Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multinational WE-ROCK Collaborative.

Rationale & Objective: There are limited studies describing the epidemiology and outcomes in children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival.

Study Design: Retrospective multicenter cohort study.

Prevention and management of CMV infection in pediatric solid organ transplant recipients.

Human cytomegalovirus (CMV) remains one of the most common opportunistic infections following solid organ transplantation in children. CMV causes morbidity and mortality through direct tissue-invasive disease and indirect immunomodulatory effects. In recent years, several new agents have emerged for the prevention and treatment of CMV disease in solid organ transplant recipients.

The role of pharmaceutical industry in building resilient health system.

Objectives: This study explores the interrelationship among the current sustainability agenda of the pharmaceutical industry, based on the United Nation sustainable development goals (SDGs), the elements of the Joint External Evaluation (JEE) tool, and the triad components of the One Health approach.

Methods: A cross-walk exercise was conducted to identify commonalities among SDGs, JEE assessment tool, and One Health approach. An in-depth study of 10 global pharmaceutical firms' corporate sustainability reports and COVID-19 response plan for 2019-2020 was also conducted.

BK DNAemia in pediatric kidney transplant recipients: Predictors and outcomes.

Background: Pediatric data on risk factors and the clinical course of BK DNAemia are limited. We aimed to determine the effects of BK DNAemia on transplant outcomes and delineate the safety and efficacy of various treatment approaches.

Methods: This retrospective-cohort study included 161 transplants (age ≤ 21 years) performed at a single center between 1/1/2012 and 1/1/2020.

Anemia in Pediatric Kidney Transplant Recipients-Etiologies and Management.

Posttransplant anemia (PTA) is a common complication of pediatric kidney transplantation, with a prevalence ranging from 22 to 85%. PTA is categorized as early (within 6 months posttransplant) and late (>6 months posttransplant). Early PTA is typically associated with surgical blood losses and iron deficiency.

Clinical and Nonclinical Disposition and In Vitro Drug-Drug Interaction Potential of Felcisetrag, a Highly Selective and Potent 5-HT Receptor Agonist.

Background And Objective: Felcisetrag (previously TAK-954 or TD-8954) is a highly selective and potent 5-HT receptor agonist in clinical development for prophylaxis and treatment of postoperative gastrointestinal dysfunction (POGD). The rat, dog, and human absorption, distribution, metabolism, and excretion (ADME) properties of felcisetrag were investigated.

Methods: The metabolism and victim and perpetrator drug interaction potentials towards cytochrome P450s (CYP) and transporters were determined using in vitro models.

Evaluation of the Pharmacokinetics of Felcisetrag (TAK-954), a 5-HT Receptor Agonist, in the Presence and Absence of Itraconazole, a Potent CYP3A4 Inhibitor.

The 5-hydroxytryptamine type-4 receptor agonist felcisetrag (TAK-954) is being investigated for improving gastrointestinal motility in postoperative gastrointestinal dysfunction. Polypharmacy often occurs in this setting, and as in vitro data indicate, felcisetrag is primarily metabolized by cytochrome P450 (CYP) 3A4, its CYP3A4-mediated drug-drug interaction potential requires consideration. This phase 1, fixed-sequence, open-label, crossover trial (ClinicalTrials.

Antineutrophilic cytoplasmic antibody-associated vasculitis and the kidney.

Purpose Of Review: The purpose of this review is to highlight recent studies that have emerged on the topic of ANCA-associated vasculitis with some historical context. The review also discusses how the adult data is relevant to pediatric patients.

Recent Findings: Pediatric studies on AAV are lacking.

Steroid avoidance/withdrawal and maintenance immunosuppression in pediatric kidney transplantation.

Background: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years.

Method/objective: This comprehensive review aims to discuss steroid-related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients.

Induction and maintenance immunosuppression in pediatric kidney transplantation-Advances and controversies.

Advances in immunosuppression have improved graft survival in pediatric kidney transplant recipients; however, treatment-related toxicities need to be balanced against the possibility of graft rejection. Several immunosuppressive agents are available for use in transplant recipients; however, the optimal combinations of agents remain unclear, resulting in variations in institutional protocols. Lymphocyte-depleting antibodies, specifically ATG, are the most common induction agent used for pediatric kidney transplantation in the US.

Evaluation of the drug-drug interaction potential for trazpiroben (TAK-906), a D/D receptor antagonist for gastroparesis, towards cytochrome P450s and transporters.

Trazpiroben (TAK-906), a peripherally selective dopamine D2/D3 receptor antagonist, is being developed for the treatment of patients with gastroparesis. The potential of trazpiroben to act as a perpetrator or a victim for cytochrome P450 (CYP)- or transporter- mediated drug-drug interactions (DDIs) was evaluated following the latest regulatory guidelines.In vitro studies revealed that trazpiroben is metabolised mainly through a non-CYP pathway (56.

Efficacy of myoinositol in treatment of gestational diabetes mellitus in Asian Indian women: A pilot randomized clinical trial.

Objective: To compare efficacy of myoinositol as an adjuvant to dietary modification for treatment of gestational diabetes mellitus in Asian Indian women compared to controls.

Study Design: Setting: This pilot randomized open label trial was conducted in a single antenatal clinic in India.

Subjects: One hundred women with singleton pregnancy and gestational diabetes diagnosed between 14-28 weeks' gestation were included.

