ACR-ACNM-ARS-SNMMI-SPR Practice Parameter for Treatment of Benign and Malignant Thyroid Disease With I-131 Sodium Iodide.

Objectives: This practice parameter was developed collaboratively by the American College of Radiology (ACR), the American College of Nuclear Medicine (ACNM), the American Radium Society (ARS), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), and the Society for Pediatric Radiology (SPR). This practice parameter is intended to guide appropriately trained and licensed physicians in the oral administration of I-131 sodium iodide for the treatment of benign and malignant thyroid diseases.

Methods: This practice parameter was revised according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.

Mechanism-Based Modeling Approaches to Quantify the Effect of Immunogenicity on the Pharmacokinetics of Therapeutic Proteins in Drug Development.

Therapeutic protein administration in both preclinical and clinical studies can result in the formation of anti-drug antibodies against the therapeutic protein. Anti-drug antibody formation may alter the pharmacokinetics of the therapeutic protein, reduce its plasma concentrations, increase exposure variability, and may lead to a loss of efficacy and adverse events. In an effort to quantitatively understand the effect of anti-drug antibodies on the concentration-time profile of a therapeutic protein, as well as develop effective strategies to mitigate its impact in the preclinical and clinical development of therapeutic proteins, mathematical models have been developed to characterize the therapeutic protein pharmacokinetics and its modulation by anti-drug antibodies in vivo.

Longitudinal changes in cortical cell body and neurite density in people with multiple sclerosis.

Detecting neuroinflammation and neurodegeneration prior to cortical atrophy and subsequent clinical disability in people with multiple sclerosis (MS) has been challenging due to limited sensitivity on MRI. Our aim was to assess longitudinal changes in cortical cell body and neurite density related to lesion formation and atrophy using high-gradient diffusion MRI. In this longitudinal study, nine people with MS underwent 3 T high-gradient diffusion MRI at baseline and follow-up (median 5 years).

Characterizing treatment interruptions in the OPERA cohort and virologic outcomes after resumption with bictegravir/emtricitabine/tenofovir alafenamide.

Background: Despite advancements in antiretroviral therapy (ART) for people with HIV, barriers to adherence remain, potentially leading to long-term gaps in adherence known as treatment interruptions. These treatment interruptions are associated with viral rebound and can impact the effectiveness of the subsequent regimen and the long-term health of the individual. We aimed to characterize unplanned ART treatment interruptions in the OPERA cohort and investigate virologic outcomes among individuals who resumed treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

A systematic literature review of the association between global brain atrophy and the Expanded Disability Status Scale score in people with multiple sclerosis.

Background: Brain atrophy (BA) is a useful predictor of clinical outcomes in people with multiple sclerosis (PwMS). For this reason, MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis), an expert consensus group, recommended that global brain volume loss (BVL) is included as a secondary outcome in therapeutic clinical trials. However, there has not been a recent review of the evidence of the association, or strength of association, between global BA and disability in PwMS.

A Phase II Study of Cabozantinib in Patients With -Altered Lung Cancers.

Introduction: Only type I MET tyrosine kinase inhibitors (TKIs) are approved for treating -altered NSCLCs. Preclinically, type II TKIs, such as cabozantinib, can rescue progression on type I TKIs. This phase 2 trial (NCT01639508) evaluated the activity of cabozantinib in patients with MET-dependent lung cancers, including TKI-pretreated cancers.

Neoadjuvant nonablative stereotactic body radiotherapy plus immunotherapy yields similar pathologic response as chemoimmunotherapy in non-small cell lung cancer.

Objective: Neoadjuvant chemoimmunotherapy is currently the standard of care for clinical stages IB (≥4 cm) to IIIB (N2) non-small cell lung cancer without EGFR or ALK alterations. We previously reported results from a phase II trial comparing neoadjuvant immunotherapy alone with nonablative stereotactic body radiotherapy plus immunotherapy. In this article, we compare the oncological outcomes associated with stereotactic body radiotherapy plus immunotherapy with those after chemoimmunotherapy in surgically resected patients.

Personalized ctDNA monitoring in metastatic HR+/HER2- breast cancer patients during endocrine and CDK4/6 inhibitor therapy.

Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2- breast cancer patients receiving endocrine and CDK4/6 inhibitor therapy. By conducting whole exome sequencing on archival tumors, highly sensitive personalized ctDNA panels were designed for blood monitoring.

Talazoparib plus enzalutamide in men with metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial.

Background: The primary analysis of this phase 3 trial combining talazoparib with enzalutamide demonstrated significantly improved radiographic progression-free survival (rPFS) versus enzalutamide plus placebo in patients with metastatic castration-resistant prostate cancer unselected for homologous recombination repair (HRR) gene alterations. Overall survival data were immature at that time. Here we report the final prespecified overall survival analysis, an updated descriptive analysis of rPFS, and safety in the cohort unselected for HRR gene alterations.

Talazoparib plus enzalutamide in men with HRR-deficient metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial.

Background: Metastatic castration-resistant prostate cancer remains incurable and is particularly aggressive in patients with alterations in DNA damage repair genes involved directly or indirectly in homologous recombination repair (HRR). In the primary analysis of TALAPRO-2, talazoparib plus enzalutamide significantly improved radiographic progression-free survival (rPFS) versus enzalutamide plus placebo in patients with metastatic castration-resistant prostate cancer harbouring HRR gene alterations. At primary analysis, overall survival was immature.

Safety and efficacy of fenebrutinib in relapsing multiple sclerosis (FENopta): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial and open-label extension study.

Background: The prospect for Bruton's tyrosine kinase (BTK) inhibition to meaningfully affect relapsing multiple sclerosis has recently been questioned due to inconsistent findings in the magnitude and sustainability of the effect of BTK inhibitors on disease activity. We assessed the safety, efficacy, and CSF drug concentrations of fenebrutinib, a highly selective, noncovalent, reversible BTK inhibitor, in patients with relapsing multiple sclerosis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (FENopta) was conducted at 18 community centres and hospitals across six countries in Europe and North America.

The RAS-MEK-ERK pathway in low-grade serous ovarian cancer.

Low-grade serous ovarian cancer (LGSC) is an uncommon subtype of epithelial ovarian cancer, often arising in association with serous borderline tumors (SBT). Compared to high-grade serous ovarian cancers, LGSCs often occur in younger patients and are relatively insensitive to platinum-based chemotherapy, though some patients with LGSC can benefit from hormonal therapies. Genomic studies have demonstrated that SBT and LGSC frequently harbor mutations in members of the RAS-MEK-ERK pathway, which can be targeted therapeutically.

Clinical Characterization and Long-Term Outcome in Children and Adults With Anti-AMPA Receptor Encephalitis.

Background And Objectives: Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (anti-AMPAR) encephalitis manifests as limbic encephalitis in adults and is often associated with cancer. Although some reports suggest that it may occur in children, the clinical features in this population, as well as the prognostic factors and long-term outcomes in children and adults, are unknown.

Methods: We performed a retrospective, international collaborative study of patients with anti-AMPAR encephalitis.

AChR Autoantibody Pathogenic Properties Are Heterogeneously Distributed and Undergo Temporal Changes Among Patients With Myasthenia Gravis.

Background And Objectives: Acetylcholine receptor (AChR) autoantibodies contribute to myasthenia gravis (MG) pathogenesis through 3 mechanisms: complement activation, receptor internalization, and acetylcholine (ACh) binding site blocking. Recently approved therapies target these autoantibodies by inhibiting the complement pathway or blocking the neonatal Fc receptor, reducing IgG autoantibody levels. However, these approaches have limitations: complement inhibitors do not address complement-independent mechanisms, and FcRn blockers only target IgG.

Sensitivity of Tepotinib to Inhibitors or Inducers of CYP3A4 and P-Gp: Drug Interaction Studies and Physiologically-Based Pharmacokinetic Analysis.

Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer harboring MET exon 14 skipping alterations. This work aimed to investigate the potential for drug-drug interactions with strong inhibitors and inducers of both cytochrome P450 (CYP) 3A4/5 and P-glycoprotein (P-gp) with tepotinib. Two clinical studies were conducted to investigate the effect of the strong CYP3A4/P-gp inhibitor itraconazole (200 mg once daily) (NCT05203822) and the strong CYP3A4/P-gp inducer carbamazepine (titrated to 300 mg twice daily) (NCT05213481) on the pharmacokinetics of single dose tepotinib 500 mg (450 mg active moiety) in healthy participants.

