The FDA has issued a major safety alert on andexanet alfa, used to reverse factor Xa inhibitors, after post-marketing data and the ANNEXA-I trial showed roughly double the risk of serious and fatal thromboembolic events versus usual care. Concluding that risks now outweigh benefits, U.S. sales will end, forcing hospitals to urgently reassess reversal protocols. Meanwhile, the CDC reports a sharp national rise in influenza activity, dominated by H3N2, with increasing hospitalizations and pediatric deaths; vaccination and early antiviral treatment remain strongly recommended. Finally, the FDA approved once-daily oral semaglutide 25 mg for weight management and cardiovascular risk reduction, offering efficacy comparable to injectable therapy and potentially expanding patient access when launched in 2026.

Drs. Yu and Herzberg discuss recent developments in HER2- and EGFR-targeted therapies for lung cancer, focusing on clinical trial results at ESMO 2025. Key highlights include promising response rates, toxicity profiles, and the potential for these targeted therapies to treat patients with specific genetic mutations, particularly those with CNS metastases.

Drs. Herzberg and Yu continue their discussion on emerging clinical data presented at ESMO and WCLC 2025. They highlight recent advancements in HER2-targeted therapies for NSCLC and review new HER2-targeted therapies, international study results, and the promise of evolving targeted approaches for HER2-altered lung cancer.

Drs. Herzberg and Yu explore emerging clinical data from the 2025 meetings of the European Society For Medical Oncology (ESMO) and World Conference on Lung Cancer (WCLC), highlighting recent advancements in HER2-targeted therapies for NSCLC. Their discussion focuses on new drugs (eg, zongertinib and trastuzumab deruxtecan), their efficacy and safety profiles, and the potential for treating HER2 mutations and overexpression.

A large cardiovascular outcomes trial in high-risk adults with type 2 diabetes showed that a dual incretin therapy was noninferior to an established comparator for major adverse cardiovascular events over four years, with similar overall safety but more gastrointestinal side effects and no added cardiovascular benefit. Separate trials demonstrated that a single-bolus thrombolytic was as effective and safe as standard infusion therapy for acute ischemic stroke while simplifying workflows, and that vascular brain injury and inherited risk independently increase dementia risk, underscoring the importance of aggressive management of modifiable vascular factors.

Drs. Kaul and Adegunsoye discuss advanced technologies to improve early detection and treatment of interstitial lung disease in veterans, with innovative approaches including the MAVRIC trial and AI-powered risk prediction models. These efforts aim to transform pulmonary care by identifying high-risk patients and developing targeted interventions.

Drs. Kaul and Adegunsoye discuss Veterans Affairs’ innovative approach to understanding and treating pulmonary fibrosis among veterans by leveraging extensive electronic health records and data repositories. The work focuses on addressing healthcare disparities, exploring risk factors, and developing a hub-and-spoke telehealth model to provide specialized care to veterans in rural and underserved areas.

Drs. Adegunsoye and Kaul review their takeaways from CHEST 2025, where pulmonary experts revealed a transformative approach to interstitial lung disease that emphasizes precision medicine and personalized treatments. The conference marked a shift from passive observation to proactive intervention, focusing on early screening, targeted therapies, and reducing healthcare disparities.

A long-term analysis of major prediabetes trials found that achieving remission or returning glucose levels to normal was associated with over a 50% reduction in cardiovascular death or heart failure, with durable benefits decades later; delaying diabetes without remission did not show similar benefit. A randomized trial in critically ill adults found no difference in 28-day mortality between ketamine and etomidate for intubation, though ketamine increased the risk of cardiovascular collapse. Finally, molecular data showed indoor tanning causes widespread DNA mutations linked to melanoma, reinforcing its carcinogenic risk.

CHEST 2025 showcased exciting advances in interstitial lung disease treatment, featuring new anti-fibrotic therapies and more personalized approaches. Drs. Adegunsoye and Kaul discuss emerging strategies for earlier detection and more targeted interventions across different lung disease phenotypes.

