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Welcome to NEJM this week. I'm Dr. Michael Bearer. This week we present advances in the treatment of multiple myeloma, systemic lupus erythematosus and coronary artery disease alongside new national data on healthcare associated infections. We also review fibromyalgia and the emerging bundibudgio virus outbreak, follow a surprising diagnostic case of alpha GAL syndrome, and explore perspectives on caring for vulnerable patients, trustworthy health information, pharmacotherapeutic decisions in autism care, and the experience of caring for a parent with dementia. Continuous or fixed duration maintenance therapy in multiple myeloma By Shaji Kumar from the Mayo Clinic, Rochester, MN and co Authors current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression. However, the appropriate duration of maintenance therapy has been unclear. In this phase 3 trial, 561 patients with standard risk newly diagnosed multiple myeloma who were not undergoing upfront autologous stem cell transplantation received induction treatment with a proteasome inhibitor lenalidomide combination. Then the patients were randomly assigned to receive indefinite duration continuous lenalidomide or fixed duration lenalidomide for 2 years at a median follow up of 86 months. Overall survival did not differ significantly between the groups. More adverse events occurred with indefinite duration lenalidomide. The incidence of non hematologic events of grade 3 or higher was 48.2% with indefinite duration therapy and 31.5% with fixed duration therapy. Hira Meehan from McMaster University, Hamilton, Ontario, Canada, and Luciano Costa from University of Alabama at Birmingham write in an editorial that multiple myeloma has undergone a therapeutic revolution at a pace nearly unmatched in oncology. Yet, amid these advances, a key assumption in multiple myeloma therapy more and longer treatment is better. The trial by Kumar and co authors challenges this assumption. The results of this trial should prompt investigators and sponsors to question whether the presumption of indefinite therapy is being carried forward uncritically into the next generation of trials in multiple myeloma. Currently, ongoing and planned trials in newly diagnosed multiple myeloma continue to use indefinite maintenance therapy in both the control and investigational groups. Sponsors are often reluctant to commit to a fixed duration of therapy for fear of compromising progression, free survival, and the inevitable economic consequences of shorter treatment periods. The results of the current trial suggest that such fear is unjustified for efficacy outcomes. They also highlight the opportunity, or even the necessity, to design trials that assign higher positions in the testing hierarchy to outcomes that better capture the benefits to patients and society of limited duration, therapy, toxic effects Second malignant neoplasm, quality of life and cost Extended dual antiplatelet therapy for multivessel coronary artery disease by Jinwei Tian from the Second Affiliated Hospital of Harbin Medical University, Harbin, China and co authors Patients with multivesal coronary artery disease often receive 12 months of dual antiplatelet therapy after stenting to reduce the risk of ischemic events. This study evaluated whether extending dapt beyond 12 months in event free patients with multivesal disease provides a benefit. In this randomized trial at 97 centers in China, 8,250 patients 18 to 75 years of age with multivesal coronary artery disease who had had no major ischemic or bleeding events while receiving DAPT for 12 months after implantation of a drug eluting stent were randomly assigned to receive an additional 12 months of DAPT, the P2Y12 inhibitor clopidogrel plus aspirin or aspirin monotherapy. The median follow up was 34.3 months. Extending DAPT with clopidogrel and aspirin for an additional 12 months led to a lower risk of death from cardiovascular causes, non fatal myocardial infarction, or non fatal stroke than continuing aspirin alone without an increased risk of bleeding. In an editorial, Kyung Woo park and Jihoon Kang from Seoul National University Hospital, South Korea, write that the appropriate duration of DAP therapy after percutaneous coronary intervention has remained the subject of a central debate in cardiovascular medicine. The clinical implications of the findings by Tian and co authors are substantial. The decision to prolong DAPT has historically been characterized by a complex risk benefit calculus in which atherothrombotic protection is weighed against the risk of bleeding complications. By strictly selecting patients younger than 75 years of age who had already received a full year of DAPT without adverse events, they successfully identified a cohort that could reap the atherothrombotic Benefits of prolonged P2Y12 inhibition with without paying the price of hemorrhage. The results of the trial by Tian and co authors suggest that identification of the right population can result in the decoupling of ischemic benefit from hemorrhagic harm. Precision medicine may warrant further identification of appropriate patient populations. Efficacy and safety of obinutuzumab in active systemic lupus erythematosus By Richard Furey from Northwell, New Hyde Park, New York Co Authors Obinutuzumab, a glyco engineered type 2 anti CD20 monoclonal antibody induces potent B cell depletion and is approved for the treatment of active lupus nephritis. This phase 3 trial evaluated its efficacy and safety in patients with active systemic lupus erythematosis. 