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IntroductionFeatures of progressive familial intrahepatic cholestasis due to deficiency in FIC1 (encoded by ATP8B1; PFIC1) may include disrupted bile acid handling, pruritus, poor growth, other extrahepatic manifestations, and progressive liver disease that can necessitate liver transplantation (LT). While certain symptoms of PFIC1 may resolve after LT, patients frequently have persistent malabsorption, diarrhoea, and failure to thrive that can impact quality of life. In this case series, we present clinical details of 3 patients with PFIC1 and post-LT diarrhoea that impacted daily activities who received odevixibat, an ileal bile acid transporter inhibitor, in clinical practice.MethodsRetrospective patient data were collected by treating physicians using standardised forms and included demographic, clinical, and treatment information.ResultsData from 3 male patients with post-LT diarrhoea were collected. Prior to LT, patient symptoms included cholestasis, elevated serum bile acids, pruritus, dystrophy, and/or vitamin deficiencies. Patients experienced symptoms ranging from 1.8 to 4.8 years before LT and had unsatisfactory responses to conventional medical therapies. All patients underwent split LT, and common indications for LT included cholestasis, dystrophy, and intractable pruritus. After LT and prior to odevixibat initiation, patients had steatosis (patients 2 and 3), inflammation (patient 3), and diarrhoea (all patients). Patient 3 underwent surgical biliary diversion at 4 years post-LT, which resolved the steatosis and inflammation. Post-LT diarrhoea impacted the daily life and/or school functioning of all patients. Attempts to treat the diarrhoea with cholestyramine (patients 2 and 3) and Oralpädon (patients 1 and 2) were unsuccessful, with unresolved diarrhoea as the reason physicians cited for initiating odevixibat. After odevixibat initiation, patients had less-frequent and/or firmer stools at last available assessment, as well as improvements in aspects of daily life.ConclusionsIn patients with FIC1 deficiency, chologenic diarrhoea after LT, which may be due to physiologic bile acid levels in the FIC1-deficient bowel, can be a frequent and severe symptom. The real-world data presented here indicate that odevixibat can improve diarrhoea and quality of life in patients with PFIC1 and severe post-LT diarrhoea.

Cigarette smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide. We aimed to elucidate whether mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology. In different models of CS exposure, we investigated the effect on lung remodeling and cell signaling of restoring mitochondrial respiratory electron flow using alternative oxidase (AOX), which bypasses the cytochrome segment of the respiratory chain. AOX attenuated CS-induced lung tissue destruction and loss of function in mice exposed chronically to CS for 9 months. It preserved the cell viability of isolated mouse embryonic fibroblasts treated with CS condensate, limited the induction of apoptosis, and decreased the production of reactive oxygen species (ROS). In contrast, the early-phase inflammatory response induced by acute CS exposure of mouse lung, i.e., infiltration by macrophages and neutrophils and adverse signaling, was unaffected. The use of AOX allowed us to obtain novel pathomechanistic insights into CS-induced cell damage, mitochondrial ROS production, and lung remodeling. Our findings implicate mitochondrial respiratory inhibition as a key pathogenic mechanism of CS toxicity in the lung. We propose AOX as a novel tool to study CS-related lung remodeling and potentially to counteract CS-induced ROS production and cell damage.

Background/Objectives: To investigate the non-inferiority of preservative-free (PF) tafluprost eye drops (Taflotan sine[sup.®]) compared to latanoprost eye drops (Xalatan[sup.®]) in reducing mean 24 h intraocular pressure (IOP) on the second day of a diurnal IOP measurement. Methods: In this retrospective monocentric cohort study, patients suffering from primary open-angle glaucoma, ocular hypertension, normal tension glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma who had undergone inpatient diurnal IOP measurement were included. Patients of cohort 1 used latanoprost eye drops as monotherapy; patients of cohort 2 used preservative-free tafluprost eye drops. Data from 7 January 2005 to 9 July 2019, inclusive, were analyzed. Results: Ninety-three eyes were included (n = 59 latanoprost group, n = 34 PF tafluprost group). Mean 24 h IOP on day 2 was 14.1 mmHg (SD 2.3) in the latanoprost group and 14.5 mmHg (SD 3.4) in the PF tafluprost group. The non-inferiority of PF tafluprost eye drops to latanoprost eye drops in efficacy on mean 24 h IOP could not be confirmed (95% CI −1.5, ∞, p = 0.235). The average difference in mean IOP at the individual measurement times between both cohorts was 0.24 mmHg (SD 0.17) on day 1 and 0.44 mmHg (SD 0.6) on day 2. The non-inferiority of PF tafluprost compared to latanoprost regarding fluctuation range could not be demonstrated for both days. Conclusions: The data suggests slight inferiority of PF tafluprost to latanoprost eye drops. There were similar mean 24 h IOP values in both cohorts. PF tafluprost eye drops remain a useful treatment option as long as the patient’s individual target pressure is achieved. Furthermore, according to the literature, it is also a treatment option for patients with symptoms of ocular surface disease and other side effects affecting the ocular surface while receiving preservative-containing topical therapy.

Background/Objectives: To investigate the non-inferiority of preservative-free (PF) tafluprost eye drops (Taflotan sine®) compared to latanoprost eye drops (Xalatan®) in reducing mean 24 h intraocular pressure (IOP) on the second day of a diurnal IOP measurement. Methods: In this retrospective monocentric cohort study, patients suffering from primary open-angle glaucoma, ocular hypertension, normal tension glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma who had undergone inpatient diurnal IOP measurement were included. Patients of cohort 1 used latanoprost eye drops as monotherapy; patients of cohort 2 used preservative-free tafluprost eye drops. Data from 7 January 2005 to 9 July 2019, inclusive, were analyzed. Results: Ninety-three eyes were included (n = 59 latanoprost group, n = 34 PF tafluprost group). Mean 24 h IOP on day 2 was 14.1 mmHg (SD 2.3) in the latanoprost group and 14.5 mmHg (SD 3.4) in the PF tafluprost group. The non-inferiority of PF tafluprost eye drops to latanoprost eye drops in efficacy on mean 24 h IOP could not be confirmed (95% CI −1.5, ∞, p = 0.235). The average difference in mean IOP at the individual measurement times between both cohorts was 0.24 mmHg (SD 0.17) on day 1 and 0.44 mmHg (SD 0.6) on day 2. The non-inferiority of PF tafluprost compared to latanoprost regarding fluctuation range could not be demonstrated for both days. Conclusions: The data suggests slight inferiority of PF tafluprost to latanoprost eye drops. There were similar mean 24 h IOP values in both cohorts. PF tafluprost eye drops remain a useful treatment option as long as the patient’s individual target pressure is achieved. Furthermore, according to the literature, it is also a treatment option for patients with symptoms of ocular surface disease and other side effects affecting the ocular surface while receiving preservative-containing topical therapy.