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Bile acid sequestrants (BASs) have often been used for bile acid diarrhea (BAD) but carry a high risk of adverse events. New generations of BASs show promising results; however, their efficacy remains unclear. This systematic review and meta‐analysis was conducted using PubMed, Cochrane, and Embase to assess randomized controlled trials (RCTs) published up to November 2023 to retrieve studies that measured the parameters before and after the administration of BASs. The outcomes assessed were cessation or improvement in diarrhea, fecal consistency, abdominal cramping, frequency of diarrhea, and adverse events. Risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled using a random‐effects model. Statistical analyses were conducted using RStudio version 4.1.2. The protocol was prospectively registered with PROSPERO (CRD42023445444). Seven RCTs with a total of 311 patients were included, of which 168 (54%) were randomized to BASs. Among BAS‐treated patients, 101 (60.1%) received colesevelam, 40 (23.8%) received chenodeoxycholate, 18 (10.7%) received cholestyramine, and 9 (5.3%) received colestid. BASs were associated with a significant improvement in the cessation of diarrhea (RR 3.27; 95% CI 2.08 to 5.15; P ≤  .05) and liquid stool to normal fecal consistency (RR 2.69; 95% CI 1.56 to 4.65; P ≤  .05), as well as an increase in abdominal cramps (RR 5.27; 95% CI 1.21 to 22.93; P ≤  .05). There were no differences in urgency, adverse events, or nausea between groups. These findings indicate that BASs are effective in the treatment of BAD, as indicated by the improvement or cessation of diarrhea episodes. [ABSTRACT FROM AUTHOR]

Background: Associated with adverse pregnancy outcomes, intrahepatic cholestasis of pregnancy is the most prevalent liver disease that women typically experience during pregnancy. This study aimed to evaluate prenatal comfort, sleep, and quality of life in pregnant women with cholestasis. Methods: This cross-sectional study was implemented between November 2022 and June 2023 at Mardin Training and Research Hospital with 150 pregnant women who received a diagnosis of pregnancy-induced intrahepatic cholestasis and agreed to participate. The following tools were utilized to collect data: A personal information form exploring socio-demographic and obstetric characteristics of participants, the Prenatal Comfort Scale (PCS), the Pittsburgh Sleep Quality Index (PSQI), and the World Health Organization Quality of Life-Brief Form (WHOQOL-BREF). Results: The mean age of participants was 27.79 ± 6.33 years. The mean PCS and PSQI scores were 61.20 ± 5.84 and 9.52 ± 3.02, respectively. The mean scores of "physical health, psychological health, social relationships, and environmental health" sub-dimensions in WHOQOL-BREF were 10.63 ± 2.18, 10.48 ± 2.10, 11.31 ± 3.28, and 11.27 ± 2.10, respectively. A significant difference was found for PSQI regarding hospitalization status and change in sleep quality variables (p = 0.025 and p = 0.035, respectively). Conclusions: Cholestasis of pregnancy creates problems such as pruritus, body image changes, hospitalization, and poor sleep quality in women. This study showed that pregnant women with cholestasis had low levels of sleep quality and quality of life, implying that cholestasis affects their sleep quality, prenatal comfort levels, and quality of life in general. In addition, it is seen that women with this problem do not want to fall pregnant again. [ABSTRACT FROM AUTHOR]

BackgroundCurrent guidelines recommend that hyperthyroid patients should be rendered euthyroid prior to surgical procedures. These guidelines rely heavily on the use of ATDs as the primary medication, and do not give recommendations for patients who have contraindications to ATDs, or for whom standalone ATD treatment is inadequate.ObjectivesTo evaluate the efficacy and safety of adjunctive pharmacological therapy and/or therapeutic plasma exchange (TPE) in the perioperative management of patients with thyrotoxicosis who were intolerant to ATD or for whom standalone ATD therapy was inadequate to achieve euthyroidism prior to surgery.MethodsA comprehensive search of MEDLINE, Google Scholar, Embase and CENTRAL up to 31 December 2023 retrieved 12,876 records. After screening titles, abstracts and full manuscripts, 16 reports were enrolled. The study quality was evaluated using the Newcastle-Ottawa Scale (NOS).ResultsPatients were primarily female (78.5%), aged between 35 and 52 years. The predominant thyroid condition was Graves’ disease (89.7%). Majority underwent thyroidectomy (99.3%). Patients treated pre-operatively with 2nd line pharmacotherapy with/without therapeutic plasma exchange (TPE) underwent surgery safely with no reports of perioperative thyroid storm. Pre-operative treatment achieved mean percentage reduction of free thyroxine and free triiodothyronine levels of 52.6 ± 8.2% and 68.1 ± 9.3% respectively. One study reported a patient who suffered from myocardial infarction and tachyarrhythmia and subsequently demised.ConclusionPreoperative management of hyperthyroidism with second line pharmacotherapy and/or TPE can be effectively and safely implemented in patients with intolerance to or ineffective treatment with ATDs. The treatment modalities were generally safe, though some complications were observed.

