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This study investigated the risk profile and the impact of dietary intervention in calcium oxalate stone formers with enteric hyperoxaluria under controlled, standardized conditions. Thirty-seven patients were included in the study. Dietary and 24-h urinary parameters were obtained on the self-selected diet and a balanced, standardized diet. Tests for [13C2]oxalate absorption, calcium- and ammonium chloride-loading were performed. Mean [13C2]oxalate absorption was 18.8%. A significant positive association was observed between urinary oxalate excretion and intestinal oxalate absorption. In addition, urinary oxalate excretion was significantly correlated with dietary oxalate intake. Mean urinary oxalate excretion decreased from 0.841 mmol/24 h on the usual diet to 0.662 mmol/24 h on the balanced diet, corresponding to a reduction of 21.3%. Besides hyperoxaluria, hypocitraturia and hypomagnesuria were the most common urinary abnormalities at baseline, being present in 83.8% and 81.1% of patients, respectively. Urinary citrate increased by 50.9% and magnesium excretion increased by 25.2% on the balanced diet. As a result, the relative supersaturation of calcium oxalate declined significantly (by 36.2%) on the balanced diet. Since 41% of patients on the balanced diet still had a urine volume of less than 2.0 L/24 h, efforts should be made to increase urine volume by increasing fluid intake and reducing intestinal fluid losses. Dietary intervention proved to be effective in reducing urinary oxalate excretion and should be a cornerstone of the treatment of patients with enteric hyperoxaluria. [ABSTRACT FROM AUTHOR]

Over the past three decades, significant efforts have been focused on unraveling congenital intestinal disorders that disrupt the absorption of dietary lipids and fat-soluble vitamins. The primary goal has been to gain deeper insights into intra-enterocyte sites, molecular steps, and crucial proteins/regulatory pathways involved, while simultaneously identifying novel therapeutic targets and diagnostic tools. This research not only delves into specific and rare malabsorptive conditions, such as chylomicron retention disease (CRD), but also contributes to our understanding of normal physiology through the utilization of cutting-edge cellular and animal models alongside advanced research methodologies. This review elucidates how modern techniques have facilitated the decoding of CRD gene defects, the identification of dysfunctional cellular processes, disease regulatory mechanisms, and the essential role of coat protein complex II-coated vesicles and cargo receptors in chylomicron trafficking and endoplasmic reticulum (ER) exit sites. Moreover, experimental approaches have shed light on the multifaceted functions of SAR1B GTPase, wherein loss-of-function mutations not only predispose individuals to CRD but also exacerbate oxidative stress, inflammation, and ER stress, potentially contributing to clinical complications associated with CRD. In addition to dissecting the primary disease pathology, genetically modified animal models have emerged as invaluable assets in exploring various ancillary aspects, including responses to environmental challenges such as dietary alterations, gender-specific disparities in disease onset and progression, and embryonic lethality or developmental abnormalities. In summary, this comprehensive review provides an in-depth and contemporary analysis of CRD, offering a meticulous examination of the CRD current landscape by synthesizing the latest research findings and advancements in the field. [ABSTRACT FROM AUTHOR]

Celiac disease, a prevalent autoimmune disorder, can present atypically with fat malabsorption and coagulopathy due to vitamin K malabsorption. A 64-year-old male presented with haemoptysis and severe anaemia (Hb 6 g/dl). Despite normal previous coagulation tests, admission laboratory tests revealed an international normalised ratio (INR) of 7.0 and iron deficiency anaemia. Initial blood products and vitamin K treatment corrected the INR temporarily, but the patient’s haemoptysis returned, and his INR values continued to rise. Further investigation revealed celiac disease with fat malabsorption, leading to vitamin K malabsorption and along with a previously prescribed antiplatelet aggregation therapy, this led to diffuse alveolar haemorrhage. A gluten-free diet and vitamin supplementation normalised the patient’s INR and stopped the bleeding. This case highlights the importance of considering celiac disease in unexplained coagulopathies and the effectiveness of dietary management.

