PVRoundup Podcast

Drs. Wierda and O'Brien discuss emerging data showing the non-covalent BTK inhibitor pirtobrutinib outperforming traditional chemoimmunotherapy and showing favorable efficacy and safety versus ibrutinib in CLL. They also highlight promising early results from a triplet regimen for Richter transformation, suggesting the best survival outcomes yet seen in this historically high‑risk, hard‑to-treat population.

New AHA/ACC guidelines overhaul pulmonary embolism management with a five-tier risk classification, endorsing ED discharge for low-risk patients and DOACs as first-line therapy. A JAMA trial confirms IV acetaminophen adds modest but real pain relief when combined with morphine. A large cohort study shows SGLT2 inhibitors dramatically reduce kidney, cardiovascular, and liver complications in diabetic cirrhosis patients.

Drs. Cytryn, Foote, and Thummalapalli discuss recent data on HER2 testing modalities and the prevalence of HER2 positivity across hepatobiliary, upper GI, and colorectal cancers, highlighting implications for precision medicine. The conversation reviews the latest clinical trial findings and the evolving landscape of HER2-targeted therapies, with insights into optimal treatment sequencing for various GI cancer subtypes.

Drs. Ailani and Dougherty discuss onabotulinumtoxinA, a cornerstone treatment for chronic migraine, which reduces headache days and disability when given regularly with the PREEMPT protocol. They emphasize its unique benefits and how it pairs with CGRP therapies, oral preventives, and lifestyle changes for individualized care.

Three major studies reshape preventive care. Long-term follow-up from diabetes prevention trials, published in The Lancet Diabetes & Endocrinology, shows that achieving remission of prediabetes—normalizing glucose levels—cuts cardiovascular death or heart failure risk by about 50%, with benefits lasting decades. In The Lancet, a multicohort analysis of 540,000 adults found obesity increases risk of severe infection by 70%, with nearly threefold higher infection-related hospitalization or death in severe obesity. Finally, a randomized trial in The Lancet Child & Adolescent Health found no increased risk of eczema or respiratory illness in infants receiving acetaminophen versus ibuprofen, providing reassurance about its safety.

Drs. Dizon and Campos discuss how new antibody drug conjugates like trastuzumab deruxtecan are transforming treatment options for HER2+ gynecological cancers, showing promising results even in patients with low HER2 expression. They shared impressive clinical trial successes while emphasizing the importance of ongoing research into treatment sequencing and patient safety.

Drs. Campos and Dizon explore how groundbreaking research is redefining HER2-targeted therapies in gynecological cancers, moving beyond the old one-size-fits-all approach. They spotlight the promise and ongoing challenges of customizing treatment using new biomarkers and clinical trial data.

A phase 3 trial in The New England Journal of Medicine found that the oral PCSK9 inhibitor enlicitide reduced LDL by 57% at 24 weeks in high-risk patients, with similar adverse events to placebo. An oral option may improve uptake and help more patients reach lipid targets. In The Lancet, SMART-CHOICE 3 showed clopidogrel monotherapy after DAPT post-PCI reduced death, MI, or stroke versus aspirin, without more bleeding. Finally, a large meta-analysis confirmed most reported statin side effects are not causally linked, reinforcing their strong benefit–risk profile.

A JAMA Network Open consensus guide standardizes adult UTI triage for telehealth and in-person care. Nonpregnant women with classic cystitis symptoms and no resistance risks may receive empiric antibiotics without testing; men and higher-risk women require urinalysis with culture before treatment. Urine color or odor alone does not justify testing, and urgent evaluation is advised for suspected complicated infection or sepsis. A Danish registry study in JAMA Internal Medicine found SGLT2 inhibitors offer greater kidney protection than GLP-1 receptor agonists in type 2 diabetes. Long-term ASPREE follow-up in JAMA Oncology showed low-dose aspirin did not lower cancer incidence and increased cancer-related mortality in older adults.

Drs. Coombs and Danilov explore how to optimally sequence covalent BTK inhibitors, non‑covalent BTK inhibitors (such as pirtobrutinib), and venetoclax-based regimens for relapsed CLL, emphasizing real-world data and emerging trial results. They highlight that treatment choices hinge on prior response depth and duration, tolerability, mutational profile, and the need to preserve future options and clinical trial eligibility.

A large Lancet meta-analysis found no clinically meaningful association between prenatal acetaminophen exposure and autism, ADHD, or intellectual disability after restricting analyses to adjusted and sibling-comparison studies, with odds ratios essentially null; acetaminophen remains first-line for pain and fever in pregnancy. A Nordic BMJ case-control study of more than 17,000 gastric cancer cases found no increased risk of non-cardia adenocarcinoma with long-term proton pump inhibitor use after comprehensive confounder adjustment. Finally, a U.S. cohort study of older adults linked shingles vaccination to lower inflammation and slower biological aging across multiple systems, though causality cannot be confirmed due to observational design.