303 adults with active SLE but without proliferative or membranous lupus nephritis who were receiving standard therapy were randomly assigned to receive obinutuzumab or placebo. Treatment with obinutuzumab was superior to placebo with respect to the primary endpoint of a response on the SLE Responder Index 4 and to all key secondary endpoints. Healthcare Associated Infections in US Hospitals 2023 vs 2015 by Nora Che from the Centers for Disease Control and Prevention, Atlanta and co authors prevalence surveys in U.S. hospitals showed that on any given day, 1 of 25 patients had a health care associated infection in 2011 as compared with 1 of 31 patients in 2015. These investigators repeated the survey in 2023 to assess changes in the prevalence of such infections. In this survey, the investigators found one of 38 patients on any given day having healthcare associated infections. This prevalence in 2023 was lower than in 2015 and reductions in C. Difficile infection, central catheter associated bloodstream infection, and catheter associated urinary tract infection were observed. However, the burden of healthcare associated infections in US Hospitals has continued to be high. A majority of the healthcare associated infections that were identified were not associated with the device or procedure. Fibromyalgia A review article by David Williams and Daniel Claw from the University of Michigan, Ann Arbor. Fibromyalgia is characterized by widespread pain involving any body tissue and typically accompanied by fatigue and problems with sleep, mood, and memory. Fibromyalgia can occur alone or in combination with other chronic overlapping primary pain conditions or it can be superimposed on other conditions such as autoimmune disorders. Secondary pain in fibromyalgia, the central nervous system is hyper responsive to sensory stimuli. Generally, successful pharmacologic and non pharmacologic interventions focus on the CNS to support CNS quiescence and a return to homeostasis. Although fibromyalgia is rarely curable, most cases can be adequately managed in the context of primary care. Bundibudgio virus disease in 2026 clinical and public health responses A review article by Nancy Sullivan from Boston University. Bundibudjo virus is a relatively rare ortho Ebola virus that has caused only two previously recognized disease outbreaks but remains capable of producing severe epidemic disease with substantial mortality. The 2026 outbreak of Bundibudjo virus disease in the Democratic Republic of Congo has highlighted persistent challenges in the detection of filovirus disease outbreaks as well as in diagnosis, clinical management, and the public health response, particularly in resource limited settings. As with other filovirus infections, effective control of the bundibudiovirus disease outbreak depends on rapid identification of cases, laboratory confirmation of infection, isolation of cases, contact tracing, infection prevention measures, protection of healthcare workers, and community engagement. Although no licensed vaccines or approved therapeutics specific to bundibudjo virus disease are currently available, advances in supportive care have improved outcomes during recent filovirus disease outbreaks. Experimental evidence from studies involving non human primates, serologic investigations with human samples, and monoclonal antibody research suggests that vaccines and therapeutics developed against Ebola virus may provide cross protective activity against Bundibudgio virus. These observations support prototype pathogen approaches to preparedness while underscoring the need for continued development of pathogen specific countermeasures. The current outbreak reinforces the principle that a successful response to filovirus disease requires integration of medical countermeasures, clinical care, surveillance, diagnostics, and coordinated multinational public health operations. A 38 year old man with abdominal pain A case record of the Massachusetts General Hospital By Ima Ahonki and colleagues a 38 year old ornithologist sought care for recurrent abdominal pain after returning from a work trip to rural Madagascar. During the trip, he had developed severe watery diarrhea with fever, chills, nausea, and vomiting that initially improved, but weeks later he began experiencing episodes of cramping, abdominal pain, bloating, and nausea several hours