Assessing the academic achievement of United States orthopaedic departments.

BACKGROUND: Assessing academic productivity allows academic departments to identify the strengths of their scholarly contribution and provides an opportunity to evaluate areas for improvement. AIM: To provide objective benchmarks for departments seeking to enhance academic productivity and identify those with significant improvement in recent past. METHODS: Our study retrospectively analyzed a cohort of orthopaedic faculty at United States-based academic orthopaedic programs. 5502 full-time orthopaedic faculty representing 178 programs were included in analysis. Variables included for analysis were National Institutes of Health funding (2014-2018), leadership positions in orthopaedic societies (2018), editorial board positions of top orthopaedic journals (2018), total number of publications and Hirsch-index. A weighted algorithm was used to calculate a cumulative score for each academic program. This study was performed at a large, United States medical school. RESULTS: All 178 programs included in analysis were evaluated using the comprehensive weighted algorithm. The five institutions with the highest cumulative score, in decreasing order, were: Washington University in St. Louis, the Hospital for Special Surgery, Sidney Kimmel Medical College (SKMC) at Thomas Jefferson University, the University of California, San Francisco (UCSF) and Massachusetts General Hospital (MGH)/Brigham and Women's/Harvard. The five institutions with the highest score per capita, in decreasing order, were: Mayo Clinic (Rochester), Washington University in St. Louis, Rush University, Virginia Commonwealth University (VCU) and MGH/Brigham and Women's/Harvard. The five academic programs that had the largest improvement in cumulative score from 2013 to 2018, in decreasing order, were: VCU, SKMC at Thomas Jefferson University, UCSF, MGH/Brigham and Women's/Harvard, and Brown University. CONCLUSION: This algorithm can provide orthopaedic departments a means to assess academic productivity, monitor progress, and identify areas for improvement as they seek to expand their academic contributions to the orthopaedic community.

Acceptability and feasibility of screening pregnant women for sexually transmitted infections in Rawalpindi, Pakistan.

Objectives: To understand the acceptability and feasibility of sexually transmitted infection (STI) testing during antenatal care, along with the prevalence of STIs, in Rawalpindi, Pakistan. Methods: We enrolled pregnant women seeking antenatal care and performed STI testing using Cepheid GeneXpert® CT/NG and TV kits and Alere Determine™ HIV and syphilis tests. We used interviewer-administered surveys to collect medical, social, and sexual histories. Participants testing positive for STIs and their partners were treated. Results: We enrolled 1001 women from September to December 2019. Nearly all women offered to participate in this study enrolled. Most women understood the effects an STI can have on their pregnancy (99.6%) and valued STI screening during pregnancy (98.1%). 11 women tested positive for any STI: (Chlamydia trachomatis = 4, Neisseria gonorrhoeae = 1, and Trichomonas vaginalis = 6). Of those, six presented for a test-of-cure, and two were positive for Trichomonas vaginalis. None tested positive for HIV infection or syphilis (n = 503). Conclusions: STI testing during antenatal care in Rawalpindi was acceptable, valued, understood, and feasible. The prevalence of STIs in pregnant women was low. Continued prevalence monitoring is warranted.

A Narrative Review of Clinical Treatment Outcomes of Neisseria gonorrhoeae Infection With Ciprofloxacin by Minimum Inhibitory Concentration and Anatomic Site.

BACKGROUND: Neisseria gonorrhoeae infections are becoming increasingly resistant to recommended treatments. Resistance-guided therapy may mitigate the continued emergence of resistance by enabling the use of previously recommended treatments like ciprofloxacin. To describe the effectiveness of ciprofloxacin to treat "susceptible" infections, we estimated the clinical efficacy of ciprofloxacin at various minimum inhibitory concentrations (MICs) and anatomic sites. METHODS: We reviewed publicly available reports using the PubMed.gov database and search terms "gonorrhea/drug therapy"[Mesh] AND "ciprofloxacin". We included clinical treatment studies in which ciprofloxacin was administered alone to treat N. gonorrhoeae, specimens were collected for N. gonorrhoeae culture from each infection, the MIC was determined for ≥90% of infective strains, and individual treatment outcomes were clearly defined. We recorded those data, ciprofloxacin dose and infection site. We calculated the frequency of treatment success and 95% confidence intervals (CIs). RESULTS: Twenty studies from 1985 to 2020 met our inclusion criteria. Ciprofloxacin at commonly used doses eliminated 99.2% (95% CI, 98.5%-99.6%; n = 1439) of gonococcal infections with MICs <0.125 µg/mL, 76.3% (95% CI, 59.8%-88.6%; n = 38) of infections with MICs from 0.125 to 0.5 µg/mL, and 30.1% (95% CI, 20.5%-41.2%; n = 83) of infections with MICs ≥1 µg/mL across anatomic sites. CONCLUSIONS: Ciprofloxacin reliably eliminated gonococcal infections with MICs <0.125 µg/mL across anatomic sites. Molecular assays predicting MICs of ciprofloxacin <0.125 µg/mL of gonococcal strains can allow for reintroduction of ciprofloxacin in gonorrhea treatment. Clinicians can confidently use ciprofloxacin to treat susceptible gonococcal infections.

