A lipoglycopeptide antibiotic for Gram-positive biofilm-related infections.

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria (Staphylococcus aureus and Streptococcus pneumoniae) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We have developed a preclinical glycopeptide antibiotic, MCC5145, that has excellent potency (MIC90 ≤ 0.06 µg/ml) against hundreds of isolates of methicillin-resistant S. aureus (MRSA) and other Gram-positive bacteria, with a greater than 1000-fold margin over mammalian cell cytotoxicity values. The antibiotic has therapeutic in vivo efficacy when dosed subcutaneously in multiple murine models of established bacterial infections, including thigh infection with MRSA and blood septicemia with S. pneumoniae, as well as when dosed orally in an antibiotic-induced Clostridioides difficile infection model. MCC5145 exhibited reduced nephrotoxicity at microbiologically active doses in mice compared to vancomycin. MCC5145 also showed improved activity against biofilms compared to vancomycin, both in vitro and in vivo, and a low propensity to select for drug resistance. Characterization of drug action using a transposon library bioinformatic platform showed a mechanistic distinction from other glycopeptide antibiotics.

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.

International Orthopaedic Volunteer Opportunities in Low and Middle-Income Countries.

ABSTRACT: Globally, the burden of musculoskeletal conditions continues to rise, disproportionately affecting low and middle-income countries (LMICs). The ability to meet these orthopaedic surgical care demands remains a challenge. To help address these issues, many orthopaedic surgeons seek opportunities to provide humanitarian assistance to the populations in need. While many global orthopaedic initiatives are well-intentioned and can offer short-term benefits to the local communities, it is essential to emphasize training and the integration of local surgeon-leaders. The commitment to developing educational and investigative capacity, as well as fostering sustainable, mutually beneficial partnerships in low-resource settings, is critical. To this end, global health organizations, such as the Consortium of Orthopaedic Academic Traumatologists (COACT), work to promote and ensure the lasting sustainability of musculoskeletal trauma care worldwide. This article describes global orthopaedic efforts that can effectively address musculoskeletal care through an examination of 5 domains: clinical care, clinical research, surgical education, disaster response, and advocacy.

Lactococcus garvieae Periprosthetic Joint Infection in a Cattle Rancher with a Total Knee Arthroplasty: A Novel Reservoir Transmission.

Introduction: Periprosthetic joint infection (PJI) remains a challenging complication of joint replacement surgery. With the more frequent use of immune modifying drugs and dietary changes in human populations, the resultant blunting of immune defenses allows for infections with less common organisms. Case Report: Lactococcus garvieae is an anaerobic, gram-positive coccus with reservoirs in fish and domesticated farm animals. Only two prior cases of PJI due to L. garvieae have been reported, both with reported marine transmission. We report a case of L. garvieae associated PJI in a cattle rancher with the first reported case of transmission from a bovine reservoir. The PJI was associated with intra-articular rice body formation, and the diagnosis confirmed with the aid of next generation DNA sequencing. A successful two stage exchange was performed. We propose a novel transmission mechanism with microbe entry via direct hematogenous inoculation during the patient's duties as a rancher. Conclusion: When an unusual organism is detected in a PJI, the treatment team should research the host reservoir(s) of the organism and correlate with the patient's exposure risk. While contamination of cultures is possible, a thorough investigation should be performed prior to that assumption. This reinforces the basic concept that a careful history remains vital when treating an unusual infection presentation. Next generation DNA sequencing is a useful confirmatory tool in establishing the offending organism. Lastly, the identification of rice bodies should raise suspicion for infection. Although not always associated with infection, efforts should be redoubled to identify or rule out a causative micro-organism(s).

Spinal Cord Drift Following Laminoplasty Versus Laminectomy and Fusion for Cervical Spondylotic Myelopathy.

BACKGROUND: Cervical laminoplasty and laminectomy and fusion (LF) are posterior-based surgical techniques for the surgical treatment of cervical spondylotic myelopathy (CSM). Interestingly, the comparative amount of spinal cord drift obtained from these procedures has not been extensively described. The purpose of this study is to compare spinal cord drift between cervical laminoplasty and LF in patients with CSM. METHODS: The laminoplasty group consisted of 22 patients, and the LF group consisted of 44 patients. Preoperative and postoperative alignment was measured using the Cobb angle (C2-C7). Spinal cord position was measured on axial T2-magnetic resonance imaging of the cervical spine preoperatively and postoperatively. Spinal cord drift was quantified by subtracting preoperative values from postoperative values. Functional improvement was assessed using the modified Japanese Orthopaedic Association (mJOA) score. RESULTS: Mean spinal cord drift was higher following LF compared to laminoplasty (2.70 vs 1.71 mm, P < .01). Using logistic regression analysis, there was no correlation between sagittal alignment and spinal cord drift. Both groups showed an improvement in mJOA scores postoperatively compared to their preoperative values (laminoplasty, +2.0, P = .012; LF, +2.4, P < .01). However, there was no difference in mJOA score improvement postoperatively between both groups (P = .482). CONCLUSIONS: This study demonstrates that patients who had LF for CSM achieved more spinal cord drift postoperatively compared to those who had laminoplasty. However, the increased drift did not translate into superior functional outcome as measured by the mJOA score. LEVEL OF EVIDENCE: 3. CLINICAL RELEVANCE: Spinal cord drift following LF may differ from laminoplasty in patients undergoing surgery for CSM. This finding should be considered when assessing CSM patients for surgical intervention.