The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The control group was fed a basic diet, while the experimental group diet contained 90 μg/kg of AFB1. Cholestyramine, atorvastatin calcium, taurine, and emodin were added to the diets of four experimental groups. The results show that in the AFB1 group, the growth properties, total bile acid (TBA) serum levels and total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) liver levels decreased, while the malondialdehyde (MDA) and TBA liver levels increased (p < 0.05). Moreover, AFB1 caused cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin could reduce the TBA serum and liver levels (p < 0.05), alleviating the symptoms of cholestasis. The qPCR results show that AFB1 upregulated cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) gene expression and downregulated ATP binding cassette subfamily B member 11 (BSEP) gene expression in the liver, and taurine and emodin downregulated CYP7A1 and CYP8B1 gene expression (p < 0.05). In summary, AFB1 negatively affects health and alters the expression of genes related to liver bile acid metabolism, leading to cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin can alleviate AFB1-induced cholestasis. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile‐acid diarrhea (BAD) investigated with 75‐selenium homocholic acid taurine (SeHCAT) test. Methods: Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4–8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results. Results: Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow‐up 14 months [interquartile range 6–16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long‐term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result. Conclusions: The SeHCAT test accurately identifies patients with BAD who benefit from long‐term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result. [ABSTRACT FROM AUTHOR]

Aim: Perinatal hypercholesterolemia exacerbates the development of atherosclerotic plaques in adult offspring. Here, we aimed to study the effect of maternal treatment with cholestyramine, a lipid‐lowering drug, on atherosclerosis development in adult offspring of hypercholesterolemic ApoE‐deficient (ApoE−/−) mice. Methods: ApoE−/− mice were treated with 3% cholestyramine (CTY) during gestation (G). After weaning, offspring (CTY‐G) were fed control diet until sacrificed at 25weeks of age. Atherosclerosis development in the aortic root of offspring was assessed after oil‐red‐o staining, along with some of predefined atherosclerosis regulators such as LDL and HDL by high‐performance liquid chromatography (HPLC), and bile acids (BA) and trimethylamine N‐oxide (TMAO) by liquid chromatography‐mass spectrometry (LC–MS/MS). Results: In pregnant dams, cholestyramine treatment resulted in significantly lower plasma total‐ and LDL‐cholesterol as well as gallbladder total BA levels. In offspring, both males and females born to treated dams displayed reduced atherosclerotic plaques areas along with less lipid deposition in the aortic root. No significant change in plasma total cholesterol or triglycerides was measured in offspring, but CTY‐G males had increased HDL‐cholesterol and decreased apolipoproteins B100 to A‐I ratio. This latter group also showed reduced gallbladder total and specifically tauro‐conjugated bile acid pools, whereas for CTY‐G females, hydrophilic plasma tauro‐conjugated BA pool was significantly higher. They also benefited from lower plasma TMAO. Conclusion: Prenatal cholestyramine treatment reduces atherosclerosis development in adult offspring of ApoE−/− mice along with modulating the plaques' composition as well as some related biomarkers such as HDL‐C, bile acids and TMAO. [ABSTRACT FROM AUTHOR]

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field. Chronic diarrhoea without an established cause is common. There are a small number of clinical trials, often with a limited number of patients or healthy volunteers. Treatment is often carried out on a trial-and-error basis, with considerable variation in the choice of treatment. There is a paucity of guidelines, and there is a gap in knowledge concerning treatment goals, such as the frequency, consistency and form of stool. The stepwise approach to the treatment of chronic idiopathic diarrhoea described in this article is based on clinical knowledge and experience. [ABSTRACT FROM AUTHOR]

Background & Aims: A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB. Methods: To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed. Results: Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination. Conclusions: R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.

The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The control group was fed a basic diet, while the experimental group diet contained 90 μg/kg of AFB1. Cholestyramine, atorvastatin calcium, taurine, and emodin were added to the diets of four experimental groups. The results show that in the AFB1 group, the growth properties, total bile acid (TBA) serum levels and total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) liver levels decreased, while the malondialdehyde (MDA) and TBA liver levels increased (p < 0.05). Moreover, AFB1 caused cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin could reduce the TBA serum and liver levels (p < 0.05), alleviating the symptoms of cholestasis. The qPCR results show that AFB1 upregulated cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) gene expression and downregulated ATP binding cassette subfamily B member 11 (BSEP) gene expression in the liver, and taurine and emodin downregulated CYP7A1 and CYP8B1 gene expression (p < 0.05). In summary, AFB1 negatively affects health and alters the expression of genes related to liver bile acid metabolism, leading to cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin can alleviate AFB1-induced cholestasis.

The article focuses on a case of fulminant severe Clostridioides difficile colitis managed with faecal microbial transplantation. A female patient in her 50s presented with abdominal symptoms and sepsis following antibiotic therapy, and despite initial medical treatment, she developed worsening colitis, leading to consideration of colectomy before opting for faecal microbial transplantation.

