Medicine is moving fast again. This edition brings updates that challenge long held assumptions and reshape daily decision making. We break down expanded thrombectomy criteria in acute stroke, rethink how aggressively to correct severe hyponatremia, and examine why current lung cancer screening may be missing the majority of cases. You will see new data linking long term air pollution exposure to motor neuron disease risk and progression, real world durability results with upadacitinib in ulcerative colitis, and a striking mortality signal for GLP 1 therapy in colon cancer.

We also explore projected obesity trends that will redefine cardiometabolic care, sex specific treatment response in cannabis use disorder, and the growing need for smarter survivorship strategies in lung cancer.

At the end, something new begins. A focused feature built to refine clinical judgment, reduce reflexive testing, and quietly strengthen your ABIM edge. Do not skip it.

Featured Story

Age-based low-dose CT screening could prevent over 25,000 deaths annually

In a cohort of 997 patients with lung cancer, 64.9% were ineligible for USPSTF screening at diagnosis. Among those excluded, 38% had never smoked and 57% lacked sufficient pack-years or quit more than 15 years earlier, revealing a major blind spot in smoking-based screening criteria (JAMA Network Open, 2025).

Patients missed by screening were younger, more often women, and disproportionately diagnosed with adenocarcinoma (72%) rather than small cell or squamous histology. Despite lower stage III disease, stage IV rates were identical between eligible and ineligible groups, indicating delayed detection regardless of guideline status.

An age-only screening model (40–85 years) would have identified 93.9% of lung cancers, compared with 62.1% using expanded smoking criteria. Screening 644 individuals prevents one lung cancer death, and capturing just 30% of stage I cases could save ~26,000 lives annually, exceeding the combined impact of breast and colorectal cancer screening.

Low-dose CT is fast, noninvasive, and cost-effective, with an estimated $101,000 per life saved, far lower than other cancer screening programs. As argued by Ankit Bharat, the data strongly support shifting from risk-factor–based screening to a universal age-based approach to meaningfully reduce lung cancer mortality.

Source: JAMA

In Focus

In a retrospective analysis of 13,988 hospitalized adults with severe hyponatremia, slower sodium correction was associated with higher mortality and neurologic complications. Over 90 days, 18% of patients died and 4% developed neurologic complications, prompting renewed scrutiny of current correction thresholds (Annals of Internal Medicine, 2026).

Patients were stratified by 24-hour sodium correction rates: slow (<8 mEq/L), medium (8–12 mEq/L), and fast (>12 mEq/L). Compared with slow correction, medium correction reduced adverse outcomes by 5.6 percentage points, while fast correction reduced risk by 9 percentage points, with consistent findings across multiple sensitivity analyses.

Notably, exploratory modeling suggested the lowest risk window occurred at correction rates of 15–20 mEq/L in the first 24 hours, a range well above traditional guideline targets aimed at preventing osmotic demyelination syndrome. Importantly, outcomes were assessed beyond classic ODS diagnoses, capturing delayed neurologic sequelae often missed in prior studies.

Although causality cannot be inferred, the signal was robust even after adjustment for acute illness severity. These findings suggest the evidence base supporting very slow correction may be weaker than assumed, and current hyponatremia guidelines warrant careful reexamination.

Source: ANNALS OF INTERNAL MEDICINE

JAMA projections signal a major shift in future clinical demand and disease burden

An estimated 107 million U.S. adults (42.5%) were living with obesity in 2022, up from 34.7 million in 1990, and that number is projected to rise to 126 million adults by 2035, representing 46.9% of the population (JAMA, 2026). The trajectory reflects a sustained, decades-long increase with no clear plateau in sight.

The rise is most concerning among younger adults, implying longer lifetime exposure to obesity-related disease. Marked disparities persist, with prevalence ranging from ~40% in non-Hispanic White men to nearly 57% in non-Hispanic Black women, and consistently higher rates across Midwestern and Southern states.

Clinically, these projections translate into a sharp increase in severe obesity, earlier onset of type 2 diabetes, cardiovascular disease, NAFLD, and CKD, and escalating demand for anti-obesity pharmacotherapy and bariatric services. Health systems will increasingly be required to manage obesity as a primary chronic disease, not a downstream risk factor.

Although newer weight-loss medications could alter future trends, their population-level impact remains uncertain due to cost and payer barriers. Absent broad access and early intervention, obesity is poised to become the dominant driver of cardiometabolic disease and healthcare utilization over the next decade.

Source: JAMA

In a propensity-matched cohort study, GLP-1 receptor agonist use was associated with a 54% reduction in all-cause mortality among patients with colon cancer and obesity compared with nonusers (HR 0.46; 95% CI 0.40–0.53). The analysis was presented at the ASCO Gastrointestinal Cancers Symposium 2026.

