NEJM Group

Most of the 50% of Americans struggling with overweight or #obesity will start their weight loss journey with their primary care physician. The challenge to stay on top of advances in obesity management and treatment can be overwhelming. Management and Treatment of Obesity in Primary Care: An Evolving Landscape is a new CME program exploring the latest evidence on lifestyle, pharmacological, and surgical interventions, as well as recent progress in understanding the causes of obesity. Consisting of four distinct learning opportunities, each activity aims to equip primary care clinicians to navigate the complex, evolving landscape of obesity management. In this course you will learn and reinforce your understanding and skills of how to: 🔍 Examine the roles of environmental and genetic factors in obesity. 🧬 Articulate the mechanisms and pathophysiology of obesity. 📝 Review common risk factors and comorbidities associated with obesity. 📊 Assess multiple factors that influence the prevalence of obesity among diverse populations. 🩺 Evaluate the evolving landscape of nutrient-stimulated hormone-based treatment options for obesity, and management of common side effects of these medications for your clinical practice. 💡 Apply knowledge of current best practices in obesity management to confidently manage patients with obesity. Confidently manage patients with obesity. Learn more about this free CME program: https://nej.md/4crgXwz

T-helper (Th) cell: A type of lymphocyte that expresses CD4 on its membrane and has specific immune stimulatory and modulatory functions. On activation of the naive CD4+ Th cell through encounter with antigen (derived from the pathogen) on the surface of an antigen-presenting cell, the Th cell may differentiate into one of several subtypes (e.g., Th1, Th2, and Th17 cells), which variously control inflammatory processes, mucosal immunity, and activation of antibacterial functions of other immune cells, such as neutrophils and macrophages. To learn more about this NEJM Illustrated Glossary term, read “Anti–Interleukin-23 Autoantibodies and Severe Infections” by Mihai Netea, M.D., Ph.D., and Frank van de Veerdonk, M.D., Ph.D., from Radboudumc and The University of Bonn: https://nej.md/43qpgVu    Explore more terms: https://nej.md/glossary  

Clinical research often generates new findings that challenge and inform current practice. The editors of NEJM Evidence have curated a collection of research articles across multiple specialties that, through varied methodologic approaches, each add important evidence in areas of either clinical or policy uncertainty. The research is accompanied by commentary that contextualizes the work or sheds light on the methods utilized to generate the evidence.    Each of the NEJM Evidence articles in this collection clarifies and builds on current medical evidence — answering previously open questions, challenging current clinical practices, or creating dialogue around health policies where more evidence and study is required.    Inside this collection, discover:    🥜 A randomized trial of oral immunotherapy for young children with a peanut allergy 💉 A randomized clinical trial evaluating dosing regimens for HPV vaccination by assessing 2 versus 3 doses of a 9-valent HPV vaccine among 15–26-year-olds 🤰 An observational study evaluating the association between hypertensive disorders in pregnancy and the later risk of stroke among Black women in the U.S. 🩺 A study exploring the common clinical question of how quickly or slowly to correct sodium in patients with severe hyponatremia    Download the collection now: https://eviden.cc/43LLilH 

Hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer is the most common subtype of breast cancer, accounting for 70 to 75% of cases. The majority of cases with this subtype are diagnosed early (at stage I to III). Early breast cancer is treated with curative intent; HR-positive, HER2-negative early breast cancer is treated with surgery with or without radiotherapy or chemotherapy, followed by adjuvant endocrine therapy for 5 to 10 years. Adjuvant endocrine therapy improves outcomes in these patients; however, recurrence occurs in 27 to 37% of patients with stage II disease and in 46 to 57% of patients with stage III disease and can occur up to 20 years after diagnosis.    The results of trials in which the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors ribociclib, palbociclib, and abemaciclib were evaluated have shown significant improvements in progression-free survival among patients with HR-positive, HER2-negative advanced breast cancer. Ribociclib and abemaciclib have also been shown to have a significant overall survival benefit in the same patient population. In early breast cancer, the use of CDK4/6 inhibitors has had varying results. In the PENELOPE-B and PALLAS trials, palbociclib plus endocrine therapy did not show a significant invasive disease–free survival benefit. Conversely, a significant invasive disease–free survival benefit was seen in the monarchE trial after 2 years of adjuvant therapy with abemaciclib; these results led to the approval of abemaciclib by international health authorities for the treatment of HR-positive, HER2-negative early breast cancer in patients with node-positive disease at high risk for recurrence.    The established benefit that was observed with ribociclib in advanced breast cancer prompted its investigation in early breast cancer. The NATALEE trial is a phase 3 trial comparing ribociclib plus endocrine therapy with endocrine therapy alone that was designed to test CDK4/6 inhibition in a broad population of patients with stage II or III HR-positive, HER2-negative early breast cancer. Dennis Slamon, M.D., Ph.D., et al. report results from a protocol-specified interim efficacy analysis.    Read the full NATALEE trial results and Research Summary: https://nej.md/3IM24rq    #ClinicalTrials #MedicalResearch 

The latest Double Take video reviews the stages of #AlzheimersDisease as well as pharmacologic and nonpharmacologic management for each stage. Watch now: https://nej.md/49Ss6oF    This is the second of a two-part series on Alzheimer’s disease. Watch part one, “Alzheimer’s Disease — Anti-Amyloid Medications, Early Detection, and Screening,” here: https://nej.md/3IsK59e 

