Inhibition of Protein-protein Interactions in Mycobacterium tuberculosis

Tuberculosis is a highly contagious, infectious disease that kills about 1.8 million people annually. Current chemotherapeutic regimens are both inefficient and taxing to the patient. In addition, the disease has suboptimal treatment due to the rise of multidrug resistant strains of Mycobacterium tuberculosis (Mtb), the causative bacterial agent of tuberculosis. Therefore, we established a critical assay to identify novel drugs that interfere with specific Mtb virulence mechanisms. The mycobacterial protein fragment complementation (M-PFC) assay was developed to screen 725 compound drug panel to find candidate drugs that interfered with important virulence-causing protein interactions of Mtb. We targeted the EsxA EsxB and EsxMEsxN interactions of the type VII secretion systems of Mtb. Our screen identified 46 small molecules that inhibited both virulence interactions, exhibiting nonspecific activity against a model cell line in vitro as well as seven hits specific to one of the two cell lines. In the future, we hope to retest the seven unique positive hits to confirm their ability to inhibit specific proteinprotein interactions of Mtb

Deep Vein Thrombosis after Cement Intravasation during Hip Hemiarthroplasty

© 2020 The Authors Cement intravasation occurs in hemiarthroplasty when pressurization of cement through the medullary canal backflows through the nutrient vessels. This case report describes a 70-year-old woman who underwent hip hemiarthroplasty for a displaced left femoral neck fracture. Postoperative radiographs demonstrated radio-opacity consistent with local cement intravasation. A Doppler ultrasound study subsequently revealed a mobile thrombus at the confluence of the femoral and profunda femoris veins, as well as a nonmobile thrombus within the profunda femoris vein. The more proximal thrombus was determined to be cement that had intravasated during the index operation. The cement likely impeded venous flow, ultimately leading to the development of deep vein thrombosis just distal to the site of cement occlusion

Mortality in patients with hepatic gas on point‐of‐care ultrasound in cardiac arrest: Does location matter?

Purpose Prior research has suggested an association of hepatic venous gas with mortality in cardiac arrest. As point of care ultrasound (POCUS) is frequently used in the context of resuscitation, we sought to evaluate if the presence of hepatic gas on POCUS had a similar mortality association. Methods A retrospective review was conducted of patients who experienced nontraumatic cardiac arrest. Archived ultrasound images were independently reviewed to determine the presence of gas in the hepatic parenchyma and vasculature. Electronic medical records were then reviewed to collect remaining clinical data. Results From 1 January 2017 through 16 June 2019, 87 patients met inclusion criteria. Among them, 68 (78.2%) patients died. Among those who died, 40 (58.8%) had hepatic gas, while 28 (41.2%) had none. Only a single survivor demonstrated hepatic venous gas (11%). While the difference in mortality with respect to presence of undifferentiated hepatic gas was not significant (P = .37), there was a significant difference with respect to the presence of venous gas (P = .004). Conclusion Our study demonstrated that the incidence of postarrest hepatic gas on POCUS was common, and that the presence of hepatic venous gas during cardiac resuscitation was associated with increased mortality, while hepatic parenchymal gas alone was not

Developmental delay: is this pediatric patient population at risk for complications following open treatment of femoral shaft fracture?