Using the TriNetX database, investigators matched 1,983 GLP-1–treated patients with an equal number of controls from more than 18,000 eligible cases. Over 5 years, GLP-1 therapy was also linked to lower rates of myocardial infarction (–17%), mechanical ventilation (–51%), and sepsis (–3.5% absolute risk reduction).

Safety outcomes were reassuring, with no differences in acute pancreatitis or need for hemodialysis between groups. The breadth of benefit across mortality and major complications suggests effects beyond weight loss, potentially mediated by cardiometabolic or inflammatory pathways.

Although observational, the findings raise an important clinical question: should metabolic therapy be considered an adjunct to oncologic care in patients with obesity? Prospective trials are needed, but these data signal a potentially meaningful expansion of GLP-1 therapy’s role.

Source: ASCO

Next in Practice

Hereditary risk strongly predicts late non-lung secondary cancers

In a retrospective cohort of 496 disease-free survivors of stage I–III non-small cell lung cancer, 23.4% developed a second primary malignancy after definitive local therapy. This included 15.5% new primary lung cancers and 7.9% non-lung secondary cancers, often occurring more than 4 years after treatment, underscoring late risk beyond recurrence (JAMA Network Open, 2025).

Non-lung secondary cancers emerged at a median of 52.3 months post-therapy and were most commonly breast (15.4%), prostate (12.8%), pancreatic (12.8%), and head and neck cancers (12.8%). Notably, none were detected through routine screening; 69% presented with symptoms and 31% were incidental, indicating that chest-only surveillance misses clinically meaningful disease.

Risk stratification revealed a striking signal: patients with hereditary cancer syndromes or pathogenic germline variants had a >10-fold higher risk of developing non-lung secondary cancers (subdistribution HR 10.76). In contrast, smoking intensity was not independently associated with extrathoracic cancer risk in adjusted analyses, shifting attention toward inherited susceptibility.

The clinical takeaway is targeted, not expansive imaging. As emphasized by Matthew T. McMillan, the most actionable steps are systematic family history, brief hereditary-risk screening with genetics referral when indicated, and prompt evaluation of new nonthoracic symptoms. Survivorship care must extend beyond stable chest CTs to reduce late, symptomatic cancer detection.

Source: JAMA

Over 60% achieved clinical remission at 1 year in a large U.S. cohort

In a multicenter real-world analysis of 416 adults with active ulcerative colitis, 62.5% achieved clinical remission at 1 year after initiating upadacitinib. Objective outcomes were concordant, with endoscopic response in 75.9%, endoscopic remission in 58.6%, and histologic remission in 66.6%, reinforcing depth of response beyond symptoms.

Early gains were sustained. At 6 months, 51.6% were in clinical remission, and among those responders, 71.4% maintained remission at 1 year or longer. Durable benefit extended to objective measures, with 45.8% maintaining endoscopic improvement and 35% maintaining histologic remission, supporting true disease modification rather than transient control.

Dose optimization proved clinically useful. Among patients requiring re-escalation to 45 mg, 100% achieved clinical response for incomplete induction, and 72.2% recaptured remission after relapse. More than half (54.3%) continued long-term therapy at the higher dose, highlighting flexibility in real-world management.

Safety was consistent with prior reports. Adverse events occurred in 12.7%, herpes zoster in 2.1%, and there were no reports of DVT, PE, or worsening cardiovascular disease. While observational, these data position upadacitinib as a durable, dose-adjustable option for moderate-to-severe UC in routine clinical practice, with longer follow-up ongoing.

Source: Oxford Academic

Evidence at a glance

The 2026 AHA/ASA acute ischemic stroke guideline expands endovascular therapy (EVT) to patients with larger ischemic cores. EVT now carries Class I recommendations for select anterior circulation strokes with ASPECTS 3–10 within 6 hours or ASPECTS 3–5 within 6–24 hours, and is reasonable down to ASPECTS 0–2 within 6 hours in the absence of mass effect. Certain basilar artery occlusions are also eligible out to 24 hours.

The guideline de-emphasizes intensive blood pressure lowering in the hyperacute phase. For patients receiving IV thrombolysis or successfully reperfused with EVT, targeting SBP <140 mm Hg is not recommended due to lack of benefit and potential harm (Class III), reinforcing that acute post-stroke hypertension may be adaptive.

For minor, nondisabling strokes (NIHSS ≤5) presenting within 4.5 hours, IV thrombolysis is no longer favored (Class III). Instead, dual antiplatelet therapy (aspirin plus clopidogrel for 21 days) is now preferred, reflecting consistent trial data showing no thrombolytic benefit over optimized medical therapy (Class IIa).

