NEJM Group

?????????? (???? ??????????) ?????????????????????? ?????? (??????????)?is defined as a short, double-stranded regulatory RNA molecule (20 to 25 nucleotides) that interferes with the expression of a specific gene. It does so by binding to and targeting for degradation the messenger RNA (mRNA) of that gene. The siRNA is processed from a longer double-stranded RNA molecule by the enzyme Dicer. One strand of the siRNA (the guide RNA) creates a complex with other proteins to form the RNA-induced silencing complex (RISC). The other strand (the passenger RNA) is degraded during or after the formation of the RISC. The residual guide RNA, ensconced in RISC, snares mRNA with with complementary sequence, bringing it into close contact with the RISC, which then degrades the mRNA. Artificial siRNAs, synthesized and chemically modified ex vivo, are the basis of some approved drugs and drugs in development. ? ??? To learn more about this NEJM Illustrated Glossary term, read the editorial “Linking a Neurodevelopmental Disorder with a lncRNA Deletion” by Ling-Ling Chen, PhD: https://nej.md/4hkctuu??? ??? Explore more terms: https://nej.md/glossary????

Lung transplantation has evolved over 60 years from an experimental to an accepted standard treatment for life-threatening lung disease. Suitable recipients can expect improved survival and quality of life despite commonly observed problems such as primary graft dysfunction, chronic lung allograft dysfunction (CLAD), increased risk for opportunistic infections, cancer, and chronic immunosuppression-related health issues. Although lung transplantation is becoming more common worldwide, the number of procedures performed is not keeping pace with growing demand. A new review focuses on the current status of and recent developments in lung transplantation and on future opportunities in the effective delivery of this challenging but potentially life-transforming therapy.? ? Continue reading the Review Article “Lung Transplantation” by Jason Christie, MD, Dirk Van Raemdonck, MD, PhD, and Andrew J. Fisher, PhD, BM, BS, from the University of Pennsylvania Perelman School of Medicine and elsewhere: https://nej.md/4fnAlvP?

Free Live Webinar: Health Care Workforce Innovation: Solutions to the Staffing Crisis? ? The health care workforce is characterized as in crisis. Staffing shortages affect care delivery organizations around the world at all levels, and clinician burnout is a longstanding and intractable problem. How can care organizations approach workforce challenges??? ? Join NEJM Catalyst for a free virtual event with an expert panel of health care executives and clinical leaders discussing different approaches they have applied with success, including:? ? ??? Leadership and organizational culture changes? ?? Technology innovations that can reduce clinician workloads? ?? New models of care to address burnout? ? ?? December 11, 2024, Noon–2 PM ET?? ?? https://nej.md/3C7jKxg?

Osteoarthritis of the knee is the most prevalent form of osteoarthritis and leads to chronic pain and impaired quality of life.? ? Obesity is a major risk factor for development of knee osteoarthritis and disease progression. Whether glucagon-like peptide-1 (GLP-1) receptor agonists can reduce pain due to knee osteoarthritis in persons with obesity is unclear.? ? In the STEP 9 trial, researchers evaluated whether the GLP-1 receptor agonist semaglutide is superior to placebo in reducing body weight and pain related to knee osteoarthritis in persons with obesity and knee osteoarthritis.? ? Adults with obesity and moderate-to-severe pain due to knee osteoarthritis were randomly assigned to receive weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet.?? ? The primary end points were the percentage change in body weight and the change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain score (scale, 0 to 100, with higher scores reflecting worse outcomes). Both end points were assessed from baseline to week 68.? ? In persons with obesity and knee osteoarthritis, once-weekly semaglutide significantly reduced body weight and knee osteoarthritis pain, as compared with placebo.? ? Read the full STEP 9 trial results and Plain Language Summary: https://nej.md/40oSLHB? ? #ClinicalTrials #MedicalResearch?

NEJM Editorial Fellow Harleen Marwah, MD MS, summarizes results of the PROHIP trial, which compared total hip replacement with resistance training in patients with severe hip #osteoarthritis and an indication for surgery. Read the Original Article "Total Hip Replacement or Resistance Training for Severe Hip Osteoarthritis" for the full trial results: https://nej.md/4e6FyGD

?????????????????????????? is the synthesis of an RNA molecule using a sequence of DNA as a template. The sequence of the RNA is therefore complementary to the strand of DNA from which it was transcribed. Transcription of chromosomal DNA, which takes place in the nucleus of eukaryotic cells, can generate functional RNAs (such as microRNAs and long noncoding RNAs) that are not translated into protein or can generate pre–messenger RNA (mRNA) that is processed into mRNA; the mRNA is transported to the cytoplasm where it is translated into protein. ?? To learn more about this NEJM Illustrated Glossary term, read the editorial “Linking a Neurodevelopmental Disorder with a lncRNA Deletion” by Ling-Ling Chen, PhD: https://nej.md/4hkctuu?? ?? Explore more terms from the NEJM Illustrated Glossary: https://nej.md/glossary???

