Faculty Bibliography

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disease that targets the peripheral nervous system. The literature on the use of regional anesthesia in CIDP is limited. We report a patient with CIDP who received a combined spinal-epidural (CSE) and saphenous and popliteal peripheral nerve blocks (PNBs) for ankle surgery. The CSE and PNBs resolved without incident. On approximately the fourth postoperative day, the patient reported a worsening of baseline CIDP symptoms in all extremities. Given the diffuse presentation, the CIDP exacerbation was attributed to the perioperative stress response. The exacerbation improved by 4 months postoperatively.

We report a 31-year-old woman with sickle beta thalassemia zero who presented at 21 weeks gestational age with multiple bilateral pulmonary emboli and no hemodynamic instability. Acquired antithrombin deficiency was suspected due to a refractory response to therapeutic anticoagulation with enoxaparin, unfractionated heparin, and fondaparinux, and a reduced antithrombin antigen level. At 26 4/7 weeks, she developed signs concerning for increased pulmonary clot burden. To avoid the use of alternative anticoagulants that may cross the placenta and impact the fetus, a planned cesarean delivery was performed without complication at 27 weeks gestation. Both mother and child experienced successful long-term outcomes.

Mycobacterium tuberculosis (Mtb) disrupts anti-microbial pathways of macrophages, cells that normally kill bacteria. Over 40 years ago, D'Arcy Hart showed that Mtb avoids delivery to lysosomes, but the molecular mechanisms that allow Mtb to elude lysosomal degradation are poorly understood. Specialized secretion systems are often used by bacterial pathogens to translocate effectors that target the host, and Mtb encodes type VII secretion systems (TSSSs) that enable mycobacteria to secrete proteins across their complex cell envelope; however, their cellular targets are unknown. Here, we describe a systematic strategy to identify bacterial virulence factors by looking for interactions between the Mtb secretome and host proteins using a high throughput, high stringency, yeast two-hybrid (Y2H) platform. Using this approach we identified an interaction between EsxH, which is secreted by the Esx-3 TSSS, and human hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), a component of the endosomal sorting complex required for transport (ESCRT). ESCRT has a well-described role in directing proteins destined for lysosomal degradation into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs), ensuring degradation of the sorted cargo upon MVB-lysosome fusion. Here, we show that ESCRT is required to deliver Mtb to the lysosome and to restrict intracellular bacterial growth. Further, EsxH, in complex with EsxG, disrupts ESCRT function and impairs phagosome maturation. Thus, we demonstrate a role for a TSSS and the host ESCRT machinery in one of the central features of tuberculosis pathogenesis.