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, Lin Ma
New England Journal of Medicine; https://doi.org/10.1056/nejmicm2111716

Abstract:
A 6-year-old girl with perennial sneezing and nasal congestion presented with transverse nasal creases. During the examination, she rubbed her nose in an upward manner, a motion known as the “allergic salute.” Allergic rhinitis was diagnosed.
Douglas B. White, Lisa Villarroel, John L. Hick
New England Journal of Medicine; https://doi.org/10.1056/nejmp2114767

Abstract:
In the spring of 2020, as the first wave of the coronavirus pandemic struck Arizona, numerous Indian Health Service and tribally operated hospitals were overwhelmed with patients in need of admission and intensive care, while hospitals elsewhere in the state had available beds. The Arizona Department of Health Services deployed the Arizona Surge Line — a centralized hospital capacity-management system — to coordinate statewide transfer of patients from hospitals that were overloaded or without needed medical services to those with available resources. On May 28, 2020, Governor Doug Ducey issued an emergency order requiring all Arizona hospitals with available resources to accept patients transferred from overloaded hospitals using the Surge Line. This “load balancing” effort was lifesaving. Since April 2020, the Arizona Surge Line has facilitated the transfer of more than 7900 patients from overloaded hospitals to hospitals with beds available. Approximately 43% of those transferred were American Indian or Alaska Native.1
Janine Knudsen, Dave A. Chokshi
New England Journal of Medicine; https://doi.org/10.1056/nejmp2114010

Abstract:
The Covid-19 pandemic has been a crucible for the U.S. health care system, particularly for the safety-net hospitals, community health centers, and independent clinicians who provide a lifeline for underinsured and uninsured people. Despite facing immeasurable strain in the past year, the safety net has played an essential and often innovative role at the intersection of health care, public health, and emergency response. As we enter a new stage of pandemic response and recovery — in which we must address issues of racial health inequities, frontline health care infrastructure, and community preparedness — the country faces questions about what constitutes adequate support for the safety net, both immediately and over the longer term.
, John P. Mills, Sanjay Saint, Michele Swanson, Jane C. Deng
New England Journal of Medicine, Volume 385, pp 2180-2185; https://doi.org/10.1056/nejmcps2108991

Abstract:
A 61-year-old woman hospitalized in Michigan for treatment of newly diagnosed acute myeloid leukemia had a fever on hospital day 10. She had no localizing symptoms.
New England Journal of Medicine, Volume 385, pp 2189-2190; https://doi.org/10.1056/nejme2116493

Abstract:
After mass vaccination with messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), myocarditis in male teenagers emerged as a possible rare side effect, which led to great concern in the public and potentially fostered vaccine hesitancy or refusal. Myocarditis in general practice, independent of vaccination, is most common in young men and resolves spontaneously in at least half of patients. However, the condition may lead to dilated cardiomyopathy, heart transplantation, or death in up to a quarter of cases.1-4
New England Journal of Medicine, Volume 385, pp 2200-2202; https://doi.org/10.1056/nejmc2115772

Abstract:
To the Editor: Bradbury et al. (Sept. 2 issue)1 designed the randomized, open-label FLIGHT trial to test the efficacy of mycophenolate mofetil plus glucocorticoids as compared with glucocorticoids alone in patients with immune thrombocytopenia (ITP). The authors conclude that mycophenolate mofetil plus glucocorticoids is a promising treatment. In previous studies, we have found that patients with ITP have a higher prevalence of other autoimmune diseases, such as systemic lupus erythematosus and Sjögren’s syndrome.2,3 We wonder whether some patients in the FLIGHT trial might have had subclinical autoimmune diseases, not only ITP. Before we generalize the results of this trial to . . .
Philipp Harter, Jalid Sehouli, Ignace Vergote, Gwenael Ferron, Alexander Reuss, Werner Meier, Stefano Greggi, Berit J. Mosgard, Frederic Selle, Frédéric Guyon, et al.
New England Journal of Medicine, Volume 385, pp 2123-2131; https://doi.org/10.1056/nejmoa2103294

