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Introduction: Gallstones are a known adverse effect of somatostatin analogs, but the exact incidence and clinical implications are unknown. Objectives: The aim of this study was to investigate the incidence of gallstones on imaging and related complications in unbiased trial data. Methods: Data from the DIPAK 1 trial, in which 305 polycystic kidney disease patients were randomized to standard of care (SoC) or lanreotide for 120 weeks, were used. Magnetic resonance imaging (MRI) was performed at baseline and end of treatment and was assessed for the presence, number, and size of gallstones. For all patients who had gallstones at the end of the trial, we obtained follow-up after the trial. Results: Of 249 patients with data available, 11 patients randomized to lanreotide and four randomized to SoC had gallstones at baseline. During the study, new gallstones were formed in 19/124 patients using lanreotide (15%) and 1/125 patients receiving SoC (1%). The odds ratio for gallstone formation with lanreotide use was 25.9 (95% confidence interval 3.37–198.8; p < 0.001). Gallstones during lanreotide treatment were multiple (> 20 stones in 69% of patients) and small (≤ 3 mm in 63% of patients). Of the 19 patients with incident gallstones during lanreotide treatment, 9 experienced gallstone-associated complications, 8 of whom experienced gallstone-associated complications after discontinuation of treatment (median time after discontinuation 2.5 years). In patients with gallstones at baseline and in patients receiving SoC, no complications occurred. Conclusions: Treatment with a somatostatin analog leads to the formation of multiple, small gallstones that are associated with severe complications, especially after discontinuation of therapy. Clinical Trial Registry Website and Trial Number: ClinicalTrials.gov (https://clinicaltrials.gov); NCT01616927. [ABSTRACT FROM AUTHOR]

Genome-wide association studies revealed that loss-of-function mutations in protein tyrosine phosphatase non-receptor type 2 (PTPN2) increase the risk of developing chronic immune diseases, such as inflammatory bowel disease (IBD) and celiac disease. These conditions are associated with increased intestinal permeability as an early etiological event. The aim of this study was to examine the consequences of deficient activity of the PTPN2 gene product, T cell protein tyrosine phosphatase (TCPTP), on intestinal barrier function and tight junction organization in vivo and in vitro. Here, we demonstrate that TCPTP protected against intestinal barrier dysfunction induced by the inflammatory cytokine IFN-γ by 2 mechanisms: it maintained localization of zonula occludens 1 and occludin at apical tight junctions and restricted both expression and insertion of the cation pore-forming transmembrane protein, claudin-2, at tight junctions through upregulation of the inhibitory cysteine protease, matriptase. We also confirmed that the loss-of-function PTPN2 rs1893217 SNP was associated with increased intestinal claudin-2 expression in patients with IBD. Moreover, elevated claudin-2 levels and paracellular electrolyte flux in TCPTP-deficient intestinal epithelial cells were normalized by recombinant matriptase. Our findings uncover distinct and critical roles for epithelial TCPTP in preserving intestinal barrier integrity, thereby proposing a mechanism by which PTPN2 mutations contribute to IBD. [ABSTRACT FROM AUTHOR]