Firearm ownership has surged in the U.S., yet safety discussions remain uncommon in clinical care. An NEJM article supports routine, nonpolitical firearm counseling using the “3 A's” (Ask, Advise, Assist) to reduce risks such as suicide and unintentional injury. Separately, a BMJ meta-analysis shows that patients stopping GLP-1 weight-loss medications typically regain weight within 1.5–2 years, reinforcing obesity as a chronic condition requiring long-term planning. Finally, a large sham-controlled trial found no meaningful benefit of trigeminal nerve stimulation for pediatric ADHD, suggesting prior perceived effects were placebo-driven.

A large U.S. cohort study found that children who were late for routine 2- or 4-month immunizations were six to seven times more likely to miss MMR vaccination entirely by age two, highlighting early delays as a strong predictor of future vaccine refusal amid rising measles cases. A long-term study of more than 27,000 women showed that very high lipoprotein(a) levels were associated with substantially increased cardiovascular risk over 30 years, supporting targeted one-time screening. Finally, Medicare data revealed that one in four older adults with dementia received CNS-active medications, often without clear indications, underscoring opportunities to reduce inappropriate prescribing.

New real-world data suggest that GLP-1 receptor agonists used for adolescent obesity are associated with roughly half the rate of asthma exacerbations, fewer emergency visits, and reduced steroid and rescue inhaler use, indicating a possible dual benefit beyond weight loss. In HIV care, Phase 3 ARTISTRY-2 topline results show a once-daily bictegravir/lenacapavir tablet was non-inferior to Biktarvy at 48 weeks, with no new safety signals, potentially expanding durable treatment options. Finally, experimental data demonstrate that even a single 10-minute bout of vigorous exercise can rapidly trigger molecular changes that suppress pathways linked to colon cancer development.

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.

Drs. Camacho and Lewiecki discuss trabecular bone score (TBS) as a groundbreaking approach to assessing fracture risk by evaluating bone quality beyond traditional bone density measurements. By integrating TBS with FRAX® and showing promise across diverse patient populations, this innovative technique helps clinicians identify patients at risk of fractures who might otherwise be overlooked by standard diagnostic methods.

Major medical societies broadly support the FDA's removal of most boxed warnings from menopausal hormone therapy, emphasizing improved access and the importance of individualized risk assessment. The Americas have lost their measles-free status due to persistent outbreaks driven by low vaccination coverage, prompting PAHO to call for renewed immunization efforts and stronger surveillance. A randomized trial in JAMA found that moderate caffeinated coffee intake may reduce recurrence of atrial fibrillation after cardioversion compared with abstinence.

A Rutgers-led trial found that ibuprofen plus acetaminophen provided better pain relief and fewer side effects than opioids following dental surgery, challenging traditional prescribing habits. A Swiss national cohort showed that non–beta-lactam antibiotics nearly doubled surgical-site infection risk compared to beta-lactams, reinforcing their role in prophylaxis. Finally, a meta-analysis confirmed that acetaminophen remains safe during pregnancy when used appropriately, with no proven link to neurodevelopmental disorders.

Drs. Cooper and Rotow review the challenges of CNS involvement in HER2+ NSCLC, emphasizing the importance of baseline and ongoing brain imaging, and the emerging understanding of CNS penetrance for HER2-targeted therapies. They explore strategies for managing brain metastases, including balancing local therapies, including radiation with systemic treatments, and highlight the need for multidisciplinary approaches and further research on CNS activity in clinical trials.

A New England Journal of Medicine study showed a novel chemotherapy regimen, trastuzumab deruxtecan combined with pertuzumab, outperformed the current standard in treating HER2-positive advanced breast cancer, demonstrating better efficacy and tolerability with fewer traditional chemotherapy-related side effects. A JAMA Oncology study by Uppsala University revealed a modest increase in breast cancer risk with hormonal contraceptive use among over two million Swedish women, emphasizing the need for balanced counseling regarding risks and benefits. The REPAIR trial in Denmark, published in the British Medical Journal, demonstrated that a short course of antibiotics significantly reduced clinically important wound complications after vaginal delivery in women with episiotomies or second-degree tears, highlighting its potential benefit in postpartum care.