Nephrolithiasis is a common urologic manifestation of Crohn's disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn's disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [13C2]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn's disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [13C2]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis. [ABSTRACT FROM AUTHOR]

Over the past three decades, significant efforts have been focused on unraveling congenital intestinal disorders that disrupt the absorption of dietary lipids and fat-soluble vitamins. The primary goal has been to gain deeper insights into intra-enterocyte sites, molecular steps, and crucial proteins/regulatory pathways involved, while simultaneously identifying novel therapeutic targets and diagnostic tools. This research not only delves into specific and rare malabsorptive conditions, such as chylomicron retention disease (CRD), but also contributes to our understanding of normal physiology through the utilization of cutting-edge cellular and animal models alongside advanced research methodologies. This review elucidates how modern techniques have facilitated the decoding of CRD gene defects, the identification of dysfunctional cellular processes, disease regulatory mechanisms, and the essential role of coat protein complex II-coated vesicles and cargo receptors in chylomicron trafficking and endoplasmic reticulum (ER) exit sites. Moreover, experimental approaches have shed light on the multifaceted functions of SAR1B GTPase, wherein loss-of-function mutations not only predispose individuals to CRD but also exacerbate oxidative stress, inflammation, and ER stress, potentially contributing to clinical complications associated with CRD. In addition to dissecting the primary disease pathology, genetically modified animal models have emerged as invaluable assets in exploring various ancillary aspects, including responses to environmental challenges such as dietary alterations, gender-specific disparities in disease onset and progression, and embryonic lethality or developmental abnormalities. In summary, this comprehensive review provides an in-depth and contemporary analysis of CRD, offering a meticulous examination of the CRD current landscape by synthesizing the latest research findings and advancements in the field.

Background: Short bowel syndrome (SBS) refers to a malabsorptive state caused by extensive resection of the intestinal tract that leads to chronic diarrhea, electrolyte disturbances, and malnutrition. Although relatively uncommon, patients with SBS can present to the emergency department with more serious complications that are potentially life-threatening. Among these complications, coagulopathy secondary to SBS is an underrecognized condition.Case Report: We present a case of severe coagulopathy secondary to vitamin K deficiency in SBS. The patient presented with unexplained coagulopathy and spontaneous bleeding in multiple organs. With a review of surgical history and detailed clinical evaluation, SBS complicated with vitamin K deficiency was diagnosed, and the patient was treated successfully. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When a patient with a history of repeated intestinal surgery presents with diarrhea, malnutrition, or electrolyte abnormalities, emergency physicians should suspect SBS. Among complications of SBS, vitamin K deficiency is a rare but serious cause of unexplained coagulopathy presenting to the emergency department. Understanding the pathophysiology of SBS facilitates early identification of complications and improves patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Oxalate nephropathy is a potentially underestimated cause of kidney failure characterized by massive deposition of calcium oxalate crystals in the renal parenchyma. The prevalence and modes of presentation of this entity are ill-defined. Methods: Here we report on the largest consecutive series of cases of adult oxalate nephropathy diagnosed on native kidney biopsies from January 2010 to December 2018 in the UCLouvain Kidney Disease Network. Results: We screened 2265 native kidney biopsies and identified 22 cases (1%) of oxalate nephropathy. Patients had a mean age at diagnosis of 61 years (±20) and presented either with acute on chronic kidney disease (CKD) (62%) or with acute kidney injury (AKI) (38%). Mean serum creatinine at biopsy was 8.0 ± 4.5 mg/dl. Kidney biopsies showed abundant calcium oxalate crystal deposits, associated with acute interstitial nephritis and tubular necrosis, and variable degrees of interstitial fibrosis and tubular atrophy. Chronic pancreatitis and gastric bypass were the most common causes of oxalate nephropathy (48%). During a mean follow-up of 29 months, half of the patients (52%) progressed to kidney failure, all within the month following diagnosis. Higher serum creatinine level at presentation and interstitial fibrosis and tubular atrophy score were associated with progression to kidney failure. Conclusion: Oxalate nephropathy is the cause of kidney disease in 1% of consecutive native kidney biopsies and typically presents as acute on CKD or AKI. The prognosis of the disease is poor, with a high rate of kidney failure within the first month after the diagnosis.