Background: The EASL cystic liver disease guideline states that drug penetration at the site of infection (liver cyst) is essential for successful treatment, but pharmacokinetic (PK) data on cyst penetration are limited., Objectives: This study aims to investigate tissue penetration of four antibiotics in non-infected liver cysts and explores influencing factors., Methods: We performed a prospective, randomized single-dose PK-study. Before percutaneous drainage of a non-infected liver cyst, an intravenous (IV) dose of either ciprofloxacin and piperacillin/tazobactam (group 1); or co-trimoxazole (trimethoprim/sulfamethoxazole) and doxycycline (group 2) was given. Cyst fluid was collected during drainage. Blood samples were obtained before, during and after drainage (within 12 h). Drug concentrations were measured with a validated LC-MS/MS. Primary outcome was liver cyst penetration, defined as the cyst-fluid-to-plasma concentration ratio (%) expressed as median (IQR)., Results: We included 20 patients, and 21 liver cysts were drained (group 1: n = 11, group 2: n = 10). Median drained cyst volume was 700 mL. Median time between infusion and drainage was 139 min (IQR 120-188 min). Median cyst-fluid-to-plasma concentration ratio was 4.2% (IQR 1.6%-8.9%) for ciprofloxacin, 0.3% (IQR 0.0%-1.3%) for piperacillin, 0.2% (IQR 0.0%-1.3%) for tazobactam, 12.2% (IQR 6.3%-16.1%) for trimethoprim, 0.4% (IQR 0.2%-3.8%) for sulfamethoxazole and 1.6% (IQR 0.9%-2.3%) for doxycycline. Time between trimethoprim infusion and cyst drainage was correlated with increased cyst-fluid-to-plasma concentration ratio (P < 0.01)., Conclusions: Trimethoprim and ciprofloxacin have the highest penetration ratios amongst antibiotics tested. We found that liver cyst penetration varies widely between drugs after a single IV dose., Clinical Trial Number: NTR8499The trial was originally registered in the Netherlands Trial Register (ID: NL7290), which was converted to the International Clinical Trials Registry Platform in 2022., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background & Aims: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting., Methods: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up., Results: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5)., Conclusions: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia., Clinicaltrials: gov, NCT02384122., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Treatment of infections with intravenous antibiotics does not always require hospital care; specialized home care nurses can administer parenteral treatment at home. Dedicated Outpatient Parenteral Antimicrobial Therapy (OPAT) teams are emerging in an increasing number of hospitals in the Netherlands to supervise treatment selection and provide safety monitoring for patients with home treatment. This specialized, nurse driven team facilitates home treatment by collaborating with infectious disease specialists, pharmacy and home care teams, as well as the patient and treating physician. Demand for OPAT treatment is increasing, but currently a structural financial endorsement is lacking in the Netherlands. A solid financial structure will be essential to ensure safe and effective parenteral antimicrobial therapy at home, which can relieve the strain on hospital care.

Background: Polycystic liver disease can cause severe symptomatic hepatomegaly. Combined partial hepatectomy and cyst fenestration can be performed to reduce liver volume and symptom burden. We aimed to assess change in symptom relief and quality of life 6 months after partial hepatectomy and cyst fenestration in polycystic liver disease patients., Method: We established a prospective cohort between 2014 and 2018 at a referral center in the United States. Patients who underwent partial hepatectomy and cyst fenestration for volume-related symptoms were included. Primary outcome was change in polycystic liver disease-related symptoms, measured with Polycystic Liver Disease Questionnaire. Secondary outcomes were change in liver volume (computed tomography/ magnetic resonance imaging) and change in quality of life, measured with the 12-Item Short Form Survey and the EuroQoL Visual Analogue Scale. Questionnaire scores range from 0 to 100 and were assessed before and 6 months after partial hepatectomy and cyst fenestration. Surgical complications were scored according to Clavien-Dindo (grade 1 to 5)., Results: We included 18 patients (mean age 52 years, 82% female). Partial hepatectomy and cyst fenestration reduced median liver volume (4,917 to 2,120 mL). Symptoms, measured with Polycystic Liver Disease Questionnaire, decreased (76.9 to 34.8 points; P < .001) 6 months after surgery; 15/16 symptoms declined after treatment, with the most impact seen on early satiety and dyspnea. Quality of life also improved after surgery: median physical and mental component scales of the 12-Item Short Form Survey and EuroQoL Visual Analog Scale increased (24.9 to 45.7, P = .004; 40.5 to 55.4, P = .02; and 40.0 to 72.5, P = .003). Major complications (grade 4) occurred in 2 patients. There was no procedure-related mortality., Conclusion: Partial hepatectomy and cyst fenestration substantially improves symptom burden and quality of life in highly symptomatic polycystic liver disease patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The association between estrogen-containing oral contraceptives and history of pregnancies with disease severity in women with polycystic liver disease (PLD) is unclear. We performed a cross-sectional cohort study to assess this association by selecting female patients with PLD of which imaging was available prior to any liver volume-reducing therapy. Patients received a questionnaire to collect detailed information on estrogen use and pregnancies. Preplanned subgroup analyses were performed on premenopausal and postmenopausal patients. The questionnaire was returned by 287 of 360 selected patients (80%). There was no significant association between estrogen-containing oral contraceptives and height-adjusted total liver volume (hTLV) in the total group (P = 0.06) and postmenopausal subgroup (P = 0.7). By contrast, each year of exposure corresponds with a 1.45% higher hTLV (P = 0.02) in the premenopausal subgroup, equivalent to a 15.5% higher hTLV for every 10 years of use. Pregnancy duration was not associated with hTLV. In conclusion, patients with PLD should avoid exogenous estrogens., (© 2019 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)