THE ROUNDS REPORT
The Super Bowl was fairly boring but it's the most topical analogy I could come up with.
Sue me.
Anyway, let's get on with it: the best in medical literature from the past 3 months.
It looks severe hypertriglyceridemia finally has an effective treatment. SGLT-2 inhibitors are again shown to cut mortality in acute HF patients. And proton therapy just delivered its first-ever survival benefit.
Between mid-November and early February, five major trials landed that are making waves in lipid management, pneumonia treatment, heart failure care, radiation oncology, and vaccine schedules.
Check them out below.
THE BIG FIVE GAME-CHANGERS
1. Olezarsen Slashes Pancreatitis Risk by 85% in Severe Hypertriglyceridemia
Severe hypertriglyceridemia (>500 mg/dL) has lacked an effective treatment for decades. Olezarsen just changed that.
CORE-TIMI 72a and CORE2-TIMI 72b (1,061 patients combined) showed dramatic triglyceride reductions: 50-mg dose achieved 62.9% placebo-adjusted reduction at 6 months and 49.2% at 12 months. The 80-mg dose delivered 72.2% and 54.5% reductions.
The headline finding: 85% reduction in acute pancreatitis (rate ratio 0.15, 95% CI 0.05-0.40, P<0.001). In the highest-risk patients (TG ≥880 mg/dL with prior pancreatitis), this represents transformative risk reduction.
Secondary endpoints: apoC-III dropped 56-77%, remnant cholesterol fell 51-70%, and 86% of patients achieved triglycerides below the 500-mg/dL pancreatitis threshold.
Practice implication: FDA approved olezarsen (TRYNGOLZA™) for familial chylomicronemia syndrome in December 2024, with expanded approval for severe hypertriglyceridemia anticipated. This antisense oligonucleotide targeting APOC3 mRNA provides the first disease-modifying therapy.
2. Low-Dose Steroids Reduce Pneumonia Mortality on General Medical Wards
The CAPE COD trial proved steroids work in ICU-level pneumonia. SONIA just extended that to the general medical ward where most CAP patients are managed.
2,180 adults with community-acquired pneumonia across 18 hospitals in Kenya were randomized to standard care plus oral glucocorticoids (10 days) versus standard care alone. Primary outcome: 30-day mortality was 22.6% versus 26.0% (HR 0.84, 95% CI 0.73-0.97, P=0.021).
This 16% relative mortality reduction was consistent across all time points (7, 14, and 21 days). Only 0.4% experienced serious adverse events from steroids.
Practice implication: Combined with CAPE COD, the evidence now supports adjunctive glucocorticoids for hospitalized CAP of moderate-to-severe intensity (CURB-65 ≥2, or requiring supplemental oxygen). The baseline mortality of 24% in this trial indicates appropriate severity.
3. In-Hospital SGLT2 Inhibitors Cut Mortality 43% in Acute Heart Failure
DAPA ACT HF-TIMI 68 missed its primary endpoint individually, but a prespecified meta-analysis combining it with EMPULSE and SOLOIST-WHF delivers the most compelling evidence yet for early SGLT2 inhibitor initiation.
2,401 patients hospitalized with acute decompensated heart failure received dapagliflozin 10 mg daily or placebo. Primary outcome (CV death or worsening HF at 60 days): 10.9% versus 12.7%, HR 0.86 (95% CI 0.68-1.08, not significant).
The meta-analysis (3,527 patients total) changed the picture: CV death or worsening HF HR 0.71 (95% CI 0.54-0.93) and all-cause mortality HR 0.57 (95% CI 0.41-0.80). That's a 43% mortality reduction. No heterogeneity between trials.
Practice implication: These studies suggest not waiting for outpatient follow-up and validate the initiation of SGLT2 inhibitors during the hospitalization for acute heart failure once patients are hemodynamically stable.
4. Proton Therapy Delivers First-Ever Survival Benefit
For 40 years, proton therapy promised less collateral damage than photon radiation. This landmark phase III trial finally proves it matters.
440 patients with stage III-IV oropharyngeal cancer received either intensity-modulated proton therapy (IMPT) or intensity-modulated radiation therapy (IMRT) at 21 sites across the USA. 3-year progression-free survival was identical: 82.5% versus 83.0%, HR 0.88 (noninferiority confirmed).
The striking finding: 5-year overall survival was 90.9% with proton versus 81.0% with photon therapy, HR 0.58 (95% CI 0.34-0.99, P=0.045). A 10 percentage-point absolute survival improvement.
Toxicity reductions were dramatic: severe dysphagia 31% versus 49%, gastrostomy tube dependence 26.8% versus 40.2% (P=0.018), and grade ≥3 lymphopenia 76% versus 89%. The reduced toxicity likely contributed to survival benefit.
Practice implication: This is the first phase III trial demonstrating a survival benefit for proton therapy in any cancer. The Lancet authors called it a "major milestone." Insurance coverage should expand given proven survival and quality-of-life benefits.