Abstract:
Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear.
Wouter I. Schievink
New England Journal of Medicine, Volume 385, pp 2173-2178; https://doi.org/10.1056/nejmra2101561

Abstract:
Spontaneous cerebrospinal fluid leakage causes orthostatic headache, and mental dullness, diplopia, and coma may occur. Most cases are due to a tear in the spinal CSF membranes. MRI shows enhancement of the dura, and special imaging, such as digital-subtraction myelography (shown in videos), may be required to show the leakage site.
New England Journal of Medicine, Volume 385, pp 2207-2208; https://doi.org/10.1056/nejmc2115966

Abstract:
To the Editor: Given that the minimal clinically important difference in the percentage of predicted forced expiratory volume in 1 second (FEV1) is considered to be 5 percentage points,1 the between-group difference of 3.5 percentage points in the percentage of predicted FEV1 with elexacaftor–tezacaftor–ivacaftor, as compared with active control treatment, that is reported by Barry et al. (Aug. 26 issue)2 is unlikely to be clinically relevant. Changes of this magnitude, reported in previous studies, have aroused questions regarding whether the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies may be considered to be suboptimal.3,4 This hypothesis is supported . . .
Jeffrey I. Weitz, John Strony, Walter Ageno, David Gailani, Elaine M. Hylek, Michael R. Lassen, Kenneth W. Mahaffey, Ravi S. Notani, Robin Roberts, Annelise Segers, et al.
New England Journal of Medicine, Volume 385, pp 2161-2172; https://doi.org/10.1056/nejmoa2113194

Abstract:
Factor XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism may be more effective and result in less bleeding than conventional anticoagulants. Additional data are needed regarding the efficacy and safety of milvexian, an oral factor XIa inhibitor.
Margot Hedlin
New England Journal of Medicine, Volume 385, pp 2119-2121; https://doi.org/10.1056/nejmp2109820

Abstract:
The traditional model of autonomy sees patients as atomistic, and the clinician’s duty as providing information and protecting the patient from undue influence. But people are interconnected and interdependent, shaped by communities and relationships with loved ones.
Young-Hoon Kim, Hyung-Youl Park
New England Journal of Medicine, Volume 385, pp 2179-2179; https://doi.org/10.1056/nejmicm2111332

Abstract:
A 36-year-old man presented with a large mass on his back after he slipped on the stairs and slid down on his back. Magnetic resonance imaging showed a large, encapsulated, subcutaneous, suprafascial lesion consistent with a Morel–Lavallée lesion.
New England Journal of Medicine, Volume 385, pp 2198-2199; https://doi.org/10.1056/nejmc2116125

Abstract:
To the Editor: The randomized, placebo-controlled trial Benefits and Risks of Iron Interventions in Young Children (BRISC) (September 9 issue)1 showed that 3 months of iron supplementation in infants reduced the prevalence of anemia but did not improve infant development. Although the daily supplementation with 12.5 mg of elemental iron was consonant with guidelines from the World Health Organization, the increased rates of iron deficiency and anemia seemed higher in the infants who received iron than in those who received placebo, both before and after the subsequent iron-free follow-up period. Table 2 and Table S2 in the Supplementary Appendix indicated . . .
David M. Weinreich, Sumathi Sivapalasingam, Thomas Norton, Shazia Ali, Haitao Gao, Rafia Bhore, Jing Xiao, Andrea T. Hooper, Jennifer D. Hamilton, Bret J. Musser, et al.
New England Journal of Medicine, Volume 385; https://doi.org/10.1056/nejmoa2108163

Abstract:
In the phase 1–2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. Covid-19–related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P=0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody–positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was −0.71 log10 copies per milliliter (95% confidence interval [CI], −0.90 to −0.53) in the 1200-mg group and −0.86 log10 copies per milliliter (95% CI, −1.00 to −0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. REGEN-COV reduced the risk of Covid-19–related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.)
, , Renata Pasqualini
New England Journal of Medicine, Volume 385, pp 2191-2194; https://doi.org/10.1056/nejmcibr2113027