Celiac disease, a prevalent autoimmune disorder, can present atypically with fat malabsorption and coagulopathy due to vitamin K malabsorption. A 64-year-old male presented with haemoptysis and severe anaemia (Hb 6 g/dl). Despite normal previous coagulation tests, admission laboratory tests revealed an international normalised ratio (INR) of 7.0 and iron deficiency anaemia. Initial blood products and vitamin K treatment corrected the INR temporarily, but the patient's haemoptysis returned, and his INR values continued to rise. Further investigation revealed celiac disease with fat malabsorption, leading to vitamin K malabsorption and along with a previously prescribed antiplatelet aggregation therapy, this led to diffuse alveolar haemorrhage. A gluten-free diet and vitamin supplementation normalised the patient's INR and stopped the bleeding. This case highlights the importance of considering celiac disease in unexplained coagulopathies and the effectiveness of dietary management., Learning Points: Celiac disease can cause severe coagulopathy due to fat malabsorption and vitamin K deficiency.High suspicion is required for atypical presentations of celiac disease.A gluten-free diet is essential for managing celiac disease and normalising coagulation profiles., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Abstract Bile acids are natural detergents that aid in the absorption of dietary lipids. Fatty acid binding protein 6 (Fabp6) is a component of the bile acid recovery system that operates in the small intestine. The aim of this study was to determine if Fabp6 deficiency causes dietary fat malabsorption. Wild‐type and Fabp6‐deficient mice were fed a Western‐style diet (WSD) or a reference low‐fat diet (LFD) for 10 weeks. The body weight gain, bile acid excretion, fat excretion, energy metabolism, and major gut microbial phyla of the mice were assessed at the end of the controlled diet period. Fabp6−/− mice exhibited enhanced excretion of both bile acids and fat on the WSD but not on the LFD diet. Paradoxically, male Fabp6−/− mice, but not female Fabp6−/− mice, had greater adiposity despite increased fat excretion. Analysis of energy intake and of expenditure by indirect calorimetry revealed sex differences in physical activity level and respiratory quotient, but these did not account for the enhanced adiposity displayed by male Fabp6−/− mice. Analysis of stool DNA showed sex‐specific changes in the abundance of major phyla of bacteria in response to Fabp6 deficiency and WSD feeding. The results obtained indicate that the malabsorption of bile acids that occurs in Fabp6−/− mice is associated with dietary fat malabsorption on the high‐fat diet but not on the low‐fat diet. The WSD induced a sexually dimorphic increase in adiposity displayed by Fabp6−/− mice and sexually distinct pattern of change in gut microbiota composition.

Bile acids are natural detergents that aid in the absorption of dietary lipids. Fatty acid binding protein 6 (Fabp6) is a component of the bile acid recovery system that operates in the small intestine. The aim of this study was to determine if Fabp6 deficiency causes dietary fat malabsorption. Wild‐type and Fabp6‐deficient mice were fed a Western‐style diet (WSD) or a reference low‐fat diet (LFD) for 10 weeks. The body weight gain, bile acid excretion, fat excretion, energy metabolism, and major gut microbial phyla of the mice were assessed at the end of the controlled diet period. Fabp6−/− mice exhibited enhanced excretion of both bile acids and fat on the WSD but not on the LFD diet. Paradoxically, male Fabp6−/− mice, but not female Fabp6−/− mice, had greater adiposity despite increased fat excretion. Analysis of energy intake and of expenditure by indirect calorimetry revealed sex differences in physical activity level and respiratory quotient, but these did not account for the enhanced adiposity displayed by male Fabp6−/− mice. Analysis of stool DNA showed sex‐specific changes in the abundance of major phyla of bacteria in response to Fabp6 deficiency and WSD feeding. The results obtained indicate that the malabsorption of bile acids that occurs in Fabp6−/− mice is associated with dietary fat malabsorption on the high‐fat diet but not on the low‐fat diet. The WSD induced a sexually dimorphic increase in adiposity displayed by Fabp6−/− mice and sexually distinct pattern of change in gut microbiota composition. [ABSTRACT FROM AUTHOR]

