PVRoundup Podcast

Drs. Wierda and O'Brien discuss how fixed-duration venetoclax-based therapy can match continuous BTK inhibitor treatment in CLL while offering deep remissions and time off therapy. They also explore promising real-world CAR T-cell (liso-cel) results and stress the growing importance of vaccination and cancer screening as CLL patients live longer.

New cardiovascular data suggest pulsed field ablation may challenge antiarrhythmic drugs as first-line therapy for persistent atrial fibrillation, while real-world evidence positions apixaban as the preferred DOAC for younger patients with nonvalvular AF due to superior safety and effectiveness. Additional findings from the SENIOR-RITA trial indicate that routine invasive management may not benefit frail older adults with NSTEMI and could worsen outcomes in the most frail patients. Together, these studies highlight a growing shift toward more individualized cardiovascular treatment strategies.

Daraxonrasib, a first-in-class oral RAS inhibitor, nearly doubled overall survival versus chemotherapy in previously treated metastatic pancreatic cancer, representing a potentially landmark advance in a historically difficult-to-treat disease. The antibody-drug conjugate datopotamab deruxtecan significantly improved progression-free and overall survival over chemotherapy in first-line triple-negative breast cancer, particularly for patients ineligible for immunotherapy. A Cochrane review of nearly 20,000 patients found anti-amyloid Alzheimer's therapies offer minimal clinically meaningful cognitive benefit while carrying meaningful safety risks, complicating their real-world use.

Drs. Maron and Rowin review how treatment for symptomatic obstructive hypertrophic cardiomyopathy has evolved from mainly using beta blockers and invasive procedures to now including newer cardiac myosin inhibitor drugs. These newer medications more reliably reduce obstruction and improve patient symptoms and exercise capacity, but require careful safety monitoring with regular heart function checks.

Shingles vaccination in adults with established cardiovascular disease was associated with dramatic reductions in heart attack, stroke, and mortality in a large real-world analysis, supporting its role as a cardiovascular risk-reduction tool beyond infection prevention. The VESALIUS-CV trial found evolocumab significantly reduced major cardiovascular events in high-risk diabetic patients without known ASCVD, challenging the convention of reserving PCSK9 inhibitors for secondary prevention only. AI-analyzed smartwatch data predicted heart failure hospitalizations days to weeks in advance, signaling a shift toward continuous remote monitoring in heart failure management.

Drs. Yiu and Emami review key themes from the 49th Annual Macula Society Meeting, emphasizing a shift toward earlier diagnosis and intervention, longer-acting therapies, and increasing reliance on advanced imaging biomarkers and AI. They also look at new and existing data on a range of emerging treatment options for both neovascular and atrophic macular conditions.

Drs. Kuruvilla and Chandwani discuss migraine as a key women's health issue driven largely by estrogen fluctuations across a woman's lifespan, influencing CGRP, serotonin, sleep, and comorbid pain conditions from menstruation through perimenopause and menopause. These experts emphasize individualized, interdisciplinary care that combines CGRP-targeted preventives, hormonal strategies, integrative medicine (eg, acupuncture, supplements), and lifestyle and sleep optimization to improve quality of life.

A trial found that discontinuing beta-blockers in stable post-MI patients without heart failure was noninferior to continuing them, suggesting long-term use may be unnecessary. Second, the 2026 ACC/AHA lipid guideline promotes earlier, personalized intervention using the PREVENT risk calculator and expanded biomarkers to reduce lifetime cardiovascular risk. Finally, a JAMA study found thiazide diuretics carry meaningful hyponatremia risk, especially in older adults and women, urging careful patient selection

Drs. Swigris and Humphries discuss how AI-driven, quantitatively trained algorithms can standardize the interpretation of high-resolution computed tomography (HRCT) in ILD by reducing inter- and intra-reader variability and improving fibrosis extent assessment. They contrast traditional visually based radiology with supervised machine learning approaches, including models trained on biopsy-confirmed diagnoses and disease behavior, to potentially enhance prognostication and clinical decision-making.

A randomized trial in the New England Journal of Medicine found prehospital whole blood transfusion did not improve 30-day mortality over standard component therapy in traumatic hemorrhage, supporting current transfusion protocols. A large population-based study showed patients with positive fecal occult blood tests who did not complete follow-up colonoscopy had significantly higher colorectal cancer incidence and more advanced-stage disease. Finally, a study in Nature Medicine of nearly 15,000 individuals found antibiotic exposure reduced gut microbial diversity for up to 4–8 years, with clindamycin and fluoroquinolones causing the most persistent disruption.

Drs. Sanossian and Saver review new evidence supporting intensified antithrombotic strategies to reduce recurrent ischemic stroke in high-risk, noncardioembolic patients without increasing intracranial hemorrhage. They place this within a comprehensive, multimodal secondary prevention framework that integrates pharmacologic therapy with aggressive risk factor modification (lipids, blood pressure, diabetes, and lifestyle).

