The Future of CMC Regulatory Submissions: Streamlining Activities Using Structured Content and Data Management.

Recent advancements in data engineering, data science, and secure cloud storage can transform the current state of global Chemistry, Manufacturing, and Controls (CMC) regulatory activities to automated online digital processes. Modernizing regulatory activities will facilitate simultaneous global submissions and concurrent collaborative reviews, significantly reducing global licensing timelines and variability in globally registered product details. This article describes advancements made within the pharmaceutical industry from theoretical concepts to utilization of structured content and data in CMC submissions.

Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease.

Background: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen.

Objective: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks.

Methods: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo).

Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease.

We investigated the effects of glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease, using intermittent intraputamenal convection-enhanced delivery via a skull-mounted transcutaneous port as a novel administration paradigm to potentially afford putamen-wide therapeutic delivery. This was a single-centre, randomized, double-blind, placebo-controlled trial. Patients were 35-75 years old, had motor symptoms for 5 or more years, and presented with moderate disease severity in the OFF state [Hoehn and Yahr stage 2-3 and Unified Parkinson's Disease Rating Scale motor score (part III) (UPDRS-III) between 25 and 45] and motor fluctuations.

Human Parechovirus as a Cause of Isolated Pediatric Acute Liver Failure.

Among infants, almost half of acute liver failure cases are classified as indeterminate, whereas only a small number of cases show a documented viral infection. We present the first reported case of isolated acute hepatic failure in an infant in the setting of a human parechovirus (HPeV) infection. HPeV also may have been contributory to the posttransplant complication of 2 intussusceptions.

Pre-Hepatectomy Assessment of Bile Transporter Expression by Gadoxetic Acid-Enhanced MRI in a Rat Model of Liver Cirrhosis.

Background: Gadoxetic acid is a liver-specific intravenous T1 magnetic resonance (MR) contrast agent that is excreted via the hepatobiliary system. We hypothesize that hepatocyte expressions of bile transporters (OATP1 and MRP2) correlate with dynamic profile of Gadoxetic acid enhanced (GE)-MR imaging (MRI).

Methods: Two groups of rats, control (n = 6) and cirrhosis (n = 12), received gadoxetic acid enhanced MRI followed by 70% hepatectomy.

Hydroxocobalamin for Vasoplegic Syndrome in Liver Transplantation: Restoration of Blood Pressure Without Vasospasm.

Systemic vasoplegia is common in patients undergoing liver transplantation. In this report, we present a case in which treatment with conventional vasopressors caused peripheral arterial spasm, rendering arterial blood pressure monitoring impossible. Administration of methylene blue resolved the vasospasm; however, concern for toxic dose requirements limited its use.

Portal Steal Syndrome After Full-Size Deceased Donor Liver Transplantation.

Successful liver transplantation typically results in an immediate decrease in intrahepatic resistance accompanied by an initial increased hepatopedal portal flow. Within a short period of time, the portal hypertension resolves and the variceal shunts involute. However, in situations in which intrahepatic vascular resistance to venous flow remains elevated, significant hepatofugal portal flow may continue through persistent mesenteric shunts.

Pathologic sequelae of allosensitization in liver transplantation.

The long-term impact of allosensitization between ABO compatible donor/recipient pairs in liver transplantation is unclear. Accumulating clinical evidence suggests that donor-specific antibody formation may lead to antibody-mediated rejection and is causally linked to pathologic injury, graft loss, and death. Although this immune-mediated graft dysfunction is increasingly being associated with poor outcomes, the specific pathologic sequelae are not defined.

Changing paradigms in organ preservation and resuscitation.

Purpose Of Review: Shortage of donor organs has increased consideration for use of historically excluded grafts. Ex-vivo machine perfusion is an emerging technology that holds the potential for organ resuscitation and reconditioning, potentially increasing the quality and number of organs available for transplantation. This article aims to review the recent advances in machine perfusion and organ preservation solutions.

Global discovery of colonization determinants in the squid symbiont Vibrio fischeri.

