Emerging Therapies for Prehospital Control of Hemorrhage.

BACKGROUND: The aim of this review was to describe emerging therapies that could serve as a prehospital intervention to slow or stop noncompressible torso hemorrhage in the civilian and military settings. Hemorrhage accounts for 90% of potentially survivable military deaths and 30%-40% of trauma deaths. There is a great need to develop novel therapies to slow or stop noncompressible torso hemorrhage at the scene of the injury. METHODS: A comprehensive literature search was performed using PubMed (1966 to present) for therapies not approved by the Food and Drug Administration for noncompressible torso hemorrhage in the prehospital setting. Therapies were divided into compressive versus intravascular injectable therapies. Ease of administration, skill required to use the therapy, safety profile, stability, shelf-life, mortality benefit, and efficacy were reviewed. RESULTS: Multiple potential therapies for noncompressible torso hemorrhage are currently under active investigation. These include (1) tamponade therapies, such as gas insufflation and polyurethane foam injection; (2) freeze-dried blood products and alternatives such as lyophilized platelets; (3) nanoscale injectable therapies such as polyethylene glycol nanospheres, polyethylenimine nanoparticles, SynthoPlate, and tissue factor-targeted nanofibers; and (4) other injectable therapies such as polySTAT and adenosine, lidocaine, and magnesium. Although each of these therapies shows great promise at slowing or stopping hemorrhage in animal models of noncompressible hemorrhage, further research is needed to ensure safety and efficacy in humans. CONCLUSIONS: Multiple novel therapies are currently under active investigation to slow or stop noncompressible torso hemorrhage in the prehospital setting and show promising results.

Fellowship or Family? A Comparison of Residency Leave Policies With the Family and Medical Leave Act.

BACKGROUND: In 1993, the Family and Medical Leave Act (FMLA) mandated 12 weeks of unpaid, job-protected leave. The current impact of taking 12 weeks of leave during residency has not been evaluated. METHODS: We examined the 2018 Accreditation Council for Graduate Medical Education (n = 24) specialty leave policies to determine the impact of 6- and 12-week leave on residency training, board eligibility, and fellowship training. We compared our findings with a 2006 study. RESULTS: In 2018, five (21%) specialties had policy language regarding parental leave during residency, and four (16%) had language regarding medical leave. Median leave allowed was 4 weeks (IQR 4-6). Six specialties (25%) decreased the number of weeks allowed for leave from 2006 to 2018. In 2006, a 6-week leave would cause a 1-year delay in board eligibility in six specialties; in 2018, it would not cause delayed board eligibility in any specialty. In 2018, a 12-week (FMLA) leave would extend training by a median of 6 weeks (mean 4.1, range 0-8), would delay board eligibility by 6-12 months in three programs (mean 2.25, range 0-12), and would delay fellowship training by at least 1 year in 17 specialties (71%). The impact of a 12-week leave was similar between medical and surgical specialties. CONCLUSIONS: While leave policies have improved since 2006, most specialties allow for 6 weeks of leave, less than half of what is mandated by the FMLA. Moreover, a 12-week, FMLA-mandated leave would cause significant delays in board certification and entry into fellowship for most residency programs.

Clinically significant ascites as an indication for resection of rapidly involuting congenital hepatic hemangiomas.

Hepatic hemangiomas are the most common benign liver tumor of infancy and are divided into two main types: rapidly involuting congenital hemangiomas (RICH) and non-involuting congenital hemangiomas. RICH typically involute by 12 months and are often asymptomatic. Surgical resection is rare. Indications for surgical resection include rupture, rapid growth, consumptive coagulopathy, and abdominal pain. We present two patients from different institutions who both developed clinically significant ascites as the RICH involuted, prompting surgical resection. This is a new indication for resection.

In Vitro Eradication of Planktonic, Saliva and Biofilm Bacteria Using Lingonberry Extract as a Photosensitizer for Visible Light Plus Water-Filtered Infrared-A Irradiation.