Malnutrition in critical illness is common and is associated with significant increases in adverse outcomes. A hypermetabolic state and underfeeding both contribute to the incidence of malnutrition. Malabsorption caused by critical illness is also an important contributor to the development of malnutrition. The early provision of enteral nutrition is associated with improved outcomes. Strategies for nutrition therapy must be informed by the alterations in absorption of macronutrients present in these patients. The following review examines alterations in fat metabolism during critical illness, and its consequences to overall nutrition status. Critical illness, as well as the sequalae of common medical interventions, may lead to alterations in the mechanical and chemical processes by which fat is digested and absorbed. Mechanical alterations include delayed gastric emptying and changes to the normal gut transit time. Pharmacologic interventions aimed at reducing these impacts may themselves, negatively affect efficient fat absorption. Exocrine pancreatic insufficiency can also occur in critical illness and may be underappreciated as a cause of fat malabsorption. Dysfunction of the gut lymphatics has been proposed as a contributing factor to fat malabsorption, and additional work is needed to better describe and quantify those effects. Achieving optimal outcomes for nutrition therapy requires recognition of these alterations in fat digestion., (© 2024 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Cystic fibrosis (CF) is a progressive, genetic, multi-organ disease affecting the respiratory, digestive, endocrine, and reproductive systems. CF can affect any aspect of the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, colon, pancreas, liver, and gall bladder. GI pathophysiology associated with CF results from CF membrane conductance regulator (CFTR) dysfunction. The majority of people with CF (pwCF) experience exocrine pancreatic insufficiency resulting in malabsorption of nutrients and malnutrition. Additionally, other factors can cause or worsen fat malabsorption, including the potential for short gut syndrome with a history of meconium ileus, hepatobiliary diseases, and disrupted intraluminal factors, such as inadequate bile salts, abnormal pH, intestinal microbiome changes, and small intestinal bacterial overgrowth. Signs and symptoms associated with fat malabsorption, such as abdominal pain, bloating, malodorous flatus, gastroesophageal reflux, nausea, anorexia, steatorrhea, constipation, and distal intestinal obstruction syndrome, are seen in pwCF despite the use of pancreatic enzyme replacement therapy. Given the association of poor nutrition status with lung function decline and increased mortality, aggressive nutrition support is essential in CF care to optimize growth in children and to achieve and maintain a healthy body mass index in adults. The introduction of highly effective CFTR modulator therapy and other advances in CF care have profoundly changed the course of CF management. However, GI symptoms in some pwCF may persist. The use of current knowledge of the pathophysiology of the CF GI tract as well as appropriate, individualized management of GI symptoms continue to be integral components of care for pwCF., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Fat malabsorption is central to the pathophysiology of short bowel syndrome (SBS). It occurs in patients with insufficient intestinal surface area and/or function to maintain metabolic and growth demands. Rapid intestinal transit and impaired bile acid recycling further contribute to fat malabsorption. A significant portion of patients require parenteral nutrition (PN) for their survival but may develop sepsis and liver dysfunction as a result. Despite advancements in the treatment of SBS, fat malabsorption remains a chronic issue for this vulnerable patient population. Peer-reviewed literature was assessed on the topic of fat malabsorption in SBS. Current management of patients with SBS involves dietary considerations, PN management, antidiarrheals, glucagon-like peptide 2 agonists, and multidisciplinary teams. Clinical trials have focused on improving intestinal fat absorption by facilitating fat digestion with pancreatic enzymes. Targeting fat malabsorption in SBS is a potential pathway to improving lifestyle and reducing morbidity and mortality in this rare disease., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Fat digestion and absorption play crucial roles in maintaining energy homeostasis and supporting essential physiological functions. The initial stage of fat digestion occurs in the stomach, where gastric lipase begins the hydrolysis of triglycerides. However, most fat digestion takes place in the small intestine via pancreatic enzymes and bile salts. Emulsification of fat by bile acids facilitates enzymatic action, breaking down triglycerides into free fatty acids and monoglycerides, which are then able to be absorbed by enterocytes. Fat malabsorption can result from various underlying conditions, such as exocrine pancreatic insufficiency, bile acid disorders, or intestinal diseases. The clinical manifestations of fat malabsorption include steatorrhea, malnutrition, and deficiencies of fat-soluble vitamins. Diagnostic approaches involve assessing fecal fat levels, imaging studies, and various functional tests to identify the specific etiology. This review article will describe the normal physiologic process of fat digestion and absorption and discuss various pathophysiology that can lead to fat malabsorption within the gastrointestinal tract as well as their respective diagnostic testing modalities. Effective digestion of fat is essential for overall health, because it allows for absorption of many essential nutrients, plays an integral role in cellular and structural function, and supplies energy to the body. When this is dysfunctional, disorders of malabsorption can occur. This article will give a brief overview of the physiologic process of fat digestion and absorption in healthy individuals as well as review important pathophysiology that can lead to fat malabsorption within the gastrointestinal tract and current diagnostic testing modalities., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Objective: To determine occurrence of malnutrition in children with cystic fibrosis and identify predictors of malnutrition at time of enrolment and after 2 years of follow up. Design: Retrospective chart review. Setting: Pediatric chest clinic at a tertiary-care center in northern India. Patients: Cystic fibrosis patients enrolled between 2009–2015 with at least 3 years follow-up. Procedure: Weight and height were noted at enrolment, and after 1 year and 2 years of follow-up. Clinical details, medications, and pulmonary exacerbations during second year were recorded. Main outcome measure: Occurrence of malnutrition i.e. weight for age Z-score < −2. Results: 61 medical records were reviewed. Occurrence of malnutrition at baseline, and 1- and 2-year follow-up was 65.5%, 54.1% and 57.3%, respectively. Weight for age Z-score at enrolment significantly correlated with time to diagnosis from onset r=0.015, P=0.029). Weight for age Z-score at 2-year follow-up was significantly associated with steatorrhea (P=0.03), increased frequency of stools (P<0.01) and pulmonary exacerbation (P=0.03) during second year. Linear regression showed significant association between weight for age Z-score at 2 years with steatorrhea and pulmonary exacerbations [r=−10.795 (−1.527, −0.062)] and [r=−0.261 (−0.493, −0.028)]. Pulmonary exacerbations during second and third year had significant correlation with weight for age Z-score at the beginning of respective years (r = −0.219, P=0.015). Conclusion: Occurrence of malnutrition is high in children with cystic fibrosis in this region, with uncontrolled fat malabsorption and recurrent respiratory infections being significant risk factors. [ABSTRACT FROM AUTHOR]