Abstract:
Over a matter of months, the application of artificial intelligence and machine learning to the prediction of three-dimensional protein structures resulted in an explosion of knowledge that augurs well for accelerating the identification and targeting of “druggable” proteins.
Lisa Simon, William V. Giannobile
New England Journal of Medicine, Volume 385; https://doi.org/10.1056/nejmp2115048

Abstract:
In 1958, the American Medical Association, the American Dental Association, and several other health professional organizations created the Joint Council to Improve the Health Care of the Aged, which was dedicated to opposing the creation of the program that would eventually become Medicare. In the years since the council’s defeat, Medicare has proved transformative, with enrollment in the program at 65 years of age resulting in improved access to care and reductions in health-related racial inequities.1 Yet organized medicine and dentistry’s historical opposition to Medicare has at least one present-day legacy: with the exception of some Medicare Advantage plans, Medicare still lacks dental coverage.
Victor J. Dzau, Rachel Levine, George Barrett, Andrew Witty
New England Journal of Medicine, Volume 385, pp 2117-2119; https://doi.org/10.1056/nejmp2115675

Abstract:
Nowhere are the effects of climate change manifesting more clearly than in human health. Although many people consider climate change a looming threat, health problems stemming from it already kill millions of people per year.1 It is well established that rising levels of greenhouse-gas emissions, which cause climate change, also cause or exacerbate myriad health problems associated with air pollution, severe weather, wildfires, extreme temperatures, changes in vector ecology, and disturbances in the food supply, among other stressors. Furthermore, these health threats are not evenly distributed or experienced across geographies or populations: they disproportionately affect the most vulnerable and disadvantaged groups. The climate crisis is thus a public health and equity crisis that, absent concerted action, will continue to pose significant threats to human health.
Eric J. Rubin, Lindsey R. Baden, Salim S. Abdool Karim, Stephen Morrissey
New England Journal of Medicine, Volume 385; https://doi.org/10.1056/nejme2118839

Abstract:
The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal.
New England Journal of Medicine, Volume 385, pp 2197-2198; https://doi.org/10.1056/nejmc2114907

Abstract:
Ivermectin is approved by the Food and Drug Administration as an oral treatment for intestinal strongyloidiasis and onchocerciasis and as a topical treatment for pediculosis and rosacea. It is also used as a treatment for parasites in pets and livestock. Ivermectin may decrease severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro,1,2 but randomized, controlled trials have shown no clinical benefit in the prevention or treatment of coronavirus disease 2019 (Covid-19).3 Veterinary use of ivermectin has increased, and the number of prescriptions for use by humans in the United States is 24 times as high as the number before the pandemic. Moreover, the number of such prescriptions in August 2021 was 4 times as high as the number in July 2021.3,4
New England Journal of Medicine, Volume 385, pp 2202-2205; https://doi.org/10.1056/nejmc2111026

Abstract:
The Journal recently published three studies involving a total of 39 persons in whom vaccine-induced immune thrombotic thrombocytopenia (VITT), a devastating syndrome characterized by thromboses in unusual sites, developed after they received the ChAdOx1 nCoV-19 vaccine. The articles by Schultz et al. and Greinacher et al. (June 3 issue)1,2 and by Scully et al. (June 10 issue)3 all conclude that it was highly unlikely that the patients had been previously infected with SARS-CoV-2, since they tested negative for antibodies to the SARS-CoV-2 nucleocapsid protein. I believe that this statement is questionable and probably erroneous.
, Chris Robertson, Bob Taylor
New England Journal of Medicine, Volume 385, pp 2195-2197; https://doi.org/10.1056/nejmc2113864

Abstract:
We recently reported vaccine effectiveness for the BNT162b2 vaccine (Pfizer–BioNTech) and the ChAdOx1 nCoV-19 vaccine (AstraZeneca) against infection and hospitalization caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Scotland.1 At that time, the number of deaths was too small to allow estimation of vaccine effectiveness against death from infection with the delta variant.
New England Journal of Medicine, Volume 385, pp 2205-2207; https://doi.org/10.1056/nejmc2114591

