Group B streptococcus commonly colonizes the human gastrointestinal and genitourinary tracts and is the single most common bacterial cause of invasive infection among newborns in the United States. Intrapartum antibiotic prophylaxis is currently used to reduce the risk of group B streptococcal disease among pregnant persons and newborns. No strategies are currently available to prevent disease in later infancy or among nonpregnant adults. Vaccines against group B streptococcal disease that consist of capsular polysaccharides linked to protein antigens are in development and may provide a means of prevention for all at-risk populations.

Tecovirimat is approved for smallpox treatment under the Food and Drug Administration Animal Rule on the basis of efficacy in nonhuman primate models of mpox (previously known as monkeypox). However, the clinical efficacy of tecovirimat against human clade II mpox is unclear.

Rezatapopt is an investigational, first-in-class, oral, selective p53 reactivator that specifically binds to Y220C-mutated p53, which stabilizes p53 in its wild-type conformation and restores its functionality.

The risk of recurrent ischemic stroke can be reduced by managing modifiable risk factors and instituting a regimen of mechanism-specific secondary stroke prevention. Strategies for secondary prevention should be instituted as early as possible. Poststroke monitoring of risk metrics, lifestyle behaviors, and medication recommendations is of key importance.

Randomized trials of long-acting injectable antiretroviral therapy (ART) in persons with human immunodeficiency virus (HIV) who face challenges with adherence to oral medication are lacking.

Patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy proceed directly to radical cystectomy with pelvic lymph-node dissection. Perioperative therapy may improve outcomes in this population.

Myotonic dystrophy type 1 is a rare, dominantly inherited, progressive, disabling, neuromuscular disease that leads to decreased life expectancy and has no approved therapies. The disease is caused by a trinucleotide repeat expansion in DMPK, which encodes myotonic dystrophy type 1 protein kinase and imparts a toxic gain of function to the transcribed messenger RNA (mRNA), resulting in dysregulated alternative splicing (missplicing). Delpacibart etedesiran (del-desiran [AOC 1001]) is a monoclonal antibody-oligonucleotide conjugate. The antibody component targets transferrin receptor 1, and the oligonucleotide component targets DMPK mRNA.

Cystinosis is a multisystemic lysosomal storage disorder caused by pathogenic variants in CTNS, the gene encoding cystinosin, a lysosomal transmembrane cystine transporter. In patients with cystinosis, cystine accumulates within lysosomes in all organs. The cystine-depleting agent cysteamine delays but does not prevent disease progression.

Mucormycosis is a rapidly progressive, invasive fungal infection that affects patients who are severely immunocompromised, as well as patients with diabetes and persons with immunocompetence who have major trauma. Mucormycosis manifests in several clinical forms, including sino-orbital, rhinocerebral, sinopulmonary, gastrointestinal, cutaneous, musculoskeletal, osteoarticular, and disseminated mucormycosis, as well as single-organ disease. Although mucormycosis is often lethal, early intervention reduces mortality. Successful treatment depends on early detection and staging of the disease, timely initiation of antifungal therapy, surgical resection of infected tissue, reversal of immunodeficiencies, and correction of metabolic abnormalities. Liposomal amphotericin B is the preferred agent for initial antifungal therapy, with oral triazoles as alternative agents. Research on rapid molecular diagnostic strategies, new antifungal agents, host-directed immune augmentation, antivirulence immune therapeutics, and risk-based stratification to inform management of disease may substantially improve outcomes in patients with this highly destructive mycosis.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare prothrombotic complication that occurs after adenoviral vector-based vaccination against coronavirus disease 2019; in rare cases, it can also occur after natural adenovirus infection. VITT is mediated by platelet-activating antibodies against the highly cationic protein platelet factor 4 (PF4). The underlying inciting antigen trigger and immunopathogenesis remain unknown.

Wild-type female Aedes aegypti mosquitoes that mate with male A. aegypti mosquitoes that have been infected with the wAlbB strain of Wolbachia pipientis bacteria produce nonviable offspring owing to cytoplasmic incompatibility. Repeated releases of wolbachia-infected males can potentially suppress wild-type mosquito populations and reduce the risk of dengue virus infection.

GM1 gangliosidosis, caused by biallelic variants in GLB1, results from deficiency of lysosomal β-galactosidase, which degrades GM1 ganglioside. This fatal neurodegenerative disease currently has no effective therapy.

Peripheral artery disease affects approximately 236 million persons worldwide and is diagnosed with an ankle-brachial index of less than 0.90. Among older persons, 3.3% of those without peripheral artery disease, 18.1% with mild disease, and 52.0% with severe disease could not complete a 6-minute walk test without resting. To prevent cardiovascular events in persons with peripheral artery disease, intensive cholesterol-lowering medications (statins), antiplatelet medications or low-dose aspirin with rivaroxaban, blood-pressure lowering to less than 130/80 mm Hg, and semaglutide are recommended, along with sodium-glucose cotransporter 2 inhibitors in patients with diabetes. Supervised walking exercise and structured home-based walking exercise each improve walking ability in persons with peripheral artery disease. Revascularization in the legs should be reserved for those with persistent disease symptoms that do not respond to exercise.

Every year, approximately 20,000 youths lose a parent to firearm injury in the United States. Many more youths have parents who sustain nonfatal firearm injuries. The effect of parents' firearm injuries on their children's health and health care is poorly understood.

Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies.

Central retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking.

Cardiac physiologic pacing, also known as cardiac resynchronization therapy, is indicated in patients with heart failure, reduced left ventricular ejection fraction (LVEF) of 50% or less, and either a high (or anticipated high) ventricular pacing burden or a wide QRS complex. Traditionally, physiologic pacing has been achieved with biventricular pacing with a right ventricular lead and a coronary sinus branch lead. Randomized trials involving more than 10,000 patients with heart failure have shown clinical, exercise, and quality-of-life benefits associated with biventricular pacing, as well as improved LVEF and reduced mitral regurgitation and ventricular volumes. These benefits are greatest in patients with left bundle-branch block and a QRS duration of 150 msec or longer. Recent studies support targeting the His bundle or left bundle branch as an alternative cardiac physiologic pacing strategy. Ongoing randomized trials are expected to more clearly define the comparative efficacy and safety of conduction system pacing as compared with biventricular pacing.

Triple-negative breast cancer is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, programmed death ligand 1 (PD-L1)-positive, locally advanced unresectable or metastatic triple-negative breast cancer.

The incidence of sudden cardiac arrest in athletes varies according to age, race and ethnic group, sex, sport, and social determinants of health. The common causes of sudden cardiac arrest include cardiomyopathies, electrical disorders, coronary-artery anomalies, and other cardiac structural abnormalities. There has not been an increase in the incidence of sudden cardiac arrest in athletes during the time frame of the coronavirus disease 2019 (Covid-19) pandemic. Primary prevention is based on cardiovascular screening before participation, and secondary prevention on implementation of emergency action plans. Diagnostic evaluation of athletes who survive sudden cardiac arrest should mirror that of age-matched nonathletes, with additional sport-specific considerations, and should be performed by medical professionals with expertise in the interpretation of test results in the context of athletic adaptation. An increasing body of evidence indicates that many athletes can return to play after disease-specific treatment, without an increase in risk, and professional societies now consider return to participation in sports to be reasonable or appropriate through shared decision making for numerous cardiac conditions.

In patients with autoimmune hemolytic anemia (AIHA), the risk of relapse is high owing to persistent autoreactive B-cell activity. Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy. CD19-directed chimeric antigen receptor (CAR) T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.