Drs. Drago and Traina explore the evolving landscape of managing central nervous system (CNS) metastases in HER2+ breast cancer, highlighting recent advances and clinical results in targeted therapies, including neratinib, tucatinib, and trastuzumab deruxtecan, that offer new hope for patients with brain metastases.

Dr. Drago and Dr. Traina continue their discussion of breakthrough developments in triple-negative breast cancer treatment, sharing highlights from the promising ASCENT-04 trial results with sacituzumab govitecan plus pembrolizumab in first-line treatment. They also address key clinical challenges around sequencing antibody-drug conjugates and managing interstitial lung disease toxicity.

The ACIP voted to replace universal newborn hepatitis B vaccination with shared clinical decision-making for infants of mothers who test negative, a move strongly criticized by major medical and public health groups who warn it could reverse decades of progress in preventing pediatric hepatitis B. A large NEJM trial found that a single dose of HPV vaccine provides protection equivalent to two doses over five years, supporting simplified global vaccination strategies. Real-world evidence from nearly 5,000 patients shows dapagliflozin and empagliflozin deliver similar safety and effectiveness across all forms of heart failure.

Dr. Tiffany Traina and Dr. Josh Drago discuss the evolving treatment landscape for HER2-low and ultralow breast cancer, highlighting how pivotal trials like Destiny Breast-04 and Destiny Breast-06 have demonstrated significant efficacy improvements with trastuzumab deruxtecan while emphasizing the need to balance its toxicity profile with benefits for individual patients.

Drs. Danilov and Coombs review the evolving treatment strategies for CLL, focusing on the use of CAR T-cell therapy and allogeneic stem cell transplant in different disease stages, particularly for patients with relapsed or refractory disease. They emphasize the importance of tailoring treatment to individual patient needs, considering clinical trials, and recognizing challenges.

Drs. Danilov and Coombs explore the potential benefits and challenges of CAR T-cell therapy in CLL, emphasizing the importance of personalized treatment decisions and shared decision-making between physicians and patients.

A large population study links trimethoprim-sulfamethoxazole to a rare yet nearly threefold higher risk of severe acute respiratory failure in healthy adolescents and young adults, reinforcing FDA warnings and the need for careful monitoring. Two extensive Cochrane reviews—including over 132 million people—confirm that HPV vaccination dramatically reduces cervical cancer, high-grade precancers, and anogenital warts without increasing serious adverse events. Kentucky's deadly pertussis surge highlights declining vaccine coverage and the critical role of maternal Tdap and timely childhood immunization to protect the most vulnerable infants.

Drs. Camacho and Lewiecki discuss emerging osteoporosis therapies that are revolutionizing bone health treatment, with promising developments like oral parathyroid hormone medications and dual-action anabolic agents that challenge traditional injection-based approaches. Biosimilars, particularly for denosumab, are expanding patient access by offering highly similar, potentially more affordable alternatives to brand-name drugs, signaling a transformative era in osteoporosis care.

Drs. Lewiecki and Camacho discuss sequential therapy in osteoporosis as a critical strategy that involves strategically switching between anabolic and antiresorptive treatments to maximize bone mineral density and reduce fracture risk. By carefully transitioning between different drug classes (eg, romosozumab; teriparatide; denosumab), clinicians can optimize patient outcomes and address the evolving needs of individuals with bone health challenges.

A long-term Framingham Heart Study analysis shows that regular physical activity beginning in midlife and continuing into older age significantly lowers the risk of dementia, including Alzheimer disease, with the most active individuals experiencing roughly 40–45% risk reduction. A phase 3 trial of the first oral PCSK9 inhibitor, enlicitide, demonstrated substantial LDL-C and apoB reductions in patients with heterozygous familial hypercholesterolemia already on statins, offering a well-tolerated oral option that helps most patients reach guideline targets. Finally, a large U.S. cohort study revealed persistent under-treatment of chronic hepatitis B—especially among women and non-Asian racial groups—highlighting the need for standardized assessment and timely antiviral therapy to close these gaps.