Ophthalmologic toxicities of antineoplastic agents in genitourinary cancers: Mechanisms, management, and clinical implications.

Genitourinary cancers affect over 480,000 patients in the United States annually. While promising therapeutic modalities continue to emerge, notably immune checkpoint inhibitors, molecular targeted therapies, antibody-drug conjugates, and radioligand therapies, these treatments are associated with a spectrum of adverse side-effects, including ophthalmologic toxicities. In this review, we cover the most commonly used antineoplastic agents for the kidneys, bladder, urinary tracts, prostate, testis, and penis, detailing mechanism, indication, and recent trials supporting their use.

Systemic lupus erythematosus is a risk factor for having multiple subtypes of cutaneous lupus erythematosus.

Background: Patients with cutaneous lupus erythematosus (CLE) can present with one or multiple different subtypes of CLE. There is limited understanding of the prevalence and associated risk factors for having multiple CLE subtype diagnoses.

Objective: This study characterized the frequency and risk factors for having multiple CLE subtypes.

Avelumab + axitinib vs sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase 3 JAVELIN Renal 101 trial.

Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).

Patients And Methods: Patients with untreated aRCC (any prognostic risk score) were enrolled.

RNA sensing induced by chromosome missegregation augments anti-tumor immunity.

Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.

Neurostatus-SMARTCARE clinical trial: Enabling health care professionals to assess EDSS for decentralized trials in multiple sclerosis.

Background: Neurostatus-Expanded Disability Status Scale (EDSS) is the standard measure used to assess impairment and disability in multiple sclerosis (MS) trials but requires trained expert neurologists.

Objectives: This study aims to evaluate the concordance of Neurostatus-EDSS assessments from specially trained health care professionals (HCPs) and standardized trained neurologists.

Methods: A Swiss multicenter, randomized, cross-over study with 100 people with MS.

Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1CD8 T cells.

The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.

Application of digital tools and artificial intelligence in the Myasthenia Gravis Core Examination.

Background: Advances in video image analysis and artificial intelligence provide opportunities to transform how patients are evaluated. In this study, we assessed the ability to quantify Zoom video recordings of a standardized neurological examination- the Myasthenia Gravis Core Examination (MG-CE)-designed for telemedicine evaluations.

Methods: We used Zoom (Zoom Video Communications) videos of patients with myasthenia gravis (MG) who underwent the MG-CE.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

A Podcast Discussion on the Intracranial Efficacy of Antibody-Drug Conjugates in Patients with EGFR-Mutated NSCLC with Brain Metastases.

The incidence of brain metastases is higher in patients with non-small cell lung cancer (NSCLC) than in patients with most other cancers, and the development of brain metastases is associated with poor prognosis. The objective of the podcast is to provide information about current and future treatments for brain metastases that develop in patients with EGFR-mutated NSCLC. The panel discusses surveillance and management of patients with brain metastases, different types of currently used treatments, and recent data on the intracranial efficacy of antibody-drug conjugates (ADCs).

Early downmodulation of tumor glycolysis predicts response to fasting-mimicking diet in triple-negative breast cancer patients.

In preclinical experiments, cyclic fasting-mimicking diets (FMDs) showed broad anticancer effects in combination with chemotherapy. Among different tumor types, triple-negative breast cancer (TNBC) is exquisitely sensitive to FMD. However, the antitumor activity and efficacy of cyclic FMD in TNBC patients remain unclear.

Real-World Prevalence, Treatment Patterns, and Outcomes for Patients With HER2 (ERBB2)-Mutant Metastatic Non-Small Cell Lung Cancer, From a US-Based Clinico-Genomic Database.

Objectives: Targeted therapies have been shown to improve outcomes in metastatic non-small cell lung cancer (mNSCLC) with driver mutations. We evaluated the real-world prevalence of human epidermal growth factor receptor 2 (HER2; ERBB2) tumor gene mutations among patients with mNSCLC and described historical treatments and outcomes in patients with HER2-mutant mNSCLC, during a period when there was no approved targeted therapy for HER2-mutant mNSCLC.

Materials And Methods: This retrospective observational study used a US nationwide de-identified NSCLC clinico-genomic database.

Morbidity and Mortality Risk Among People With Human Immunodeficiency Virus and Central or Visceral Adiposity: A Targeted Literature Review.

Background: Given the known relationship between human immunodeficiency virus (HIV), antiretroviral therapies, and excess visceral adipose tissue (VAT), this review sought to characterize risk of negative health outcomes associated with excess VAT and increased waist circumference (WC) in people with HIV (PWH).