In the latest Case Record of the Massachusetts General Hospital, an 84-year-old man was admitted to this hospital after having a fall.    Three weeks before the current presentation, the patient was evaluated in the emergency department of another hospital because of a transient episode of gross hematuria. Urinalysis showed trace blood (reference value, negative), and microscopic examination of the urinary sediment revealed 4 or 5 red cells per high-power field (reference range, 0 to 3). Results of tests of coagulation were normal, and the complete blood count showed anemia, which had been diagnosed previously and was stable as compared with findings obtained 11 months earlier. Computed tomography (CT) of the abdomen, performed after the administration of intravenous contrast material, reportedly showed a linear density in the bladder that measured 10 mm in diameter. The cause of the episode of hematuria was thought to be a kidney stone that had passed into the bladder. The patient was discharged home with a plan to follow up in the urology clinic affiliated with the other hospital; he was instructed to continue treatment with rivaroxaban, which he had been taking for many years to prevent stroke in the context of atrial fibrillation. Read more about the case in “An 84-Year-Old Man with a Fall,” which includes differential and final diagnoses from guest physicians based on evidence from the test results, by Zaven Sargsyan, M.D., Sunita D. Srivastava, M.D., Virginia Triant, M.D., M.P.H., and Brian B. Ghoshhajra, M.D., from Baylor College of Medicine, Massachusetts General Hospital, and Harvard Medical School: https://nej.md/3TtfI7F

Wearable digital health technologies (DHTs) offer the potential to affect health care by making behavioral and physiological patterns in daily life outside the clinic visible to patients and medical professionals. The Wearable Digital Health Technologies in Medicine series to date has covered areas of clinical care in which there are reasonably robust clinical trial data showing the value of these technologies: diabetes and two types of cardiovascular disease. These trials have shown that enabling more personalized data-driven interventions and objective measurement of treatment effects can lead to results that are in many cases superior to those achieved with the use of intermittent clinical data, which is the current basis for the standard of care. The authors have also highlighted areas showing the nascent effect on patients and clinicians of wearable DHTs that measure movement and sleep for the management of depression and wearable DHTs that use #ArtificialIntelligence (AI) to monitor patients for seizures, improve seizure quantification, reduce injuries, and lower the risk of sudden unexpected death from epilepsy. The evidentiary basis for the broad clinical effect of wearable DHTs in these areas is in its infancy, but our series has shown the potential for real-world medical benefits. Well-designed longitudinal trials will show which of these transformative aims can be realized.    Geoffrey Ginsburg, M.D., Ph.D., Rosalind Picard, Sc.D., and Stephen Friend, M.D., Ph.D., address the issues that must be confronted if we are to integrate the use of wearable digital health technologies into clinical care in a way that provides an enduring benefit to patients. Read the Review Article “Key Issues as Wearable Digital Health Technologies Enter Clinical Care”: https://nej.md/3vjcGL1 

Encapsulated bacterium: A bacterium covered with a polysaccharide capsule that lies outside the plasma membrane and (for gram-negative bacteria) the outer lipid membrane. Both gram-positive and gram-negative bacteria can be encapsulated. The capsule contributes to the pathogenicity of the bacterium by increasing its adherence to surfaces and shielding and by protecting it against toxins and the host’s immune system. To learn more about this NEJM Illustrated Glossary term, read “Anti–Interleukin-23 Autoantibodies and Severe Infections” by Mihai Netea, M.D., Ph.D., and Frank van de Veerdonk, M.D., Ph.D., from Radboudumc and The University of Bonn: https://nej.md/43qpgVu    Explore more terms: https://nej.md/glossary  

In a new Double Take video from the New England Journal of Medicine, Drs. Nathaniel Chin and Stephen Salloway define the stages of dementia and the effect of each stage on the activities of daily living. They also discuss ways to support persons with #AlzheimersDisease at every stage of the disease, including available medications and potential side effects. The video also emphasizes the importance of advance care planning for persons with mild cognitive impairment and providing support to care partners.    Watch the full video: https://nej.md/49Ss6oF    This is the second of a two-part series on Alzheimer’s disease. Watch part one, “Alzheimer’s Disease — Anti-Amyloid Medications, Early Detection, and Screening,” here: https://nej.md/3IsK59e 

Anti–Interleukin-23 Autoantibodies and Severe Infections    This editorial describes the science behind a study of an autoimmune response against cytokines in persons with thymoma and severe infections.    Figure 1 from the editorial illustrates interleukins 12 and 23 and the effects of anti–interleukin-23 autoantibodies.     Interleukins 12 and 23 are produced mainly by myeloid cells on recognition of pathogen-associated molecular patterns (PAMPs) by pattern-recognition receptors (Panel A). On release, they stimulate T cells and other innate lymphoid populations such as natural killer cells and mucosal-associated invariant T cells, which then go on to produce immune-activating cytokines such as interferon-γがんま and interleukins 17 and 22 (Panel B). Autoantibodies against both interleukin-12 and interleukin-23 have been described, more often in patients with thymoma than in healthy persons or persons with autoimmune polyglandular syndrome type 1, but only anti–interleukin-23 autoantibodies seem to be clearly associated with opportunistic infections, whereas anti–interleukin-12 antibodies result only in a partial immune deficit (Panel C). Anti–interleukin-23 antibodies block the intracellular signaling downstream of receptors for interleukin-23, such as that mediated by signal transducer and activator of transcription 3 and 4 (STAT3 and STAT4), and block production of granulocyte–macrophage colony-stimulating factor (GM-CSF), interleukins 17 and 22, and interferon-γがんま (Panel D). IFN denotes interferon, IL interleukin, Th1 type 1 helper T cell, and Th17 type 17 helper T cell.    Read the science behind the study in the editorial “Anti–Interleukin-23 Autoantibodies and Severe Infections” by Mihai G. Netea, M.D., Ph.D., and Frank van de Veerdonk, M.D., Ph.D., from Radboudumc and The University of Bonn: https://nej.md/43qpgVu