Open-source code maps traumas for targeting interventions: Applying the model to compare penetrating traumas with "Stop the Bleed" training locations.

BACKGROUND: To improve equitable access to geospatial analysis, a free open-source R package, called Rosymap, was created to map trauma incident locations. METHODS: To demonstrate the R package, penetrating trauma events for all patients who received care at a level one trauma center, and the locations of all "Stop the Bleed" training locations between 2019 and 2022 were geospatially analyzed. RESULTS: The level one trauma center treated 1531 patients for penetrating traumas between 2019 and 2022. Using Rosymap, a map was produced showing the poor overlap in distribution between penetrating traumas and "Stop the Bleed" training locations. CONCLUSION: Rosymap, a free open-source GIS R package, visualized that the majority of "Stop the Bleed" training locations were not performed within clusters of penetrating traumas serviced by our level one trauma center. These results suggest that trauma providers and public health advocates should consider geospatial analysis when planning interventions and when attempting to choose locations equitably and accurately. To facilitate and promote the implementation of geospatial analysis, Rosymap is available as open-source code.

Case Reports of Heroin Injection Site Necrosis: A Novel Antecedent of Nicolau Syndrome.

Heroin injection-site necrosis (HISN) is a novel and poorly understood complication of intravenous drug abuse (IVDA). We present three cases of HISN that were evaluated and treated in Charleston, West Virginia, in 2019 and 2020. The documented cases show similarities involving patient care, follow-up, clinical progression, patient demographic, and dermatologic sequelae. We discuss these similarities, provide clinical recommendations, review proposed etiologies of HISN, and introduce Nicolau syndrome as a potential mechanism.

Incident disease associations with mosaic chromosomal alterations on autosomes, X and Y chromosomes: insights from a phenome-wide association study in the UK Biobank.

BACKGROUND: Mosaic chromosomal alterations (mCAs) are large chromosomal gains, losses and copy-neutral losses of heterozygosity (LOH) in peripheral leukocytes. While many individuals with detectable mCAs have no notable adverse outcomes, mCA-associated gene dosage alterations as well as clonal expansion of mutated leukocyte clones could increase susceptibility to disease. RESULTS: We performed a phenome-wide association study (PheWAS) using existing data from 482,396 UK Biobank (UKBB) participants to investigate potential associations between mCAs and incident disease. Of the 1290 ICD codes we examined, our adjusted analysis identified a total of 50 incident disease outcomes associated with mCAs at PheWAS significance levels. We observed striking differences in the diseases associated with each type of alteration, with autosomal mCAs most associated with increased hematologic malignancies, incident infections and possibly cancer therapy-related conditions. Alterations of chromosome X were associated with increased lymphoid leukemia risk and, mCAs of chromosome Y were linked to potential reduced metabolic disease risk. CONCLUSIONS: Our findings demonstrate that a wide range of diseases are potential sequelae of mCAs and highlight the critical importance of careful covariate adjustment in mCA disease association studies.

Exposure to second-hand cigarette smoke exacerbates the progression of osteoarthritis in a surgical induced murine model.

Osteoarthritis (OA), formerly understood to be a result of passive wear, is now known to be associated with chronic inflammation. Cigarette smoking promotes systemic inflammation and has been implicated in increased joint OA incidence in some studies, though the recent observational data on the association are contradictory. We hypothesize that second-hand smoke (SHS) treatment will increase the incidence of OA in a mouse model that has been subjected to a surgical destabilization of the medial meniscus (DMM). To test this hypothesis, we applied either SHS treatment or room air (RA) to mice for 28 days post-DMM surgery. Histopathology findings indicated that the knees of SHS mice exhibited more severe OA than their control counterparts. Increased expression of matrix metalloprotease-13 (MMP-13), an important extracellular protease known to degrade articular cartilage, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), an intracellular effector of inflammatory pathways, were observed in the SHS group. These findings provide greater understanding and evidence for a detrimental role of cigarette smoke on OA progression and systemic inflammation.

Topical Application of Wogonin Provides a Novel Treatment of Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by inflammatory degradation of articular cartilage and subchondral bone. Wogonin, a compound extracted from the plant Scutellaria baicalensis (colloquially known as skullcap), has previously been shown to have direct anti-inflammatory and antioxidative properties. We examined the pain-reducing, anti-inflammatory, and chondroprotective effects of wogonin when applied as a topical cream. We validated the efficacy of delivering wogonin transdermally in a cream using pig ear skin in a Franz diffusion system. Using a surgical mouse model, we examined the severity and progression of OA with and without the topical application of wogonin. Using a running wheel to track activity, we found that mice with wogonin treatment were statistically more active than mice receiving vehicle treatment. OA progression was analyzed using modified Mankin and OARSI scoring and direct quantification of cyst-like lesions at the chondro-osseus junction; in each instance we observed a statistically significant attenuation of OA severity among mice treated with wogonin compared to the vehicle treatment. Immunohistochemistry revealed a significant decrease in protein expression of transforming growth factor ß1 (TGF-ß1), high temperature receptor A1 (HTRA1), matrix metalloprotease 13 (MMP-13) and NF-κB in wogonin-treated mice, further bolstering the cartilage morphology assessments in the form of a decrease in inflammatory and OA biomarkers.