5. One Dose of HPV Vaccine Is Enough
With only 27% of adolescent girls worldwide vaccinated against HPV, simplifying vaccination from two doses to one could be transformative. ESCUDDO proves it works.
20,330 girls aged 12-16 were randomized to one or two doses of either bivalent (Cervarix) or nonavalent (Gardasil 9) HPV vaccine with 5 years of follow-up.
One dose was noninferior to two doses for both vaccines, with vaccine effectiveness exceeding 97% across all four groups. Bivalent rate difference: -0.13 per 100 (95% CI -0.45 to 0.15, P<0.001 for noninferiority). Nonavalent rate difference: 0.21 per 100 (95% CI -0.09 to 0.51, P<0.001).
Practice implication: The accompanying NEJM editorial called this "the strongest evidence to date" supporting the WHO's 2022 recommendation for single-dose HPV vaccination. This could dramatically improve global vaccine coverage and cervical cancer prevention.
CLINICAL PEARLS THAT MATTER
1. Occult Hypercortisolism in Refractory Diabetes
One in four patients with refractory type 2 diabetes has occult hypercortisolism. CATALYST trial screening (1,057 patients with HbA1c 7.5-11.5% despite multiple medications) found 24% had abnormal overnight dexamethasone suppression tests. Mifepristone reduced HbA1c by 1.3% versus placebo and produced 5 kg weight loss. Consider screening in difficult-to-control diabetes. CATALYST Trial - Diabetes Care
2. Age-Adjusted D-Dimer for DVT Exclusion
Age-adjusted D-dimer safely rules out DVT. ADJUST-DVT (3,205 patients) showed using age × 10 µg/L cutoff for patients ≥50 identified 161 additional patients (5%) who could safely avoid imaging without missed thromboses. Sensitivity remained >97% while reducing unnecessary imaging. ADJUST-DVT Trial - JAMA
3. Faster Hyponatremia Correction Is Safer
Faster hyponatremia correction is safer. Kaiser Permanente cohort (13,988 patients with Na ≤120 mEq/L) showed medium-rate correction (8-12 mEq/L/24h) had lowest mortality (9%) versus slow (<8, 13% mortality) or rapid (>12, 12% mortality). Osmotic demyelination occurred in only 0.1%. Consider target of 8-12 mEq/L in first 24 hours. Hyponatremia Study - Annals
4. Shingles Vaccine May Prevent Dementia
Shingles vaccine may prevent dementia. Welsh natural experiment follow-up (282,557 cognitively healthy adults) showed vaccine eligibility reduced new dementia diagnoses by 18% over 7 years, especially vascular dementia (36% reduction). Anti-inflammatory effects beyond VZV prevention may explain cognitive benefits. Shingles Vaccine Study - Cell
MONDAY MORNING ROUNDS: 5 KEY DISCUSSION POINTS
1. Olezarsen achieved 85% pancreatitis risk reduction (rate ratio 0.15) in severe hypertriglyceridemia across 1,061 patients, with triglyceride reductions of 50-72%. FDA-approved December 2024 for familial chylomicronemia syndrome. First disease-modifying therapy targeting APOC3.
2. Low-dose oral steroids reduced 30-day mortality by 16% (HR 0.84) in ward-level CAP patients across 2,180 Kenyan adults, extending CAPE COD evidence beyond ICU. Combined trials support glucocorticoids for CURB-65 ≥2 or oxygen-requiring pneumonia.
3. Meta-analysis of in-hospital SGLT2 inhibitor initiation (3,527 acute HF patients) showed 43% mortality reduction (HR 0.57) and 29% reduction in CV death/worsening HF. Validates early initiation during hospitalization once hemodynamically stable.
4. Proton therapy demonstrated first-ever survival benefit versus photon radiation in oropharyngeal cancer: 5-year OS 90.9% versus 81.0% (HR 0.58), with dramatic toxicity reductions including severe dysphagia (31% vs 49%) and G-tube dependence (27% vs 40%).
5. Single-dose HPV vaccination proved noninferior to two doses with >97% vaccine effectiveness across 20,330 girls, supporting WHO's 2022 single-dose recommendation. Could dramatically improve global cervical cancer prevention coverage.
ESSENTIAL READING BY SUBSPECIALTY
Lipidology
Pulmonary/Critical Care
Cardiology
Radiation Oncology
Preventive Medicine
Endocrinology
Hematology/Thrombosis
Nephrology
Neurology/Prevention
Disclaimer
The content provided in The Rounds Report is for educational and informational purposes only and does not constitute medical advice, diagnosis, treatment recommendations, or professional medical guidance. This newsletter presents summaries and analysis of published medical research and should not be used as a substitute for professional medical judgment, clinical decision-making, or consultation with qualified healthcare providers. Always consult with appropriate medical professionals and refer to original research sources before making any clinical decisions. The Rounds Report does not establish a doctor-patient relationship and readers should not rely on this content for patient care decisions.
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