THE ROUNDS REPORT
High-flow nasal oxygen will keep more of your ICU patients off the ventilator. It won't keep more of them alive. SOHO just drew that distinction in permanent ink.
Oh, and semaglutide doesn't treat Alzheimer's disease. Definitively. That one result will change more clinic conversations than almost anything else in this issue.
And there's plenty more here. IgA nephropathy gets its first oral disease-modifying therapy with hard eGFR endpoint data. Dermatomyositis — managed with blunt tools for decades — finally has a targeted treatment. And left atrial appendage closure goes head-to-head with DOACs for the first time.
Five subspecialties. Five conversations worth having on Monday morning. Here's what you need to know.
THE BIG FIVE GAME-CHANGERS
1. CHAMPION-AF: Left Atrial Appendage Closure Goes Head-to-Head With DOACs
For the first time, the WATCHMAN FLX device was tested against modern NOACs — not warfarin — in 3,000 AF patients eligible for anticoagulation at sites across 16 countries. The primary composite of stroke, cardiovascular death, or systemic embolism at 36 months: 5.7% with LAAC versus 4.8% with DOAC, meeting noninferiority (95% CI −0.8 to 2.6). Non-procedural major or clinically relevant bleeding favored the device: 10.9% versus 19.0% (HR 0.55; P<0.001). Ischemic stroke was numerically higher with LAAC (3.2% vs. 2.0%; HR 1.61; 95% CI 1.00–2.59).
Practice implication: This gives a meaningful option for AF patients with high bleeding risk who struggle with long-term anticoagulation. But the numerical excess of ischemic stroke prevents LAAC from replacing DOACs as first-line therapy for the average patient. Note: trial was industry-sponsored by Boston Scientific.
2. APPLAUSE-IgAN: Iptacopan Slows Kidney Decline in IgA Nephropathy
Final 24-month data from APPLAUSE-IgAN established iptacopan as the first oral disease-modifying therapy with confirmed eGFR-slope benefit in IgA nephropathy. Adults with biopsy-confirmed IgAN on optimized RAS blockade were randomized to iptacopan 200 mg twice daily or placebo. Annualized eGFR decline: −3.10 mL/min/1.73 m²/year with iptacopan versus −6.12 with placebo — a 49.3% slower decline (difference 3.02; 95% CI 2.02–4.01; P<0.001). Composite kidney failure events: 21.4% versus 33.5% (HR 0.57).
Practice implication: The old "supportive care and watch" approach to IgAN is over. Patients with persistent proteinuria >0.75 g/g despite optimized RAS and SGLT2 blockade should be referred to nephrology for disease-modifying therapy sooner rather than later.
3. VALOR: First Targeted Therapy Proven Effective in Dermatomyositis
241 adults with dermatomyositis were randomized to brepocitinib 30 mg, 15 mg, or placebo for 52 weeks on top of standard therapy with mandated steroid taper. The primary outcome (Total Improvement Score at week 52): 46.5 with 30 mg versus 31.2 with placebo (difference 15.3 points; P<0.001). All nine key secondary endpoints were met. Nearly twice as many patients in the brepocitinib 30 mg group successfully tapered to ≤2.5 mg/day prednisone-equivalent compared with placebo. Serious infections were more common at 30 mg (9.9% vs. 1.3%).
Practice implication: VALOR is the first-ever positive registrational trial for a targeted therapy in dermatomyositis. The FDA has accepted the NDA with a PDUFA date in Q3 2026 and a planned U.S. launch by end of September. Patients on chronic steroids for DM warrant early rheumatology referral now.
4. EVOKE & EVOKE+: Semaglutide Does Not Slow Alzheimer Disease
Two parallel multinational Phase 3 trials enrolled amyloid-confirmed AD patients (mild cognitive impairment or mild dementia, ages 55–85, across 566 sites in 40 countries) and randomized them to oral semaglutide titrated to 14 mg/day or placebo for 104 weeks. CDR-Sum of Boxes change from baseline showed no difference in either trial: estimated difference −0.08 (95% CI −0.35 to 0.20; P=0.57) in EVOKE and 0.10 (95% CI −0.17 to 0.38; P=0.46) in EVOKE+. All secondary cognitive and functional endpoints were neutral across both trials.
Practice implication: This definitively closes the GLP-1 for symptomatic Alzheimer hypothesis. Patients and families are asking about this regularly — EVOKE and EVOKE+ are the citations to anchor that conversation. Do not start or continue semaglutide for cognitive indications.