after eating. The attacks left him fatigued and were accompanied by weight loss and marked eosinophilia. Because of his extensive international travel and environmental exposures, he was evaluated for parasitic and other tropical infections, but the results were unrevealing. The patient reported that his symptoms did not worsen after ingestion of dairy, grains, fruits, or vegetables, but he recalled that an episode of cramping, pain and bloating occurred after he had eaten a hamburger. The patient noted that he had had previous tick exposures, including one tick that had attached to his body in eastern Massachusetts five months before the trip to Madagascar and as well as possible tick exposures in South America one month before the trip. Testing confirmed a diagnosis of alpha GAL syndrome, a delayed allergic reaction to mammalian meat triggered by tick bite sensitization after eliminating red meat, dairy, gelatin, and other mammalian products from his diet. The patient's abdominal pain and fatigue resolved his eosinophil count declined and he remained well one year later. The Exam Room as Sanctuary Caring for Undocumented Patients A Perspective by Miguel Linares from the University of California, Los Angeles, and co Authors A physician shall be dedicated to providing competent medical care with compassion and respect for human dignity and rights. A physician shall support access to medical care for for all people. These foundational principles from the American Medical Association's Code of Medical Ethics establish physicians responsibility to serve all people irrespective of immigration status. Yet translating this duty into care for undocumented immigrants, especially during periods of heightened fear, requires actionable frameworks guided by compassion and respect. Approximately 13 million U.S. residents are undocumented immigrants, many of whom have endured treacherous journeys in search of stability and safety. Fear, exclusion, and mistrust of institutions can fundamentally shape interactions with the healthcare system. Trauma informed care offers a vital approach for physicians seeking to bridge the gaps. The approach reflects a shift in the framing of care. Instead of asking patients what is wrong with you? Clinicians ask what happened to you? The Substance Abuse and Mental Health Services Administration defines a trauma informed approach as acknowledging the widespread effect of trauma, recognizing its signs, integrating this knowledge into practice, and actively resisting retraumatization. Six core components of trauma informed care safety, empowerment, peer support, collaboration, trustworthiness and transparency, and cultural and historical context are explained in a table available with this article in print or online@nejm.org the foundation of trauma informed care is safety Supporting access to reliable health information with public private collaboration A perspective by Victor zhao and Laura DiStefano from the National Academy of Medicine, Washington, DC. Although digital media and generative artificial intelligence platforms have dramatically expanded access to health information and empowered patients to participate more actively in health related decision making, they have also accelerated the spread of inaccurate information, which can cause harm. Promoting reliable health information in digital spaces is a critical public health goal. Digital media and technology companies exert enormous influence over what information is seen and shared, yet as private commercial entities, they cannot be the sole arbiters of information credibility. Meanwhile, independent scientific organizations are often trusted evaluators but lack the reach of commercial platforms. Collaboration between these sectors could represent a path forward for supporting broad access to high quality health information, but collaborative efforts have elicited concern among members of the scientific community who worry that standards for integrity and independence may be compromised. These National Academy of Medicine authors discuss their recent engagement in collaborations with two digital media and technology companies, YouTube and Google. Although important questions and limitations remain, the authors believe that thoughtful, transparent, and carefully governed collaborations with such companies, grounded in rigorous standards, strong governance, and clear conflict of interest protections can result in important outcomes that align with the missions and values of scientific and public health organizations. Pharmacotherapeutic Decisions in Autism A Perspective by Yara Zizman Ilani from Temple University, Philadelphia and co authors despite decades of research and substantial public demand for treatment options, progress toward developing medications for treating autism has been limited. Autism is highly heterogeneous, causing widely variable symptoms. No medication has been shown to modify the core characteristics associated with the