Background: Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients. Methods: We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four pediatric centers and one adult center between April 2007 and March 2022. Demographics, clinical course, laboratory results, molecular genetic findings concerning ATP8B1 and ABCB11 genes, histopathology, and treatment response were examined retrospectively. Results: Seven Japanese patients with BRIC were enrolled (four male, three female; four BRIC-1 and three BRIC-2). The median age at onset for BRIC-1 was 12 years; for BRIC-2, it was 1 month. Intermittent cholestatic attacks numbered from one to eight during the 11 years of median follow-up. Six patients received a mainstream education; only one patient attended special education. None developed cirrhosis. Three with BRIC-1 showed compound heterozygosity for a variant ATP8B1 gene, while one was heterozygous; two BRIC-2 patients showed compound heterozygosity in ABCB11 and one was heterozygous. Liver biopsy specimens obtained during cholestatic attacks showed fibrosis varying from none to moderate; inflammation was absent or mild. Rifampicin administered to three patients for cholestatic attacks was effective in all, as was cholestyramine in two of three. Conclusions: To our knowledge, this is the first East Asian multicenter study of BRIC patients. Onset age and number of cholestatic attacks varied. Rifampicin and cholestyramine were effective against attacks. No patient developed cirrhosis; most had normal growth and development. The long-term outcomes were satisfactory. [ABSTRACT FROM AUTHOR]

BACKGROUND Dyslipidemia is characterized by an increase in low-density lipoprotein (LDL) and triglyceride (TG) levels and a decrease in high-density lipoprotein (HDL). Cholestyramine as an antidyslipidemia has several side effects, so an alternative is needed. Pectin is a natural substance with a mechanism of action similar to that of cholestyramine. Mango peel is one of the sources of pectin, containing 10--15% of this substance. This study aimed to prove the effect of arum manis mango (Mangifera indica L.) peel extract on LDL, HDL, and TG levels in dyslipidemic Sprague-Dawley rats. METHODS 25 Sprague-Dawley rats were divided into 5 groups. All groups were given high-fat diet for the first 18 days, followed by standard feed (negative control group), cholestyramine (Sequest®) 80 mg/200 g body weight (standard treatment group), and mango peel extract (M-90 [90 mg/day], M-180 [180 mg/day], and M-360 [360 mg/day] groups) for the next 15 days. LDL and HDL levels were analyzed using the cholesterol oxidase-phenyl aminopyrazolone method and TG level using the glycerol-3-phosphateoxidase- phenol-aminophenazone method. RESULTS The M-360 group reduced the LDL level (p = 0.015), while the standard treatment group increased the HDL level (p = 0.042). Although significant TG level changes were found in the negative control, standard treatment, and M-360 groups (p = 0.042), the mean differences of LDL, HDL, and TG levels between groups were not significantly different (p = 0.245, 0.328, and 0.454, respectively). CONCLUSIONS M. indica peel extract reduced LDL and TG levels at 360 mg/day. [ABSTRACT FROM AUTHOR]

Cholestasis is defined as stagnation or a marked reduction in bile secretion and flow. Cholestatic jaundice can thus be classified as intrahepatic or extrahepatic cholestatic, depending on the level of obstruction to bile flow. It is important to recognize the complications of cholestatic in patients with chronic cholestatic liver disease. The two most common complications of cholestasis are pruritus and fatigue, with the former being the most responsive to treatment. Cholestyramine is the first-line treatment for cholestatic pruritus. Rifampicin and oral opioid antagonist naltrexone are extremely effective second-line treatments. To date, there are no specific treatments for chronic cholestatic fatigue management. Osteoporosis is a complication that can arise in chronic cholestatic conditions. It appears to be more prominent in individuals with cholestatic liver disease than in patients with other chronic liver diseases with an increased risk of fracture. The evaluation of osteoporosis in individuals with chronic cholestasis is similar to that in the general population. Antiresorptive agents such as bisphosphonates are the first-line treatment choice for osteoporosis in patients with chronic cholestasis. Other less common complications include dyslipidemia, fat-soluble vitamin deficiency, and steatorrhea. Understanding and treating these conditions can have a significant impact on the morbidity and quality of life in this group of patients. This review aimed to provide further information about the complications of chronic cholestasis and to highlight evidence-based test practices for the evaluation and effective management of these complications. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICI) are effective against various malignancies. However, adverse events including diarrhea and colitis can lead to significant morbidity and mortality. Recommendations for the management of ICI mediated diarrhea and colitis include steroids and biologics. Given their associated risks, this study evaluated the role of the non-immunosuppressive agents, mesalamine and or cholestyramine. Methods: This is a retrospective, descriptive, single-center study of adults who developed ICI diarrhea and colitis between 2010 and 2020 at MD Anderson Cancer Center. Clinical data and outcomes were compared between those treated with the non-immunosuppressive therapies mesalamine and/or cholestyramine alone versus those who received additional immunosuppression with steroids and biologics. Results: Our sample comprised 66 patients wherein, the mean age was 63 years, 71% were males, and 97% had stage III/IV cancers. Fourteen patients were treated successfully with non-immunosuppressive therapy. They had grade 1–3 diarrhea and 1–2 colitis with no difference in the rate of histologic colitis compared to those who received immunosuppressive therapy. They had less CTLA-4 inhibitor-based therapy (36% vs. 73%, p = 0.034), delayed onset of symptoms (159 vs. 64 days, p = 0.011), lower fecal calprotectin levels (56 vs. 234, p = 0.012) and were more likely to resume ICI therapy (64% vs. 25%, p = 0.006). Conclusion: Mesalamine and/or cholestyramine may be effective for mild ICI diarrhea and colitis among patients with delayed symptom onset with lower colonic inflammatory burden. Prospective studies randomizing patients with mild colitis between mesalamine/cholestyramine and immunosuppressive treatment are warranted to assess their efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolaemia (FH) is associated with a significant increase in the risk of premature coronary artery disease. Pregnancy is likely a vulnerable time for atherosclerosis progression, with a physiological rise in low‐density lipoprotein cholesterol (LDL‐C) further exaggerated by the discontinuation of cholesterol‐lowering therapy. Materials and Methods: A retrospective review was undertaken of 13 women with familial hypercholesterolemia who were managed during pregnancy between 2007 and 2021 by a multidisciplinary team following individualised risk assessment. Results: Overall, pregnancy outcomes were good, with no maternal or fetal complications, including congenital abnormalities, maternal cardiac events or hypertensive complications. Loss of statin treatment time ranged between 12 months and 3.5 years resulting from the accumulation of the preconception, pregnancy and lactation periods and was magnified in women having more than one pregnancy. Of seven women treated with cholestyramine, one developed abnormal liver function with an elevated international normalisation ratio which was corrected with vitamin K. Conclusion: Pregnancy is associated with prolonged cessation of cholesterol‐lowering therapy, a concern with respect to the risk of coronary artery disease in FH. Continuation of statin therapy up to conception and even during pregnancy in patients at higher risk of cardiovascular disease may be justified, especially with increasing evidence supporting the safety of statin therapy during pregnancy. However, more long‐term maternal and fetal data are required for the routine use of statins during pregnancy. Guideline‐informed models of care covering family planning and pregnancy should be implemented for all women with FH. [ABSTRACT FROM AUTHOR]

