Risk factors associated with 30-day mortality following COVID-19 infection in patients receiving kidney replacement therapy in Australian and New Zealand.

Background And Aims: The COVID-19 pandemic impacted greatest among patients with pre-existing chronic health conditions, including chronic kidney disease. This retrospective cohort study aimed to investigate the 30-day mortality of patients receiving kidney replacement therapy (KRT) after infection with COVID-19, living in Australia and New Zealand between 2020 and 2022, including patients on haemodialysis (HD), peritoneal dialysis (PD) and renal transplant (KT) recipients.

Methods: This is a retrospective cohort study using data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA).

Achieving the Needed Correction in Vertebral Body Tethering: The Relationship Between Preoperative Flexibility, Intraoperative Correction, and First Erect Imaging.

Background: Vertebral body tethering (VBT) is a nonfusion surgical treatment for scoliosis. Recent data have shown that intraoperative correction is critical for successful curve correction over time. This study aims to evaluate the relationship between preoperative, intraoperative, and postoperative correction.

Microbeam Radiation Therapy Bio-Dosimetry Enhanced by Novel Radiosensitiser Combinations in the Treatment of Brain Cancer.

: Brain cancer is notoriously resistant to traditional treatments, including radiotherapy. Microbeam radiation therapy (MRT), arrays of ultra-fast synchrotron X-ray beams tens of micrometres wide (called peaks) and spaced hundreds of micrometres apart (valleys), is an effective alternative to conventional treatments. MRT's advantage is that normal tissues can be spared from harm whilst maintaining tumour control.

Vertebral Body Tethering in Skeletally Immature Patients: Results of a Prospective U.S. FDA Investigational Device Exemption Study.

Background: The purpose of this study was to report on 2-year results of vertebral body tethering (VBT), performed under a Food and Drug Administration protocol, to obtain insight into outcomes and complications.

Methods: Forty prospectively enrolled patients with adolescent idiopathic scoliosis (AIS) who had a Sanders score of ≤4 or a Risser score of ≤2 underwent VBT for curves between 40° and 70°. Surgical, radiographic, and patient-reported outcomes were reviewed at a minimum 2-year follow-up.

A novel approach to double-strand DNA break analysis through γ-H2AX confocal image quantification and bio-dosimetry.

DNA damage occurs in all living cells. γ-H2AX imaging by fluorescent microscopy is widely used across disciplines in the analysis of double-strand break (DSB) DNA damage. Here we demonstrate a method for the quantitative analysis of such DBSs.

Serum glutamate dehydrogenase activity enables sensitive and specific diagnosis of hepatocellular injury in humans.

Serum activities of alanine- and aspartate aminotransferases (ALT and AST) are considered the "gold standard" biomarkers of hepatocyte injury in clinical practice and drug development. However, due to the expression of ALT and AST in myocytes, the diagnosis of hepatocellular injury in patients with underlying muscle diseases, including drug-induced muscle injury, is severely limited. Thus, we proposed glutamate dehydrogenase (GLDH) as a liver-specific alternative to serum ALT and AST.

Perioperative Outcomes Related to Thoracic and Lumbar Spine Exposure During Vertebral Body Tethering for Adolescent Idiopathic Scoliosis: A Large, Single-institution Retrospective Review.

Background: Vertebral body tethering (VBT) is a novel non-fusion technique for the management of scoliosis. Despite growing popularity, data concerning complications and thoracic surgery-related outcomes are lacking.

Methods: A single-institution retrospective review was conducted of patients who underwent VBT with video-assisted thoracic surgical exposure from 1/1/2015-3/1/2022.

The FSGS protein actinin-4 interacts with NKCC2 to regulate thick ascending limb NaCl reabsorption.

In the kidney, the thick ascending limb (TAL) of the loop of Henle plays a vital role in NaCl homeostasis and blood pressure regulation. In human and animal models of salt-sensitive hypertension, NaCl reabsorption via the apical Na/K/2Cl cotransporter (NKCC2) is abnormally increased in the TAL. We showed that NaCl reabsorption is controlled by the presence of NKCC2 at the apical surface of TALs.

Qualified kidney injury biomarkers demonstrate value during early clinical drug development.

Drug-induced kidney injury (DIKI) is of significant concern, both during drug development and in clinical practice. We report a patient-centric approach for clinical implementation of the FDA-qualified kidney safety biomarker panel, highlighting Phase 1 and 2 trials for candidate therapeutics in Pfizer's portfolio (PFE-1 and PFE-2, respectively) that induced kidney tubular injury in rat toxicity studies. Clusterin (CLU), cystatin-C (CysC), kidney injury molecule-1 (KIM-1), N-acetyl-beta-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin (OPN) were measured in urine samples from (i) Phase 1 healthy volunteers (HVs; n = 12) dosed with PFE-1, (ii) Phase 2 rheumatoid arthritis (RA) patients (n = 266) dosed with PFE-2, (iii) lupus patients on standard-of-care therapies (n = 121), and (iv) healthy volunteers (n = 60).