Background Abetalipoproteinemia, a recessive disease resulting from deleterious variants in MTTP (microsomal triglyceride transfer protein), is characterized by undetectable concentrations of apolipoprotein B, extremely low levels of low-density lipoprotein cholesterol in the plasma, and a total inability to export apolipoprotein B–containing lipoproteins from both the intestine and the liver. Objective To study lipid absorption after a fat load and liver function in 7 heterozygous relatives from 2 abetalipoproteinemic families, 1 previously unreported. Results Both patients are compound heterozygotes for p.(Arg540His) and either c.708_709del p.(His236Glnfs*11) or c.1344+3_1344+6del on the MTTP gene. The previously undescribed patient has been followed for 22 years with ultrastructure analyses of both the intestine and the liver. In these 2 families, 5 relatives were heterozygous for p.(Arg540His), 1 for p.(His236Glnfs*11) and 1 for c.1344+3_1344+6del. In 4 heterozygous relatives, the lipid absorption was normal independent of the MTTP variant. In contrast, in 3 of them, the increase in triglyceride levels after fat load was abnormal. These subjects were additionally heterozygous carriers of Asp2213 APOB in-frame deletion, near the cytidine mRNA editing site, which is essential for intestinal apoB48 production. Liver function appeared to be normal in all the heterozygotes except for one who exhibited liver steatosis for unexplained reasons. Conclusion Our study suggests that a single copy of the MTTP gene may be sufficient for human normal lipid absorption, except when associated with an additional APOB gene alteration. The hepatic steatosis reported in 1 patient emphasizes the need for liver function tests in all heterozygotes until the level of risk is established. Highlights • Genetic, clinical, ultrastructural, and biological characteristics of a new abetalipoproteinemia (ABL) case. • Postprandial studies in the new ABL case and 7 heterozygous carriers. • Normal lipid absorption in MTTP heterozygotes except if additional APOB alteration. • Need for genetic cascade screening in ABL relatives. • Need for liver and lipid absorption monitoring in ABL heterozygotes. [ABSTRACT FROM AUTHOR]