Today, pharmaceutical drugs have been shown to have serious side effects, while the bioactive components of botanical plants are proven to be effective in the treatment of several diseases marked by enhanced oxidative stress and mild inflammation, often associated with minimal adverse events. Coumaroyltyramine, designated by various nomenclatures such as paprazine, N-p- trans-coumaroyltyramine, p -coumaroyltyramine and N-p- coumaroyltyramine, could be a promising bioactive ingredient to address health issues thanks to its powerful anti-inflammatory and antioxidant effects. This review represents the first in-depth analysis of coumaroyltyramine, an intriguing phenylpropanoid substance found in many species of plants. In fact, an in-depth examination of coumaroyltyramine's biological characteristics, chemical attributes, and synthesis process has been undertaken. All previous research relating to the discovery, extraction, biosynthesis, and characterization of the biologically and pharmacologically active properties of coumaroyltyramine has been reviewed and taken into consideration in this analysis. All articles published in a peer-reviewed English-language journal were examined between the initial compilations of the appropriate database until February 12, 2024. A variety of phytochemicals revealed that coumaroyltyramine is a neutral amide of hydroxycinnamic acid that tends to concentrate in plants as a reaction against infection caused by pathogens and is extracted from several medicinal herbs such as Cannabis sativa , Solanum melongena , Allium bakeri , Annona cherimola , Polygonatum zanlanscianense, and Lycopersicon esculentum. Thanks to its effectiveness in suppressing the effect of the enzyme α-glucosidase, coumaroltyramine has demonstrated antihyperglycemic activity and could have an impact on diabetes and metabolic disorders. It has considerable anti-inflammatory and antioxidant effects. These results were obtained through biological and pharmacological studies in silico, in vivo , and in vitro. In addition, coumaroyltyramine has demonstrated hypocholesterolemic and neuroprotective benefits, thereby diminishing heart and vascular disease incidence and helping to prevent neurological disorders. Other interesting properties of coumaroltyramine include anticancer, antibacterial, anti-urease, antifungal, antiviral, and antidysmenorrheal activities. Targeted pathways encompass activity at different molecular levels, notably through induction of endoplasmic reticulum stress-dependent apoptosis, arrest of the cell cycle, and inhibition of the growth of cancer cells, survival, and proliferation. Although the findings from in silico , in vivo, and in vitro experiments illustrate coumaroyltyramine's properties and modes of action, further research is needed to fully exploit its therapeutic potential. To improve our understanding of the compound's pharmacodynamic effects and pharmacokinetic routes, large-scale research should first be undertaken. To determine whether coumaroyltyramine is clinically safe and effective, further studies are required in the clinical and toxicological fields. This upcoming research will be crucial to achieving the overall potency of this substance as a natural drug and in terms of its potential synergies with other drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

Hepatic pruritus is common in liver conditions, including cholestasis and nonalcoholic fatty liver disease. The pruritus can be severe enough to diminish sleep and decrease quality of life. The pathophysiology likely involves many molecules and receptors, including bile acids, bilirubin, lysophosphatidic acid (LPA), endogenous opioids, and serotonin. Recent advances suggest a significant role of Mas-related G protein-coupled receptor X4 (MRGPRX4) and autotaxin/LPA as key players in cholestatic pruritus. Further research is needed to develop increasingly targeted therapies with greater efficacy, especially given that many patients report itch refractory to various treatments. Cholestyramine was the only US FDA-approved drug for cholestatic pruritus until recent approval of ileal bile acid transporter (IBAT) inhibitors for use in the pediatric cholestatic conditions, progressive familial intrahepatic cholestasis and Alagille syndrome. Both medications decrease the bile acid pool. IBAT inhibitors are under investigation for broader use, and targeting LPA receptors and MRGPR4 are additional attractive options. [ABSTRACT FROM AUTHOR]