Abstract:
In the Covid-19 Convalescent Plasma in Outpatients (C3PO) trial,1 Korley et al., members of the Strategies to Innovate Emergency Care Clinical Trials Network (SIREN), administered convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19. It is unclear why the authors selected 1 week instead of a shorter time frame, since it has been shown that the 30-day and 60-day mortality benefits of convalescent plasma have been observed when it is administered within 3 days after diagnosis and that the benefit dissipates after this point.2,3
Ginger J. Gardner, Dennis S. Chi
New England Journal of Medicine, Volume 385, pp 2187-2188; https://doi.org/10.1056/nejme2116353

Abstract:
The combination of surgery and chemotherapy is a hallmark of the management of ovarian cancer.1 Although surgery is an integral component of management of this disease, its role in recurrent disease has been a topic of debate. After the collection of decades of data from retrospective studies,2 the results of prospective, randomized trials to guide management are now becoming available.
Colleen L. Barry, Brendan Saloner
New England Journal of Medicine, Volume 385, pp 2113-2116; https://doi.org/10.1056/nejmp2102323

Abstract:
Policy has been critical to achieving major public health advances, including in tobacco control, maternal and child health, and injury prevention. The opioid crisis illustrates five steps essential for using policy to produce substantial gains in population health.
Sagar Khanna, Michael Turner
New England Journal of Medicine, Volume 385; https://doi.org/10.1056/nejmicm2112363

Abstract:
A 38-year-old man presented to the otolaryngology clinic with a long history of difficulty in breathing through his right nostril. Rhinoscopy and computed tomographic imaging showed an inverted ectopic tooth in the nasal cavity.
, Hanna Gerlovin, , Katherine E. Kurgansky, Brian R. Ferolito, Michael J. Figueroa Muñiz, David R. Gagnon, J. Michael Gaziano, Kelly Cho, Juan P. Casas, et al.
New England Journal of Medicine; https://doi.org/10.1056/nejmoa2115463

Abstract:
The messenger RNA (mRNA)–based vaccines BNT162b2 and mRNA-1273 are more than 90% effective against coronavirus disease 2019 (Covid-19). However, their comparative effectiveness for a range of outcomes across diverse populations is unknown. We emulated a target trial using the electronic health records of U.S. veterans who received a first dose of the BNT162b2 or mRNA-1273 vaccine between January 4 and May 14, 2021, during a period marked by predominance of the SARS-CoV-2 B.1.1.7 (alpha) variant. We matched recipients of each vaccine in a 1:1 ratio according to their risk factors. Outcomes included documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, symptomatic Covid-19, hospitalization for Covid-19, admission to an intensive care unit (ICU) for Covid-19, and death from Covid-19. We estimated risks using the Kaplan–Meier estimator. To assess the influence of the B.1.617.2 (delta) variant, we emulated a second target trial that involved veterans vaccinated between July 1 and September 20, 2021. Each vaccine group included 219,842 persons. Over 24 weeks of follow-up in a period marked by alpha-variant predominance, the estimated risk of documented infection was 5.75 events per 1000 persons (95% confidence interval [CI], 5.39 to 6.23) in the BNT162b2 group and 4.52 events per 1000 persons (95% CI, 4.17 to 4.84) in the mRNA-1273 group. The excess number of events per 1000 persons for BNT162b2 as compared with mRNA-1273 was 1.23 (95% CI, 0.72 to 1.81) for documented infection, 0.44 (95% CI, 0.25 to 0.70) for symptomatic Covid-19, 0.55 (95% CI, 0.36 to 0.83) for hospitalization for Covid-19, 0.10 (95% CI, 0.00 to 0.26) for ICU admission for Covid-19, and 0.02 (95% CI, −0.06 to 0.12) for death from Covid-19. The corresponding excess risk (BNT162b2 vs. mRNA-1273) of documented infection over 12 weeks of follow-up in a period marked by delta-variant predominance was 6.54 events per 1000 persons (95% CI, −2.58 to 11.82). The 24-week risk of Covid-19 outcomes was low after vaccination with mRNA-1273 or BNT162b2, although risks were lower with mRNA-1273 than with BNT162b2. This pattern was consistent across periods marked by alpha- and delta-variant predominance. (Funded by the Department of Veterans Affairs and others.)
Kevin Kalinsky, William E. Barlow, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Stephen K.L. Chia, et al.
New England Journal of Medicine; https://doi.org/10.1056/nejmoa2108873