The partnership between statisticians and the Institutional Animal Care and Use Committee (IACUC).

In this tutorial we explore the valuable partnership between statisticians and Institutional Animal Care and Use Committees (IACUCs) in the context of animal research, shedding light on the critical role statisticians play in ensuring the ethical and scientifically rigorous use of animals in research. Pharmaceutical statisticians have increasingly become vital members of these committees, contributing expertise in study design, data analysis, and interpretation, and working more generally to facilitate the integration of good statistical practices into experimental procedures. We review the "3Rs" principles (Replacement, Reduction, and Refinement) which are the foundation for the humane use of animals in scientific research, and how statisticians can partner with IACUC to help ensure robust and reproducible research while adhering to the 3Rs principles.

Applying machine learning to international drug monitoring: classifying cannabis resin collected in Europe using cannabinoid concentrations.

In Europe, concentrations of ∆-tetrahydrocannabinol (THC) in cannabis resin (also known as hash) have risen markedly in the past decade, potentially increasing risks of mental health disorders. Current approaches to international drug monitoring cannot distinguish between different types of cannabis resin which may have contrasting health effects due to THC and cannabidiol (CBD) content. Here, we compared concentrations of THC and CBD in different types of cannabis resin collected in Europe (either Moroccan-type, or Dutch-type).

Endothelial dysfunction in breast cancer survivors on aromatase inhibitors: changes over time.

Background: Breast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive (ER+) breast carcinoma in postmenopausal women, which includes approximately two-thirds of all women with breast cancer. AIs inhibit the peripheral conversion of androgens to estrogen by deactivation of the aromatase enzyme, leading to a reduction in serum estrogen level in postmenopausal women with ER+ breast carcinoma.

Biocompatible Cable Ties Are an Alternative to Metal Stabilizers for Bar Securement During Minimally Invasive Pectus Excavatum Repair.

Bar stabilization during minimally invasive pectus excavatum repair (MIRPE) is critical to avoid dislodgement. Multiple techniques are described including stabilizers, wires, and sutures. This retrospective study compared bar movement and outcomes between existing techniques and ZipFix™, a biocompatible cable tie.

Dissociation of Hypertension and Renal Damage After Cessation of High-Salt Diet in Dahl Rats.

Background: Every year, thousands of patients with hypertension reduce salt consumption in an effort to control their blood pressure. However, hypertension has a self-sustaining character in a significant part of the population. We hypothesized that chronic hypertension leads to irreversible renal damage that remains after removing the trigger, causing an elevation of the initial blood pressure.

A prospective observational cohort study of covid-19 epidemiology and vaccine seroconversion in South Western Sydney, Australia, during the 2021-2022 pandemic period.

Background: It is known that COVID-19 disproportionally adversely affects the immunocompromised, including kidney transplant recipients (KTR), as compared to the general population. Risk factors for adverse outcomes and vaccine seroconversion patterns are not fully understood. Australia was uniquely positioned to reduce initial case numbers during the 2021-2022 pandemic period due to its relative isolation and several significant public health interventions.

Translation of nonclinical to clinical safety findings for 27 biotherapeutics.

Human adverse drug reactions (ADRs), and in vivo nonclinical adverse and nonadverse findings, were identified in 27 biotherapeutic programs and placed into organ categories to determine translation. The sensitivity of detecting human ADRs was 30.8% with a positive predictive value (PPV) of 53.

Health Is Power, and Health Is Wealth: Understanding the Motivators and Barriers of African American/Black Male Immigrants With Gastrointestinal Conditions.

The digestive health of African American/Black male immigrants in the United States has not been previously studied. Much of what is known about gastrointestinal (GI) concerns in this population is based on studies conducted on the overall Black American population. The purpose of this narrative study was to understand how African American/Black male immigrants with GI concerns navigated their GI condition.

The Traumatic Inoculation Process Affects TSPO Radioligand Uptake in Experimental Orthotopic Glioblastoma.

Background: The translocator protein (TSPO) has been proven to have great potential as a target for the positron emission tomography (PET) imaging of glioblastoma. However, there is an ongoing debate about the potential various sources of the TSPO PET signal. This work investigates the impact of the inoculation-driven immune response on the PET signal in experimental orthotopic glioblastoma.