Drs. O'Brien and Wierda discuss how fixed-duration venetoclax-based therapy can match continuous BTK inhibitor treatment in CLL while offering deep remissions and time off therapy. They also explore promising real-world CAR T-cell (liso-cel) results and stress the growing importance of vaccination and cancer screening as CLL patients live longer.

Drs. Dougherty and Ailani discuss the 2025 International Headache Society guidelines indicating that neuromodulation is an effective, non-invasive option for both acute and preventive migraine treatment. They stress that it works best as part of a personalized, multimodal plan alongside medications, behavioral therapies, and lifestyle changes.

Drs. Maron and Rowin provide an overview of hypertrophic cardiomyopathy, explaining how it is diagnosed by heart imaging and classified into obstructive and non-obstructive forms. They highlight that obstruction is a major cause of symptoms and stress the importance of carefully assessing patients' day-to-day limitations to guide treatment decisions.

Drs. Petri and Woolfson discuss a simple risk score using autoantibodies, complement, and demographics to predict which SLE patients are most likely to develop proteinuria and lupus nephritis. They also highlight evidence showing that earlier kidney biopsies at lower proteinuria levels, especially in patients with low complement, can detect serious disease sooner and improve outcomes.

This week's podcast covers three NEJM trials. First, apixaban showed over 50% less clinically relevant bleeding than rivaroxaban in acute venous thromboembolism patients, with similar efficacy. Second, romiplostim helped 84% of patients on oxaliplatin-based chemotherapy avoid dose modifications due to thrombocytopenia, versus 36% with placebo. Third, inhaled treprostinil slowed lung function decline in idiopathic pulmonary fibrosis patients over 52 weeks, though cough and discontinuation rates were higher.

Drs. Isaacs and Traina discuss DESTINY-Breast09, where first‑line T‑DXd + pertuzumab clearly outperforms the CLEOPATRA regimen in progression-free survival for metastatic HER2+ breast cancer. They focus on the dilemma of when to use T‑DXd: earlier, for maximal efficacy, or later, to protect quality of life and manage ILD and cardiac risks.

The WISDOM trial found risk-based breast cancer screening — using genetic and polygenic risk scores — is non-inferior to annual mammography, enabling more intensive surveillance for high-risk women while reducing unnecessary imaging for low-risk individuals. Among hypertensive adults, prediabetes combined with elevated cardiac biomarkers significantly increases heart failure risk, suggesting combined metabolic and biomarker screening could guide earlier prevention. RSV vaccination in older adults appears to reduce not only respiratory illness but also associated cardiovascular complications including heart attack and stroke.

Drs. Cytryn, Foote, and Thummalapalli review evolving HER2-targeted treatment strategies for upper GI, biliary, and colorectal cancers, emphasizing challenges with disease heterogeneity and treatment sequencing. They also highlight the importance of HER2 reassessment after progression and advancing diagnostic approaches.

Three studies highlight new findings: A phase 3 trial showed obinutuzumab significantly improved lupus responses versus placebo in active SLE patients on standard therapy. A trial of finerenone in type 1 diabetes with chronic kidney disease demonstrated meaningful reductions in albuminuria compared to placebo, suggesting a new renal-protective option. Finally, paired pediatric trials found that adding acetaminophen or hydromorphone to ibuprofen provided no additional pain relief for children's acute limb injuries, with opioids causing four times more adverse events. Ibuprofen alone remains the recommended first-line approach.

Drs. Isaacs and Traina review how HER2CLIMB‑05 and PATINA challenge the old CLEOPATRA‑based approach by showing that adding tucatinib or palbociclib to maintenance therapy can extend progression‑free survival in metastatic HER2+ breast cancer. They stress tailoring maintenance regimens to each patient's hormone receptor status, CNS risk, and tolerance for side effects.

Drs. Petri and Woolfson review the American College of Rheumatology Convergence 2025 data that suggest belimumab might lower mortality in SLE compared with traditional oral immunosuppressants, supporting earlier biologic use. They also discuss an observational study in lupus nephritis that links GLP-1 agonists to better kidney, survival, and cardiovascular outcomes than SGLT2 inhibitors, particularly in overweight patients.

Drs. Vakharia and Danzig highlight new AAO 2025 data on high-dose aflibercept, sleep apnea as a potential AMD risk factor, and an AI-guided anti-VEGF regimen that cuts injections while maintaining vision. Together, these advances point toward more personalized, efficient care for patients with neovascular AMD and DME.

Drs. Isaacs and Traina discuss new data in HER2+ breast cancer from the 2025 San Antonio Breast Cancer Symposium, focusing on early-stage studies including DESTINY-Breast11 and DESTINY-Breast05 and how data from these studies could potentially impact patient care in the future.

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.