Nirmatrelvir is an M^pro inhibitor active against SARS-CoV-2 and is given with ritonavir, a pharmacokinetic enhancer. In this double-blind, placebo-controlled trial, nirmatrelvir plus ritonavir, when given within 5 days after symptom onset to patients at high risk for disease progression, decreased the risk of Covid-19–related hospitalization or death by 87.8%.

Sixty patients with ITP were enrolled in a phase 1–2 trial of the Bruton’s tyrosine kinase inhibitor rilzabrutinib for increasing platelet count. During 24 weeks, 40% of the patients who started rilzabrutinib at the 400-mg twice-daily dose had a platelet count of at least 50×10³ per cubic millimeter. Adverse events were grade 1 or 2 and transient, with no high-grade bleeding or thrombotic events.

Pyruvate kinase deficiency, the most common genetic lesion in the glycolytic pathway, leads to chronic hemolytic anemia. Mitapivat, an oral agent, can activate some mutant enzymes and restore red-cell ATP generation. In this trial, hemoglobin levels increased from baseline by 1.5 g per deciliter or more at 24 weeks in 40% of the patients with pyruvate kinase deficiency who received mitapivat.

An 80-year-old woman was admitted with pancytopenia. Five weeks earlier, nausea, vomiting, diarrhea, chills, and fever had developed. CT revealed bilateral pelvic masses; examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count. What is the diagnosis?

This interactive feature about the use of bisphosphonates to treat osteoporosis offers a case vignette accompanied by two essays, one supporting continuation of bisphosphonate therapy beyond 5 years and the other supporting a “drug holiday.” Vote and comment.

The diagnosis of Creutzfeldt–Jakob disease has advanced from detection of characteristic EEG and MRI features to include the detection in CSF of 14-3-3 protein and, with the use of RT-QuIC assays, of abnormally folded prion protein, with close to 100% sensitivity and specificity.