Approximately 20 to 30% of patients with non–small-cell lung cancer (NSCLC) present with locally advanced stage III disease at the time of diagnosis. Of these patients, 60 to 90% are considered to have unresectable disease. Osimertinib is a recommended treatment for advanced NSCLC with an epidermal growth factor receptor (𝘌𝘎𝘍𝘙) mutation and as adjuvant treatment for resected 𝘌𝘎𝘍𝘙-mutated NSCLC. EGFR tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III 𝘌𝘎𝘍𝘙-mutated NSCLC. In the LAURA trial, researchers examined the efficacy and safety of adjuvant osimertinib in patients with unresectable, stage III NSCLC that had an 𝘌𝘎𝘍𝘙 mutation. 216 adults with stage III, unresectable, 𝘌𝘎𝘍𝘙-mutated NSCLC who had not had disease progression during or after chemoradiotherapy were randomly assigned in a 2:1 ratio to receive oral osimertinib or placebo until disease progression or a serious toxic effect had occurred or until the patient wished to stop treatment. The primary end point was progression-free survival. Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III 𝘌𝘎𝘍𝘙-mutated NSCLC. Read the full LAURA trial results and Plain Language Summary: https://nej.md/451OXwi #ClinicalTrials #MedicalResearch
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NEJM Group brings together the people and products that have made the New England Journal of Medicine, NEJM AI, NEJM Evidence, NEJM Catalyst, NEJM Journal Watch, and NEJM CareerCenter leaders in providing the medical knowledge health care professionals need to deliver the best patient care. The goal of NEJM Group is to meet the rapidly growing demand for essential medical information and to disseminate that content in new ways to a broader global health care community than ever before. Our publications reach health care professionals around the globe — making connections between clinical science and clinical practice that advance medical knowledge, health care delivery, and patient outcomes. NEJM Group is a division of the Massachusetts Medical Society.
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𝗘𝗻𝗱𝗼𝗰𝘆𝘁𝗼𝘀𝗶𝘀 is a process by which cells actively internalize extracellular substances by invagination of the cellular membrane and subsequent formation of vesicles. Types of endocytosis are phagocytosis (e.g., microorganisms), pinocytosis (e.g., fluid), and receptor-mediated endocytosis (e.g., binding of extracellular molecules to specific receptors). To learn more about this NEJM Illustrated Glossary term, read the editorial “Inhibiting IgG in Hemolytic Disease of the Fetus” by Emeline Maisonneuve, M.D., Alice Panchaud, Ph.D., and David Baud, M.D., Ph.D.: https://nej.md/3YS7Scb Explore more terms: https://nej.md/glossary
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The September 2024 issue of NEJM Catalyst Innovations in Care Delivery includes an in-depth look at the African American Transplant Access Program (Northwestern Medicine), which is working to help Black patients with end-stage kidney disease receive access to transplantation. Read the article: https://nej.md/3YTnvA5 Here are more highlights from the September issue: 𝗖𝗔𝗦𝗘 𝗦𝗧𝗨𝗗𝗜𝗘𝗦 ⚖️ The Journey to an Incentive-Based Health Equity Quality Index https://nej.md/3yCbNyV 💡 A Physician-Created Platform to Speed Clinical Decision-Making and Referral Workflow https://nej.md/3WNYWSj 𝗔𝗥𝗧𝗜𝗖𝗟𝗘𝗦 🏥 How a Robust Community Clinical Practice Arm Can Support an Academic Health System’s Tripartite Mission https://nej.md/3X9ZkuL 🌐 Comparable Real-World Patient-Reported Outcomes Data Across Health Conditions, Settings, and Countries: The PROMIS International Collaboration https://nej.md/4ct9EDI 𝗖𝗢𝗠𝗠𝗘𝗡𝗧𝗔𝗥𝗬 🩺 Longitudinal Care Management for Diabetes and Hypertension https://nej.md/4dJn92R 𝗜𝗡𝗦𝗜𝗚𝗛𝗧𝗦 𝗥𝗘𝗣𝗢𝗥𝗧 🛡️ Quality and Patient Safety Improvement Is Never Finished https://nej.md/3X5dK0d 𝗙𝗥𝗢𝗠 𝗧𝗛𝗘 𝗘𝗗𝗜𝗧𝗢𝗥𝗦 📈 Novel Approaches and Actionable Insights to Improve Outcomes https://nej.md/3yTEYNU Explore the current issue: https://nej.md/3YTnvA5 #CareDelivery
