- N Engl J Med 2022; 387:753-756
Genomes have different types of genetic variation, and many changes are assumed to be “silent” — that is, they have no effect on biology, health, or fitness. A recent study shows that it is not that simple.
- N Engl J Med 2022; 387:658-660
A study of DNA sequencing of reproductive tissues (e.g., products of conception after miscarriage) to test for aneuploidy supports the use of this approach to guide prenatal and fertility care.
- N Engl J Med 2022; 387:514-524
Severe AAT deficiency is caused by a mutation in SERPINA1, which encodes AAT. Mutant AAT protein accumulates in the liver and can lead to liver disease. This phase 2 trial of an agent targeting SERPINA1 messenger RNA showed a reduction in levels of mutant AAT protein...
- N Engl J Med 2022; 387:462-465
Monoclonal antibodies are commonly used in the treatment of diseases, including cancer. A next-generation antibody for the prevention of malaria exploits different vulnerabilities of Plasmodium falciparum, the major cause of malaria.
- N Engl J Med 2022; 387:332-344
Rare mutations in CIDEB protect against liver disease, making the gene a candidate target for treatment. Suppression of CIDEB interferes with the formation of fat droplets in cells.
- N Engl J Med 2022; 387:237-247
Nine of 10 patients with hemophilia B who received a liver-directed adeno-associated viral vector containing a hyperactive variant of factor IX maintained factor IX activity for up to 42 months. Thrombosis developed in 1 patient.
- N Engl J Med 2022; 387:184-186
The authors examine the science behind the induction of objective responses in patients with NSCLC who received adagrasib, an inhibitor of a mutant version of KRAS, which was previously thought to be “undruggable.”
- N Engl J Med 2022; 387:120-131
Adagrasib produced responses in 43% of previously treated patients with non–small-cell lung cancer containing a KRASG12C mutation, with median overall survival of 12.6 months. Regressions of stable brain metastases were noted in one third of evaluable patients. Gastrointestinal toxic effects dominated the adverse events, but fewer than 7%...
- N Engl J Med 2022; 387:180-183
Activating mutations in the KRAS proto-oncogene were identified and characterized more than 40 years ago across several distinct human cancers, including pancreatic and colorectal cancers as well as non–small-cell lung cancer (NSCLC). KRAS somatic alterations are found in approximately 25 to 30% of lung adenocarcinomas and...
- N Engl J Med 2022; 387:77-78
Since 1902, animals have been studied and occasionally used as sources of organs for transplantation, usually when human organs were unavailable. Clinical organ xenotransplantation invariably failed, whereas clinical organ allotransplantation rose to become a primary treatment for failure of the heart, kidneys, liver, and lungs. Still, a shortage of human...
- N Engl J Med 2022; 387:35-44
In this report, a porcine-to-human heart transplantation is described. Videos show transthoracic echocardiography in the patient who received the heart.
- N Engl J Med 2022; 387:79-82
In a recent case of xenotransplantation, now described in the Journal, a porcine heart was transplanted into a human patient, an advance made possible through genetic alterations in the animal donor.
- N Engl J Med 2022; 386:2523-2525
The overrepresentation of a silent variant in KRAS led investigators to explore whether this mutation was biologically relevant (it was) and could be exploited in a mouse model to treat KRAS-mutant cancer.
- N Engl J Med 2022; 386:e72
An 8-month-old girl presented with strabismus and developmental delay. Physical examination was notable for macrocephaly, exotropia, and hypotonia. Funduscopic examination revealed a key finding.
- N Engl J Med 2022; 386:2359-2361
The rheumatologist had been drawn to her specialty by the diagnostic mysteries and long-term patient relationships, but faced with Mr. C., she found herself failing not only to diagnose his condition but also to keep him out of the hospital as his condition deteriorated.
- N Engl J Med 2022; 386:2316-2326
A 29-year-old woman presented with recurrent bone fractures and hypophosphatemia. The patient had been well until 19 months before admission, when pain in the right foot developed. During the next 19 months, multiple fractures of the metatarsal bones of the right foot occurred. On admission, the blood phosphorus level was...
- N Engl J Med 2022; 386:2138-2138
The editors announce a new article type, the Science behind the Study. The articles, which include illustrations and glossary terms, are meant to elucidate the scientific foundations of new clinical studies published in the Journal.
- N Engl J Med 2022; 386:1998-2010
In two small series of patients with myelodysplastic syndrome, the use of demethylating-agent therapy that was aimed at inducing cell differentiation resulted in induction of expression of the SALL4 oncogene in more than 30% of patients, and such expression was associated with a poorer natural history.
- N Engl J Med 2022; 386:1873-1875
Medicine promotes a logically inconsistent message regarding SIDS: authoritative statements imply that SIDS is a consequence of unsafe sleep in biologically normal children, but there is vague acknowledgment that important biologic factors are involved in these deaths.
- N Engl J Med 2022; 386:1950-1952
A recent study of mouse models implicates dopaminergic nerve terminals in the amygdala in releasing the brakes on rapid-eye-movement sleep and on cataplexy in a mouse model of narcolepsy. REM sleep is believed to have a role in processing emotional memories and is under investigation in persons with post-traumatic stress...