PURPOSE: Femoral shaft fractures are common in the pediatric population, accounting for over 20% of inpatient pediatric fractures. Patients with developmental delays are a population group whose medical care and recovery come with a unique set of considerations and challenges. The purpose of this study was to evaluate the impact of developmental delay on outcomes following open treatment of femoral shaft fractures in the pediatric population. METHODS: Pediatric patients undergoing open treatment of femoral shaft fracture from 2012 to 2019 were identified in the National Surgical Quality Improvement Program-Pediatric database. Patients were divided into two groups: patients with developmental delay and patients without developmental delay. Patient demographics, comorbidities, and various postoperative outcomes were compared between the two groups using bivariate and multivariate analyses. RESULTS: Of the 5896 pediatric patients who underwent open treatment of femoral shaft fracture, 5479 patients (92.9%) did not have developmental delay whereas 417 (7.1%) had developmental delay. Patients with developmental delay were more likely to have other medical comorbidities. Following adjustment on multivariable regression analysis to control for the baseline differences between the two groups, patients with developmental delay had an increased risk of readmission to the hospital (OR 4.762; p = 0.014). CONCLUSION: Developmental delay in the pediatric population was found to be an independent risk factor for hospital readmission following open treatment of femoral shaft fractures. Taking these patients into special consideration when evaluating the optimal treatment plan can be beneficial to reduce the risks of readmission, which can decrease costs for both the patient and the hospital

No change in performance metrics in major league baseball players sustaining wrist fractures after being struck by an errant pitch

© 2020 Professor P K Surendran Memorial Education Foundation Objective: This study aimed to determine the effect of wrist fractures on performance metrics in Major League Baseball Players after they were hit by an errant pitch. Methods: Players who sustained wrist fractures after being struck by a pitch were identified and changes in performance metrics were calculated. Results: In both the short- and medium-term analysis, there were no significant differences in all pre- and post-injury offensive statistics following return to play. Conclusion: Wrist fractures sustained after being struck by an errant pitch do not significantly impact professional baseball player performance if the player is able to return to sport

No change in performance metrics in major league baseball players sustaining wrist fractures after being struck by an errant pitch

© 2020 Professor P K Surendran Memorial Education Foundation Objective: This study aimed to determine the effect of wrist fractures on performance metrics in Major League Baseball Players after they were hit by an errant pitch. Methods: Players who sustained wrist fractures after being struck by a pitch were identified and changes in performance metrics were calculated. Results: In both the short- and medium-term analysis, there were no significant differences in all pre- and post-injury offensive statistics following return to play. Conclusion: Wrist fractures sustained after being struck by an errant pitch do not significantly impact professional baseball player performance if the player is able to return to sport

Economic and educational disparities are associated with an increased risk of revision surgery following shoulder arthroplasty.

BACKGROUND: There is limited literature exploring how nonmedical factors such as social determinants of health (SDOHs) are associated with postoperative outcomes following shoulder arthroplasty. METHODS: A retrospective cohort review of the Pearl Diver Database was used to capture patients undergoing either primary anatomic total or reverse shoulder arthroplasty from the fourth quarter of 2015 to the third quarter of 2019 with at least 1 year of active longitudinal follow-up. Patients with proximal humeral fractures, stress fractures, or septic arthritis were excluded. The included patients were then divided into 2 cohorts based on the presence of current SDOHs or a history of SDOHs. The SDOH cohort comprised 4 non-mutually exclusive categories: economic, educational, social, and environmental disparities. Subsequently, a control cohort was matched at a 1:1 ratio to the SDOH cohort. Primary outcome measures were assessed using a logistic regression and consisted of the following 90-day postoperative complications: minor and major medical complications and infection. Emergency department (ED) visits and readmissions for any cause were also assessed. Additionally, the following 1-year outcomes were assessed: aseptic loosening, instability, and revision arthroplasty. Surgical costs and 90-day postoperative costs were collected using averaged insurance reimbursements for both the control and SDOH cohorts. RESULTS: There were 5190 patients in each cohort. Economic disparities made up the largest portion of the SDOH cohort (n = 4631, 89.2%), followed by social (n = 741, 14.3%), environmental (n = 417, 8.0%), and educational (n = 99, 1.9%) disparities. Compared with the control cohort, SDOHs were associated with an increased risk of major complications (2.3% vs. 1.4%; odds ratio [OR], 1.55; 95% confidence interval [CI], 1.29-1.87; P \u3c .001), minor complications (5.7% vs. 3.8%; OR, 1.62; 95% CI, 1.21-1.95; P = .001), readmissions (4.3% vs. 2.8%; OR, 1.56; 95% CI, 1.26-1.84; P \u3c .001), and ED visits (15.2% vs. 11.0%; OR, 1.45; 95% CI, 1.29-1.63; P \u3c .001) within 90 days following surgery. Additionally, SDOHs were associated with an increased risk of aseptic loosening (1.1% vs. 0.6%; OR, 1.85; 95% CI, 1.20-2.65; P = .006), instability (4.0% vs. 2.2%; OR, 1.80; 95% CI, 1.43-2.28; P \u3c .001), and ipsilateral revision (9.2% vs. 7.6%; OR, 1.24; 95% CI, 1.08-1.43; P \u3c .001) at 1 year postoperatively compared with the control cohort. CONCLUSION: SDOHs are associated with increased rates of adverse outcomes following shoulder arthroplasty including revision surgery, ED visits, length of stay, and overall cost compared with matched controls without SDOHs. Specifically, economic and educational disparities are associated with increased rates of adverse outcomes following surgery including revision surgery, ED visits, length of stay, and overall cost

Does Timing of Subtalar Arthrodesis Affect Reoperation or Revision Rates for Total Ankle Arthroplasty?

Introduction/Purpose: The incidence of primary total ankle arthroplasty (TAA) in the treatment of end-stage ankle arthritis has increased substantially over the last decade. TAA may be performed alone or in conjunction with additional procedures including subtalar (ST) or triple arthrodesis as end-stage ankle arthritis is often associated with degenerative disease affecting neighboring joints. Prior literature has demonstrated that the ipsilateral hindfoot arthrodesis may increase the risk for revision after TAA and that simultaneous ST arthrodesis with TAA could result in significant short term clinical and radiologic improvements. However, there is limited research comparing staged versus simultaneous hindfoot arthrodesis with concomitant TAA. The purpose of this study is to compare the reoperation rates after TAA with simultaneous hindfoot arthrodesis versus staged hindfoot arthrodesis followed by TAA. Methods: Patients who underwent primary TAA from 2015-2022 were identified in the PearlDiver database using international classification of diseases (ICD) and current procedural (CPT) codes. Patients were only selected if they contained 1-year database follow-up after the index TAA. Patients were sorted into three cohorts: (1) primary TAA without any history of hindfoot arthrodesis (control), (2) those with staged hindfoot arthrodesis prior to TAA, and (3) those with hindfoot arthrodesis at the same time as TAA. Demographic characteristics including age, gender, and Charlson Comorbidity Index (CCI) were assessed for each cohort. The 1-year rate of reoperation and revision were the primary outcomes of this study. Univariate analysis using chi- square tests and student T-tests were performed to analyze any differences in patient demographics, comorbidities, and complications. Multivariate analysis using logistic regression was subsequently conducted to account for any confounding variables and covariates. Results: 9,912 patients underwent TAA without prior hindfoot arthrodesis, 297 patients underwent TAA with prior hindfoot arthrodesis and 174 with hindfoot arthrodesis concurrently with TAA. The incidences of reoperation (OR 3.52, 12.6% vs. 3.9%, P<0.001) and revision (OR 3.66, 4.0% vs. 1.1%, P=0.001) were higher in the simultaneous cohort when compared to the control. However, there were no statistically significant differences in rates of reoperation (OR 0.96, 4.0% vs. 3.9%, P= 0.891) or revision (OR 1.94, 2.4% vs. 1.1 %, P= 0.095) when comparing staged hindfoot arthrodesis to the control. Conclusion: Patients undergoing concurrent hindfoot arthrodesis with TAA had a 3.5 times higher odds of reoperation and revision when compared to the control. Patients undergoing staged procedures did not demonstrate a difference in revision or reoperation rates when compared to the control. Staged hindfoot arthrodesis and TAA may be an effective option in treating complex end-stage ankle and hindfoot arthritis whereas a simultaneous approach may lead to higher rates of complications