Injury severity score associated with concurrent bladder injury in patients with blunt urethral injury.

BACKGROUND: Delayed diagnosis of concurrent bladder damage in a patient with blunt urethral trauma can lead to a high rate of morbidity. In patients with a high index of suspicion, genitourinary workup is recommended. In complicated patients with multi-trauma, this workup has a risk of being delayed. A proven prognostic indicator to evaluate the likelihood of bladder injury in this population has not been established. The aim of this study was to determine if there was a clinical association between the Injury Severity Score (ISS) and bladder injury involvement among these patients. METHODS: Retrospective analysis was performed on a cohort of 98 patients who presented with blunt urethral trauma to R. Adams Cowley Shock Trauma Center between 2002 and 2014. Univariate analysis was performed to determine if there was an association between concurrent bladder injuries and ISS among other factors. A receiver operating characteristic curve plot was performed to analyze the association between ISS and bladder involvement. RESULTS: Of the 98 patients with blunt urethral trauma, 28 had concurrent bladder injury. ISS was shown to have a significant correlation with concurrent bladder injury (OR = 2.2 per 10 unit change in ISS, p = 0.0001). ROC curve analysis showed an area under the curve for the prediction of bladder injury. Patients with ISS ≥ 34 had a 54% chance of bladder injury, while patients with ISS < 34 had a 13% chance. CONCLUSION: ISS ≥ 34, a score in the range of severe multi-trauma, may be a clinical indicator of bladder injury in patients presenting with blunt urethral trauma. FUNDING: This research was supported in part by the Proposed Research Initiated by Students and Mentors (PRISM) Program, University of Maryland School of Medicine Office of Student Research.

Connexin43 enhances the expression of osteoarthritis-associated genes in synovial fibroblasts in culture.

BACKGROUND: Recent work has shown that the gap junction protein connexin43 (Cx43) is upregulated in cells of the joint during osteoarthritis (OA). Here we examined if the OA-associated increase in Cx43 expression impacts the function of synovial fibroblasts by contributing to the production of catabolic and inflammatory factors that exacerbate joint destruction in arthritic disease. METHODS: Using rabbit and human synovial fibroblast cell lines, we examined the effects of Cx43 overexpression and Cx43 siRNA-mediated knockdown on the gene expression of OA-associated matrix metalloproteinases (MMP1 and MMP13), aggrecanases (ADAMTS4 and ADAMTS5), and inflammatory factors (IL1, IL6 and PTGS2) by quantitative real time RT-PCR. We examined collagenase activity in conditioned media of cultured synovial cells following Cx43 overexpression. Lastly, we assessed the interplay between Cx43 and the NFκB cascade by western blotting and gene expression studies. RESULTS: Increasing Cx43 expression enhanced the gene expression of MMP1, MMP13, ADAMTS4, ADAMTS5, IL1, IL6 and PTGS2 and increased the secretion of collagenases into conditioned media of cultured synovial fibroblasts. Conversely, knockdown of Cx43 decreased expression of many of these catabolic and inflammatory genes. Modulation of Cx43 expression altered the phosphorylation of the NFκB subunit, p65, and inhibition of NFκB with chemical inhibitors blocked the effects of increased Cx43 expression on the mRNA levels of a subset of these catabolic and inflammatory genes. CONCLUSIONS: Increasing or decreasing Cx43 expression alone was sufficient to alter the levels of catabolic and inflammatory genes expressed by synovial cells. The NFκB cascade mediated the effect of Cx43 on the expression of a subset of these OA-associated genes. As such, Cx43 may be involved in joint pathology during OA, and targeting Cx43 expression or function may be a viable therapeutic strategy to attenuate the catabolic and inflammatory environment of the joint during OA.

The state of telehealth: 2 years into the COVID-19 pandemic - back to business as usual?

INTRODUCTION: Telemedicine (TM) was underutilized prior to the COVID-19 pandemic presumably due to non-standardized reimbursement routes and a perceived lack of need. Early experience with the pandemic necessitated this form of medical care, although durability of consistent delivery remains in question. We quantify the utilization patterns of TM over the past 2 years over multiple waves of the pandemic across various service lines in a large rural health system. MATERIALS: Data of TM utilization were prospectively collected between March 2020-January 2022. Rates of adoption among the various surgical and non-surgical services disciplines were compared. Subgroup analyses between different surgical subspecialties and within the urologic subspecialties was performed. RESULTS: 3.5 million visits were recorded; 3.14 million (90%) on-site and 349,989 (10%) TM; 254,919 (73%) video-assisted and 95,070 (27%) were telephonic. Throughout the pandemic, non-surgical services utilized TM to a greater extent than surgical services (mean% 12 vs 6). Significant variation in the utilization among surgical services was reported, with Urology representing a high utilizer (15%); Among Urologic subspecialties utilization, Endourology (28%) was highest and Pediatric Urology (5%) was lowest. Following an initial spike in TM utilization during the pandemic, rates have declined and plateaued at 5-7% of all visits over the past 6-months. CONCLUSION: TM utilization in this large health system has remained under 10% following the initial surge in 2020. Non-surgical services preferentially use TM more than surgical domains. Certain subspecialties utilize TM more than others, possible due to patient population, practice patterns and medical conditions. Barriers to adoption are essential to determine the relatively low volume of use across this health system.

A Qualitative Analysis of Malpractice Litigation in Cardiology Using Case Summaries Through a National Legal Database Analysis.