condition. Pharmacotherapy has, however, been directed at coexisting conditions that cause distress or functional impairment. Only two medications, risperidone and aripiprazole, have been approved by the Food and Drug Administration for use in autism. Both target irritability and agitation rather than core symptoms. In addition, although psychoeducational interventions remain the cornerstone of evidence based care in autism, these interventions often do not completely address the functional challenges that autistic people face and are frequently inaccessible because of cost, workforce shortages, or geographic barriers. Autistic people, their families, and clinicians are therefore often caught between the imperative to address impairing symptoms and the reality that available options are are associated with uncertain benefits and potential harms. An important question in autism care is not only how to treat the condition, but what constitutes an appropriate treatment target. In the absence of clear guidance, autistic people often receive off label medications and unproven therapies. Uncertainty may be one of the defining characteristics of the current state of autism treatment, and medication management in autism requires clinicians to navigate this uncertainty or while respecting the experiences of autistic people and their families. Shared decision making is a promising framework that could help facilitate this task. The Symptom Tracker A perspective by Stephen McGaughey from Oregon Health and Science University, Portland. His father's hands rise before Dr. McGaughey is fully through the door, his father shooing him back from across the room. His father's eyes are wide with panic. Is the door locked? Can you leave? You must leave now, his father whispers urgently. Dr. McGaughey smiles and tries to reassure him that he is fine. Yes, the door is locked, but he can leave. It reminds Dr. McGaughey of his work in the pediatric emergency department. They also have safe rooms, drab, Spartan, with a TV behind reinforced plexiglass. Later, at his parents home, Dr. McGaughey pulls up his spreadsheet and types October 21 visited dad continues to be delusional about money. Scared of our visits. Dr. McGaughey scrolls up through the entries to the top, where he first documented his father's decline. April 15 Family first noticed severe symptoms. Emotional apologizing constantly. Says he's sowing chaos. May 5 dad convinced he had ischemic bowel. Mom drove to Ed, talked them down by phone. They returned home. June 20 really good day. Lucid. Laughed at my mom's jokes. June 21 Confused again. Didn't recognize his sister on the phone. September 15 Met with movement neurologist, PET scan and skin biopsy Ordered likely Lewy body dementia or multisystem atrophy. September 27th refused medications. Argument he hit mom. October 6th he left the house. Mom is frantic. Police called. Found him three hours later, one block away. October 8th psychiatrist says he needs hospitalization. Brother drove dad to the ED boarding. October 9th admitted after his father's admission, Dr. McGaughey toured memory care facilities with his mother. He stood there evaluating care quality while his heart broke at the thought of leaving his father in one of these places. Dr. McGaughey was used to compartmentalizing his life. He moves between rooms, telling a father that his child's MRI shows a mass. Then in another room, quickly reassuring a mother that her febrile child is fine. But Dr. McGaughey has no compartments left. There is no separation for him between physician and son, between clinical observation and personal grief. Medical Training has taught Dr. McGohy to document carefully. He does. It taught him to be objective, but he cannot be. The symptom tracker was supposed to help his doctors. It does. But along the way it became something else, Dr. McGaughey's way of holding on. In our images in clinical medicine, a six month old baby boy was transferred to a quaternary children's hospital for seizures. An X ray of a hand and wrist showed dense transverse bands of metaphyseal sclerosis in the radius, ulna, metacarpals and phalanges in the context of the patient's symptoms. These bands were suspected to represent lead lines as seen in severe lead poisoning. The infant's blood lead levels confirmed the diagnosis. On further history taking the source of lead exposure was found to be an Ayurvedic medication that had been given to the baby since early infancy to treat colic. In another image, a man presented with a two month history of chest heaviness and a two week history of shortness of breath. Pulsations were visible between his ribs, shown in a video@nejm.org ultrasonography revealed a rounded structure near the heart. Connecticut Angiography of the chest showed a large fusiform aneurysm in the descending thoracic aorta. Read more from our issue@nejm.org let us know what you think about our podcast. Any comments or suggestions may be sent to audiog. Thank you for listening.