New Drugs and Regimens for Tuberculosis Disease Treatment in Children and Adolescents.

After almost 30 years of relative stagnation, research over the past decade has led to remarkable advances in the treatment of both drug-susceptible (DS) and drug-resistant (DR) tuberculosis (TB) disease in children and adolescents. Compared with the previous standard therapy of at least 6 months, 2 new regimens lasting for only 4 months for the treatment of DS-TB have been studied and are recommended by the World Health Organization (WHO), along with a shortened 6-month regimen for treatment of DS-TB meningitis. In addition, the 18- to 24-month regimens previously used for DR-TB that included painful injectable drugs with high rates of adverse effects have been replaced with shorter, safer all-oral regimens. Advances that have improved treatment include development of new TB drugs (bedaquiline, delamanid, pretomanid), reapplication of older TB drugs (rifampicin and rifapentine), and repurposing of other drugs (clofazimine and linezolid). The development of child-friendly formulations for many of these drugs has further enhanced the ability to safely and effectively treat DS- and DR-TB in children and adolescents. The characteristics and use of these drugs, regimens, and formulations are reviewed.

The Volume of the Spleen and Its Correlates after Acute Stroke.

BACKGROUND: Animal studies describe changes in the spleen following a stroke, with an immediate reduction in volume associated with changes in the counts of specific blood white blood cell (WBCs). This brain-spleen cell cycling after stroke affects systemic inflammation and the brain inflammatory milieu and may be a target for emerging therapeutic studies. This study aimed to evaluate features of this brain-spleen model in human patients admitted for acute stroke. METHODS: Medical and imaging records were retrospectively reviewed for 82 consecutive patients admitted for acute stroke in whom an abdominal computed tomography scan was performed. RESULTS: Mean ± SD splenic volume was 224.5 ± 135.5 cc. Splenic volume varied according to gender (P = .014) but not stroke subtype (ischemic versus hemorrhagic, P = .76). The change in splenic volume over time was biphasic (P = .04), with splenic volumes initially decreasing over time, reaching a nadir 48 hours after stroke onset, then increasing thereafter. Splenic volume was related inversely to percent blood lymphocytes (r = -.36, P = .001) and positively to percent blood neutrophils (r = .30, P = .006). CONCLUSIONS: Current results support that several features of brain-spleen cell cycling after stroke described in preclinical studies extend to human subjects, including the immediate contraction of splenic volume associated with proportionate changes in blood WBC counts. Splenic volume may be useful as a biomarker of systemic inflammatory events in clinical trials of interventions targeting the immune system after stroke.