NEJM Evidence

A 53-year-old woman with a history of breast cancer presented for routine oncologic care. She had received a diagnosis of invasive ductal carcinoma of the right breast 11 years earlier. A right mastectomy and sentinel lymph node dissection were performed, and the right breast was reconstructed with a silicone implant. Neither chemotherapy nor radiotherapy were included in the management strategy. She received treatment with an aromatase inhibitor for 10 years after the mastectomy. As part of the surveillance strategy for cancer recurrence, mammography and breast ultrasonography were performed annually, and the results had been normal for the past 10 years. The most recent ultrasonography, however, demonstrated enlarged lymph nodes in the left axilla. She had not noticed any palpable masses, redness, drainage, or skin breakdown around the reconstructed breast tissue.    Read the Morning Report “A 53-Year-Old Woman with Axillary Lymphadenopathy” by Liem Pham, BS, Javier Gomez Farias, MD, Jennifer Bacci, PA-C, Asina Wahab, BS, and Anish Nihalani, MD, from the Hackensack Meridian School of Medicine: https://eviden.cc/3zSsHcQ    #MedicalEducation #Oncology 

Volume 3 Issue 9 of 𝘕𝘌𝘑𝘔 𝘌𝘷𝘪𝘥𝘦𝘯𝘤𝘦 is now available! Here is a preview of the latest content:      𝗢𝗿𝗶𝗴𝗶𝗻𝗮𝗹 𝗔𝗿𝘁𝗶𝗰𝗹𝗲𝘀  Rivaroxaban for Patients with Intermittent Claudication https://eviden.cc/3Mku8Ug     Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis https://eviden.cc/3XhfHa7    Pregnancy after Tubal Sterilization in the United States, 2002 to 2015 https://eviden.cc/3YWvBI1    Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Kidney Disease https://eviden.cc/3z2CLzM    𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗧𝗿𝗶𝗮𝗹𝘀 𝗪𝗼𝗿𝗸𝘀𝗵𝗼𝗽  The Case for Access to Data Monitoring Committee Charters https://eviden.cc/3yRs8jg      𝗠𝗼𝗿𝗻𝗶𝗻𝗴 𝗥𝗲𝗽𝗼𝗿𝘁   A 36-Year-Old Man with Persistent Headache https://eviden.cc/3yEg7hi    𝗣𝗮𝘁𝗶𝗲𝗻𝘁 𝗣𝗹𝗮𝘁𝗳𝗼𝗿𝗺  Looking in the Mirror — My Experience in a Clinical Trial for the Treatment of Pancreatic Cancer https://eviden.cc/3T2cUz3    𝗦𝘁𝗮𝘁𝘀, 𝗦𝗧𝗔𝗧!  How Factorial Design Works https://eviden.cc/3AC6oIL    Explore all the latest original research and specialty articles in the September issue: https://eviden.cc/current  

Despite significant advancements in diabetes management, the prevalence of diabetic retinal disease remains a major public health concern. Diabetic retinopathy remains one of the leading causes of vision loss among adults with diabetes. Because current treatments primarily focus on advanced stages of diabetic retinopathy, there is a critical need for cost-effective therapies that can intervene earlier in disease development. An article about the LENS (Lowering Events in Non-proliferative Retinopathy in Scotland) trial, published in NEJM Evidence, offers a promising approach using fenofibrate, a lipid-lowering medication, to reduce the progression of diabetic retinopathy.    The LENS trial showed that 22.7% of patients treated with fenofibrate compared to 29.2% with placebo had progression of early diabetic retinopathy. Paolo Silva, MD, and Lloyd Paul Aiello, MD, PhD, believe that fenofibrate treatment in this setting represents a significant advance.    Read the full editorial: https://eviden.cc/4d8MqTP    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Original Article: Effect of Fenofibrate on Progression of Diabetic Retinopathy https://eviden.cc/3RYG2GX    #ClinicalTrials #MedicalResearch 