Osteoarthritis-Like Changes in Bardet-Biedl Syndrome Mutant Ciliopathy Mice (Bbs1M390R/M390R): Evidence for a Role of Primary Cilia in Cartilage Homeostasis and Regulation of Inflammation.

Osteoarthritis (OA) is a debilitating inflammation related disease characterized by joint pain and effusion, loss of mobility, and deformity that may result in functional joint failure and significant impact on quality of life. Once thought of as a simple "wear and tear" disease, it is now widely recognized that OA has a considerable metabolic component and is related to chronic inflammation. Defects associated with primary cilia have been shown to be cause OA-like changes in Bardet-Biedl mice. We examined the role of dysfunctional primary cilia in OA in mice through the regulation of the previously identified degradative and pro-inflammatory molecular pathways common to OA. We observed an increase in the presence of pro-inflammatory markers TGFß-1 and HTRA1 as well as cartilage destructive protease MMP-13 but a decrease in DDR-2. We observed a morphological difference in cartilage thickness in Bbs1 M390R/M390R mice compared to wild type (WT). We did not observe any difference in OARSI or Mankin scores between WT and Bbs1M390R/M390R mice. Primary cilia appear to be involved in the upregulation of biomarkers, including pro-inflammatory markers common to OA.

A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology.

Matrix metalloproteinases are a class of enzymes involved in the degradation of extracellular matrix molecules. While these molecules are exceptionally effective mediators of physiological tissue remodeling, as occurs in wound healing and during embryonic development, pathological upregulation has been implicated in many disease processes. As effectors and indicators of pathological states, matrix metalloproteinases are excellent candidates in the diagnosis and assessment of these diseases. The purpose of this review is to discuss matrix metalloproteinases as they pertain to cartilage health, both under physiological circumstances and in the instances of osteoarthritis and rheumatoid arthritis, and to discuss their utility as biomarkers in instances of the latter.

La Crosse Encephalitis: An Adult Case Series.

BACKGROUND: La Crosse viral encephalitis is well described in children, but to date, there are only 2 adult cases described in the literature. Despite the fact that pediatric infection can be life threatening and typically presents as a febrile meningoencephalitis often complicated by seizures and mental status changes, little is known about the presentation and course of adult infection. We report the largest case series of adult La Crosse encephalitis. METHODS: Inpatient data were reviewed between 2001 and 2012 to identify adults (≥18 years of age) with possible La Crosse encephalitis. Subsequent review of serologic testing was followed by a comprehensive chart review. RESULTS: Ten cases were identified, with ages ranging from 20 to 80 years. Fever, headache, and hyponatremia were seen in the majority, while mental status changes occurred in 5 patients and seizures in 2 patients. The mean length of stay was 8.4 days (± 8.4); 3 patients required intensive care unit admission, 2 of them were intubated, and 4 patients required discharge to a rehabilitation facility. CONCLUSIONS: La Crosse Virus produces a clinically significant encephalitis in adults, and a high level of suspicion should be maintained, particularly in endemic areas. There were no deaths, but La Crosse encephalitis in adults remained a morbid illness often associated with mental status changes, prolonged length of stay or intensive care unit admission, and frequent need for postdischarge rehabilitation.

Detecting initial orthostatic hypotension: a novel approach.

Our purpose, by modification of standard bedside tilt-testing, was to search for lesser known but important initial orthostatic hypotension (IOH), occurring transiently within the first 30 seconds of standing, heretofore only detectable with sophisticated continuous photoplethysmographic monitoring systems, not readily available in most medical facilities. In screened outpatients over 60 years of age, supine blood pressure (BP) parameters were recorded. To achieve readiness for immediate BP after standing, the cuff was re-inflated prior to standing, rather than after. Immediate, 1-, and 3-minute standing BPs were recorded. One hundred fifteen patients were studied (mean age, 71.1 years; 50.5% male). Eighteen (15.6%) had OH, of whom 14 (12.1%) had classical OH, and four (3.5%) had IOH. Early standing BP detection time was 20.1 ± 5.3 seconds. Immediate transient physiologic systolic BP decline was detected in non-OH (-8.8 ± 9.9 mm Hg; P < .0001). In contrast to classical OH (with lesser but persistent orthostatic BP decrements), IOH patients had immediate mean orthostatic systolic/diastolic BP change of -32.8 (±13.8) mm Hg/-14.0 (±8.5) mm Hg (P < .02), with recovery back to baseline by 1 minute. Two of the four IOH patients had pre-syncopal symptoms. For the first time, using standard inflation-deflation BP equipment, immediate transient standing physiologic BP decrement and IOH were demonstrated. This preliminary study confirms proof of principle that manual BP cuff inflation prior to standing may be useful and practical in diagnosing IOH, and may stimulate direct comparative studies with continuous monitoring systems.