Inhibition of Angiotensin Converting Enzyme Impairs Anti-staphylococcal Immune Function in a Preclinical Model of Implant Infection.

Background: Evidence suggests the renin-angiotensin system (RAS) plays key immunomodulatory roles. In particular, angiotensin-converting enzyme (ACE) has been shown to play a role in antimicrobial host defense. ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) are some of the most commonly prescribed medications, especially in patients undergoing invasive surgery. Thus, the current study assessed the immunomodulatory effect of RAS-modulation in a preclinical model of implant infection. Methods:In vitro antimicrobial effects of ACEi and ARBs were first assessed. C57BL/6J mice subsequently received either an ACEi (lisinopril; 16 mg/kg/day), an ARB (losartan; 30 mg/kg/day), or no treatment. Conditioned mice blood was then utilized to quantify respiratory burst function as well as Staphylococcus aureus Xen36 burden ex vivo in each treatment group. S. aureus infectious burden for each treatment group was then assessed in vivo using a validated mouse model of implant infection. Real-time quantitation of infectious burden via bioluminescent imaging over the course of 28 days post-procedure was assessed. Host response via monocyte and neutrophil infiltration within paraspinal and spleen tissue was quantified by immunohistochemistry for F4/80 and myeloperoxidase, respectively. Results: Blood from mice treated with an ACEi demonstrated a decreased ability to eradicate bacteria when mixed with Xen36 as significantly higher levels of colony forming units (CFU) and biofilm formation was appreciated ex vivo (p < 0.05). Mice treated with an ACEi showed a higher infection burden in vivo at all times (p < 0.05) and significantly higher CFUs of bacteria on both implant and paraspinal tissue at the time of sacrifice (p < 0.05 for each comparison). There was also significantly decreased infiltration and respiratory burst function of immune effector cells in the ACEi group (p < 0.05). Conclusion: ACEi, but not ARB, treatment resulted in increased S. aureus burden and impaired immune response in a preclinical model of implant infection. These results suggest that perioperative ACEi use may represent a previously unappreciated risk factor for surgical site infection. Given the relative interchangeability of ACEi and ARB from a cardiovascular standpoint, this risk factor may be modifiable.

Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types.

Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Here, we generate distinct imageable syngeneic mouse GBM-tumor models and utilize RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identify immunologically-inert and -active syngeneic-tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells and resident macrophages; fewer eosinophils and SiglecF+ macrophages. To mimic the clinical-settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decreasing resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM-patients and mouse GBM-tumors show stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients.

In vivo Mouse Model of Spinal Implant Infection.

Spine implant infections portend poor outcomes as diagnosis is challenging and surgical eradication is at odds with mechanical spinal stability. The purpose of this method is to describe a novel mouse model of spinal implant infection (SII) that was created to provide an inexpensive, rapid, and accurate in vivo tool to test potential therapeutics and treatment strategies for spinal implant infections. In this method, we present a model of posterior-approach spinal surgery in which a stainless-steel k-wire is transfixed into the L4 spinous process of 12-week old C57BL/6J wild-type mice and inoculated with 1 x 103 CFU of a bioluminescent strain of Staphylococcus aureus Xen36 bacteria. Mice are then longitudinally imaged for bioluminescence in vivo on post-operative days 0, 1, 3, 5, 7, 10, 14, 18, 21, 25, 28, and 35. Bioluminescence imaging (BLI) signals from a standardized field of view are quantified to measure in vivo bacterial burden. To quantify bacteria adhering to implants and peri-implant tissue, mice are euthanized and the implant and surrounding soft tissue are harvested. Bacteria are detached from the implant by sonication, cultured overnight and then colony forming units (CFUs) are counted. The results acquired from this method include longitudinal bacterial counts as measured by in vivo S. aureus bioluminescence (mean maximum flux) and CFU counts following euthanasia. While prior animal models of instrumented spine infection have involved invasive, ex vivo tissue analysis, the mouse model of SII presented in this paper leverages noninvasive, real time in vivo optical imaging of bioluminescent bacteria to replace static tissue study. Applications of the model are broad and may include utilizing alternative bioluminescent bacterial strains, incorporating other types of genetically engineered mice to contemporaneously study host immune response, and evaluating current or investigating new diagnostic and therapeutic modalities such as antibiotics or implant coatings.