The incidence and geographic spread of Lyme disease are increasing, and more than 476,000 new cases a year are estimated to occur in the United States. Therefore, many clinicians in North America will need to consider how to approach a patient with a concern for Lyme disease. A Curbside Consult by Steven E. Schutzer, MD, and Patricia Coyle, MD, addresses common clinical considerations, including discussion of signs of early Lyme disease, available laboratory tests, when to treat and with which antibiotics.    Read the Curbside Consult article “How Do I Approach the Evaluation and Treatment of Early Lyme Disease?” by Steven E. Schutzer, MD, and Patricia Coyle, MD: https://eviden.cc/3WbWTap    #Immunology #ClinicalMedicine 

The 21-gene recurrence score (RS) assay (Oncotype DX) is used to guide adjuvant chemotherapy use for patients with hormone receptor–positive, HER2 (human epidermal growth factor receptor 2)-negative, axillary node-negative breast cancer. Its role, however, in providing prognostic information for late distant recurrence when added to clinicopathologic prognostic factors is unknown.    A patient-specific meta-analysis including 10,004 women enrolled in three trials was updated using extended follow-up data from TAILORx, integrating the RS with histologic grade, tumor size, and age at surgery for the RSClin tool. Cox models integrating clinicopathologic factors and the RS were compared by using likelihood ratio tests. External validation of prognosis for distant recurrence in years 0 to 10 and 5 to 10 was performed in an independent cohort of 1098 women in a real-world registry.    The RSClin provides significantly more prognostic information than either clinicopathologic factors or a 21-gene recurrence score alone in patients with hormone-receptor positive, HER2-negative, node-negative breast cancer.    Read the Original Article “Clinical and Genomic Risk for Late Breast Cancer Recurrence and Survival” by Joseph Sparano, MD, et al.: https://eviden.cc/4de1EXF    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Editorial by William R. Gwin, III, MD, and Nancy E. Davidson, MD: TAILORing Estimates of Late Breast Cancer Recurrence with the RSClin Tool https://eviden.cc/4ff1YaM    #ClinicalTrials #MedicalResearch 

Type 1 diabetes is an autoimmune disease affecting genetically predisposed individuals that leads to chronic hyperglycemia. It is well established that the disease progresses through multiple phases that can extend over several years, from early risk development to clinical disease. The disease starts with presymptomatic islet autoimmunity (stage 1), marked by the presence of two or more islet autoantibodies; it progresses to stage 2, characterized by persistent autoantibodies and glucose abnormalities; and it culminates in stage 3, with clinical onset of hyperglycemia and declining beta-cell function. Novel interventions at each of these early stages have been attempted, with varying degrees of success as measured by delayed progression to stage 3 type 1 diabetes. Of the various approaches, immunomodulation has emerged as the most promising, particularly in stages 2 and 3. Teplizumab, an anti-CD3 antibody, was shown in a randomized trial to slow progression from stage 2 to stage 3 by 2.7 years and to preserve stimulated C-peptide levels in stage 3. The drug was recently approved by the U.S. Food and Drug Administration in children 8 years of age and older at stage 2. Highly promising is another immunomodulatory drug inhibiting the Janus kinase (JAK) pathway called baricitinib, which has been shown to preserve stimulated beta-cell function in patients with stage 3 type 1 diabetes. Because the decline in beta-cell function starts months before stage 3, testing disease-modifying drugs in presymptomatic stages is needed to prevent or delay clinical diagnosis.    In an editorial, Alessandra Petrelli, MD, PhD, and Clifford J. Rosen, MD, discuss the RCT from Gaglia et al. that investigated the potential of AVT001, an autologous dendritic cell vaccine, to preserve beta cell function in individuals aged ≥16 with stage 3 type 1 diabetes.    Read the full editorial: https://eviden.cc/4exyG6J    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Original Article by Jason L. Gaglia, MD, et al.: Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes https://eviden.cc/4biuOUl    #ClinicalTrials #MedicalResearch 

