Loss of C-5 Sterol Desaturase Activity Results in Increased Resistance to Azole and Echinocandin Antifungals in a Clinical Isolate of Candida parapsilosis

Among emerging non-albicans Candida species, Candida parapsilosis is of particular concern as a cause of nosocomial bloodstream infections in neonatal and intensive care unit patients. While fluconazole and echinocandins are considered effective treatments for such infections, recent reports of fluconazole and echinocandin resistance in C. parapsilosis indicate a growing problem. The present study describes a novel mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicated differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing revealed that the resistant isolate possessed an ERG3 mutation resulting in a G111R amino acid substitution. Sterol profiles indicated a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restored wild-type susceptibility to all azoles and echinocandins tested. Disruption of ERG3 in the susceptible and resistant isolates resulted in a loss of sterol desaturase activity, high-level azole resistance, and an echinocandin-intermediate to -resistant phenotype. While disruption of ERG3 in C. albicans resulted in azole resistance, echinocandin MICs, while elevated, remained within the susceptible range. This work demonstrates that the G111R substitution in Erg3 is wholly responsible for the altered azole and echinocandin susceptibilities observed in this C. parapsilosis isolate and is the first report of an ERG3 mutation influencing susceptibility to the echinocandins

Evidence Versus Practice: Operative Treatment Preferences in Hallux Valgus

Background: There is substantial variability in the operative treatment of hallux valgus despite the existence of high quality evidence to guide treatment decisions. The purpose of this study was to determine the current trends in the treatment of mild, moderate, and severe hallux valgus and if greater degrees of consensus correlate with the presence of higher-level evidence. Methods: Members of the American Orthopaedic Foot & Ankle Society completed a 14-item survey. A total of 131 (14%) of 922 members completed the survey. Three cases representing 3 stages of HV were presented, and respondents selected their preferred treatment. Preferred forms of proximal and distal metatarsal osteotomies, as well as mode of fixation for each, were inquired. Results: In the treatment of mild hallux valgus without second metatarsalgia, 80% of those surveyed chose a distal metatarsal osteotomy, while, if second metatarsalgia was present, 56% chose a distal metatarsal osteotomy with a second metatarsal-shortening osteotomy. In the treatment of moderate hallux valgus, there was generally less consensus, while, in the treatment of severe hallux valgus, a majority of those surveyed chose a Lapidus procedure, with the addition of a second metatarsal-shortening osteotomy in the presence of second metatarsalgia. The most popular distal and proximal metatarsal osteotomies, respectively, were chevron osteotomy (80%) and opening wedge osteotomy (33%). The presence of Level I evidence did not significantly correlate with higher degrees of consensus. Conclusion: Despite the existence of high-quality evidence supporting the use of certain procedures in the treatment of HV, there exists an apparent lack of consensus among surgeons about the choice of surgical procedures. Moreover, higher-level evidence was not correlated with greater consensus in hallux valgus. Level of Evidence: Level II

The Current Utilization of Patient-reported Outcome Measurement Information System in Shoulder, Elbow, and Sports Medicine

Clinical research using patient-reported outcome measures has been critical within the field of shoulder, elbow, and sports medicine in helping clinicians deliver evidence-based and value-based medicine. Recently, however, clinicians have advocated for improving the process of obtaining clinically meaningful information from patients while decreasing survey fatigue and increasing compliance. To that end, the National Institutes of Health created the Patient-Reported Outcome Measures Information System (PROMIS) in which a number of institutions and research investigations have adopted for reporting outcomes. A special focus has also been placed on PROMIS Computer Adaptive Testing forms, which tailor questioning through item response theory. The purpose of this study was to provide insight into the utilization, advantages, and disadvantages of PROMIS within the field of shoulder, elbow, and sports medicine and provide a comparison with legacy patient-reported outcome measure measurements

Distal Knee Medial Collateral Ligament Repair With Suture Augmentation

The medial collateral ligament (MCL) is the most commonly injured ligament of the knee. Given its extra-articular location, the MCL has great healing capacity such that the mainstay of treatment for most injuries remains conservative management. However, certain injury patterns place patients and athletes at risk of residual valgus laxity, which may require delayed surgical care and prolonged time out from sports. As such, identifying the specific injuries known to place patients at risk for failure with nonoperative management is of paramount importance. Although controversy remains regarding the optimal treatment of grade III MCL injuries, it is generally accepted that MCL ruptures from the distal tibia attachment require operative fixation. This technique article with accompanying video provides a detailed description of a technique for repairing the distal MCL attachment with suture augmentation. There are several advantages associated with an augmented direct repair including early, safe rehabilitation; prevention of valgus instability; and avoiding the comorbidities associated with a larger reconstruction

Elbow Arthroscopy for Treatment of Valgus Extension Overload

Valgus extension overload syndrome (VEO) is the result of supraphysiologic stresses placed across the posterior elbow during pitching. Following failure of nonoperative measures, surgical options consist of arthroscopic or limited incision posteromedial decompression. Although technically challenging, arthroscopic treatment offers many advantages over open treatment, including improved joint visualization, decreased soft-tissue dissection, decreased postoperative pain, and quicker rehabilitation. Arthroscopic treatment of VEO consists of soft tissue and bony debridement, loose body removal, and osteophyte resection. This technique report details the steps of arthroscopic treatment of VEO in a patient with a subluxating ulnar nerve

The current utilization of the patient-reported outcome measurement information system (PROMIS) in isolated or combined total knee arthroplasty populations

Abstract Patient reported outcome measures (PROMs) are essential for clinical research and patient-centric care because they allow us to capture patient perspectives on their health condition. In knee arthroplasty, PROMs are frequently used to assess the risks and benefits of new interventions, surgical approaches, and other management strategies. A few examples of PROMs used in total knee arthroplasty (TKA) include the Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Forgotten Joint Score (FJS) (collectively referred to as “legacy” PROMs). More recently, attention has been brought to another PROM called the Patient-Reported Outcomes Measurement Information System (PROMIS). PROMIS was developed by the National Institute of Health (NIH) and has over 300 domains assessing various aspects of patient health, including pain, physical function, and mental health. With the use of PROMIS increasing in TKA literature, there is a need to review the advancements being made in understanding and applying PROMIS for this population. Thus, the purpose of this study is to provide insight on the utilization, advantages, and disadvantages of PROMIS within the field of knee arthroplasty and to provide a comparison to legacy PROMs

Patient-Reported Outcome Measurement Information System (PROMIS) in Orthopaedic Trauma Research

This review describes the development, advantages and disadvantages, and applications of the Patient-Reported Outcome Measurement Information System (PROMIS) in orthopaedic trauma. PROMIS is a useful tool for quantifying outcomes in orthopedic trauma. It allows measurement of outcomes across multiple domains while minimizing administration time. PROMIS also reliably identifies clinical, social, and psychological risk factors for poor outcomes across a variety of orthopaedic injuries and disease states. However, PROMIS lacks specificity for certain anatomic regions and validation for mental health outcomes. It also is limited by ceiling effects in certain active patient populations. Orthopaedic traumatologists should be familiar with PROMIS, as its use is increasing and it is a valuable tool that can aid in clinical decision making

Ulnar Collateral Ligament Repair With Suture Augmentation

Reconstruction of the ulnar collateral ligament (UCL) remains the gold standard for treating overhead throwing athletes with valgus instability secondary to UCL pathology. Although surgical techniques for reconstruction have evolved over time, current methods allow 90% of patients to return to their preinjury level of activity. Despite encouraging results with reconstruction, UCL repair remains a valuable treatment option for patients with UCL pathology fitting specific criteria. There are a number of advantages associated with a direct repair, and further, the development of collagen-coated sutures for ligament repair augmentation makes this procedure an attractive surgical option under the correct circumstances. This article provides a detailed description and video demonstration of the surgical steps used to perform a UCL repair with suture augmentation

Academic Influence as Reflected by h Index Is Not Associated With Total Industry Payments but Rather With NIH Funding Among Academic Orthopaedic Sports Medicine Surgeons

PURPOSE: (1) To compare the total number and dollar amount of industry funding and National Institutes of Health (NIH) funding to academic orthopaedic sports medicine surgeons and (2) to examine the impact of academic influence on industry funding and NIH funding to academic orthopaedic sports medicine surgeons. METHODS: Academic orthopaedic sports medicine surgeons were identified using faculty web pages. Academic influence was approximated by a physician\u27s Hirsch index (h index) and number of publications and obtained from the Scopus database. Total industry payments were acquired through the Open Payments Database, and NIH funding was determined from the NIH website. Statistical analysis was performed using Mann-Whitney U test and Spearman correlations with significance set at P \u3c .05. RESULTS: Physicians who received industry research payments and NIH funding had a significantly higher mean h index and more mean total publications than physicians who did not receive industry research payments and NIH funding. There were no significant differences in h index (P = .374) or number of publications (P = .126) between surgeons receiving industry nonresearch funding and those who did not. h Index and number of publications were both weakly correlated with the amount of industry research and nonresearch funding. CONCLUSION: Although academic influence is associated with industry research funding and NIH funding, there is no association between measures of academic influence and total industry and industry nonresearch payments. Combined with the weak associations between academic influence and the amount of industry payments, academic influence does not appear to be a major determinant of industry funding to academic orthopaedic sports medicine surgeons. CLINICAL RELEVANCE: Surgeons should be cognizant of potential conflicts with industry, but the relationship between academic sports medicine surgeons and industry may be less subject to bias than previously believed

Patient-reported outcomes measurement information system instruments in knee arthroplasty patients: a systematic review of the literature

Abstract Background The purpose of this study is to provide a systematic review of the literature pertaining to Patient-Reported Outcome Measurement Information System (PROMIS) validation and utilization as an outcomes metric in total knee arthroplasty (TKA) patients. This is the first systematic review on PROMIS use in total knee arthroplasty patients. Methods A systematic search of the Pubmed/MEDLINE and Embase databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study characteristics, patient demographics, psychometric properties (Pearson and Spearman correlation) with legacy patient-reported outcome measurement (PROM) instruments, floor and ceiling effects, responsiveness, and minimum clinically important difference (MCID) and PROMIS outcomes were recorded and analyzed. Results Fifteen studies investigating PROMIS in 11,140 patients were included. The weighted-average Pearson correlation coefficient comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.62 [standard error (SE) = 0.06] and the weighted-average Spearman correlation comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.59 (SE = 0.06), demonstrating moderate-to-strong correlation and validity. There were no differences in weighted average floor [0.03% (SE = 3.1) versus 0% (SE = 0.1) versus 0.01% (SE = 1.1); p = 0.25] or ceiling effects [0.01% (SE = 0.7) versus 0.02% (SE = 1.4) versus 0.04% (SE = 3.5); p = 0.36] between PROMIS and legacy instruments. The weighted average for percentage of patients achieving MCID was 59.1% for global physical health (GPH), 26.0% for global mental health (GMH), 52.7% for physical function (PF), 67.2% for pain interference (PI), and 37.2% for depression. Conclusion Notably, PROMIS global physical health, physical function, and pain interference were found to be significantly responsive, with PROMIS pain interference most effectively capturing clinical improvement as evidenced by the achievement of MCID