In this Double Take video, Drs. Marcus Couldridge, Lance Whitehair, and Heather Kovich discuss patients’ anxieties regarding the lack of continuity of care at the Northern Navajo Medical Center. They describe efforts to combat the doctor shortage with a local residency program and to build trust through community engagement. The video covers the broad scope of practice offered to address patients’ complex medical and social needs.? ? For information on the Shiprock–UNM Family Medicine Residency program discussed in this video, please visit the Indian Health Service website at ihs.gov/shiprockfm.?? ? Further reading: Rural Health Care: And How Long Will You Be Staying, Doctor? (Kovich, in the April 6, 2017, issue of the ??????????????) https://nej.md/2oIHeie? ? #RuralHealth?

Uterine fibroids (leiomyomas) are myometrial masses and are the leading indication for hysterectomy.?? ? Fibroids affect 70 to 80% of persons with a uterus during their lifetime. Up to 50% of persons with fibroids have symptoms, including heavy and prolonged menstrual bleeding, anemia-associated fatigue, pelvic pressure, and both menstrual and nonmenstrual pain.?? ? Fibroids can cause compression of surrounding structures with resultant bulk-related symptoms, including in the bowel (constipation), bladder (urinary frequency, urgency, or retention), and vagina (painful intercourse). Slow growth of uterine fibroids is typical, although both shrinkage and growth spurts do occur.? ? Learn more in “Uterine Fibroids,” a new Clinical Practice article, by Elizabeth A. Stewart, MD, and Shannon K. Laughlin-Tommaso, MD, MPH, from the Mayo Clinic and the Mayo Clinic College of Medicine and Science: https://nej.md/3YQLejR

Clinical Decisions: Watchful Waiting versus Antibiotics for Acute Otitis Media in Pediatric Patients? ? A previously healthy 13-month-old girl is brought to her primary care pediatrician’s office after having rhinorrhea and a mild cough for a few days and fever (maximum temperature, 38°C [100.4°F]) and tugging of the left ear for 1 day. She has had one previous ear infection, which was treated with amoxicillin; she has not had other clinically significant medical problems apart from intermittent viral infections. She has never been hospitalized.? ? On physical examination, fluid is visible in the left ear behind the tympanic membrane, which is bulging slightly. The light reflex and landmarks are distorted. The right tympanic membrane appears to be within normal limits. Both conjunctivae are mildly injected but not purulent. Her mucous membranes are moist, and capillary refill is appropriate. However, her parents report that her intake of milk and solids has decreased slightly in the past few days with this illness. You diagnose unilateral acute otitis media in this patient.?? ? Her parents, who tell you that they understand that overprescription of antibiotics can result in resistant “bugs,” stress that they want the best for their child, and ask you what you would recommend. You must decide whether you should recommend a watchful waiting approach or prescribe antibiotics now.? ? Read more about the case and treatment options in “Watchful Waiting versus Antibiotics for Acute Otitis Media in Pediatric Patients” by Julie Barzilay, MD, Mary Anne Jackson, MD, and David Tunkel, MD: https://nej.md/48AbwKn?

Effective therapies are needed for patients with heart failure and mildly reduced or preserved ejection fraction.? ? Large trials of finerenone have shown a reduced risk of hospitalization for heart failure in patients with chronic kidney disease and diabetes, but studies involving patients with heart failure are needed.? ? In the FINEARTS-HF trial, researchers examined the efficacy and safety of finerenone in patients with heart failure with mildly reduced or preserved ejection fraction.? ? Adults 40 years of age or older with symptomatic heart failure and mildly reduced or preserved ejection fraction were randomly assigned to receive finerenone (maximum dose, 20 mg or 40 mg once daily) or placebo in addition to their usual therapy.?? ? The primary outcome was a composite of total worsening heart failure events and death from cardiovascular causes. A worsening heart failure event was defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure.? ? In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo.? ? Read the full FINEARTS-HF trial results and Plain Language Summary: https://nej.md/470x4ix? ? #ClinicalTrials #MedicalResearch?