Abstract:
The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary lymph-node–negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.
Eric J. Rubin, Dan L. Longo
New England Journal of Medicine; https://doi.org/10.1056/nejme2117446

Abstract:
In many countries, the availability of vaccines has marked a turning point in the Covid-19 pandemic. Although the vaccines are imperfect, breakthrough infections in fully vaccinated people remain quite rare, even with recently emerging variants. Countries with high vaccination rates have largely been able to reopen, and rates of severe illness and death have dropped dramatically. But this has not been a smooth process. Different vaccines have become available at different times, and access to them has varied markedly from country to country. Thus, the choice of which vaccine to use has been driven in great part by availability rather than by science. In fact, it has not been entirely clear how the vaccines we have compare with one another. Comparing the safety and effectiveness of vaccines is not simple in the absence of head-to-head trials. Data on real-world effectiveness can be subject to many limitations because the treated populations may vary in unanticipated ways. In addition, real-world data often provide relatively imprecise estimates of effectiveness that can be of limited value when highly effective agents are being compared.
Eli S. Rosenberg, Vajeera Dorabawila, Delia Easton, Ursula E. Bauer, Jessica Kumar, Rebecca Hoen, Dina Hoefer, Meng Wu, Emily Lutterloh, Mary Beth Conroy, et al.
New England Journal of Medicine; https://doi.org/10.1056/nejmoa2116063

Abstract:
Population-based data from the United States on the effectiveness of the three coronavirus disease 2019 (Covid-19) vaccines currently authorized by the Food and Drug Administration are limited. Whether declines in effectiveness are due to waning immunity, the B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or other causes is unknown. We used data for 8,690,825 adults in New York State to assess the effectiveness of the BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines against laboratory-confirmed Covid-19 and hospitalization with Covid-19 (i.e., Covid-19 diagnosed at or after admission). We compared cohorts defined according to vaccine product received, age, and month of full vaccination with age-specific unvaccinated cohorts by linking statewide testing, hospital, and vaccine registry databases. We assessed vaccine effectiveness against Covid-19 from May 1 through September 3, 2021, and against hospitalization with Covid-19 from May 1 through August 31, 2021. There were 150,865 cases of Covid-19 and 14,477 hospitalizations with Covid-19. During the week of May 1, 2021, when the delta variant made up 1.8% of the circulating variants, the median vaccine effectiveness against Covid-19 was 91.3% (range, 84.1 to 97.0) for BNT162b2, 96.9% (range, 93.7 to 98.0) for mRNA-1273, and 86.6% (range, 77.8 to 89.7) for Ad26.COV2.S. Subsequently, effectiveness declined contemporaneously in all cohorts, from a median of 93.4% (range, 77.8 to 98.0) during the week of May 1 to a nadir of 73.5% (range, 13.8 to 90.0) around July 10, when the prevalence of the delta variant was 85.3%. By the week of August 28, when the prevalence of the delta variant was 99.6%, the effectiveness was 74.2% (range, 63.4 to 86.8). Effectiveness against hospitalization with Covid-19 among adults 18 to 64 years of age remained almost exclusively greater than 86%, with no apparent time trend. Effectiveness declined from May through August among persons 65 years of age or older who had received BNT162b2 (from 94.8 to 88.6%) or mRNA-1273 (from 97.1 to 93.7%). The effectiveness of Ad26.COV2.S was lower than that of the other vaccines, with no trend observed over time (range, 80.0 to 90.6%). The effectiveness of the three vaccines against Covid-19 declined after the delta variant became predominant. The effectiveness against hospitalization remained high, with modest declines limited to BNT162b2 and mRNA-1273 recipients 65 years of age or older.
, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Mallery I. Breban, Anne E. Watkins, Radhika M. Samant, Deverick J. Anderson, Jessica Metti, Gaurav Khullar, et al.
New England Journal of Medicine; https://doi.org/10.1056/nejmc2102507