Antimicrobial photodynamic treatment (aPDT) with visible light plus water-filtered infrared-A irradiation (VIS-wIRA) and natural single- or multi-component photosensitizers (PSs) was shown to have potent antimicrobial activity. The aim of this study was to obtain information on the antimicrobial effects of aPDT-VIS-wIRA with lingonberry extract (LE) against bacteria that play a role in oral health. Planktonic bacterial cultures of the Gram-positive E. faecalis T9, S. mutans DSM20523, S. oralis ATCC 35037 and S. sobrinus PSM 203513, the Gram-negative N. oralis 14F2 FG-15-7B, F. nucleatum ATCC 25586, and V. parvula DSM, the anaerobic F. nucleatum ATCC 25586 and V. parvula DSM 2008, and the total mixed bacteria from pooled saliva and supra- and subgingival plaques of volunteers were all treated and compared. aPDT-VIS-wIRA with LE as PS significantly (p < 0.008) reduced the growth of all tested Gram-positive, Gram-negative, as well as aerobic and anaerobic bacterial strains, whereas without irradiation no reductions were seen (p < 0.0001). NaCl, with or without irradiation, was ineffective. After treatment with CHX 0.2%, the highest killing rate (100%) was observed, and no bacteria (0 log10 CFU) were cultivable. The method also significantly reduced all of the bacteria present in saliva and in the gingival biofilms. Three-dimensional visualization of viable and non-viable microorganisms revealed that LE penetrated deeper into the cell wall layers than CHX 0.2%. LE was an appropriate PS for eradicating microorganisms with VIS-wIRA, either in their planktonic form or in saliva and gingival plaque biofilms. These results encourage further investigation in order to determine which LE compounds contribute to the photosensitizing effect and to evaluate the size of the effect on maintaining oral health.

Sex bias persists in surgical research: A 5-year follow-up study.

BACKGROUND: Federal initiatives have recently addressed the sex bias that exists in biomedical and clinical research. However, improvement to the inclusion of sex as a biological variable remains unknown. METHODS: We performed a 5-year follow-up study of all clinical and biomedical research articles published in 5 surgical journals from January 1, 2017, through December 31, 2018. Human, animal, and cell subjects were analyzed for study/subject type, sex of participants, sex matching, and sex-based data reporting, analysis, and discussion. RESULTS: Comparing 2017 to 2018 with 2011 to 2012, slightly more articles reported the sex of the human studied (87% vs 83%; P = .001). Inclusion of both sexes remained high (94% vs 95%; P = .22), but sex-based data reporting (36% vs 38%; P = .17), analysis (35% vs 33%; P = .39), and discussion of results (10% vs 23%; P < .0001) remained unchanged or worsened. Regarding animal research, the number of articles that stated the sex studied remained unchanged (79% vs 78%; P = .67); if stated, slightly more included both sexes (7% vs 3%; P = .002). Regarding cell research, fewer articles reported the sex of the cells studied (5% vs 24%; P = .0001); if stated, more articles included both sexes, but the difference did not reach statistical significance (25% vs 7%; P = .34). Sex matching remained poor with only 50% of human, 4% of animal, and 9% of cell studies matching the inclusion of both sexes by at least 50%. CONCLUSION: Sex bias persists in surgical research. The majority of articles failed to report, analyze, or discuss results based on sex, which will negatively affect clinical translatability and outcomes of evidence-based medicine.

Development of Optimized Tissue-Factor-Targeted Peptide Amphiphile Nanofibers to Slow Noncompressible Torso Hemorrhage.

Noncompressible torso hemorrhage accounts for a significant portion of preventable trauma deaths. We report here on the development of injectable, targeted supramolecular nanotherapeutics based on peptide amphiphile (PA) molecules that are designed to target tissue factor (TF) and, therefore, selectively localize to sites of injury to slow hemorrhage. Eight TF-targeting sequences were identified, synthesized into PA molecules, coassembled with nontargeted backbone PA at various weight percentages, and characterized via circular dichroism spectroscopy, transmission electron microscopy, and X-ray scattering. Following intravenous injection in a rat liver hemorrhage model, two of these PA nanofiber coassemblies exhibited the most specific localization to the site of injury compared to controls (p < 0.05), as quantified using immunofluorescence imaging of injured liver and uninjured organs. To determine if the nanofibers were targeting TF in vivo, a mouse saphenous vein laser injury model was performed and showed that TF-targeted nanofibers colocalized with fibrin, demonstrating increased levels of nanofiber at TF-rich sites. Thromboelastograms obtained using samples of heparinized rat whole blood containing TF demonstrated that no clots were formed in the absence of TF-targeted nanofibers. Lastly, both PA nanofiber coassemblies decreased blood loss in comparison to sham and backbone nanofiber controls by 35-59% (p < 0.05). These data demonstrate an optimal TF-targeted nanofiber that localizes selectively to sites of injury and TF exposure, and, interestingly, reduces blood loss. This research represents a promising initial phase in the development of a TF-targeted injectable therapeutic to reduce preventable deaths from hemorrhage.