5. SOHO: High-Flow Oxygen Cuts Intubation but Not Mortality in Acute Respiratory Failure
1,110 adults with non-hypercapnic acute hypoxemic respiratory failure across 42 French ICUs were randomized to high-flow nasal oxygen or standard oxygen. 28-day mortality: 14.6% in both groups (P=0.98). Intubation by day 28 was lower with high-flow oxygen: 42.4% versus 48.4% (difference −5.93 percentage points; 95% CI −11.78 to −0.08). Serious adverse events — cardiac arrest or pneumothorax during spontaneous breathing — were more common in the high-flow arm: 2.3% versus 1.1%.
Practice implication: Nearly 11 years after the original FLORALI trial suggested a mortality benefit, SOHO — larger and better powered — finds none. HFNC remains reasonable in selected patients with type 1 respiratory failure, but stop framing it as a mortality intervention. Don't let it delay timely intubation when clinically indicated.
CLINICAL PEARLS THAT MATTER
Rapid AST Doesn't Improve Outcomes in Gram-Negative Bacteremia — FAST trial (gram-negative bacteremia, 7 centers) showed rapid phenotypic susceptibility testing meaningfully reduced time to optimal antibiotic therapy but did not improve the 30-day DOOR primary outcome versus standard testing. Good stewardship infrastructure matters more than the speed of the assay. FAST Trial - JAMA
Defer Coronary PCI Before TAVI in Selected Patients — PRO-TAVI (466 patients, 12 Dutch hospitals) showed PCI deferral was noninferior to pre-TAVI PCI for the 1-year composite of death, MI, stroke, and major bleeding in TAVI candidates with stable CAD and no clear ischemic indication. Investigator-initiated; no industry funding. PRO-TAVI - The Lancet
DASH Grocery Delivery Lowers Blood Pressure 5 mmHg in Food-Insecure Patients — GoFreshRx (176 Black adults with treated hypertension in Boston food deserts) showed 12 weeks of home-delivered DASH groceries reduced SBP 5.0 mmHg more than a cash stipend (95% CI −8.0 to −1.9; P=0.002), with benefit persisting 3 months post-intervention — equivalent to adding a low-dose antihypertensive. GoFreshRx - Nature Medicine
Reaching Patients Directly Doubles PPI Deprescribing Rates — Cluster-randomized trial (34,409 adults on PPIs ≥1 year across 683 French primary care practices) found a combined patient-plus-GP deprescribing intervention achieved ≥50% PPI reduction in 14.9% of patients versus 7.0% with usual care (adjusted absolute difference 6.9%; 95% CI 5.7–8.3; P<0.001); a GP-only intervention performed no better than usual care. Last month's EHR nudge pearl showed digital prompts move the needle in older adults — this trial shows that going directly to the patient doubles the effect. JAMA Internal Medicine
MONDAY MORNING ROUNDS: 5 KEY DISCUSSION POINTS
CHAMPION-AF showed LAAC was noninferior to DOACs for stroke/CV death/embolism (5.7% vs 4.8%) with a 45% reduction in non-procedural bleeding — but a numerical excess of ischemic stroke (HR 1.61; 95% CI 1.00–2.59) keeps it out of first-line for most patients.
Iptacopan slowed IgAN eGFR decline by 49.3% (−3.10 vs −6.12 mL/min/1.73 m²/year; P<0.001) — the first oral disease-modifying therapy with confirmed eGFR-slope benefit; early nephrology referral is now the standard for high-risk IgAN.
Brepocitinib met all primary and secondary endpoints in dermatomyositis (TIS difference 15.3 points; P<0.001) with significant steroid-sparing — FDA PDUFA expected Q3 2026, planned launch end of September.
Oral semaglutide failed to slow Alzheimer disease in two large Phase 3 trials across 3,808 patients — the GLP-1/dementia hypothesis is closed at the symptomatic stage.
High-flow oxygen reduced intubation (42.4% vs 48.4%) but not 28-day mortality (14.6% both arms) in 1,110 patients with acute hypoxemic respiratory failure, with a higher rate of serious adverse events in the HFNC arm (2.3% vs 1.1%).
ESSENTIAL READING
Cardiology
Nephrology
Rheumatology/Dermatology
Neurology
Pulmonary/Critical Care
Infectious Disease
Cardiology/Interventional
Preventive Medicine
Gastroenterology/General IM
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