Abstract:
Two opposing forces that are shaping the coronavirus disease 2019 (Covid-19) pandemic are the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern and the uptake of vaccines. Measurement of SARS-CoV-2 viral load over the course of acute infection can inform hypotheses about the mechanisms that underlie variation in transmissibility according to variant and vaccination status.1
New England Journal of Medicine, Volume 385, pp 2105-2107; https://doi.org/10.1056/nejmc2115776

Abstract:
To the Editor: In the AMPLITUDE-O trial, Gerstein et al. (Sept. 2 issue)1 found a lower risk of cardiovascular events among participants with type 2 diabetes who received a weekly injection of efpeglenatide than among those who received placebo. This trial confirms the interest in glucagon-like peptide-1 (GLP-1) receptor agonists in terms of cardiovascular protection in patients with type 2 diabetes.2-5 However, some concerns persist regrading retinal safety, as observed with semaglutide in SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes).3 Persons with severe retinal disease were excluded from the AMPLITUDE-O . . .
Junhao Yan, Yingying Qin, Han Zhao, Yun Sun, Fei Gong, Rong Li, Xiaoxi Sun, Xiufeng Ling, Hong Li, Cuifang Hao, et al.
New England Journal of Medicine, Volume 385, pp 2047-2058; https://doi.org/10.1056/nejmoa2103613

Abstract:
Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF).
James O’Connell, David M. Nathan, Timothy O’Brien, Derek T. O’Keeffe
New England Journal of Medicine, Volume 385, pp 2092-2095; https://doi.org/10.1056/nejmclde2112076

Abstract:
This interactive feature about a person with type 1 diabetes mellitus and impaired awareness of hypoglycemia offers a case vignette accompanied by two essays supporting the use of a continuous glucose monitor paired with an insulin pump or a continuous glucose monitor with alerts.
Manuela Schmidinger
New England Journal of Medicine, Volume 385, pp 2090-2091; https://doi.org/10.1056/nejme2114846

Abstract:
Patients with von Hippel–Lindau (VHL) disease, a rare autosomal dominant inherited disease,1 have a shorter life expectancy than the general population.2,3 A prospective analysis involving 128 patients in Italy showed that mortality among persons in the VHL population who were between 25 and 64 years of age was significantly higher than that in the general population (P=0.0001).3 The development of clear-cell renal cell carcinoma is usually a late event in the course of VHL disease (at a mean of 34 to 61.8 years of age).3,4 However, extrarenal manifestations of the disease typically occur earlier and are associated with substantial morbidity . . .
James C. Robinson
New England Journal of Medicine, Volume 385, pp 2017-2019; https://doi.org/10.1056/nejmp2113679

Abstract:
Aducanumab’s price can inform the drug-pricing policy debate because it responds to key features of the market environment for physician-administered drugs: Medicare’s reimbursement formula, payment to physicians for infused drugs, and cost-sharing requirements.
, Noam Barda, Michael Leshchinsky, Eldad Kepten, , , , Ran D. Balicer
New England Journal of Medicine, Volume 385, pp 2101-2103; https://doi.org/10.1056/nejmc2114290