Purpose: Peony (Paeonia spp.) seed oil (PSO) contains a high amount of α-linolenic acid. The effects of PSO on hypercholesterolemia and gut microbiota remains unclear. The present study was to investigate effects of PSO supplementation on cholesterol metabolism and modulation of the gut microbiota. Methods: Male Golden Syrian hamsters (n = 40) were randomly divided into five groups (n = 8, each) fed one of the following diets namely low-cholesterol diet (LCD); high cholesterol diet (HCD); HCD with PSO substituting 50% lard (LPSO), PSO substituting 100% lard (HPSO) and HCD with addition of 0.5% cholestyramine (PCD), respectively, for 6 weeks. Results: PSO supplementation dose-dependently reduced plasma total cholesterol (TC) by 9–14%, non-high-density lipoprotein cholesterol (non-HDL-C) by 7–18% and triacylglycerols (TG) by 14–34% (p < 0.05). In addition, feeding PSO diets reduced the formation of plaque lesions by 49–61% and hepatic lipids by 9–19% compared with feeding HCD diet (p < 0.01). PSO also altered relative genus abundance of unclassified_f__Coriobacteriaceae, unclassified_f__Erysipelotrichaceae, Peptococcus, unclassified_f__Ruminococcaceae, norank_o__Mollicutes_RF9 and Christensenellaceae_R-7_group. Conclusions: It was concluded that PSO was effective in reducing plasma cholesterol and hepatic lipids and favorably modulating gut microbiota associated with cholesterol metabolism. [ABSTRACT FROM AUTHOR]

Bile acid metabolism, involved with the digestion and absorption of nutrients in the gut, is linked to the gut microbiota community, greatly impacting the host's metabolism. We examined the hypothesis that the modulation of bile acid metabolism by dietary fat contents, gallbladder removal (GBX; cholecystectomy), and bile acid sequestrant (BAS; cholestyramine) treatment could alter energy, glucose, and lipid metabolism through the changes in the gut microbiota. Mice were randomly assigned to the following six groups: (1) Sham GBX surgery (Sham) + low fat/high carbohydrate diet (LFD), (2) Sham + high fat diet (HFD), (3) Sham + HFD + BAS, (4) GBX + LFD, (5) GBX + HFD, and (6) GBX + HFD + BAS. BAS groups received 2% cholestyramine. After an 8-week intervention, energy, glucose, and lipid metabolism, and the gut microbiota community were measured. HFD groups exhibited higher body weight gain than LFD, and GBX increased the weight gain comped to Sham groups regardless of BAS in HFD (p < 0.05). Homeostatic model assessment for insulin resistance (HOMA-IR) was higher in HFD than LFD, and GBX increased it regardless of BAS. Serum lipid profiles were worsened in GBX + HFD compared to Sham + LFD, whereas BAS alleviated them, except for serum HDL cholesterol. Hepatic tumor-necrosis-factor-α (TNF-α) mRNA expression and lipid peroxide contents increased with GBX and BAS treatment compared to Sham and no BAS treatment (p < 0.05). Hepatic mRNA expression of sterol regulatory element-binding transcription factor 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma (PPAR-γ) exhibited the same trend as that of tumor necrosis factor-α (TNF-α). The α-diversity of gut bacteria decreased in GBX + HFD and increased in GBX + HFD + BAS. Akkermentia, Dehalobacterium, SMB53, and Megamonas were high in the Sham + LFD, and Veillonella and Streptococcus were rich in the Sham + HFD, while Oscillospira and Olsenella were high in Sham + HFD + BAS (p < 0.05). GBX + LFD increased Lactobacillus and Sutterella while GBX + HFD + BAS elevated Clostridium, Alistipes, Blautia, Eubacterium, and Coprobacillus (p < 0.05). In conclusion, the modulation of bile acid metabolism influences energy, glucose, and lipid metabolisms, and it might be linked to changes in the gut microbiota by bile acid metabolism modulation. [ABSTRACT FROM AUTHOR]

Abstract Background Bile acid malabsorption occurs in up to one third of patients with chronic diarrhoea of functional characteristics. The gold standard test for its diagnosis is the 75Selenium homocholic acid taurine (75SeHCAT) test. The aim of this work is to confirm previous data suggesting that bile acid malabsorption, diagnosed by 75Se-HCAT test, is the underlying cause of diarrhoea in a significant proportion of patients previously diagnosed with a functional disorder. In addition, we have analysed the clinical response of bile acid sequestrants in those patients with a bile acid diarrhoea diagnosis. Methods This is a prospective, single-centre study including consecutive adult patients diagnosed with chronic diarrhoea of unknown origin and with functional characteristics; systematic rule out of common causes of chronic diarrhoea was performed before bile acid malabsorption evaluation by 75SeHCAT scanning. A retention percentage less than 10% was considered positive. Clinical response to cholestyramine was further evaluated in those patients with a positive diagnosis of bile acid diarrhoea Results 38 patients (20 male, mean age 37.5 years) were finally included. Twenty (52.6%) patients included had a positive 75SeHCAT test. Median body mass index was significantly higher in those patients. We did not find significant differences in other clinical or biochemical variables 75SeHCAT-positive and 75SeHCAT-negative groups. Only 6 of 17 (35.3%) patients responded to cholestyramine treatment; 10 patients did not have response or withdraw the drug due to adverse events. Logistic regression analysis showed that none of the included variables was a predictor of clinical response to cholestyramine. Conclusions Bile acid malabsorption occurs in a high proportion of patients suffering from chronic diarrhoea with functional characteristics. Systematic investigation of bile acid malabsorption should be included in the diagnostic algorithms of patients with chronic watery diarrhoea in the routine clinical practice. Absence of response to cholestyramine does not rule out bile acid diarrhoea.