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This editorial describes the science behind reports of communication facilitated by brain–computer interfaces. Card et al. describe the acquisition of at-home recordings to decode speech in a person with dysarthria (Panel A). Cortical signals were first acquired from a penetrating interface, comprising 256 electrodes, implanted in the precentral gyrus. The signals were then filtered to extract the neural activity features related to intended speech. A computational algorithm translated the neural activity into specific speech sounds, called phonemes, at each time point. The sequence of phoneme predictions was assembled and integrated with a statistical model of language to generate text sentences on a screen. ALS denotes amyotrophic lateral sclerosis. Vansteensel et al. describe a person with anarthria who was fitted with a wireless brain–computer interface (BCI) for at-home independent use (Panel B). Low-channel-count cortical signals were recorded from electrodes on the brain surface for click and call-caregiver commands and click spelling. Recordings were performed for 8 years, and the person relied on this communication brain–computer interface as she became progressively weaker. HFB denotes high-frequency band, and LFB low-frequency band. In the future, communication neuroprosthetics will integrate current knowledge for high performance and robustness over decades, with the goal of retaining autonomy and societal participation of persons with severe motor impairments. Read the editorial “Brain–Computer Interfaces for Restoring Communication” by Edward Chang, M.D., from the University of California, San Francisco: https://nej.md/46ZSpc5 𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚 📄 “Cognitive Motor Dissociation in Disorders of Consciousness” by Yelena Bodien, Ph.D., et al.: https://nej.md/3X2abYs 📄 “An Accurate and Rapidly Calibrating Speech Neuroprosthesis” by Nicholas Card, Ph.D., et al.: https://nej.md/3yBmrWC 📄 “Longevity of a Brain–Computer Interface for Amyotrophic Lateral Sclerosis” by MJ Vansteensel et al.: https://nej.md/4dbofER
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Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive disorder characterized by impaired synthesis of cortisol and often aldosterone. To control androgen excess in children with CAH, supraphysiologic doses of glucocorticoids are often required. However, this treatment can adversely affect growth and other outcomes. Crinecerfont — a new oral corticotropin-releasing factor type 1 receptor antagonist — might reduce androstenedione, a key adrenal androgen, while limiting the need for supraphysiologic doses of glucocorticoids. In the CAHtalyst Pediatric trial, researchers assessed the efficacy of crinecerfont in lowering androstenedione levels and reducing the need for supraphysiologic glucocorticoid doses in children with classic 21-hydroxylase deficiency CAH. 103 children 2 to 17 years of age with classic CAH who were receiving supraphysiologic glucocorticoid doses were assigned in a 2:1 ratio to receive oral crinecerfont (25 mg, 50 mg, or 100 mg, depending on body weight) or placebo twice daily for 28 weeks. A stable glucocorticoid dose was maintained for 4 weeks; the dose was then lowered to a target of 8 to 10 mg per square meter of body-surface area per day, provided that androstenedione was controlled. The primary efficacy end point was the change in the androstenedione level from baseline to week 4. In children with classic CAH, crinecerfont was superior to placebo in lowering elevated androstenedione levels and allowed for reductions in glucocorticoid doses while androstenedione control was maintained. Read the full CAHtalyst Pediatric trial results and Plain Language Summary: https://nej.md/4aAQKcR #ClinicalTrials #MedicalResearch
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Communication is a priority for people with dysarthria from neurologic disorders such as stroke and amyotrophic lateral sclerosis (ALS). People with diseases that impair communication have an increased risk of isolation, depression, and decreased quality of life; losing communication may determine whether a person will pursue or withdraw life-sustaining care in advanced ALS. Although augmentative and assistive communication technologies such as eye trackers (also called eye-gaze–tracking devices) or head trackers are available, they have low information-transfer rates and become increasingly difficult to use as patients lose voluntary muscle control. Brain–computer interfaces are a promising type of communication technology that can directly decode the user’s intended speech from neural signals. In a man with impaired speech from amyotrophic lateral sclerosis, an intracortical speech neuroprosthesis achieved more than 97% accuracy in decoding his intended speech and making it audible in his natural voice. Read the full results in the Original Article “An Accurate and Rapidly Calibrating Speech Neuroprosthesis” by Nicholas Card, Ph.D., et al., from the University of California, Davis, and elsewhere: https://nej.md/3yBmrWC #MedicalResearch