Abstract:
The B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the dominant strain circulating in many regions worldwide. The BNT162b2 mRNA vaccine against coronavirus disease 2019 (Covid-19) was found to be effective in preventing infection with the delta variant in a recent observational study,1 but other reports have suggested reduced vaccine effectiveness against this variant.2,3 On May 10, 2021, the U.S. Food and Drug Administration approved the emergency use of BNT162b2 in adolescents 12 years of age or older on the basis of a clinical trial that had been conducted before the delta variant had become prevalent in the United States.4 Additional evidence was needed regarding the effectiveness of the BNT162b2 vaccine among adolescents, particularly against the delta variant.
Mark D. Neuman, Rui Feng, Jeffrey L. Carson, Lakisha J. Gaskins, Derek Dillane, Daniel I. Sessler, Frederick Sieber, Jay Magaziner, Edward R. Marcantonio, Samir Mehta, et al.
New England Journal of Medicine, Volume 385, pp 2025-2035; https://doi.org/10.1056/nejmoa2113514

Abstract:
The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied.
Farid Salih, Linda Schönborn, Siegfried Kohler, Christiana Franke, Martin Möckel, , Hans C. Bauknecht, Christian Pille, Jan A. Graw, Angelika Alonso, et al.
New England Journal of Medicine, Volume 385, pp 2103-2105; https://doi.org/10.1056/nejmc2112974

Abstract:
Vaccine-induced immune thrombotic thrombocytopenia (VITT), a serious adverse event after vaccination with ChAdOx1 nCoV-19 (AstraZeneca) or Ad26.COV2.S (Johnson & Johnson–Janssen), is caused by platelet factor 4 (PF4)–dependent, platelet-activating antibodies.1-3 High-dose immune globulins and anticoagulation are the main treatments.4,5 In this report, we present evidence that vaccine-induced thrombocytopenia (VIT) without associated cerebral venous sinus thrombosis (CVST) or other thromboses and with severe headache as the heraldic symptom may precede VITT (“pre-VITT syndrome”).
Jessica C. Stuart
New England Journal of Medicine, Volume 385, pp 2021-2023; https://doi.org/10.1056/nejmp2112424

Abstract:
“This guy was on the brink of death 10 days ago, but really he just wants his cheeseburger.” The medical team chuckles, but one member, a former patient, understands that this focus on the small, pragmatic things derives from some fundamental aspects of being a patient.
Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
New England Journal of Medicine, Volume 385; https://doi.org/10.1056/nejme2118514

Abstract:
The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal.
New England Journal of Medicine, Volume 385, pp 2109-2111; https://doi.org/10.1056/nejmc2115775

Abstract:
To the Editor: In the STHLM3-MRI trial, Eklund et al. (July 9 issue)1 report that the percentage of men in whom clinically insignificant cancer was detected was lower with the use of magnetic resonance imaging (MRI)–targeted biopsy than with standard systematic biopsy, whereas the percentage of those who received a diagnosis of clinically significant cancer was higher with MRI-targeted biopsy. The authors acknowledge the lack of consensus in the definition of clinically significant cancer and, in line with previous studies, used a biopsy Gleason score of 7 or higher to define this end point (scores range from 6 to 10, . . .
, Lee J. Helman
New England Journal of Medicine, Volume 385, pp 2066-2076; https://doi.org/10.1056/nejmra2103423

Abstract:
Osteosarcoma, which is most common in people 10 to 30 years of age, is generally treated with resection and adjuvant chemotherapy. Detection of gene rearrangements, copy-number variations, and targeted disruption of tumor suppressors by whole-genome sequencing has not yet led to improved treatment.
Massimo Petruzzi, Fedora della Vella
New England Journal of Medicine, Volume 385; https://doi.org/10.1056/nejmicm2108327

Abstract:
A 50-year-old woman with Crohn’s disease presented with painful, shallow erosions in “snail track” formations on her dorsal tongue and inner cheek and with peripheral-blood eosinophilia. A biopsy revealed findings consistent with pyostomatitis vegetans.
Lisa G. Winston, Marisa L. Winkler, Arvin Kheterpal, Julian A. Villalba
New England Journal of Medicine, Volume 385, pp 2078-2086; https://doi.org/10.1056/nejmcpc2107357