Background: Exocrine pancreatic insufficiency (EPI) is characterized by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption. Numerous conditions account for the etiology of EPI, with the most common being diseases of the pancreatic parenchyma including chronic pancreatitis, cystic fibrosis, and a history of extensive necrotizing acute pancreatitis. Treatment for EPI includes dietary management, lifestyle changes (i.e., decrease in alcohol consumption and smoking cessation), and pancreatic enzyme replacement therapy.Discussion: Many diagnostic tests are available to diagnose EPI, however, the criteria of choice remain unclear and the causes for a false-positive test are not yet understood. Despite multiple studies on the treatment of EPI using exogenous pancreatic enzymes, there remains confusion amongst medical practitioners with regard to the best approach to diagnose EPI, as well as dosing and administration of pancreatic enzymes. Appropriate use of diagnostics and treatment approaches using pancreatic enzymes in EPI is essential for patients. This opinion piece aims to address the existing myths, remove the current confusion, and function as a practical guide to the diagnosis and treatment of EPI. [ABSTRACT FROM AUTHOR]

El páncreas es un órgano retroperitoneal que segrega agua, bicarbonato y enzimas digestivos a través del conducto pancreático principal (CPP) al duodeno. La pancreatitis crónica (PC) está causada típicamente en el adulto por abuso crónico de alcohol, y, con menor frecuencia, hipertrigliceridemia, hiperparatiroidismo primario o fibrosis quística. La disfunción exocrina ocasiona malabsorción grasa y la consiguiente esteatorrea. El daño en la función endocrina es un hallazgo tardío que se presenta como hiperglucemia o diabetes mellitus franca. El cuidado de pacientes con PC conlleva, de forma primordial, el tratamiento del dolor. Un cambio significativo en su patrón o la aparición súbita y persistente de otros síntomas obligan a descartar otras entidades, incluyendo úlcera péptica, obstrucción biliar, pseudoquistes, cáncer de páncreas, estenosis de conductos pancreáticos o litiasis. Por tanto es importante asegurar el diagnóstico. El manejo del dolor debe realizarse de forma escalonada y prudente tratando de evitar la dependencia de opiáceos. Debe advertirse a los pacientes que interrumpan la ingesta de alcohol. El tratamiento de la malabsorción grasa comienza con pequeñas tomas de alimento y restricción grasa. El uso de suplementos de enzimas pancreáticos puede mejorar los síntomas y reducir la malabsorción en pacientes que no respondan al tratamiento dietético. Deben usarse dosis elevadas de enzimas con cada comida. Se recomienda tratamiento supresor de la acidez gástrica para evitar la inactivación de los enzimas. Puede ser necesaria la suplementación con triglicéridos de cadena media (MCT) y vitaminas liposolubles. El manejo de otras complicaciones (como pseudoquistes, obstrucción biliar o duodenal, ascitis pancreática, trombosis de la vena esplénica y pseusoaneurismas) con frecuencia requiere maniobras agresivas manteniendo al paciente bajo nutrición parenteral para minimizar la estimulación pancreática.The pancreas is a retroperitoneal organ that releases water, bicarbonate and digestive enzymes by the main pancreatic duct (MPD) into the duodenum. Chronic pancreatitis (CP) is typically caused, in adults, by chronic alcohol abuse and, less frequently hypertriglyceridemia, primary hyperparathyroidism or chystic fibrosis. Exocrine dysfunction results in malabsorption of fat and subsequent steatorrhea. Damage to pancreatic endocrine function is a late finding in CP and results in hyperglycaemia or overt diabetes mellitus. Care of patients with CP principally involves management of pain. A significant change in the pain pattern or the sudden onset of persistent symptoms suggests the need to rule out other potential etiologies, including peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones, then is important to establish a secure diagnosis. Management of pain should then proceed in a judicious stepwise approach avoiding opioids dependence. Patients should be advised to stop alcohol intake. Fat malabsorption and other complications may also arise. Management of steatorrhea should begin with small meals and restriction in fat intake. Pancreatic enzyme supplements can relieve symptoms and reduce malabsorption in patients who do not respond to dietary restriction. Enzymes at high doses should be used with meals. Treatment with acid suppression to reduce inactivation of the enzymes from gastric acid are recommended. Supplementation with medium chain triglycerides and fat soluble vitamin replacement may be required. Management of other complications (such as pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein thrombosis and pseudoaneurysms) often requires aggressive approach with the patient kept on total parenteral nutrition to minimize pancreatic stimulation.

