Remote Delivery of Thrombolytics Prior to Transfer to a Regional Burn Center for Tissue Salvage in Frostbite: A Single-center Experience of 199 Patients.

While much has been published on the efficacy and safety of systemic thrombolytics in the treatment of acute frostbite, there has been limited investigation into administration outside a tertiary care setting. Here, we present a single-center experience with remote initiation of intravenous tissue plasminogen activator (tPA) at referring hospitals prior to transfer to a regional burn center. A modified Hennepin Quantification Score based on tissue involvement was used to determine eligibility for tPA and to quantify the severity of amputation. This is a retrospective review of patients with acute frostbite of the digits admitted to a single verified burn center over a 5-yr period. Of 199 patient admissions, 40 received tPA remotely pre-transfer, 32 received tPA on admission to our institution, and 127 patients did not qualify for tPA therapy according to the protocol. Comparing patients who required any amputation (n = 99, 49.7%) to those who did not, patients who received remote tPA had lower odds of any amputation compared to both those receiving tPA at our institution (OR 0.19, 95% CI 0.05-0.65, P = 0.01) and the group receiving no tPA (OR 0.14, 95% CI 0.05-0.40, P < 0.001) after controlling for confounders. Only one patient receiving pre-transfer tPA according to the protocol (2.3%) had a significant bleeding event requiring transfusion. These results support the protocolized use of thrombolytic therapy for frostbite prior to transfer to a tertiary center.

Steroid-Peptide Immunoconjugates for Attenuating T Cell Responses in an Experimental Autoimmune Encephalomyelitis Murine Model of Multiple Sclerosis.

Diseases of immunity, including autoimmune diseases such as multiple sclerosis, transplantation graft rejection, allergy, and asthma, are prevalent and increasing in prevalence. They contribute to significant morbidity and mortality; however, few if any curative therapies exist, and those that are available lack either potency or specificity. Dendritic cells (DCs) are sentinels of the immune system that connect the innate and adaptive immune system and are critical regulators of both immunity and tolerance. We posited that the tolerogenic potential of DC could be harnessed to develop more specific and potent therapies for diseases of immunity by delivering autoantigen to a sufficient number of tolerogenic DCs in situ that could then inhibit pathogenic effector T cell responses. Specifically, we hypothesized that the steroid dexamethasone covalently coupled to a peptide antigen could be processed by DCs, induce tolerogenic DCs, and attenuate antigen-specific pathogenic T cell responses. To test this hypothesis, we synthesized a series of dexamethasone-peptide immunoconjugates by standard solid-phase peptide synthesis. The antigenic portion of the immunoconjugate could be presented by DCs, and the immunoconjugate induced a tolerogenic phenotype in DCs that then inhibited antigen-specific T cell proliferation in vitro. When the immunoconjugate was administered prophylactically in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis, disease was attenuated compared to dexamethasone and peptide delivered as uncoupled components. Together, this work demonstrates the utility of immunoconjugates for inducing tolerance while establishing the foundation for future studies exploring methods to enrich and target DCs for tolerogenic therapies.

Investigating the relationship between weather and violence in Baltimore, Maryland, USA.

BACKGROUND: It is a common refrain at major urban trauma centers that caseloads increase in the heat of the summer. Several previous studies supported this assertion, finding trauma admissions and crime to correlate positively with temperature. We examined links between weather and violence in Baltimore, MD, through trauma presentation to Johns Hopkins Hospital and crime reports filed with the Baltimore Police Department. METHODS: Crime data were obtained from the Baltimore City Police Department from January 1, 2008 to March 31, 2013. Trauma data were obtained from a prospectively collected registry of all trauma patients presenting to Johns Hopkins Hospital from January 1, 2007 to March 31, 2013. Weather data were obtained from the National Climatic Data Center. Correlation coefficients were calculated and negative binomial regression was used to elucidate the independent associations of weather and temporal variables with the trauma and crime data. RESULTS: When adjusting for temporal and meteorological factors, maximum daily temperature was positively associated with total trauma, intentional injury, and gunshot wounds presenting to Johns Hopkins Hospital along with total crime, violent crime, and homicides in Baltimore City. Associations of average wind speed, daily precipitation, and daily snowfall with trauma and crime were far weaker and, when significant, nearly universally negative. CONCLUSION: Maximum daily temperature is the most important weather factor associated with violence and trauma in our study period and location. Our findings suggest potential implications for hospital staffing to be explored in future studies.