, and decreased bone mineral density are seen in both human and rodent RYGB. Our model suggests that a low-fat, low-oxalate diet combined with calcium supplementation can decrease urinary oxalate and improve skeletal bone health. Our model is a useful tool to study renal and bone RYGB effects. Studies of longer duration are required to further evaluate mechanisms of disease and durability of therapeutics.