High levels of plasma apolipoprotein B-100 (apoB-100), the principal apolipoprotein of LDL, are associated with cardiovascular disease. We hypothesized that suppression of apoB-100 mRNA by an antisense oligonucleotide (ASO) would reduce LDL cholesterol (LDL-C). Because most of the plasma apoB is made in the liver, and antisense drugs distribute to that organ, we tested the effects of a mouse-specific apoB-100 ASO in several mouse models of hyperlipidemia, including C57BL/6 mice fed a high-fat diet, Apoe-deficient mice, and Ldlr-deficient mice. The lead apoB-100 antisense compound, ISIS 147764, reduced apoB-100 mRNA levels in the liver and serum apoB-100 levels in a dose- and time-dependent manner. Consistent with those findings, total cholesterol and LDL-C decreased by 25–55% and 40–88%, respectively.Unlike small-molecule inhibitors of microsomal triglyceride transfer protein, ISIS 147764 did not produce hepatic or intestinal steatosis and did not affect dietary fat absorption or elevate plasma transaminase levels. These findings, as well as those derived from interim phase I data with a human apoB-100 antisense drug, suggest that antisense inhibition of this target may be a safe and effective approach for the treatment of humans with hyperlipidemia.

The malabsorption blood test (MBT), consisting of pentadecanoic acid (PA), a free fatty acid, and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of the heptadecanoic acid (HA), was developed to assess fat malabsorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). The objective was to construct a population pharmacokinetic (PK) model to describe PA and HA disposition in healthy subjects and CF subjects. A model was simultaneously fit to PA and HA concentrations, consisting of 1-compartment disposition and a transit model to describe absorption. PA bioavailability estimates for CF subjects without pancreatic enzyme administration (1.07 [0.827, 1.42]) and with enzymes (0.88 [0.72, 1.09]) indicated PA absorption comparable to healthy subjects. HA bioavailability in CF without enzyme administration was 0.0292 (0.0192, 0.0459) and with enzymes increased to 0.606 (0.482, 0.823). In CF, compared with taking enzymes with the MBT, HA bioavailability was further decreased by factors of 0.829 (0.664, 0.979) and 0.78 (0.491, 1.13) with enzymes taken 30 and 60 minutes after MBT, respectively. The MBT detected differences in fat absorption in subjects with CF with and without enzyme administration and with changes in enzyme timing. Future studies will address application of the MBT in CF and other malabsorption diagnoses. [ABSTRACT FROM AUTHOR]

With the development of new drugs that directly affect CFTR protein function, clinical trials are being designed or initiated for a growing number of patients with cystic fibrosis. The currently available and accepted clinical endpoints, FEV1 and BMI, have limitations. The aim of this report is to draw attention to the need and the ample possibilities for the development and validation of relevant gastrointestinal clinical endpoints for scientific evaluation of CFTR modulation treatment, particularly in young children and infants. The gastrointestinal tract offers very good opportunities to measure CFTR protein function and systematically evaluate CF related clinical outcomes based on the principal clinical gastrointestinal manifestations of CF: intestinal pH, intestinal transit time, intestinal bile salt malabsorption, intestinal inflammation, exocrine pancreatic function and intestinal fat malabsorption. We present a descriptive analysis of a variety of gastrointestinal outcome measures for clinical relevance, reliability, validity, responsiveness to interventions, feasibility in particular in young children and the availability of reference values. [ABSTRACT FROM AUTHOR]