Introduction Physicians are increasingly practicing defensive medicine as a response to society's litigious climate. This study sought to characterize cardiology malpractice claims and elucidate the allegations underlying the use of defensive medicine. Methods The WestlawNext™ database was queried to obtain state and federal jury verdicts and settlements related to medical malpractice and cardiology that occurred in the United States between 2010 and 2015. Cardiology cases were identified using the search terms "medical malpractice" and "cardiology" and reviewed by two individuals utilizing available case documents. Duplicate and nonpertinent cases were excluded. Binary logistic regression models were created to predict the likelihood of defendant verdict, plaintiff verdict, and settlement based on the various reasons for litigation cited. Results Inclusion criteria were met in 166 cases. The plaintiffs were predominantly male (94 cases; 56.6%), and the average patient age was 53.3±17.5 years. More than half of the cases involved a cardiologist as a defendant. The most common reasons for litigation were: failure to treat (129; 77.7%), failure to diagnose (115; 69.3%), failure to refer/order diagnostic tests (107; 64.5%), and patient death (118; 71.1%). Among cases tried for failure to diagnose, the most commonly missed diagnosis was myocardial infarction. Cases most commonly resulted in a defendant verdict (94; 56.6%). However, odds of a plaintiff verdict were significantly higher when failure to diagnose was alleged with an odds ratio (OR) of 7.60 (95% confidence interval 1.14 - 50.87, p = 0.0365). Conclusions Failure to diagnose remains a commonly alleged base for litigation. In conclusion, our analysis suggests increased training for non-cardiologists in the recognition of the acute coronary syndrome and enhanced awareness of inherent biases among all physicians may facilitate reducing missed diagnoses.

Linking cellular metabolism and metabolomics to risk-stratification of prostate cancer clinical aggressiveness and potential therapeutic pathways.

Prostate cancer treatment is based on the stratification of disease as low-, intermediate- or high-risk. This stratification has been largely based on anatomic pathology of the disease, as well as through the use of prostate specific antigen (PSA). However, despite this stratification, there remains heterogeneity within the current classification schema. Utilizing a metabolic approach may help to further establish novel biomolecular markers of disease aggressiveness. These markers may eventually be useful in not only the diagnosis of disease but in creating tumor specific targeted therapy for improved clinical outcomes.

The Metabolic Phenotype of Prostate Cancer.

Prostate cancer is the most common non-cutaneous cancer in men in the United States. Cancer metabolism has emerged as a contemporary topic of great interest for improved mechanistic understanding of tumorigenesis. Prostate cancer is a disease model of great interest from a metabolic perspective. Prostatic tissue exhibits unique metabolic activity under baseline conditions. Benign prostate cells accumulate zinc, and this excess zinc inhibits citrate oxidation and metabolism within the citric acid cycle, effectively resulting in citrate production. Malignant cells, however, actively oxidize citrate and resume more typical citric acid cycle function. Of further interest, prostate cancer does not exhibit the Warburg effect, an increase in glucose uptake, seen in many other cancers. These cellular metabolic differences and others are of clinical interest as they present a variety of potential therapeutic targets. Furthermore, understanding of the metabolic profile differences between benign prostate versus low- and high-grade prostate cancers also represents an avenue to better understand cancer progression and potentially develop new diagnostic testing. In this paper, we review the current state of knowledge on the metabolic phenotypes of prostate cancer.

Connexin43 and Runx2 Interact to Affect Cortical Bone Geometry, Skeletal Development, and Osteoblast and Osteoclast Function.

The coupling of osteoblasts and osteocytes by connexin43 (Cx43) gap junctions permits the sharing of second messengers that coordinate bone cell function and cortical bone acquisition. However, details of how Cx43 converts shared second messengers into signals that converge onto essential osteogenic processes are incomplete. Here, we use in vitro and in vivo methods to show that Cx43 and Runx2 functionally interact to regulate osteoblast gene expression and proliferation, ultimately affecting cortical bone properties. Using compound hemizygous mice for the Gja1 (Cx43) and Runx2 genes, we observed a skeletal phenotype not visible in wild-type or singly hemizygous animals. Cortical bone analysis by micro-computed tomography (µCT) revealed that 8-week-old male, compound Gja1+/- Runx2+/- mice have a marked increase in cross-sectional area, endosteal and periosteal bone perimeter, and an increase in porosity compared to controls. These compound Gja1+/- Runx2+/- mice closely approximate the cortical bone phenotypes seen in osteoblast-specific Gja1-conditional knockout models. Furthermore, µCT analysis of skulls revealed an altered interparietal bone geometry in compound hemizygotes. Consistent with this finding, Alizarin red/Alcian blue staining of 2-day-old Gja1+/- Runx2+/- neonates showed a hypomorphic interparietal bone, an exacerbation of the open fontanelles, and a further reduction in the hypoplastic clavicles compared to Runx2+/- neonates. Expression of osteoblast genes, including osteocalcin, osterix, periostin, and Hsp47, was markedly reduced in tibial RNA extracts from compound hemizygous mice, and osteoblasts from compound hemizygous mice exhibited increased proliferative capacity. Further, the reduced osteocalcin expression and hyperproliferative nature of osteoblasts from Cx43 deficient mice was rescued by Runx2 expression. In summary, these findings provide evidence that Cx43 and Runx2 functionally intersect in vivo to regulate cortical bone properties and affect osteoblast differentiation and proliferation, and likely contributes to aspects of the skeletal phenotype of Cx43 conditional knockout mice. © 2017 American Society for Bone and Mineral Research.