Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Neonatal Fc Receptor Inhibitor Rozanolixizumab: An Ethnic Sensitivity Study in Healthy Japanese, Chinese, and White Participants.

Rozanolixizumab is an anti-human neonatal Fc receptor humanized immunoglobulin (Ig) G4 monoclonal antibody that reduces IgG, including pathogenic IgG autoantibodies. Rozanolixizumab safety and tolerability have been assessed in previous clinical studies with predominantly White participants. We assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of rozanolixizumab in healthy Japanese and Chinese participants compared with White participants.

Optimization of Fluorescence In Situ Hybridization Protocols in the Era of Precision Medicine.

Fluorescence in situ hybridization (FISH) is a cytogenetic assay that is widely used in both clinical and research settings to validate genetic aberrations. Simple in principle, it is based on denaturation and hybridization of a DNA probe and its complementary sequence; however, it is subject to continuous optimization. Here we share how in-house FISH can be optimized using different control tissues to visualize and ultimately validate common and novel genetic abnormalities unearthed by next-generation sequencing (NGS).

Electronic Real-Time Monitoring Reveals Limited Adherence to Long-Term Opioid Prescriptions in Pain Patients.

Background: Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens.

Objective: We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians' opinions.

Whole-Genome Sequencing Analysis of Male Breast Cancer Unveils Novel Structural Events and Potential Therapeutic Targets.

The molecular characterization of male breast cancer (MaBC) has received limited attention in research, mostly because of its low incidence rate, accounting for only 0.5% to 1% of all reported cases of breast cancer each year. Managing MaBC presents significant challenges, with most treatment protocols being adapted from those developed for female breast cancer.

Access to Medications for Opioid Use Disorder During COVID-19: Retrospective Study of Commercially Insured Patients from 2019-2022.

Introduction: This study assesses disparities in medications for opioid use disorder in adults with opioid use disorder and examines the associations between state-level COVID-19 lockdown and telehealth policies and medications for opioid use disorder utilization rates during the COVID-19 pandemic.

Methods: This retrospective cohort study of 396,872 adults with opioid use disorder analyzed monthly medications for opioid use disorder utilization rates between January 2019 and June 2022 using data from Clinformatics Data Mart Database. Primary outcome measure was monthly medications for opioid use disorder utilization rates.

Pain Control Associated With Gabapentinoid Prescription After Elective Total Knee Arthroplasty.

Background: Gabapentinoid (GABA) prescribing has substantially increased as a nonopioid analgesics for surgical conditions. We examined the effectiveness of GABA use for postoperative pain control among patients receiving total knee arthroplasty (TKA).

Methods: This retrospective cohort study using 2016 to 2019 data from a 20% national sample of Medicare enrollees included patients aged 66 and over years who received an elective TKA, were discharged to home, received home health care, and had both admission and discharge assessments of pain (n = 35,186).

Diversity, Equity, and Inclusion in the Pediatric Pulmonary Workforce: An Official American Thoracic Society Workshop Report.

Despite growing recognition of the need for increased diversity among students, trainees, and faculty in health care, the medical workforce still lacks adequate representation from groups historically underrepresented in medicine (URiM). The subspecialty field of pediatric pulmonology is no exception. Although there have been efforts to address issues of diversity, equity, and inclusion (DEI) in our own field, gaps persist.

Comparative effectiveness of pain control between opioids and gabapentinoids in older patients with chronic pain.

Gabapentinoid (GABA) prescribing has substantially increased while opioid prescribing has decreased since the 2016 Centers for Disease Control and Prevention Guidelines restricted opioid prescribing for chronic pain. The shift to GABA assumes equal analgesic effectiveness to opioids, but no comparative analgesic effectiveness data exist to support this assumption. We compared GABA to opioids by assessing changes in pain interfering with activities (activity-limiting pain) over time in patients with chronic pain.

Building Career Paths for Ph.D., Basic and Translational Scientists in Clinical Departments in the United States: An Official American Thoracic Society Workshop Report.

To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units.

SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers.

SLN124, an N-acetylgalactosamine conjugated 19-mer short interfering RNA, is being developed to treat iron-loading anemias (including beta-thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis.

Epinephrine iontophoresis attenuates changes in skin blood flow and abolishes cutaneous contamination of near-infrared diffuse correlation spectroscopy estimations of muscle perfusion.

Near-infrared diffuse correlation spectroscopy (NIR-DCS) is an optical imaging technique for measuring relative changes in skeletal muscle microvascular perfusion (i.e., fold change above baseline) during reactive hyperemia testing and exercise and is reported as a blood flow index (BFI).

Semi-Supervised Contrastive Learning for Remote Sensing: Identifying Ancient Urbanization in the South-Central Andes.

Archaeology has long faced fundamental issues of sampling and scalar representation. Traditionally, the local-to-regional-scale views of settlement patterns are produced through systematic pedestrian surveys. Recently, systematic manual survey of satellite and aerial imagery has enabled continuous distributional views of archaeological phenomena at interregional scales.

Whole-genome characterization of myoepithelial carcinomas of the soft tissue.

Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been comprehensively explored through genome sequencing. Here, we present the whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing findings of two MECs. Patients 1 and 2 (P1, P2), both male, were diagnosed at 27 and 37 yr of age, respectively, with shoulder (P1) and inguinal (P2) soft tissue tumors.

GLI1 -Rearranged Enteric Tumor : Expanding the Spectrum of Gastrointestinal Neoplasms With GLI1 Gene Fusions.

GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. GLI1 gene fusions were initially described in pericytomas with a t[7;12] translocation and more recently in gastric plexiform fibromyxomas and gastroblastomas. This study describes the clinicopathologic, immunohistochemical, and molecular features of three intestinal-based neoplasms harboring GLI1 gene fusions.

Loss of stromal cell Thy-1 plays a critical role in lipopolysaccharide induced chronic lung allograft dysfunction.

Background: Long-term survival of lung transplants lags behind other solid organs due to early onset of a fibrotic form of chronic rejection known as chronic lung allograft dysfunction (CLAD). Preventing CLAD is difficult as multiple immunologic and physiologic insults contribute to its development. Targeting fibroblast activation, which is the final common pathway leading to CLAD, offers the opportunity to ameliorate fibrosis irrespective of the initiating insult.

Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer.

Genetic alterations in RET lead to activation of ERK and AKT signaling and are associated with hereditary and sporadic thyroid cancer and lung cancer. Highly selective RET inhibitors have recently entered clinical use after demonstrating efficacy in treating patients with diverse tumor types harboring RET gene rearrangements or activating mutations. In order to understand resistance mechanisms arising after treatment with RET inhibitors, we performed a comprehensive molecular and genomic analysis of a patient with RET-rearranged thyroid cancer.

Pharmacokinetics, safety, tolerability, and immunogenicity of FKB238, a new biosimilar of bevacizumab, in healthy participants.

Objective: To compare the pharmacokinetics (PK), safety, tolerability, and immunogenicity of single intravenous doses of FKB238, a proposed biosimilar of bevacizumab, with European Union (EU)-approved and United States (US)-licensed bevacizumab in healthy participants.

Materials And Methods: In a randomized, double-blind, parallel-group study, 99 healthy men received 5 mg of FKB238, EU-bevacizumab, or US-bevacizumab in a 1 : 1 : 1 ratio by intravenous infusion. PK, immunogenicity, adverse events, local tolerability, vital signs, electrocardiogram, and safety tests of blood and urine were assessed before and up to 99 days after treatment.