Drs. Rotow and Cooper explore the evolving landscape of HER2+ NSCLC treatment, highlighting recent advancements in targeted therapies like HER2 TKIs and antibody-drug conjugates. They emphasize the importance of comprehensive biomarker testing, the significance of personalized treatment approaches, and the exciting progress in providing more effective and tolerable second-line therapies for patients. The discussion underscores the field's movement toward precision medicine and the potential for future combination strategies and improved patient outcomes.

Drs. Cooper and Rotow discuss first-line treatment strategies for HER2+ NSCLC, highlighting the importance of comprehensive molecular testing and emerging targeted therapies. Key considerations include the efficacy of antibody-drug conjugates and TKIs, with ongoing clinical trials evaluating their potential as frontline treatments. The discussion emphasizes the need for personalized treatment approaches based on individual patient characteristics, molecular features, and the evolving landscape of HER2-targeted therapies.

Drs. Lynce and Waks explore whether advances in HER2-targeted therapy are making metastatic HER2+ breast cancer potentially curable, highlighting long-term remissions, survival gains from trials, and ongoing studies testing treatment-free remission.

Drs. Waks and Lynce review the PATINA trial, which showed that adding a CDK4/6 inhibitor to HER2-targeted and endocrine therapy improved progression-free survival in triple-positive breast cancer, shaping how this subgroup may be managed.

New research presented at ESMO 2025 confirms that datopotamab deruxtecan significantly improves progression-free and overall survival compared with chemotherapy in advanced triple-negative breast cancer, supporting its role as a first-line standard of care. Updated SELECT trial analyses demonstrate that semaglutide reduces major cardiovascular events by 20% independent of weight loss, suggesting cardioprotective mechanisms beyond adiposity reduction. Long-term data show that HPV vaccination has led to dramatic declines in vaccine-type infections and strong herd protection, although global coverage remains suboptimal.

Drs. Lynce and Waks discuss advances in early-stage HER2+ breast cancer, focusing on how targeted therapies have transformed outcomes. They explore de-escalation strategies, the role of platinum drugs, insights from the COMPASS trial, and the importance of pathologic complete response in guiding treatment decisions.

A large real-world study of over 1.2 million adults with type 2 diabetes found that SGLT2 inhibitors and GLP-1 receptor agonists reduced major cardiovascular events compared with metformin, while sulfonylureas and insulin increased risk. A separate French population study showed no association between first-trimester mRNA COVID-19 vaccination and congenital malformations, supporting vaccine safety in pregnancy. Finally, researchers at Mass General Brigham reported that large language models can produce “sycophantic” but incorrect medical advice, emphasizing the need for clinician oversight when using AI in healthcare.

Data in ~300,000 U.S. veterans show the 2024–2025 COVID-19 booster cut COVID-related ED visits (−29%), hospitalizations (−39%), and deaths (−64%) over six months, with modest yet meaningful absolute gains. In JAMA Psychiatry, a cohort linked risperidone use in dementia to a 28% higher stroke risk, especially in those with prior cardiovascular disease and within the first three months, warranting cautious, time-limited prescribing and monitoring. An article in JAMA Network Open found restless leg syndrome associated with higher subsequent Parkinson's incidence, supporting RLS as a practical marker for heightened PD risk.

An analysis of 35,000 stage II–III colon cancer cases shows relapse risk peaks in year one and falls below 0.5% per six-month interval by year six, offering a practical definition of cure and a basis to taper long-term follow-up. A second study estimates U.S. inhaler use generates over two million metric tons of annual emissions, with propellant-free devices offering lower-impact alternatives. Finally, lifestyle cohorts reveal about one-quarter of people with prediabetes can normalize glucose without weight loss, conferring >70% risk reduction over a decade and spotlighting fat distribution as a modifiable target.

Drs. Fahkri and Seshadri review abstracts from the 18th International Conference on Malignant Lymphoma in Lugano, Switzerland, exploring investigational novel agents in CLL.

A new meta-analysis in HeartRhythm found that SGLT2 inhibitors reduced sudden cardiac death risk by about 18% across patients with type 2 diabetes, heart failure, or chronic kidney disease, with consistent effects and minimal trial variation. A Cochrane review of over 100,000 participants showed RSV vaccines are highly effective and safe: protein-based shots cut severe lower respiratory infections in older adults by ~75% and protected infants when given to pregnant mothers, halving RSV-related care and hospitalizations. Finally, WHO and EMA reaffirmed acetaminophen's safety in pregnancy, rejecting suggested links to autism or neurodevelopmental harm, noting decades of safe use and the risks of untreated pain or fever.

Drs. Seshadri and Fahkri review abstracts exploring treatments for patients with high-risk CLL, including SEQUOIA Arm C and CLL16 studies.