Animal epithelial tissue becomes reproducibly colonized by specific environmental bacteria. The bacteria (microbiota) perform critical functions for the host's tissue development, immune system development, and nutrition; yet the processes by which bacterial diversity in the environment is selected to assemble the correct communities in the host are unclear. To understand the molecular determinants of microbiota selection, we examined colonization of a simplified model in which the light organ of Euprymna scolopes squid is colonized exclusively by Vibrio fischeri bacteria.

Renal mucormycosis: a rare and potentially lethal complication of kidney transplantation.

Renal mucormycosis is a rare and potentially lethal complication of kidney transplantation. We describe two cases of renal mucormycosis following deceased donor kidney transplantation. This is the second report of renal mucormycosis following kidney transplantation in the United States, and the first case of renal mucormycosis infection presumed to be of recipient origin.

New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications.

Improved neonatal medical care and renal replacement technology have improved the long-term survival of patients with ARPKD. Ten-yr survival of those surviving the first year of life is reported to be 82% and is continuing to improve further. However, despite increases in overall survival and improved treatment of systemic hypertension and other complications of their renal disease, nearly 50% of survivors will develop ESRD within the first decade of life.

Donor and recipient BKV-specific IgG antibody and posttransplantation BKV infection: a prospective single-center study.

Background: The study evaluated the relationship of pretransplantation BK virus (BKV)-specific donor and recipient serostatus to posttransplantation BKV infection.

Methods: Two hundred forty adult de novo kidney-only recipients and 15 pediatric recipients were prospectively enrolled and followed for a minimum of 18 months. Pretransplantation BKV serostatus was available for 192 adult and 11 pediatric donor-recipient pairs.

Australian blue-collar men's health and well-being: contextual issues for workplace health promotion interventions.

In Australia, blue-collar workers are predominantly male and form a unique and large (approximately 30%) subset of the Australian workforce. They exhibit particular health-related issues and, in comparison to other groups, often a lack of health promoting behavior. This article briefly discusses the Australian context and some of the key health issues blue-collar men face, in particular as it relates to construction workers.

Dyskalaemia following diffuse axonal injury: case report and review of the literature.

Traumatic brain injury, and its management, commonly causes derangements in potassium balance. There are a number of recognised causative factors including head trauma, hypothermia and iatrogenic factors such as pharmacological agents and permissive cooling. We describe a case of a 19-year-old man with a severe traumatic brain injury.

Anomalous hepatic vein anatomy of left lateral section grafts and customized unification venoplasty for pediatric living donor liver transplantation.

In liver transplantation, a left lateral section (LLS) graft may have an unusual variant left hepatic vein (LHV) anatomy. This study was designed to analyze the incidence of unusual LHV variants and to determine technical methods for effective reconstruction in infant recipients weighing approximately 10 kg or less. The study comprised 3 parts: an LHV variation analysis, a simulation-based design for the technical modification of graft LHV venoplasty, and its clinical application.

Anaphylaxis on reperfusion during liver transplantation with coagulopathy.

We present a case in which anaphylaxis on hepatic reperfusion during liver transplantation presented only with hypotension and coagulopathy. There were no cutaneous manifestations or clinical features distinguishing anaphylaxis from postreperfusion syndrome. The recipient regularly consumed seafood, and the organ donor died of anaphylaxis to shellfish.

Diagnostic accuracy of solid phase HLA antibody assays for prediction of crossmatch strength.

Solid phase antibody assays are increasingly used to provide quantitative measures of donor-specific HLA antibodies for assessment of pretransplant risk, although cell-based crossmatches continue to serve as gold standards for determination of donor HLA antibody strength. This study determined the ability of HLA antibody solid phase assays to predict the strength of cell-based flow cytometric (FC) and complement-dependent cytotoxicity (CDC) crossmatches. Eighty-two recipient/donors pairs were analyzed using receiver operating characteristic (ROC) curve analyses to determine the accuracy of donor-specific median fluorescence intensity values (Σ MFI) from single antigen bead assays for predicting strong FC and CDC crossmatches.

Draft genome sequence of Vibrio fischeri SR5, a strain isolated from the light organ of the Mediterranean squid Sepiola robusta.

Here, we describe the draft genome sequence of Vibrio fischeri SR5, a squid symbiotic isolate from Sepiola robusta in the Mediterranean Sea. This 4.3-Mbp genome sequence represents the first V.