Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer.

Objective: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer.

Methods: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically.

Examination of fully automated mammographic density measures using LIBRA and breast cancer risk in a cohort of 21,000 non-Hispanic white women.

Background: Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and breast cancer risk and compared results to prior assessments using Cumulus, an established computer-assisted method requiring manual thresholding.

Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones.

Insufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE associated with high maternal and fetal morbidity and mortality. Kisspeptins, a family of peptides previously shown to inhibit trophoblast cell invasion, have been implicated in the pathogenesis of early-onset PE. However, a role of kisspeptin signaling during the genesis of this syndrome has not been elucidated.

Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel.

Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more widely used in clinical practice. However, this new class of therapies is associated with a distinct adverse event (AE) profile that includes cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as AEs leading to increased infection risk such as cytopenias and hypogammaglobulinemia, and infections themselves. As preliminary data with this class of agents shows an increased risk of infections as compared with conventional MM treatment regimens, such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies (mAbs), guidance on infection monitoring, prophylaxis and treatment is required.

Impacts of COVID-19 on sexual risk behaviors, safe injection practices, and access to HIV services among key populations in Zambia: Findings from a rapid qualitative formative assessment.

Background: Despite achievements in the HIV response, social and structural barriers impede access to HIV services for key populations (KP) including men who have sex with men (MSM), transgender women (TGW), and people who inject drugs (PWID). This may be worsened by the COVID-19 pandemic or future pandemic threats. We explored the impact of COVID-19 on HIV services and sexual and substance use behaviors among MSM/TGW and PWID in Zambia as part of a formative assessment for two biobehavioral surveys.

Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia.

The COVID-19 pandemic continues to be a health crisis with major unmet medical needs. The early responses from airway epithelial cells, the first target of the virus regulating the progression toward severe disease, are not fully understood. Primary human air-liquid interface cultures representing the broncho-alveolar epithelia were used to study the kinetics and dynamics of SARS-CoV-2 variants infection.

AAV- partially corrects motor deficits and ALS/FTLD-related pathology in mice.

Loss of function of progranulin (PGRN), encoded by the () gene, is implicated in several neurodegenerative diseases. Several therapeutics to boost PGRN levels are currently in clinical trials. However, it is difficult to test the efficacy of PGRN-enhancing drugs in mouse models due to the mild phenotypes of mice.

Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions of the Pouch in a Prospective Cohort.

Background: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited.

Methods: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse.

Artificial Intelligence-Enhanced Breast MRI: Applications in Breast Cancer Primary Treatment Response Assessment and Prediction.

Primary systemic therapy (PST) is the treatment of choice in patients with locally advanced breast cancer and is nowadays also often used in patients with early-stage breast cancer. Although imaging remains pivotal to assess response to PST accurately, the use of imaging to predict response to PST has the potential to not only better prognostication but also allow the de-escalation or omission of potentially toxic treatment with undesirable adverse effects, the accelerated implementation of new targeted therapies, and the mitigation of surgical delays in selected patients. In response to the limited ability of radiologists to predict response to PST via qualitative, subjective assessments of tumors on magnetic resonance imaging (MRI), artificial intelligence-enhanced MRI with classical machine learning, and in more recent times, deep learning, have been used with promising results to predict response, both before the start of PST and in the early stages of treatment.

European Society of Breast Imaging (EUSOBI) guidelines on the management of axillary lymphadenopathy after COVID-19 vaccination: 2023 revision.

Axillary lymphadenopathy is a common side effect of COVID-19 vaccination, leading to increased imaging-detected asymptomatic and symptomatic unilateral axillary lymphadenopathy. This has threatened to negatively impact the workflow of breast imaging services, leading to the release of ten recommendations by the European Society of Breast Imaging (EUSOBI) in August 2021. Considering the rapidly changing scenario and data scarcity, these initial recommendations kept a highly conservative approach.

A primer on common supplements and dietary measures used by patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disease of the intestines. The pathophysiology of IBD, namely Crohn's disease and ulcerative colitis, is a complex interplay between environmental, genetic, and immune factors. Physicians and patients often seek complementary and alternative medicines (CAMs) as primary and supplementary treatment modalities.

Real-World Outcomes for Basilar Artery Occlusion Thrombectomy With Mild Deficits: The National Inpatient Sample.

Background: Thrombectomy for basilar artery occlusion (BAO) has proven efficacy in patients with moderate-to-severe deficits, but has unclear benefits for those with mild symptoms.

Methods: Using an observational cohort design, the US National Inpatient Sample (2018-2020) was queried for adult patients with basilar artery occlusion and National Institutes of Health Stroke Scale (NIHSS) <10 for patients treated with thrombectomy versus medical management. The primary outcome of routine discharge (to home or self-care) was evaluated using multivariable logistic regression and propensity score matching, adjusted for baseline characteristics, stroke severity, and treatment with thrombolysis.

Immune profiling after allogeneic hematopoietic cell transplantation in pediatric acute myeloid leukemia.

Although allogeneic hematopoietic cell transplant (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of posttransplant mortality. To identify pressures imposed by allo-HCT on AML cells that escape the graft-versus-leukemia effect, we evaluated immune signatures at diagnosis and posttransplant relapse in bone marrow samples from 4 pediatric patients using a multimodal single-cell proteogenomic approach. Downregulation of major histocompatibility complex class II expression was most profound in progenitor-like blasts and accompanied by correlative changes in transcriptional regulation.

Comparison of Mammography AI Algorithms with a Clinical Risk Model for 5-year Breast Cancer Risk Prediction: An Observational Study.

Background Although several clinical breast cancer risk models are used to guide screening and prevention, they have only moderate discrimination. Purpose To compare selected existing mammography artificial intelligence (AI) algorithms and the Breast Cancer Surveillance Consortium (BCSC) risk model for prediction of 5-year risk. Materials and Methods This retrospective case-cohort study included data in women with a negative screening mammographic examination (no visible evidence of cancer) in 2016, who were followed until 2021 at Kaiser Permanente Northern California.

Impact of social determinants of health on individuals living with generalized myasthenia gravis and implications for patient support programs.

Introduction: Social determinants of health (SDOH) are important contributors to health outcomes, and better understanding their impact on individuals diagnosed with rare, chronic diseases with high burden and unmet need is critical. Characterizing SDOH burden can help improve the design of patient support programs (PSPs), using targeted approaches to remove barriers to access.

Methods: This study used a mixed-methods strategy employing a quantitative survey, which was designed based on qualitative interviews, to understand the unmet needs and awareness/utilization of PSPs among individuals living with generalized myasthenia gravis (gMG) and experiencing SDOH barriers.

Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging.

This review is focused on the mechanisms that regulate health, disease and aging redox status, the signal pathways that counteract oxidative and reductive stress, the role of food components and additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), and the role of the hormones irisin and melatonin in the redox homeostasis of animal and human cells. The correlations between the deviation from optimal redox conditions and inflammation, allergic, aging and autoimmune responses are discussed.

Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).

Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula.

An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability.

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.

Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial.

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate.

Sarcopenia and Cardiovascular Diseases.

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration.

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines . Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin).

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

Background: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown.

Methods: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months.

The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

Objective: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction.

Methods: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included.

Evaluation of Immunohistochemical Expression of Enhancer of Zeste Homolog 2 (EZH2) and Its Association With Clinicopathological Variables in Carcinoma Cervix.

Introduction:  Carcinoma cervix is the fourth most common cancer worldwide and is one of the leading causes of cancer death in women. Recently, immunohistochemical expression of biomarkers has been utilized as indicators of disease progression, aggressiveness for predicting the prognosis in various cancers. DNA methylation of genes plays an important role in pathogenesis of carcinoma cervix and detection of aberrant methylation can be utilized for detection of carcinoma cervix and monitoring of its progression.