Fremanezumab, a humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, is approved for the prevention of migraine in adults. Evidence from randomized, controlled trials in children and adolescents is needed.

Functional dyspepsia is a common but serious medical syndrome that can induce weight loss and food aversion and may be associated with increased risks of hospitalization and death. It probably comprises several different and as yet incompletely characterized disorders. Patients with local mucosal microinflammation driven by an aberrant Th2 response may represent an important subgroup. There is overlap with other gastrointestinal syndromes, particularly irritable bowel syndrome and gastroesophageal reflux disease, and patients with overlap have more severe symptoms. There is no approved drug for functional dyspepsia. Treatment is empirical and directed at symptoms and consists of acid suppressants and low-dose tricyclic antidepressants (and other neuromodulators) along with appropriate nutritional and psychological support.

Cardiogenic shock is characterized by depression of cardiac function that leads to low blood pressure, coronary ischemia, and further decreased cardiac contractility resulting in tissue hypoxemia. The condition is associated with high early mortality, approaching 50%, which is largely influenced by the underlying etiologic factors. In infarct-related cardiogenic shock, rapid restoration of coronary blood flow substantially reduces mortality. Mechanical circulatory support devices offer hemodynamic stabilization and improved outcomes in carefully selected patients, although optimal patient selection and timing of initiation of mechanical circulatory support remain areas of active investigation. Although there have been advances in coronary revascularization techniques and mechanical circulatory support devices, overall survival in cardiogenic shock has improved only modestly. Therefore, future research should focus on refining treatment algorithms, optimizing device use, and developing new strategies to address the high mortality associated with cardiogenic shock.

Tividenofusp alfa, comprising iduronate-2-sulfatase fused to an engineered transferrin receptor-binding Fc domain, has been developed to treat neurologic and peripheral manifestations of mucopolysaccharidosis type II (MPS II), a rare lysosomal disorder causing progressive multisystem and neurologic decline.

Tuberculous meningitis is often lethal, and many survivors have disabilities despite antimicrobial treatment and adjunctive glucocorticoid therapy. Standard-dose rifampin has limited central nervous system penetration. Whether high-dose rifampin could improve survival outcomes is unknown.

Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain.

Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer and residual disease after neoadjuvant therapy are at high risk for recurrence.

For critically ill adults undergoing tracheal intubation, observational studies suggest that the use of etomidate to induce anesthesia may increase the risk of death. Whether the use of ketamine rather than etomidate decreases the risk of death is uncertain.

CD7 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory T-cell acute lymphoblastic leukemia (ALL). Supportive results of first-in-human studies of base-edited anti-CD7 CAR (BE-CAR7) T cells with triple C→T deamination-mediated knockouts of TCRαβ, CD52, and CD7 have been reported previously.

In a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma.

Current second-line treatments for immune thrombocytopenia (ITP) require long-term administration. Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP.

Treatment of chronic lymphocytic leukemia (CLL) currently consists of two main approaches - continuous therapy with Bruton's tyrosine kinase inhibitors and fixed-duration regimens combining venetoclax with either CD20 antibodies or Bruton's tyrosine kinase inhibitors. Comparisons of these two therapeutic approaches are lacking.

Chronic granulomatous disease (CGD) is a severe monogenic immunodeficiency caused by damaging variants in genes required for microbicidal NADPH oxidase activity. Autosomal recessive p47phox-deficient CGD (p47-CGD) is predominantly caused by a two-nucleotide deletion in exon 2 (delGT) of NCF1. We developed PM359, an autologous CD34+ hematopoietic stem-cell therapy in which prime editing is used to correct delGT. Two participants received PM359 after myeloid conditioning with busulfan: neutrophils and platelets engrafted promptly in both patients. Adverse events were consistent with myeloid conditioning with busulfan. NADPH oxidase activity was observed in neutrophils within 1 month and was maintained for 6 months and 4 months as of the last follow-up visit in Participants 1 and 2, respectively. These results support further investigation of prime editing of CD34+ cells to treat p47-CGD. (Funded by Prime Medicine; ClinicalTrials.gov number, NCT06559176.).

Prophylactic treatment for hemophilia B necessitates lifelong, regular intravenous factor IX infusions. Gene therapy offers the possibility of a single-dose treatment that produces durable endogenous factor IX expression and disease control. Etranacogene dezaparvovec comprises an adeno-associated virus serotype 5 (AAV5) vector and the highly active Padua factor IX variant. The primary analysis of this study showed that etranacogene dezaparvovec reduced annualized bleeding rates and adverse events were mainly of low-grade severity. Final data from 5 years of follow-up are now available.

Patients with plasmacytomas that are noncontiguous with bone marrow (true extramedullary myeloma) are at high risk for disease progression or relapse. Phase 1 of the RedirecTT-1 study showed promising efficacy with dual-antigen targeting of myeloma with talquetamab (anti-G protein-coupled receptor family C group 5 member D) plus teclistamab (anti-B-cell maturation antigen) in patients with triple-class-exposed relapsed or refractory multiple myeloma, including those with true extramedullary myeloma.

Multidose human papillomavirus (HPV) vaccination is efficacious, yet the vaccine has been underused globally. Emerging data suggest that a single dose may provide protection. Whether a single dose of HPV vaccine would provide similar protection to two doses is uncertain.

C3 glomerulopathy and primary immune-complex membranoproliferative glomerulonephritis (MPGN) generally result in glomerular C3 deposition and irreversible kidney damage. The efficacy and safety of pegcetacoplan, a C3 and C3b inhibitor, in persons with C3 glomerulopathy or primary immune-complex MPGN are unclear.

Hereditary hemorrhagic telangiectasia (HHT) can cause recurrent, severe epistaxis, as well as anemia and reduced quality of life. The disease remains without licensed therapies worldwide.

Approximately half the worldwide population is at risk for dengue. No antiviral prophylaxis or treatment options are available.

Improvements in medical therapy, carotid-artery stenting, and carotid endarterectomy call into question the preferred management of asymptomatic carotid stenosis. Whether adding revascularization to intensive medical management would provide greater benefit than intensive medical management alone is unclear.