Spontaneous chondrosarcoma in Wistar rat: a case report.

In rats, chondrosarcomas have been reported to occur both spontaneously and secondary to chemical induction. In a rare case, a spontaneous chondrosarcoma was identified in the deformed femur of a young male Wistar rat. After gross examination of the femur and knee joint, tissue was collected and preserved.

Single-cell analysis of autophagy activity in normal and de novo transformed human mammary cells.

Assessment of autophagy activity has historically been limited to investigations of fixed tissue or bulk cell populations. To address questions of heterogeneity and relate measurements to functional properties of viable cells isolated from primary tissue, we created a lentiviral (RFP-GFP-MAP1LC3B) vector that allows the autophagosome and autolysosome content of transduced cells to be monitored at the single-cell level. Use of this strategy to analyze purified subsets of normal human mammary cells showed that both the luminal progenitor-containing (LP) subset and the basal cells (BCs) display highly variable but overall similar autophagic flux activity despite differences suggested by measurements of the proteins responsible (i.

Burosumab in X-linked hypophosphatemia and perspective for chronic kidney disease.

Purpose Of Review: Perturbations in phosphate and vitamin D homeostasis impacts skeletal health in children and adults. Study of inherited and acquired hypophosphatemic syndromes led to the discovery of fibroblast growth factor 23 (FGF23) as a potent regulator of phosphate and vitamin D metabolism, and advanced our understanding of the pathophysiology of mineral and bone disorder in chronic kidney disease (CKD-MBD). Here, we review a recently approved therapy for patients with X-linked hypophosphatemia (XLH) using a novel anti-FGF23 antibody, burosumab, and discuss the implications of such targeted therapy in CKD.

Biotransformation Pathways and Metabolite Profiles of Oral [C]Alisertib (MLN8237), an Investigational Aurora A Kinase Inhibitor, in Patients with Advanced Solid Tumors.

Alisertib (MLN8237) is an investigational, orally available, selective aurora A kinase inhibitor in clinical development for the treatment of solid tumors and hematologic malignancies. This metabolic profiling analysis was conducted as part of a broader phase 1 study evaluating mass balance, pharmacokinetics, metabolism, and routes of excretion of alisertib following a single 35-mg dose of [C]alisertib oral solution (∼80 μCi) in three patients with advanced malignancies. On average, 87.

Initiation of human mammary cell tumorigenesis by mutant KRAS requires YAP inactivation.

High YAP activity is associated with poor prognosis human breast cancers, but its role during the initial stage of mammary cell transformation is unknown. To address this question, we designed experiments that exploit the ability of KRAS-transduced subsets of freshly isolated normal human mammary cells to form invasive tumors rapidly and efficiently when transplanted into immunodeficient mice. Initial examination of the newly developing tumors thus generated revealed a consistent marked loss of nuclear YAP, independent of the initial primary human mammary cell type transduced.

Expression of p-16, Ki-67 and p-53 markers in dysplastic and malignant lesions of the oral cavity and oropharynx.

Background: Understanding the markers for predicting degree of dysplasia and progression to malignancy can help early identification and prompt treatment of patients with oral cancers. In this study, we aim to identify and characterize different tumor suppressor genes such as p-53 and p-16 and proliferation marker Ki-67 in defining stages of dysplasia of oral mucosa and grading of tumor.

Settings And Design: Oral biopsy tissues (for neoplastic lesions) received for histopathological evaluation were included in the study.

Fibroblast growth factor 23 and phosphate homeostasis.

Purpose Of Review: The current review highlights recent advances in the area of renal tubular phosphate transport and its regulation by fibroblast growth factor 23 (FGF23), a potent regulator of phosphate homeostasis.

Recent Findings: Recent studies demonstrate that FGF23 binds to both membrane and soluble form of α-klotho to activate FGF receptor signaling pathways. Parathyroid hormone and FGF23 equivalently decrease sodium-dependent phosphate cotransport but the effect is not additive, suggesting a shared but not synergistic mechanism of action.

CYP Suppression in Human Hepatocytes by Monomethyl Auristatin E, the Payload in Brentuximab Vedotin (Adcetris), is Associated with Microtubule Disruption.

Background And Objectives: Monomethyl auristatin E (MMAE), the toxin linked to CD30-specific monoclonal antibody of Adcetris (brentuximab vedotin), is a potent anti-microtubule agent. Brentuximab vedotin has been approved for the treatment of relapsed or refractory Hodgkin lymphoma and anaplastic large cell lymphoma. Cytochrome P450 (CYP) induction assessment of MMAE was conducted in human hepatocytes to assess DDI potentials and its translation to clinic.

Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidance from Regulatory Agencies: Focus on Downregulation, CYP2C Induction, and CYP2B6 Positive Control.

The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency (PMDA), and the Food and Drug Administration (FDA) have issued guidelines for the conduct of drug-drug interaction studies. To examine the applicability of these regulatory recommendations specifically for induction, a group of scientists, under the auspices of the Drug Metabolism Leadership Group of the Innovation and Quality (IQ) Consortium, formed the Induction Working Group (IWG). A team of 19 scientists, from 16 of the 39 pharmaceutical companies that are members of the IQ Consortium and two Contract Research Organizations reviewed the recommendations, focusing initially on the current EMA guidelines.