Multiple Sclerosis in People of Diverse Racial and Ethnic Backgrounds: Presentation, Disease Course, and Interactions with Disease-Modifying Therapy.

Multiple sclerosis (MS) affects people of all racial and ethnic backgrounds, with greatest prevalence noted in Black and white individuals living in Europe and North America. Age of MS onset seems to be earlier in Black, Latino/Hispanic, and South Asian people living with MS in North America and the United Kingdom. Additionally, Black and Latino/Hispanic people with MS in the USA are more likely to have severe initial presentations and earlier accumulation of disability compared with white people with MS.

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

Background: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis.

Results: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.

Early real-world utilization of avelumab switch maintenance among patients with advanced urothelial carcinoma without progression following treatment with first-line platinum-based chemotherapy.

Background: A standard treatment option for patients with locally advanced/metastatic urothelial carcinoma (la/mUC) is first-line platinum-based chemotherapy (1L PBC) followed by avelumab 1L switch maintenance (1LM) in patients without progression. This study aimed to evaluate the real-world treatment patterns and outcomes in patients with la/mUC in the US treated with 1L PBC and characterize the early adoption of avelumab 1LM following FDA approval in June 2020.

Methods: This retrospective cohort study identified adults diagnosed with la/mUC between January 2017 and September 2021 using electronic health records from the Flatiron Health database.

Risk Factors for COVID-19-Related Hospitalization and Death in Patients With Cancer: The National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS).

Importance: Retrospective case series have identified having cancer and receiving treatment for cancer as risk factors for inferior COVID-19 outcomes.

Objective: To determine risk factors for hospitalization and death in patients with cancer with COVID-19 infection.

Design, Setting, And Participants: The National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) is a prospective longitudinal natural history cohort study examining the impact of COVID-19 on patients with cancer.

Patients With Head and Neck Cancer and High Health Care Costs: A Population-Based Study.

Importance: The care for a small subset of patients is responsible for a disproportionately large share of health care expenditures. Head and neck cancer is associated with significant health care costs due to complex treatment regimens and long-term sequelae. Given this high baseline cost, identifying patients with high care costs within a population with cancer might help inform interventions to optimize resource allocation.

Ongoing genome doubling shapes evolvability and immunity in ovarian cancer.

Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing, we analysed 70 high-grade serous ovarian cancer samples from 41 patients (30,260 tumour genomes) and observed near-ubiquitous evidence that WGD is an ongoing mutational process.

Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex.

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia.

Remission and low disease activity definitions in adult idiopathic inflammatory myopathies: A narrative review by myositis clinical trials consortium (MCTC).

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare systemic autoimmune rheumatic diseases. Despite advances in treatment, the definition of remission and low disease activity (LDA) in IIM remains inconsistent and lacks consensus and validation. This review summarizes existing published definitions, achievement rates, and predictive factors of remission/LDA in adult IIM, focusing on dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathies (IMNM).

Concurrent treatment with transarterial immunoembolization of hepatic metastases and systemic immune checkpoint inhibitors to overcome immune evasion in patients with metastatic uveal melanoma.

Background: Metastatic uveal melanoma (mUM) is an uncommon melanoma subtype, poorly immunogenic with low objective response rates (ORR) to immune checkpoint inhibitors (ICI). Liver-directed therapies (LDT) are commonly used given the strong predilection for hepatic metastases. Transarterial immunoembolization (TAIE) with granulocyte-macrophage colony stimulating factor (GM-CSF) can potentially synergize with concurrent systemic ICI to overcome immune evasion.

Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis.

Introduction: Lebrikizumab is a novel monoclonal antibody that selectively binds to interleukin (IL)-13 with high affinity and a slow dissociation rate.

Methods: We assayed serum from select patients enrolled in ADvocate1 and ADvocate2 to determine the impact of lebrikizumab on circulating biomarkers and pathways relevant to atopic dermatitis (AD) and to assess the correlation between key biomarkers and clinical measures of improvement.

Results: At baseline, IL-13, CC motif chemokine ligand (CCL)13, CCL17, CCL22, total immunoglobulin (Ig)E, IL-5, and periostin were elevated in patients with moderate-to-severe AD versus healthy controls (p < 0.