Abstract:
A 22-year-old man was admitted with pain and erythema of the left hand. On the day of admission, he awoke with pain and swelling of the hand that involved the second and fourth fingers. Over several hours, the pain progressed and bullae began to form. The patient had recently begun practicing taxidermy. A diagnostic test was performed.
New England Journal of Medicine, Volume 385, pp 2111-2112; https://doi.org/10.1056/nejmc2115673

Abstract:
To the Editor: The lower mortality reported by Deprest et al. (July 8 issue)1 among infants with severe congenital diaphragmatic hernia who were assigned to fetoscopic intervention than among those who were assigned to expectant care should not be interpreted as endorsing broad application outside well-designed trials at experienced centers. Despite the standardized protocol, the report does not include information regarding adherence to standardized care2 during a trial period of more than 10 years at 10 fetal centers and 26 neonatal centers with variable experience treating infants with congenital diaphragmatic hernia. The low use of extracorporeal life support appears inconsistent . . .
James P. Rathmell, Michael S. Avidan
New England Journal of Medicine, Volume 385, pp 2088-2089; https://doi.org/10.1056/nejme2116017

Abstract:
General anesthesia, a state of reversible unconsciousness, is one of the most important advances in medicine, enabling more than 300 million people annually to safely undergo invasive procedures. Concern has emerged that the effects of general anesthesia may not be transient, especially in patients with underlying neurologic disorders. In 1955, on the basis of a retrospective study entitled “Adverse Cerebral Effects of Anaesthesia on Old People,”1 Bedford postulated that anesthetic drugs might damage the brain through synaptic depression and by decreasing cerebral oxygen uptake. He concluded that “operations on elderly people [under general anesthesia] should be confined to unequivocally necessary . . .
Rachel E. Sachs, Nicholas Bagley
New England Journal of Medicine, Volume 385, pp 2019-2021; https://doi.org/10.1056/nejmp2115297

Abstract:
CMS is considering whether and under what circumstances Medicare will pay for aducanumab for Alzheimer’s disease. A restrictive coverage determination could save the federal government money, but it would also shift substantial costs to states.
Eric Jonasch, Frede Donskov, Othon Iliopoulos, W. Kimryn Rathmell, Vivek K. Narayan, Benjamin L. Maughan, Stephane Oudard, Tobias Else, Jodi K. Maranchie, Sarah J. Welsh, et al.
New England Journal of Medicine, Volume 385, pp 2036-2046; https://doi.org/10.1056/nejmoa2103425

Abstract:
Patients with von Hippel–Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to VHL gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α).
New England Journal of Medicine, Volume 385, pp 2096-2100; https://doi.org/10.1056/nejmsb2101718

Abstract:
This Sounding Board article discusses the absence of data to support the current widespread use of preimplantation genetic testing for aneuploidy as an example of a broader concern in reproductive medicine.
Junne Kamihara, Kayla V. Hamilton, Jessica A. Pollard, Catherine M. Clinton, Jill A. Madden, Jasmine Lin, Alma Imamovic, Catherine B. Wall, Ari J. Wassner, Brent R. Weil, et al.
New England Journal of Medicine, Volume 385, pp 2059-2065; https://doi.org/10.1056/nejmoa2110051

Abstract:
The integration of genomic testing into clinical care enables the use of individualized approaches to the management of rare diseases. We describe the use of belzutifan, a potent and selective small-molecule inhibitor of the protein hypoxia-inducible factor 2α (HIF2α), in a patient with polycythemia and multiple paragangliomas (the Pacak–Zhuang syndrome). The syndrome was caused in this patient by somatic mosaicism for an activating mutation in EPAS1. Treatment with belzutifan led to a rapid and sustained tumor response along with resolution of hypertension, headaches, and long-standing polycythemia. This case shows the application of a targeted therapy for the treatment of a patient with a rare tumor-predisposition syndrome. (Funded by the Morin Family Fund for Pediatric Cancer and Alex’s Lemonade Stand Foundation.)
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