Methods: Comprehensive targeted literature searches were conducted in Medline/Embase (27 June 2022), identifying peer-reviewed articles and conference abstracts reporting on cohorts of PWH. Screening was guided by PECOS (Population, Exposure, Comparator, Outcomes, Study design) criteria.

Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.

Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

The Role of Antibody-Drug Conjugates in Urothelial Cancer: A Review of Recent Advances in the Treatment of Locally Advanced and Metastatic Urothelial Cancer.

Locally advanced and metastatic urothelial cancer (la/mUC) is an aggressive disease with poor prognosis. Platinum-based chemotherapy has remained the first-line treatment for decades and until recently no other treatment options existed. Today, novel agents called antibody drug conjugates (ADCs), including enfortumab vedotin (EV) and sacituzumab govitecan (SG), have been approved for la/mUC offering patients treatment options following or instead of traditional chemotherapy.

A High-Throughput Neurosphere-Based Colony Formation Assay to Test Drug and Radiation Sensitivity of Different Patient-Derived Glioblastoma Lines.

The gold standard assay for radiation response is the clonogenic assay, a normalized colony formation assay (CFA) that can capture a broad range of radiation-induced cell death mechanisms. Traditionally, this assay relies on two-dimensional (2D) cell culture conditions with colonies counted by fixing and staining protocols. While some groups have converted these to three-dimensional (3D) conditions, these models still utilize 2D-like media compositions containing serum that are incompatible with stem-like cell models such as brain tumor initiating cells (BTICs) that form self-aggregating spheroids in neural stem cell media.

Predictive and Interpretable Machine Learning of Economic Burden: The Role of Chronic Conditions Among Elderly Patients with Incident Primary Merkel Cell Carcinoma (MCC).

Objective: To evaluate chronic conditions as leading predictors of economic burden over time among older adults with incident primary Merkel Cell Carcinoma (MCC) using machine learning methods.

Methods: We used a retrospective cohort of older adults (age ≥ 67 years) diagnosed with MCC between 2009 and 2019. For these elderly MCC patients, we derived three phases (pre-diagnosis, during-treatment, and post-treatment) anchored around cancer diagnosis date.

Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study.

Introduction: Dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-release DMF in patients with relapsing forms of MS in routine clinical practice. We report final outcomes from ESTEEM with up to 6.

Body mass index trends over four years in persons with multiple sclerosis.

Background: The role of obesity in persons with multiple sclerosis (PwMS) is incompletely understood. Obesity predisposes individuals to a pro-inflammatory state and cardiovascular comorbidities, both of which can negatively impact MS disease course. A better understanding of weight trends in PwMS will inform optimal management of those who are overweight or obese.

Patients achieving low lupus disease activity state, systemic lupus erythematosus disease control or remission showed lower rates of organ damage during longitudinal follow-up: analysis of the Hopkins Lupus Cohort.

Objective: One key target of treating patients with systemic lupus erythematosus (SLE) is to prevent organ damage. This analysis quantified the association between time spent in four specific SLE low disease activity (LDA) states and organ damage rate.

Methods: This retrospective real-world data analysis (GSK Study 207168), undertaken to help contextualise the BLISS-BELIEVE clinical trial, included adults with SLE enrolled for≥1 year in the Hopkins Lupus Cohort and treated with standard therapy in a specialist care centre between 1987 and 2019.

Improving Access to MS Care Through Technology.

People with multiple sclerosis (PwMS) experience many barriers to accessing multiple sclerosis (MS) care that lead to diagnostic delays, delayed treatment, interrupted care, and significant economic burden. These barriers include limited geographic healthcare resources, financial burden, physical limitations, and inequities within the healthcare system. Telemedicine has the potential to reduce these barriers and improve access to care.

Imaging the Choroid Plexus.

The choroid plexus (CP), a highly vascularized structure within the ventricles of the brain, has come under increased scrutiny over the last several years as potentially having a role in the pathophysiology of multiple sclerosis (MS). Originally consider as being only responsible for the production of cerebrospinal fluid, it is now widely recognized that the CP is also involved in immunosurveillance and immune cell trafficking. Histopathology studies have found several immunological changes in donor tissue, including the accumulation of inflammatory cells.

Physician Reasons for or Against Treatment Intensification in Patients With Metastatic Prostate Cancer.

Importance: Clarifying the underutilization of treatment intensification (TI) for metastatic castration-sensitive prostate cancer (mCSPC) may improve implementation of evidence-based medicine and survival outcomes.

Objective: To investigate physicians' beliefs about TI in mCSPC to understand the gap between evidence-based guidelines and clinical practice.

Design, Setting, And Participants: This survey study analyzed data from the Adelphi Real World retrospective survey, which comprised physician surveys that were linked to medical record reviews of US adult patients treated for mCSPC between July 2018 and January 2022.