Abstract Background Cancer cachexia is a debilitating metabolic syndrome contributing to cancer death. Organs other than the muscle may contribute to the pathogenesis of cancer cachexia. This work explores new mechanisms underlying hepatic alterations in cancer cachexia. Methods We used transcriptomics to reveal the hepatic gene expression profile in the colon carcinoma 26 cachectic mouse model. We performed bile acid, tissue mRNA, histological, biochemical, and western blot analyses. Two interventional studies were performed using a neutralizing interleukin 6 antibody and a bile acid sequestrant, cholestyramine. Our findings were evaluated in a cohort of 94 colorectal cancer patients with or without cachexia (43/51). Results In colon carcinoma 26 cachectic mice, we discovered alterations in five inflammatory pathways as well as in other pathways, including bile acid metabolism, fatty acid metabolism, and xenobiotic metabolism (normalized enrichment scores of −1.97, −2.16, and −1.34, respectively; all Padj

Abstract Background In people, bile acid diarrhoea is a prevalent complication of Crohn’s disease and diarrhoea-associated irritable bowel syndrome. Affected patients typically respond to bile acid sequestrants, such as cholestyramine, but human gastroenterologists often fail to recognize bile acid diarrhoea. Consequently, bile acid diarrhoea is regarded as an underrecognized and undertreated condition in human medicine. Due to lack of diagnostic tools, clinical response to bile acid sequestrants is often used to confirm a diagnosis of bile acid diarrhoea in people. Several recent studies have shown that bile acid dysmetabolism also occurs in dogs with chronic enteropathies. It has further been shown that dogs with chronic enteropathies have significantly decreased expression of a bile acid transport protein in the ileum compared to healthy dogs, which correlates with faecal bile acid dysmetabolism. Consequently, in spite of the lack of reports in the literature, bile acid diarrhoea is likely to exist in dogs as well. Case descriptions Two dogs, an 8-year old Rottweiler and a 4.5-year old Siberian Husky were evaluated for chronic watery diarrhoea. Neither dog responded to dietary trials, probiotics, cyclosporine, faecal microbial transplantations or metronidazole. One of the dogs responded to high daily doses of corticosteroids, which were however associated with unacceptable side effects. The other dog was refractory to all standard treatment protocols, including cyclosporine and corticosteroids. Since none of the dogs responded satisfactorily to standard treatment or modulation of the intestinal microbiome, a suspicion of possible bile acid diarrhoea was raised. Treatment with cholestyramine, a bile acid sequestrant was initiated and resulted in marked improvement of faecal consistency, frequency of defecation and activity level in both dogs. Conclusion This report presents two dogs with presumed bile acid diarrhoea that were successfully treated with cholestyramine. Therefore, bile acid diarrhoea should be considered as a possible diagnosis in dogs with treatment-refractory chronic diarrhoea.

Simple Summary: Annually, more than 450,000 people are diagnosed with pancreatic cancer worldwide with over 430,000 mortalities. Pancreatic ductal carcinoma (PDAC) accounts for around 80% of pancreatic cancer cases with an extremely high mortality rate. Emerging research has demonstrated that gut dysbiosis is closely associated with pancreatic cancer, while the underlying mechanisms remain elusive. In this study, we found that elevated levels of endotoxin (LPS) and bile acids were associated with malignant progression in Kras-driven pancreatic cancer mice. Importantly, oral administration of cationic resins to sequestrate intestinal endotoxins and bile acids efficiently attenuated tumor progression. Thus, sequestration of intestinal acidic toxins by oral administration of cationic resins may have potential as an intervention strategy for pancreatic malignancy. Pancreatic cancer is driven by risk factors such as diabetes and chronic pancreatic injury, which are further associated with gut dysbiosis. Intestinal toxins such as bile acids and bacterial endotoxin (LPS), in excess and persistence, can provoke chronic inflammation and tumorigenesis. Of interest is that many intestinal toxins are negatively charged acidic components in essence, which prompted us to test whether oral administration of cationic resin can deplete intestinal toxins and ameliorate pancreatic cancer. Here, we found that increased plasma levels of endotoxin and bile acids in Pdx1-Cre: LSL-KrasG12D/+ mice were associated with the transformation of the pancreatic ductal carcinoma (PDAC) state. Common bile-duct-ligation or LPS injection impeded autolysosomal flux, leading to Yap accumulation and malignant transformation. Conversely, oral administration of cholestyramine to sequestrate intestinal endotoxin and bile acids resumed autolysosomal flux for Yap degradation and attenuated metastatic incidence. Conversely, chloroquine treatment impaired autolysosomal flux and exacerbated malignance, showing jeopardization of p62/ Sqxtm1 turnover, leading to Yap accumulation, which is also consistent with overexpression of cystatin A (CSTA) in situ with pancreatic cancer cells and metastatic tumor. At cellular levels, chenodeoxycholic acid or LPS treatment activated the ligand–receptor-mediated AKT-mTOR pathway, resulting in autophagy-lysosomal stress for YAP accumulation and cellular dissemination. Thus, this work indicates a potential new strategy for intervention of pancreatic metastasis through sequestration of intestinal acidic toxins by oral administration of cationic resins. [ABSTRACT FROM AUTHOR]