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Guideline Watch 2024, an exclusive collection of 12 clinical guideline summaries that will directly impact how you practice medicine, is available to download for free for a limited time. The annual collection, curated by NEJM Journal Watch physician-editors, includes 12 new and updated guideline summaries to help you stay informed and confident in your practice. Inside Guideline Watch 2024: 📋 Updated Guideline for Management of Lower Extremity Peripheral Artery Disease 🩺 Managing Acute Pancreatitis 🌿 Managing Cannabis Hyperemesis Syndrome 🔍 Prostate Cancer Screening Guidelines for Black Men 🩻 USPSTF Releases New Breast Cancer Screening Guidelines 🩸 The Role of Imaging in Managing Patients with Gastrointestinal Bleeding 📉 Managing Patient Deterioration Outside of the ICU 🧠 Managing Post-Traumatic Stress Disorder ❤️ Best Practices for Advanced Cardiac Life Support 🦠 Management of HIV During Pregnancy 🫁 Managing Acute Respiratory Distress Syndrome 💉 Updated Guidelines for Use of Pneumococcal Vaccines in Adults Get your copy: https://nej.md/4dnWMj0
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A 𝗹𝘆𝘀𝗼𝘀𝗼𝗺𝗲 is an acidic intracellular organelle, bound by a phospholipid bilayer membrane, that has key functions in cellular homeostasis, including the breakdown and recycling of macromolecules (carbohydrates, lipids, nucleic acids, and proteins), control of nutrient sensing, and calcium signaling. Lysosomes can fuse with endosomes, phagosomes, and autophagosomes and, by fusing with the plasma (cell) membrane, facilitate cell–cell communication. To learn more about this NEJM Illustrated Glossary term, read the editorial “Inhibiting IgG in Hemolytic Disease of the Fetus” by Emeline Maisonneuve, M.D., Alice Panchaud, Ph.D., and David Baud, M.D., Ph.D.: https://nej.md/3YS7Scb Explore more terms: https://nej.md/glossary
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Excerpt from a Perspective by Annie R. Abruzzo, B.A.: In medical school, I am repeatedly reminded that knowing their family history can protect and empower patients. Though the predictive value of family history has been questioned with the rise of new diagnostic and genetic tests, a positive family history can earn a patient earlier access to the information such modern tools might provide. How do you know when to undergo screening for colon cancer? Count your relatives who were diagnosed at a young age with colon cancer or adenomatous polyps. What might tell you to pay more careful attention to cardiovascular health? First-degree relatives who had heart attacks before 50 years of age. Lessons on pathophysiology are accompanied by statistics about heritability, and my clinical preceptors coach me to better elicit information from patients about their family members’ health. But what if the patients don’t have any information to give? In my own chart, the family history section is a blank box. Negatives are reported elsewhere in the history — “patient reports no known allergies to drugs” and “never tobacco user.” But family history? An empty, textless field. Patients with unknown family histories should not be treated the same way as patients with known negative family histories. Medicine should distinguish between patients who do not know whether any of their biologic relatives had cancer and those who know that none of their biologic relatives had cancer. Read the Perspective “Family History: Unknown” by Annie R. Abruzzo, B.A., from Harvard Medical School: https://nej.md/3yz238q
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Frailty is a clinically identifiable state of diminished physiological reserve and increased vulnerability to a broad range of adverse health outcomes. Frailty becomes more common as populations age. In a report covering 62 countries worldwide, the prevalence of frailty among community-dwelling persons ranged from 11% among those who were 50 to 59 years of age to 51% among those who were 90 years of age or older. Older persons in acute care hospitals and nursing homes, those in low- or middle-income countries, and those with a socially vulnerable status are all at increased risk for frailty. Continue reading the Review Article “Frailty in Older Adults” by Dae Hyun Kim, M.D., Sc.D., M.P.H., and Kenneth Rockwood, M.D., from the Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife; Beth Israel Deaconess Medical Center; Harvard Medical School; and Dalhousie University: https://nej.md/3WV9SyV
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