Chloroquine (CQ) and Hydroxychloroquine (HCQ), initially utilized in the treatment of malaria, have now developed a long list of applications. Despite their clinical relevance, their mechanisms of action are not clearly defined. Major pathways by which these agents are proposed to function include alkalinization of lysosomes and endosomes, downregulation of C-X-C chemokine receptor type 4 (CXCR4) expression, high-mobility group box 1 protein (HMGB1) inhibition, alteration of intracellular calcium, and prevention of thrombus formation. However, there is conflicting data present in the literature. This is likely the result of the complex overlapping pathways between these mechanisms of action that have not previously been highlighted. In fact, prior research has focused on very specific portions of particular pathways without describing these in the context of the extensive CQ/HCQ literature. This review summarizes the detailed data regarding CQ/HCQ’s mechanisms of action while also providing insight into the overarching themes. Furthermore, this review provides clinical context to the application of these diverse drugs including their role in malaria, autoimmune disorders, cardiovascular disease, thrombus formation, malignancies, and viral infections.

Background Nearly 40% of trauma deaths result from uncontrolled hemorrhage. Most of these deaths occur within 24 hours, highlighting the importance of early resuscitation. Balanced component resuscitation has been shown to improve outcomes in hemorrhagic shock. However, hemostatic properties may then be decreased, leading to inadequate coagulopathy treatment or higher transfusion requirements. Data comparing the efficacy of component vs. whole blood (WB) resuscitation in early trauma is poor, particularly in the rural population. This study investigates WB use and resource utilization at a rural Level 1 trauma center. Methods A prospective cohort study with historical controls (HC) was performed using patients over age 17 presenting as the highest priority trauma. Two units of WB were available to patients with signs of hemorrhagic shock, with subsequent transfusions via massive transfusion protocol or thromboelastography guidance. Component utilization, time to hemorrhage control, complications, and transfer times were examined. Results Forty patients received WB vs. 153 HC. WB patients had lower complication rates (35% vs. 55.6%; P = .02), and a significant reduction in pRBC utilization in the emergency department (0 vs. 2; P < .0001) and throughout admission (2.0 vs. 4.0; P = .0003). All patients had prolonged transport times given the rural setting (1.42 hours HC vs. 2.03 hours WB; P = .002). Discussion Unlike most urban WB studies, this study occurred in a rural area with extended transportation times, when WB is inaccessible for patients. Despite this delay, WB patients demonstrated lower component utilization and complication rates. Further research is needed to characterize the impact of early WB access.

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Background: Simulation in surgical training continues to evolve. As surgical trainees have limited opportunities to regularly practice hand-sewn bowel anastomoses, the aim of this pilot study was to design a low-cost simulation system, the bowel anastomosis training simulator (b-ATS), for teaching hand-sewn small bowel anastomoses and providing learners with real-time feedback via leak testing. Methods: The study consisted of three phases. Phase 1 was the initial design of the b-ATS. The b-ATS consists of a base, stand, fluid bags, tubing, and a novel silicone bowel (bowel A). Phase 2 consisted of data collection. Two PGY-1 residents and one bariatric surgeon created multiple anastomoses using bowel A, several commercially available synthetic bowels, and porcine small bowel. Leak pressures were compared to determine which synthetic bowel most closely resembled biologic tissue. Phase 3 implemented the findings from phase 2 to refine the b-ATS and select the optimal bowel for use in the simulator. Results: The synthetic bowel had the following average leak pressures with polydioxanone (PDS)/Vicryl (cmH 2 O): bowel A, 39.2/37.1; bowel B, 11.4/17; bowel C; 30/ 36.2; bowel D, 68/65.1; bowel E, 38.2/38.1; and bowel F, 55.2/39.2. The average leak pressures for porcine bowel were 62.3/61.6 cmH 2 O with PDS/Vicryl. The most common location of leaks was between the suture and suture holes, followed by the site of attachment to the circular stand. Porcine bowel had the lowest cost at US$0.10 per inch compared with the synthetic bowel tissues which ranged from US$1.66 to US$6.00 per inch. Based on these results, phase 3 consisted of refinements to the simulator structure to prevent the latter leaks and selection of bowel D for use in the final simulator model. Conclusion: The b-ATS is a functional simulator for teaching hand-sewn small bowel anastomosis. Bowel A had significantly lower leak pressures compared with porcine bowel. Bowel D had the closest leak pressure to porcine bowel, at low cost and with adequate durability. Further research is needed to validate the efficacy of this tool.