Sleep is what we spend (or should spend) one third of our lives doing. Unfortunately, many individuals fall short of their biological need for sleep many nights of the week. The reasons for this are varied and include professional or personal obligations and social determinants, including loud noises or safety concerns in one’s neighborhood. An article in NEJM Evidence reviews the architecture of sleep; evidence for sleep health, including impacts of sleep health on mental and emotional health as well as cognitive function and performance; and strategies for improving sleep health.    Read the Review Article “Sleep Health” by Rebecca Robbins, PhD, and Stuart Quan, MD: https://eviden.cc/4fc7hrm    #SleepMedicine 

Operative treatment is widely used for acute proximal hamstring avulsions, but its effectiveness compared with that of nonoperative treatment has not been shown in randomized trials. In this noninferiority trial at 10 centers in Sweden and Norway, Elsa Pihl, M.D., Ph.D., et al. enrolled patients 30 to 70 years of age with a proximal hamstring avulsion in a randomized trial and a parallel observational cohort. Treatments were operative reinsertion of the tendons or nonoperative management. The primary end point was the Perth Hamstring Assessment Tool (PHAT) at 2 years of follow-up. Secondary outcomes included scores on the Lower Extremity Functional Scale (LEFS).    Nonoperative treatment for proximal hamstring avulsions was found to be noninferior to operative treatment. PHAT scores (functional outcomes, range 0-100, higher score = higher function)) at 2 years: 79.9 (operative) vs. 78.5 (nonoperative).    Read the Original Article “Operative versus Nonoperative Treatment of Proximal Hamstring Avulsions” by Elsa Pihl, MD, PhD, et al.: https://eviden.cc/4d87cTx    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Editorial by Maegan Shields, MD, MSc, and Tim Dwyer, MBBS, PhD: Acute Proximal Hamstring Tear — Who Will Benefit from Surgical Intervention? https://eviden.cc/3zKBc9J    #ClinicalTrials #MedicalResearch  

In NEJM Evidence, de Boer et al. investigate a linkage between acute myocardial infarction and influenza infection with the application of a self-controlled risk interval study, a design commonly applied to evaluate increased risk of rare side effects from vaccines. The authors studied whether acute myocardial infarction was more likely to occur within 1 week after influenza diagnosis through a comparison of the relative likelihood of two types of events: acute myocardial infarction within 7 days after a positive influenza test result and acute myocardial infarction with influenza infection occurring outside a 7-day window. Basically, the authors evaluated whether the sequential but nearly coincident occurrence of influenza and acute myocardial infarction was more likely than the two events occurring far apart in time.    In an editorial, Lori Dodd, PhD, explores the study by de Boer et al. and discusses the challenges of assessing a true causal link between these conditions.    Read the full editorial: https://eviden.cc/3zhs0tl    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  📄 Original Article by Annemarijn R. de Boer, MD, PhD, et al.: Influenza Infection and Acute Myocardial Infarction https://eviden.cc/3RHpRO2  📄 Editorial by C. Raina MacIntyre, MBBS, FRACP, FAFPHM, PhD, Zubair Akhtar, MPH, and Aye Moa, MPH, PhD: Influenza Vaccine — Low-Hanging Fruit for Prevention of Myocardial Infarction https://eviden.cc/3RE2Jjt    #Cardiology #MedicalResearch 

Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available.      Derick Adigbli, MBBS, PhD, et al. conducted a systematic review that pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome.    Continue reading the Original Article “A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults” by Derick Adigbli, MBBS, PhD, et al.: https://eviden.cc/4cdAtvB    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Editorial by Shohinee Sarma, MD, MPH, FRCPC: Intensive Glucose Control in Critically Ill Patients — How Low Do We Go? https://eviden.cc/3WwnP5V    #ClinicalTrials #MedicalResearch