Background and objectives Previously, we showed proof-of-concept in a mouse model that oral administration of cholestyramine prevented enrichment of daptomycin-resistant Enterococcus faecium in the gastrointestinal (GI) tract during daptomycin therapy. Cholestyramine binds daptomycin in the gut, which removes daptomycin selection pressure and so prevents the enrichment of resistant clones. Here, we investigated two open questions related to this approach: (i) can cholestyramine prevent the enrichment of diverse daptomycin mutations emerging de novo in the gut? and (ii) how does the timing of cholestyramine administration impact its ability to suppress resistance? Methodology Mice with GI E. faecium were treated with daptomycin with or without cholestyramine, and E. faecium was cultured from feces to measure changes in daptomycin susceptibility. A subset of clones was sequenced to investigate the genomic basis of daptomycin resistance. Results Cholestyramine prevented the enrichment of diverse resistance mutations that emerged de novo in daptomycin-treated mice. Whole-genome sequencing revealed that resistance emerged through multiple genetic pathways, with most candidate resistance mutations observed in the clsA gene. In addition, we observed that cholestyramine was most effective when administration started prior to the first dose of daptomycin. However, beginning cholestyramine after the first daptomycin dose reduced the frequency of resistant E. faecium compared to not using cholestyramine at all. Conclusions and implications Cholestyramine prevented the enrichment of diverse daptomycin-resistance mutations in intestinal E. faecium populations during daptomycin treatment, and it is a promising tool for managing the transmission of daptomycin-resistant E. faecium. [ABSTRACT FROM AUTHOR]

Abstract Background Most of the patients with type 1 and V hyperlipoproteinemia (HLP) present with symptoms and signs of acute pancreatitis due to marked elevation of triglycerides, but this baby presented with a chest infection, which was later diagnosed as type V HLP on laboratory workup. Case presentation We report a case of a 1 month and 15 days old baby boy, product of 2-nd degree consanguinity admitted to a nearby hospital with complaints of refusal to feed, cough and excessive crying. On examination his heart rate was 102 beats/min, respiratory rate was 55 breaths/min and temperature was within the normal range, provisional diagnosis of Pneumonia was made. His samples were tested at our laboratory, the lipid Profile at age of 1 month 15 days showed total cholesterol (TC) of 1400 mg/dl reference range (RR 885 mg/dl after dilution it was 31,400 mg/dl (RR 40 mg/dl) and low density cholesterol (LDL) of 200 mg/dl (RR

Graves' disease is the most common form of hyperthyroidism in children and adolescents. There are three primary lines of treatment for Graves' disease: antithyroid drugs (ATDs), thyroidectomy, and radioactive iodine. Ideally, patients should be rendered euthyroid before surgery to minimize complications. Here, we report on a 14-year-old girl with severe Graves' disease refractory to conventional treatments despite maximal therapy over 18 months. The patient received two types of ATDs, beta-blockers, and different courses of steroids; however, her thyroid function tests remained high. She was then given an adjunctive four-week course of cholestyramine, to which she responded well and became euthyroid. Subsequently, a thyroidectomy was performed without complications. Cholestyramine is an effective adjunctive treatment for refractory Graves' disease in adolescents., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alsaidalani et al.)

Background: Bile acid malabsorption (BAM) is a common entity in patients experiencing chronic watery diarrhea. However, literature suggests that BAM is underdiagnosed and undertreated. In many countries 75SeHCAT is the gold standard for diagnosing BAM (1-5). The aim of this retrospective study was to investigate the frequency of BAM using 75SeHCAT scintigraphy and the response to treatment with bile acid sequestrants., Methods: We retrospectively evaluated the clinical data of 420 patients who had a 75SeHCAT scan from January 2016 to January 2023. Electronic medical records were investigated for risk factors of BAM. BAM was defined as a 75SeHCAT retention of less than 15%. Response to bile acid sequestrants was evaluated based on outpatient clinical reports., Results: Median age at the time of 75SeHCAT test was 47 years (range 14-87). Out of 420 patients, 192 (46%) had a positive result for BAM. Cholecystectomy and ileal resection were significant predictors for BAM (p<0.001). BAM type 1 is statistically more likely to be more severe compared to type 2 (p<0.0001) and compared to type 3 (p=0.0021). In patients who fulfilled Rome IV criteria for IBS-D or functional diarrhea, 75 out of 121 (38%) tested positive for BAM. Overall, treatment with bile acid binders was effective in 76%., Conclusions: This retrospective study of patients who underwent SeHCAT scanning confirms that about 1/3 patients presenting with therapy-resistant chronic diarrhea in secondary care suffer from BAM. Including the test in clinical management protocols of chronic diarrhea allows early and quantitative diagnosis and treatment of BAM., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Purpose: Exemestane, a steroidal aromatase inhibitor, is an important therapeutic option in the treatment of post-menopausal hormone receptor positive breast cancer. Adverse effects include hot flashes and bone loss, but rarely is hepatotoxicity reported. We report a case of exemestane induced cholestatic liver injury following exemestane initiation. Case report: A now 77-year-old Caucasian female with primary biliary cirrhosis (PBC), and metastatic hormone receptor positive breast cancer originally diagnosed in 2000 who developed symptoms of pruritus, diarrhea, grade 2 transaminitis, and grade 1 hyperbilirubinemia three weeks after exemestane initiation. Management and outcome: Due to the patient's signs and symptoms, exemestane was discontinued and the patient was continued on cholestyramine until resolution of her laboratory abnormalities. Approximately a week after discontinuation, the patient was started and maintained on anastrozole without recurrence of her symptoms. Discussion: Hepatotoxicity with aromatase inhibitors have rarely been reported in clinical trials and to date, instances of exemestane induced hepatotoxicity has only been reported in two case reports. The patient's history of primary biliary cirrhosis may be an important risk factor for the development of hepatotoxicity from exemestane. [ABSTRACT FROM AUTHOR]