Finally, mobile stroke units receive a Class I endorsement, driven by strong outcome gains when treatment occurs within the golden hour. Additional updates include equal endorsement of tenecteplase and alteplase, first-time pediatric stroke guidance, and pharyngeal electrical stimulation for post-stroke dysphagia (Class IIa).

Source: AHA

In a nationwide Swedish study, long-term exposure to air pollution was associated with a higher risk of motor neuron disease (MND), including ALS, with risk increasing steadily across 1-, 3-, 5-, and 10-year exposure windows. The analysis compared 1,463 patients with MND to 7,310 matched population controls, with parallel confirmation in a sibling-control cohort, strengthening causal inference (JAMA Neurology, 2026).

Across pollutants, higher exposure consistently increased MND risk. For 10-year average exposure, odds ratios ranged from 1.21 to 1.30 per interquartile range increase for PM2.5, PM10, PM2.5–10, and NO₂, with similar magnitudes seen in sibling comparisons. These findings suggest an effect independent of shared genetics or early-life environment.

Pollution exposure also tracked with disease severity after diagnosis. Higher long-term particulate levels were associated with faster functional decline, defined by accelerated worsening on the ALS Functional Rating Scale–Revised, particularly affecting motor and respiratory domains. Elevated PM10 and NO₂ exposure was additionally linked to a higher hazard of death or need for invasive ventilation.

Given the limited disease-modifying options for MND, these data highlight air pollution as a potentially modifiable risk factor. While observational, the consistency across exposure windows, outcomes, and analytic approaches suggests environmental exposure may influence both disease onset and trajectory, reinforcing the neurologic relevance of air quality in population health.

Source: JAMA

In a prospective analysis of 88,092 participants from the PLCO Cancer Screening Trial, higher average lifetime alcohol intake was associated with increased colorectal cancer (CRC) risk over 20 years of follow-up. Individuals consuming ≥14 drinks per week had a 25% higher CRC risk compared with those drinking ≤1 drink per week (HR 1.25; 95% CI 1.01–1.53), with a nearly twofold increase in rectal cancer (HR 1.95).

Consistent heavy drinkers had a 91% higher CRC risk compared with consistent light drinkers. In contrast, former moderate-to-heavy drinkers did not have increased CRC risk, with hazard ratios approximating 1.0, suggesting that cessation may attenuate long-term risk.

Adenoma data aligned with cancer findings. Among 12,327 screened participants, former drinkers had 42% lower odds of nonadvanced adenoma (OR 0.58), reinforcing a potential biologic effect on early neoplasia.

An unexpected signal showed moderate current drinking (7 to <14 drinks per week) associated with lower CRC risk compared with very light drinking, though this finding warrants cautious interpretation given residual confounding. Overall, the data reinforce heavy alcohol use as a modifiable CRC risk factor, with evidence that risk may decline after cessation.

Source: AMERICAN CANCER SOCIETY

In a randomized phase 2 trial of 174 adults with cannabis use disorder, varenicline 1 mg twice daily did not significantly reduce cannabis use overall compared with placebo during weeks 6 to 12 of treatment, with 8.9 vs 10.7 weekly sessions, respectively. However, sex-stratified analysis revealed a significant effect in men.

Among men, varenicline reduced weekly cannabis sessions from 12.2 to 7.9 compared with placebo, a difference of 4.2 sessions (95% CI 0.6 to 7.8; P = .04). The effect persisted 1 week after treatment, with 5.7 vs 12.9 sessions (difference 7.3; P = .003). No significant reduction was observed in women.

Women receiving varenicline reported higher withdrawal scores, greater craving, and increased anxiety, along with lower medication adherence compared with placebo. Treatment-related adverse events were more frequent with varenicline overall, occurring in 83% vs 56% of participants.

With no FDA-approved medication for cannabis use disorder, these findings suggest varenicline may offer sex-specific benefit, though larger trials are needed before routine use can be recommended.

Source: SSA

New Series

Choosing Wisely in Allergy and Immunology

The Choosing Wisely campaign, led by the American Board of Internal Medicine Foundation, identifies common tests and treatments that add cost, create harm, or lack evidence. Specialty societies publish “Five Things Physicians and Patients Should Question” to promote high-value, evidence-based care and eliminate low-yield practices we often order out of habit.

One recommendation that frequently appears in both real-world practice and board-style questions:

Do not diagnose or manage asthma without spirometry.

Asthma is commonly treated based on symptoms alone, yet symptoms are unreliable. Spirometry is essential to confirm airflow obstruction, assess severity, and prevent years of misdiagnosis or unnecessary therapy. On exams and in clinic, skipping objective testing is a classic mistake.

📥 Download and save the full Choosing Wisely Allergy & Immunology list here: