JAMA

on the third day of no podiatry consult, no hospital supplies, and no patience, i left at lunch, walked two minutes to the drugstore, procured three-dollar toenail clippers in pink plastic packaging. her gray heel settled heavy in my hand, peeled from its sock, careful not to snag the gnarled toes, yellow nails so long and crusted that they curled, angry red half-moons.

The Original Investigation titled “Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: the PDA Randomized Clinical Trial,” published on February 17, 2026, was corrected to remove and add names to the byline. “Anne Marie Reynolds, MD, MPH” was removed from the byline and “Praveen K. Chandrasekharan, MD, MS” was added where Dr Reynolds’ name had appeared. Dr Reynolds’ information was added to the “Additional Contributions” section. This article was corrected online.

This study reports decreasing out-of-pocket costs for insulin among Medicare beneficiaries not receiving the low-income subsidy and examines the distribution of costs by state from 2019 through 2023.

This JAMA Insights explores how using numerical comparisons during patient-clinician encounters can help patients better understand their clinical situation and inform their decision-making.

In Reply We thank Dr Fukushima and colleagues for their insightful comments.

To the Editor As members of the executive committee of the European Group on Immunology of Sepsis (EGIS), we are writing about the recent article describing the development and validation of the SOFA-2 score. The authors revised the original SOFA score by integrating modern intensive care unit (ICU) interventions such as kidney replacement therapy and extracorporeal membrane oxygenation, resulting in an updated index reflecting contemporary ICU practice.

This randomized clinical trial evaluated whether adding tumor debulking to palliative chemotherapy improves overall survival for patients with multiorgan metastatic colorectal cancer.

A review of cannabis use and mental health published in JAMA Internal Medicine may help clinicians advise patients on potential risks.

Reduced-frequency maintenance dosing of glucagon-like peptide-1 (GLP-1) receptor agonists may preserve successful initial treatment effects from standard therapy.

Most older adults with advanced cancer would rather prioritize preserving quality of life vs prolonging survival, but these preferences may not be taken into account, a study published in JAMA Oncology found.

The blood biomarker phosphorylated tau 217 (p-tau217) may predict dementia in women up to 25 years before onset, according to a study published in JAMA Network Open.

Adverse childhood experiences may lead to digestive issues later in life, according to research published in Gastroenterology.

The US Food and Drug Administration (FDA) approved the first generic version of fluticasone propionate inhalation aerosol, marketed as Flovent HFA, for maintenance treatment of asthma.

Listen to the JAMA Editor’s Summary for an overview and discussion of the important articles appearing in JAMA.

Colorectal cancer (CRC) remains one of the few solid tumors for which surgical intervention to remove limited metastatic disease has been associated with curative outcomes or improved overall survival. This has been demonstrated in liver-limited, lung-limited, and peritoneal-limited disease. Encouraging findings from hepatectomy in liver-limited disease led to extrapolation of resection to patients with multiple organ involvement in whom complete resection could be attained. Indeed, resection in patients with liver and lung metastases has been linked to favorable survival, as has resection in patients with peritoneal metastases with limited liver involvement. Although most patients undergoing curative resections have metastases recur, their median overall survival has typically been favorable compared with historic controls.

This Medical News article discusses a new scientific statement from the American Heart Association on acute coronary syndromes in premenopausal women.

To the Editor The SOFA-2 score is an important step toward improving the precision of organ dysfunction assessment in contemporary critical care. By redefining thresholds within its 6 organ domains using data-driven modeling, SOFA-2 enhances calibration and predictive performance in sepsis cohorts. However, its direct application to tropical infections such as dengue, scrub typhus, leptospirosis, and malaria warrants cautious interpretation. The physiological foundations of SOFA-2 are largely derived from bacterial sepsis, and certain domains, particularly hepatic and coagulation, may not fully capture the pathophysiological profiles seen in these infections.

This Medical News article discusses updated cholesterol and triglyceride management recommendations from the American College of Cardiology and the American Heart Association.

In Reply We appreciate the interest in the updated SOFA score (SOFA-2). We reiterate herein that SOFA-2 is primarily a descriptive scale to quantify organ dysfunction and is not a predictive score. The area under the receiver operating curve mentioned by Mr Matos and colleagues is reported as a metric to demonstrate predictive validity, 1 of 6 utility domains prespecified in our protocol.

The Original Investigation titled “Risk-Based vs Annual Breast Cancer Screening: The WISDOM Randomized Clinical Trial,” published on December 12, 2025, was corrected to update values throughout the Table. This article was corrected online.

This Guide to Statistics and Methods provides an overview of the Hochberg procedure, an effective tool for avoiding false-positive conclusions in clinical trials reporting multiple end points.

China’s rise as a major center of drug development represents one of the most consequential shifts in the global life sciences landscape in a generation. From the patient perspective, a key policy question is how China’s expanding capacity, spanning follow-on products that are based on an approved drug to first-in-class innovation, can be integrated into regulatory frameworks to ensure timely and equitable access to medicines.

The Original Investigation titled “Microultrasonography-Guided vs MRI-Guided Biopsy for Prostate Cancer Diagnosis: The OPTIMUM Randomized Clinical Trial,” published on March 23, 2025, was corrected to add Chirag Patel to the nonauthor collaborator list in Supplement 3. This article was corrected online.

This study examines changes from 2015 through 2025 in the country of origin of early-stage biopharmaceutical development programs worldwide.

This Perspective discusses the implications of the recent US Food and Drug Administration (FDA) label change on menopausal hormone therapy for clinicians to better integrate hormone therapy options and personalized, shared decision-making to improve care for midlife women.

JAMA+ AI Associate Editor Yulin Hswen, ScD, MPH, spoke with John Torous, MD, MBI, host of the JAMA Psychiatry Author Interviews podcast and director of digital psychiatry for the Department of Psychiatry at Beth Israel Deaconess Medical Center in Boston, Massachusetts, for JAMA+ AI Conversations.

General knowledge of the pathology of scurvy dates back to Lind’s classic Treatise on the Scurvy, published in 1772. Hess has designated Barlow’s publication in 1883, establishing the identity of the scurvy of adults and of infants, as the modern milestone in the study of the disorder, so that “Barlow’s disease” is no longer looked on as a distinct entity. The theories of its etiology have been varied. For many years the potassium deficiency theory, suggested by Garrod, gained wide acceptance. That scurvy should be attributed to a lack of this element is, as Hess remarks, readily comprehensible in view of the abundance of potassium in the antiscorbutic [fruits and vegetables]. The citric acid theory had “a short but popular career,” as did the hypothesis including acidosis as the etiologic factor.…Toxins of alleged microbic origin have formed a favorite theme, almost since the birth of modern bacteriology, for exploitation in relation to the genesis of disorders of obscure origin; there has often been a sort of contest for favor in the eyes of students between the postulate of a specific detrimental bacterium and the mysterious pathogenic toxin.…Today there is all but universal acceptance of the interpretation of scurvy as an avitaminosis—an expression of the lack of the labile vitamin C in the diet.…

Sepsis is a leading cause of hospital admissions, mortality, and health care expenditure worldwide. It disproportionally affects very young and very old individuals. Sepsis in young individuals carries a magnified societal impact through potential years of life lost and reductions in quality-adjusted life-years. Sepsis increases the risk of functional impairment that may persist for decades, translating into sustained health care needs and reduced lifetime economic productivity. While many countries maintain public surveillance systems for common infectious diseases such as influenza, the absence of systematic sepsis surveillance obscures the full societal burden of disease, limits benchmarking of care, and hinders effective public health measures.

This Viewpoint discusses the evolving use of artificial intelligence (AI) by graduate medical education programs for initial review of medical residency applications; highlights some of the legal risks of such use; and suggests several voluntary AI standards to mitigate these risks.

This cohort study assesses US incidence, mortality, and trends of sepsis in nonneonatal children using a Pediatric Sepsis Event (PSE) definition adapted from the 2024 Phoenix criteria for scalable electronic health record (EHR)–based surveillance.

A fundamental aspect of medicine is service. Although the term can be repurposed in various mundane ways (eg, customer service or hospital service), clinicians idealistically define it in the selflessness of our vocation—perhaps what initially drew many of us to practice medicine. The poem “maundy” provides a wrenching example of the depth and complexity that the dedication to such service to patients can entail. The title recalls Maundy Thursday in the Christian tradition, which commemorates Jesus’ humility in washing the feet of his disciples before his crucifixion. The speaker’s Christlike humility, expressed textually in the poem’s lack of capitalization and literally in the graphic details of the careful attention given to an older patient’s overgrown toenails, is complicated by other feelings. The poem unabashedly juxtaposes a litany of the challenging, concrete realities of providing medical care—impatience, staffing and supply shortages, racism, sexism, difficulties accessing care—with the speaker’s clinical insights and human compassion. The reader, mirroring many clinicians’ own frustrations as the health care landscape evolves, may recognize similar internal conflicts. The poem depicts both the best and worst of health care, cascading morbidities met with limited resources, aspirational kindness coexisting with disgusted cynicism. Yet the speaker almost miraculously insists “i thought,/this is what i came to medicine to do.” How can we reconcile continually giving of ourselves in a relentlessly imperfect environment? Perhaps the answer lies in the living poetry of holding fast to our purpose and offering service where healing, even if seemingly not valued, remains direly needed.

The Oncology Care Model (OCM) was the first Centers for Medicare & Medicaid Services (CMS) alternative payment model in oncology. In this issue of JAMA, Brooks et al report the final evaluation, concluding that the OCM was associated with a relative reduction of $616 per episode in total Medicare payments, excluding Monthly Enhanced Oncology Services (MEOS) and performance-based payments to practices. Strikingly, savings grew over time, reaching –$1282 per episode in the final performance period, roughly quadrupling the –$297 per-episode reduction reported in the interim 3-year evaluation. Yet the headline will be the net loss to Medicare: between MEOS payments and performance-based payments, the program paid out $639 million more than it gained in spending reductions over 6 years. This framing that growing spending reductions were insufficient to offset program payments has already shaped policy. The Enhancing Oncology Model (EOM), which launched in July 2023 with significantly less participation than the OCM, was designed to correct the interim evaluation’s net-loss finding. But did the CMS learn the right lessons from the OCM, or did a premature reading of the evidence produce a struggling successor model that may forfeit the gains the OCM was beginning to achieve?

To the Editor Dr Ranzani and colleagues described the development and validation of the SOFA-2 score in a large international cohort of critically ill patients. The updated score represents a major step toward aligning organ dysfunction assessment with contemporary ICU practice. However, one crucial aspect remains unclear: the potential effect of the COVID-19 pandemic on the definition and calibration of SOFA-2.

To the Editor A recent study delivered a well-executed analysis of a complex question: Is universal pediatric low-density lipoprotein cholesterol (LDL-C) screening with reflex familial hypercholesterolemia (FH) genotyping cost-effective in the US? Under a conventional threshold of $100 000 per quality-adjusted life-year and a 3% discount rate, the answer is no. The study’s model necessarily simplified reality, with results based on the appropriateness of numerous inputs and assumptions. The most reasonable changes in inputs had little effect, except for the discount rate.

To the Editor Dr Ranzani and colleagues described the development and validation of the SOFA-2 score, a major update of an organ dysfunction index central to both clinical research and bedside assessment in critical care medicine.

To the Editor A recent article performed cost-effectiveness modeling of youth universal lipid screening to identify and mitigate the approximate 25% sex-pooled risk of coronary heart disease (CHD) before age 40 years in individuals with FH. Most people with FH are undiagnosed until a CHD event occurs. Detecting FH in childhood allows reduction of LDL-C before irreversible plaques develop and may identify previously undiagnosed older relatives prior to an impending CHD event. Because decades-long trials are not feasible, this study’s model allowed an efficient theoretical evaluation of various youth lipid screening pathways. However, we have several concerns about this study’s modeling parameters, which, in combination, may have skewed the model so that it does not evaluate the current approach. Using a flawed model to justify abandoning lipid screening would preclude reducing morbidity and mortality for persons with unrecognized FH.

To the Editor Nearly 3 decades after the release of the original Sequential Organ Failure Assessment score (SOFA-1), which was designed to provide a straightforward method for assessing organ dysfunction in critically ill patients, we read the recent article on development and validation of SOFA-2 with great anticipation.

In Reply We thank Dr Olson and colleagues and Dr Burns and colleagues for their Letters on our cost-effectiveness analysis of FH screening strategies.

This randomized clinical trial examines whether tumor debulking added to palliative chemotherapy improves survival of patients with multiorgan metastatic colorectal cancer.

This difference-in-differences regression analysis evaluates the association of the Medicare Oncology Care Model (OCM) with changes in Medicare spending, utilization, and quality of care in oncology practices voluntarily participating in the OCM vs propensity-matched comparison practices.

This translational science review summarizes current evidence about the primary biologic pathways by which obesity may promote development of cancer and interventions that may reduce obesity-associated cancer risk.

This Viewpoint discusses the importance of rethinking care for pediatric patients with genetic disorders and how alignment between health systems, payers, professional societies, and clinicians could lead to a higher standard of care.

In this narrative medicine essay, an internal medicine physician ponders the myriad experiences that follow a simple icebreaker posed to students upon first meeting their attending physicians during medical school and throughout their careers.

To the Editor The BICARICU-2 trial investigated the effect of sodium bicarbonate infusion on mortality in critically ill patients with severe metabolic acidemia and acute kidney injury. Although the study reported no significant difference in the primary outcome of 90-day all-cause mortality, the observation that sodium bicarbonate administration was associated with a reduced need for kidney replacement therapy initiation is of clinical importance. These findings suggest that sodium bicarbonate may serve as a strategy to delay or avoid kidney replacement therapy.

This JAMA Patient Page describes microplastics and the potential health effects of human exposure to microplastics.