A two and a half year old spayed female Miniature Australian Shepherd presented to a Montana veterinary clinic with acute onset of anorexia, vomiting and depression. Two days prior, the dog was exposed to an algal bloom in a community lake.Within h, the animal became lethargic and anorexic, and progressed to severe depression and vomiting. A complete blood count and serum chemistry panel suggested acute hepatitis, and a severe coagulopathy was noted clinically. Feces from the affected dog were positive for the cyanobacterial biotoxin, microcystin-LA (217 ppb). The dog was hospitalized for eight days. Supportive therapy consisted of fluids, mucosal protectants,vitamins, antibiotics, and nutritional supplements. On day five of hospitalization, a bile acid sequestrant, cholestyramine, was administered orally. Rapid clinical improvement was noted within 48 h of initiating oral cholestyramine therapy. At 17 days post-exposure the dog was clinically normal, and remained clinically normal at re-check, one year post-exposure. To our knowledge, this is the first report of successful treatment of canine cyanobacterial (microcystin) toxicosis. Untreated microcystin intoxication is commonly fatal, and can result in significant liver damage in surviving animals. The clinical success of this case suggests that oral administration of cholestyramine, in combination with supportive therapy, could significantly reduce hospitalization time, cost-of-care and mortality for microcystin-poisoned animals.

Background: Bile acid malabsorption occurs in up to one third of patients with chronic diarrhoea of functional characteristics. The gold standard test for its diagnosis is the 75Selenium homocholic acid taurine (75SeHCAT) test. The aim of this work is to confirm previous data suggesting that bile acid malabsorption, diagnosed by 75Se-HCAT test, is the underlying cause of diarrhoea in a significant proportion of patients previously diagnosed with a functional disorder. In addition, we have analysed the clinical response of bile acid sequestrants in those patients with a bile acid diarrhoea diagnosis.Methods: This is a prospective, single-centre study including consecutive adult patients diagnosed with chronic diarrhoea of unknown origin and with functional characteristics; systematic rule out of common causes of chronic diarrhoea was performed before bile acid malabsorption evaluation by 75SeHCAT scanning. A retention percentage less than 10% was considered positive. Clinical response to cholestyramine was further evaluated in those patients with a positive diagnosis of bile acid diarrhoea RESULTS: 38 patients (20 male, mean age 37.5 years) were finally included. Twenty (52.6%) patients included had a positive 75SeHCAT test. Median body mass index was significantly higher in those patients. We did not find significant differences in other clinical or biochemical variables 75SeHCAT-positive and 75SeHCAT-negative groups. Only 6 of 17 (35.3%) patients responded to cholestyramine treatment; 10 patients did not have response or withdraw the drug due to adverse events. Logistic regression analysis showed that none of the included variables was a predictor of clinical response to cholestyramine.Conclusions: Bile acid malabsorption occurs in a high proportion of patients suffering from chronic diarrhoea with functional characteristics. Systematic investigation of bile acid malabsorption should be included in the diagnostic algorithms of patients with chronic watery diarrhoea in the routine clinical practice. Absence of response to cholestyramine does not rule out bile acid diarrhoea. [ABSTRACT FROM AUTHOR]

Sodium taurocholate co‐transporting polypeptide deficiency is a rare metabolic autosomal recessive condition resulting in critically elevated plasma bile acid levels. Hypercholanaemia in similar conditions such as intrahepatic cholestasis of pregnancy has been associated with an increased risk of adverse obstetric outcomes including stillbirth. We present the first case of Sodium taurocholate co‐transporting polypeptide deficiency in a current pregnancy in a patient with one previous stillbirth in the context of severe hypercholanaemia, where conventional treatments for cholestasis including ursodeoxycholic acid, rifampicin and cholestyramine were ineffective. Therapeutic plasma exchange and novel treatment with elobixibat were trialed with mixed results. The pregnancy resulted in an iatrogenic preterm delivery of a live infant at 32 weeks gestation. [ABSTRACT FROM AUTHOR]