Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.

Background And Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study.

A comparative experimental investigation of dynamic viscosity of ZrO/DW and SiC/DW nanofluids: Characterization, rheological behavior, and development of new correlation.

In general, A nanofluid is a substance in which solids and fluids are mixed. The nano-powder of zirconium oxide (ZrO) and silicon carbide (SiC) was dispersed into the distilled water (DW) using the widely adopted two-step technique. A Brookfield viscometer was used to measure the viscosity of the nanoparticles of ZrO/DW and SiC/DW, where the temperature ranged between 20 and 60 °C and different solid volume fractions of 0.

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor.

Background And Aims: Refractory pruritus and other complications of cholestasis are indications for liver transplantation (LT) in patients with Alagille syndrome (ALGS). We evaluated predictors of event-free survival and transplant-free survival in patients with ALGS treated with maralixibat (MRX), an ileal bile acid transporter inhibitor.

Approach And Results: We assessed patients with ALGS from 3 clinical trials of MRX with up to 6 years of follow-up.

Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study.

Background: Primary sclerosing cholangitis (PSC) is frequently associated with pruritus, which significantly impairs quality of life. Maralixibat is a selective ileal bile acid transporter (IBAT) inhibitor that lowers circulating bile acid (BA) levels and reduces pruritus in cholestatic liver diseases. This is the first proof-of-concept study of IBAT inhibition in PSC.

Overview of radiotherapy-induced chronic pain in childhood cancer survivors: A narrative review.

Radiotherapy is an important aspect of oncological treatment in several childhood cancers. However, radiotherapy is known to have numerous side effects, including detrimental effects on growth, neurocognitive impairment, and the development of secondary malignancies. One less studied long-term side effect of pediatric radiotherapy treatment is chronic pain.

Protocol to Study West Nile Virus Infection in Brain Slices In Vitro.

Ex vivo slice cultures of the brain tissue can maintain the cytoarchitecture of the central nervous system (CNS), which allows a thorough understanding of the functions of multiple interconnected cells in a culture system that closely resembles the in vivo environment. Additionally, slice cultures of the brain tissue are advantageous in tracking complex connectivity between neurons and glia both under normal and pathologic conditions, which is not possible in in vitro cell lines. Here, we describe the method of preparing ex vivo slice culture from the mouse cerebellum and the protocol of studying the effects of West Nile virus infection on cerebellar cells.

Serum Bile Acid Profiling and Mixed Model Analysis Reveal Biomarkers Associated with Pruritus Reduction in Maralixibat-Treated Patients with BSEP Deficiency.

Progressive familial intrahepatic cholestasis (PFIC) is a debilitating disease manifest by severe cholestasis, intractable pruritus and growth delay that ultimately leads to liver failure or transplantation. Maralixibat (MRX) was recently approved for the treatment of cholestatic pruritus in patients with Alagille syndrome. The aim of this study was to determine whether specific changes in the composition of the serum bile acid metabolome could predict pruritus response to treatment.

Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life.

Objective: The objective of this study was to assess the impact of treatment response to the ileal bile acid transporter inhibitor maralixibat on health-related quality of life (HRQoL) in children with Alagille syndrome.

Study Design: This analysis used data from the ICONIC trial, a phase 2 study with a 4-week double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille syndrome with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in the Itch-Reported Outcome (Observer) score, from baseline to week 48.

Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study.

Children with progressive familial intrahepatic cholestasis, including bile salt export pump (BSEP) and familial intrahepatic cholestasis-associated protein 1 (FIC1) deficiencies, suffer debilitating cholestatic pruritus that adversely affects growth and quality of life (QoL). Reliance on surgical interventions, including liver transplantation, highlights the unmet therapeutic need. INDIGO was an open-label, Phase 2, international, long-term study to assess the efficacy and safety of maralixibat in children with FIC1 or BSEP deficiencies.

Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study.

Background: Alagille syndrome is a rare genetic disease that often presents with severe cholestasis and pruritus. There are no approved drugs for management. Maralixibat, an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation.

Parental bereavement - impact of death of neonates and children under 12 years on personhood of parents: a systematic scoping review.

Background: Losing a child tragically impacts the well-being and functioning of parents. With these effects extending beyond emotional, physical morbidity and compromising self-perceptions, appropriate, longitudinal, timely and personalised support is key to effective care of bereaved parents. However, in the absence of a comprehensive understanding of parental bereavement, effective support of bereaved parents remains suboptimal.

Comparison of ADAPT, FIB-4 and APRI as non-invasive predictors of liver fibrosis and NASH within the CENTAUR screening population.

Background & Aims: The development of accurate non-invasive tests to detect and measure the extent of fibrosis and disease activity in patients with non-alcoholic steatohepatitis (NASH) - the progressive phenotype of non-alcoholic fatty liver disease (NAFLD) - is of great clinical importance. Herein, we aimed to validate the performance of PRO-C3 and ADAPT for the detection of moderate/severe fibrosis within the CENTAUR screening population.

Methods: PRO-C3 was assessed in plasma from the screening population of the phase IIb CENTAUR study (NCT02217475) in adults with NASH and liver fibrosis.

Impact of Dying Neonates on Doctors' and Nurses' Personhood: A Systematic Scoping Review.

Context: Caring for dying neonates is distressing for healthcare professionals (HCP)s. Yet, the extent of these effects is poorly understood, compromising support of HCPs. To better understand and support HCPs, a systematic scoping review (SSR) of prevailing data is proposed.

Estimation of x-ray radiation related cancers in US dental offices: Is it worth the risk?

Objectives: The objective of this study was to estimate the possible number of cancer cases produced during 2019 in US dental offices from radiography, estimate the possible reduction in those rates resulting from use of intraoral rectangular collimation and selection criteria, and determine the frequency and quality of website radiation risk information and informed consent forms.

Study Design: An analysis of dental radiation examinations in 2014 to 2015 US national survey data, Nationwide Evaluation of X-ray Trends, and National Council on Radiation Protection and Measurements surveys was performed, in addition to an analysis of 2008 to 2020 Journal of Clinical Orthodontics national orthodontic surveys for radiographic examination frequencies. Lifetime attributable cancer risk estimates from US and European studies were used to generate the total dental and orthodontic office cancer totals.

Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease with no approved treatments. C-C chemokine receptor types 2 and 5 (CCR2/CCR5) play an important role in inflammation and fibrosis and are potential therapeutic targets for PSC. We evaluated the efficacy and safety of cenicriviroc (CVC), a dual antagonist of CCR2 and CCR5, for the treatment of PSC.

Tumor Necrosis Factor-Alpha Signaling May Contribute to Chronic West Nile Virus Post-infectious Proinflammatory State.

West Nile virus (WNV) causes a spectrum of human disease ranging from a febrile illness (WNV fever) to severe neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis). Since WNV gained entry into North America in 1999, clinicians caring for WNV survivors have observed persistent neurological symptoms occurring long-after the production of neutralizing antibodies and clearance of the virus. Accordingly, alternative pathogeneses other than direct viral invasion have been hypothesized to explain these post-infectious symptoms.

Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications.

West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999.

Malignant Glial Neuronal Tumors After West Nile Virus Neuroinvasive Disease: A Coincidence or a Clue?

Following acute West Nile virus (WNV) infection in humans, there is upregulation of pro-inflammatory molecules that promote neuroinflammation, including S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), and osteopontin (OPN). The effects of S100B and HMGB1 are transduced by the receptor for advanced glycation end products (RAGE). Interestingly, the same immunoregulatory proteins that fuel neuroinflammation can also promote tumorigenesis.

Particulate production during debonding of fixed appliances: Laboratory investigation and randomized clinical trial to assess the effect of using flash-free ceramic brackets.

Introduction: The aim of this laboratory and randomized clinical trial was to investigate particulate production at debonding and enamel clean-up following the use of flash-free ceramic brackets and to compare them with non-flash-free metal and ceramic brackets.

Methods: In the laboratory study, brackets were bonded to bovine teeth. After 24 hours of immersion in water, the brackets were debonded, the adhesive remnant scores noted, and the enamel cleaned with the use of rotary instruments.

Current strategies for therapeutic drug delivery after traumatic CNS injury.

Therapeutic strategies for traumatic injuries in the central nervous system (CNS) are largely limited to the efficiency of drug delivery. Despite the disrupted blood-CNS barrier during the early phase after injury, the drug administration faces a variety of obstacles derived from homeostatic imbalance at the injury site. In the late phase after CNS injury, the restoration of the blood-CNS barrier integrity varies depending on the injury severity resulting in inconsistent delivery of therapeutics.

Differential Expression of Genes Related to Innate Immune Responses in Ex Vivo Spinal Cord and Cerebellar Slice Cultures Infected with West Nile Virus.

West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage.

Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits.

A small percentage of babies born to Zika virus (ZIKV)-infected mothers manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood.