High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC.

Introduction: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

Methods: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869).

Inhibition of the PI3K-AKT-MTORC1 axis reduces the burden of the m.3243A>G mtDNA mutation by promoting mitophagy and improving mitochondrial function.

Mitochondrial DNA (mtDNA) encodes genes essential for oxidative phosphorylation. The m.3243A>G mutation causes severe disease, including myopathy, lactic acidosis and stroke-like episodes (MELAS) and is the most common pathogenic mtDNA mutation in humans.

Association of Antibody-Drug Conjugate (ADC) Target Expression and Interstitial Lung Disease (ILD) in Non-Small-Cell Lung Cancer (NSCLC): Association or Causation or Neither?

Introduction: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, despite advances in immune checkpoint inhibitors and targeted therapies. Antibody-drug conjugates (ADCs) represent a promising therapeutic approach by delivering cytotoxic agents specifically to cancer cells, potentially reducing harm to healthy tissues. This study aims to explore the effectiveness and challenges associated with ADCs in NSCLC, with a focus on drug-induced interstitial lung disease (D-ILD).

Frailty integration in medical specialties: Current evidence and suggested strategies from the Clin-STAR frailty interest group.

Frailty is a syndrome that can inform clinical treatments and interventions for older adults. Although implementation of frailty across medical subspecialties has the potential to improve care for the aging population, its uptake has been heterogenous. While frailty assessment is highly integrated into certain medical subspecialties, other subspecialties have only recently begun to consider frailty in the context of patient care.

Diaphragmatic Myopathy Associated with Dual Immune Checkpoint Inhibitors in a Patient with Renal Cell Carcinoma.

Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases.

Updates in Drug-Related Pneumonitis Due to Targeted Oncologic Therapies.

An increasing number of newer targeted oncologic therapies approved for clinical use can cause drug-related pneumonitis. Drug-related pneumonitis can be difficult to diagnose and requires a high index of suspicion. This review serves as an update to a prior review in this journal about pneumonitis with precision oncology therapies.

Inflammation and aging-related disease: A transdisciplinary inflammaging framework.

Inflammaging, a state of chronic, progressive low-grade inflammation during aging, is associated with several adverse clinical outcomes, including frailty, disability, and death. Chronic inflammation is a hallmark of aging and is linked to the pathogenesis of many aging-related diseases. Anti-inflammatory therapies are also increasingly being studied as potential anti-aging treatments, and clinical trials have shown benefits in selected aging-related diseases.

Dementia Care Among United States Dialysis Providers: A Mixed Methods Study Evaluating Clinician Comfort and Knowledge.

Rationale & Objective: Given the high burden of dementia in dialysis patients, the dialysis workforce needs to be prepared to provide high-quality, person-centered dementia care. We explored comfort with and knowledge of dementia among US dialysis care providers.

Study Design: Web-based survey.

Toxicity in the era of immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression.

Long-Term Clinical, Radiological, and Mortality Outcomes Following Pneumonitis in Nonsmall Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Analysis.

Aims: Despite known short-term mortality risk of immune checkpoint inhibitor (ICI) pneumonitis, its impact on 1-year mortality, long-term pulmonary function, symptom persistence, and radiological resolution remains unclear.

Methods: We retrospectively analyzed 71 nonsmall cell lung cancer (NSCLC) patients treated with anti-PD(L)1 monoclonal antibodies between 2018-2021, who developed pneumonitis. Clinical and demographic covariates were collected from electronic medical record.

Patient-Reported Outcomes to Achieve Person-Centered Care for Aging People With Kidney Disease.

Person-centered care is a system of care delivery that supports effective patient-clinician communication and empowers patients to partner with their clinical providers to develop goal-concordant treatment plans. Models of person-centered care often involve the implementation of patient-reported outcomes (PROs) to measure patients' symptoms and quality of life as they navigate complex chronic health conditions. Models of person-centered care have been particularly effective in improving the quality of care delivery for older adults as well as younger adults with aging-associated conditions such as physical function decline.

Gravity Wave Momentum Fluxes from 1 km Global ECMWF Integrated Forecast System.

Progress in understanding the impact of mesoscale variability, including gravity waves (GWs), on atmospheric circulation is often limited by the availability of global fine-resolution observations and simulated data. This study presents momentum fluxes due to atmospheric GWs extracted from four months of an experimental "nature run", integrated at a 1 km resolution (XNR1K) using the Integrated Forecast System (IFS) model. Helmholtz decomposition is used to compute zonal and meridional flux of vertical momentum from ~1.

CT strain metrics allow for earlier diagnosis of bronchiolitis obliterans syndrome after hematopoietic cell transplant.

Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative computed tomography (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using pulmonary function tests (PFTs) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from 2 large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS.

Task-sharing spinal anaesthesia care in three rural Indian hospitals: a non-inferiority randomised controlled clinical trial.

Background: Task-sharing of spinal anaesthesia care by non-specialist graduate physicians, termed medical officers (MOs), is commonly practised in rural Indian healthcare facilities to mitigate workforce constraints. We sought to assess whether spinal anaesthesia failure rates of MOs were non-inferior to those of consultant anaesthesiologists (CA) following a standardised educational curriculum.

Methods: We performed a randomised, non-inferiority trial in three rural hospitals in Tamil Nadu and Chhattisgarh, India.

Clinical Profile and Efficacy of Long-Acting Octreotide in Hyperinsulinemic Hypoglycaemia.

Introduction: Hyperinsulinemic hypoglycaemia (HH) is characterised by unregulated insulin secretion, leading to persistent non-ketotic hypoglycaemia with a lack of alternate fuel that induces a severe risk for brain damage and neurodevelopmental abnormalities. Octreotide, a somatostatin analogue, has been effectively administered as subcutaneous injections or depot preparations in diazoxide-unresponsive HH.

Methods: Children and infants with HH receiving short-acting octreotide injections were included.

Postinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report.

Continued improvements in the treatment of pulmonary infections have paradoxically resulted in a growing challenge of individuals with postinfectious pulmonary complications (PIPCs). PIPCs have been long recognized after tuberculosis, but recent experiences such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored the importance of PIPCs following other lower respiratory tract infections. Independent of the causative pathogen, most available studies of pulmonary infections focus on short-term outcomes rather than long-term morbidity among survivors.

Gravity- vs Wall Suction-Driven Large-Volume Thoracentesis: A Randomized Controlled Study.

Background: Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated.

Research Question: Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis?

Study Design And Methods: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥ 500 mL were assigned at a 1:1 ratio to wall suction or gravity drainage.

Detection of Bronchiolitis Obliterans Syndrome after Pediatric Hematopoietic Stem Cell Transplantation: An Official American Thoracic Society Clinical Practice Guideline.

Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring.

Respiratory Syncytial Virus Vaccination in the Adult Pulmonary Patient.

Topic Importance: Since its discovery in 1957, respiratory syncytial virus (RSV) has been widely recognized as a common and deadly pathogen. Although early studies focused on the impact of RSV on the health of children, more recent data show that RSV imposes a significant burden on individuals aged ≥ 70 years. RSV also substantially harms the health of individuals with cardiopulmonary diseases.

Drug-induced Lung Disease in the Oncology Patient: From Cytotoxic Agents to Immunotherapy.

Drug-induced lung disease is commonly encountered, especially in the oncology setting. Diagnosis is challenging because clinical and radiologic findings are nonspecific, often overlapping with other lung pathologies in these patients due to underlying neoplasia, infection, or other treatment effects such as radiotherapy. Furthermore, oncology patients often receive multiple antineoplastic agents concurrently, and virtually every agent has an association with lung injury.