A study of the pharmacokinetics, safety, and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed pregnant women with HIV.

OBJECTIVE: The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy. DESIGN: An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1. METHODS: Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum. Steady-state maternal plasma pharmacokinetic samples were collected at the second and third trimesters and 6 and 12 weeks postpartum for BIC, FTC, and TAF. Neonates ( n  = 29) were followed from birth to 4-8 weeks with sparse washout pharmacokinetic sampling for BIC and TAF. The proportion of participants with HIV-1 RNA less than 50 copies/ml at delivery (missing = excluded) was evaluated. RESULTS: Mean areas under the concentration-time curve over the dosing interval (AUC tau ) for BIC, FTC, and TAF were lower during pregnancy versus postpartum but were closer to AUC tau values for nonpregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC, and TAF AUC tau during pregnancy versus postpartum ranged from 41 to 45%, 64 to 69% and 57 to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43 h. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission. CONCLUSION: Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. Pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.

Heparin-induced thrombocytopenia after total knee arthroplasty, with subsequent adrenal hemorrhage.

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune-mediated adverse effect of chemoprophylaxis for venous thromboembolic events. We present the case of a 44-year-old man who developed bilateral adrenal hemorrhage (BAH) as a sequela of HIT after bilateral total knee arthroplasty. In our review of clinical management of HIT-induced BAH, we discuss the 21 published cases of this phenomenon, 14 of which occurred after orthopedic surgery. Given the potentially fatal consequences and the importance of early intervention, physicians should be on the alert for recognizing HIT-induced BAH in patients experiencing shock unresponsive to fluid resuscitation. In addition, chemoprophylaxis with alternative agents such as a synthetic pentasaccharide factor Xa inhibitor and oral direct thrombin inhibitors that are associated with lower risks of HIT in orthopedic patients merits exploration.

End-stage pulmonary disease and brachial plexus regional anesthesia: their implications on perioperative pulmonary function.

The authors present the challenging clinical scenario of managing a patient with end-stage chronic obstructive pulmonary disease requiring anesthesia for a proximal humerus open reduction and internal fixation who likely would have failed to wean from mechanical ventilation if general anesthesia and endotracheal intubation had been chosen as the maintenance technique. They discuss the effects of general and regional anesthesia on respiratory physiology and describe the perioperative implications of severe pulmonary disease. They also review the various brachial plexus block options that could achieve a satisfactory outcome, with the objective of helping guide practitioners to a rational choice of anesthetic techniques when caring for patients with end-stage pulmonary disease.

Paradigm of the injury-repair continuum during critical illness.

OBJECTIVES: To define injury and repair in the context of critical illness. DESIGN: Review of the literature. RESULTS: The medical practice of critical care medicine has long been one of aggressive assistance and support: utilizing state of the art technology to support the functions of the human body until homeostasis is again achieved and the patient is functioning sufficiently to allow the support to discontinue. Injury is defined as the disruption of molecular, cellular, or organ functions resulting from an external or internal stimulus. Repair is defined as an adaptive process that occurs in response to injury and involves both local and systemic responses that serve to restore structure and regulation for the purpose of organ/tissue function. The study of injury in critical illness is now occurring "upstream," at the genetic and cellular levels, to understand how damaging effects of acute inflammation from injury can be prevented or modulated. CONCLUSION: To treat the patient with critical illness more effectively, it is important to understand both the cause of the insults and the repair processes triggered by the insults because both processes affect the eventual course of the critical illness.