Occlusion of an Aortobifemoral Graft after Revision Total Hip Arthroplasty.

With the aging population, the demand for total hip arthroplasty is rising. Improvements in arthroplasty techniques and design allow for total hip arthroplasty to be increasingly performed in older patients and those with multiple comorbidities. Complications are rare in young and healthy patients; however, there is greater risk in patients with multiple medical comorbidities and those who have had prior revision procedures. Large-vessel thrombosis is an especially rare, but potentially devastating, complication, particularly in patients with existing major-vessel bypass grafts. Only 3 case reports of major-vessel graft occlusion after total hip arthroplasty have been reported in the literature, and none after revision. In this article, we report a case of occlusion of an aortobifemoral graft after revision total hip arthroplasty for periprosthetic joint infection.

Evading the host response: Staphylococcus "hiding" in cortical bone canalicular system causes increased bacterial burden.

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this "limb salvage" surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar-canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.

Management of Pigmented Villonodular Synovitis (PVNS): an Orthopedic Surgeon's Perspective.

PURPOSE OF REVIEW: Pigmented villonodular synovitis (PVNS) or tenosynovial giant cell tumor (TGCT) encompasses a wide spectrum of disease and is divided into localized and diffuse variants. Surgical resection remains the principal treatment for nearly all localized type disease and most diffuse type. Recent mechanistic understanding of the disease led to drug discovery that has opened new avenues for patients with recalcitrant disease. In this manuscript, we review the current treatment options for TGCT, presenting outcomes from traditional surgical approaches as well as those from nonsurgical approaches. RECENT FINDINGS: Arthroscopic and/or open surgery remains the mainstay of treatment for TGCT for the vast majority of patients. While radiosynoviorthesis and external beam radiation have been used for recalcitrant disease, recent understanding of the colony stimulating factor 1 receptor (CSF1R) pathway and its paracrine and autocrine role in TGCT has led to the development of targeted inhibitors. Their optimal role and efficacy are unclear due to limited number of high-quality studies and contradictory results; however, recent and ongoing studies suggest there may be a role for their use, especially in diffuse and/or refractory disease. Surgery remains the most common treatment for TGCT, however, there may be an increasing role for adjuvant therapies, including the new targeted agents. Weighing the side effects of these treatments against the symptomatic benefit on a patient-by-patient basis in this benign disease remains critical.

Current Trends in Orthopaedic Surgery Residency Applications and Match Rates.

BACKGROUND: The current U.S. orthopaedic residency application process is becoming increasingly impersonal in the wake of an increasing number of applications. Through an analysis of orthopaedic surgery residency application statistics, we have highlighted the effect that the number of orthopaedic applications has on match rate, and we have suggested methods for a more personalized application process. METHODS: Data from the Association of American Medical Colleges (AAMC) and the National Resident Matching Program (NRMP) for United States orthopaedic residency applicants from 2008 to 2018 were collected. These data included the average number of applications submitted per applicant, the average number of applications received per program, the total number of residency positions offered in the U.S., the total number of U.S. applicants, and the total number of U.S. applicants who matched to a U.S. orthopaedic surgery residency program. U.S. applicant match rates and the average number of applications received per residency position offered were calculated. Linear regression models were used to determine the rate at which these variables changed over time. RESULTS: The average number of applications submitted by an applicant increased from 46.5 in 2008 to 74.9 in 2018. The average number of applications received per residency position offered increased from 54.1 in 2008 to 85.7 in 2018. The number of U.S. applicants was 740 in 2008 and 849 in 2018. The number of U.S. orthopaedic residency programs only slightly increased from 160 in 2008 to 171 in 2018. The match rate for U.S. medical school applicants has remained stable from 2008 to 2018 at a mean of 76.9% and a standard deviation of 2.3%. CONCLUSIONS: The match rate has remained stable from 2008 to 2018 despite an increase in the number of applications per position. This discrepancy suggests that increasing the number of submitted applications may not correlate with applicant success. We address this discrepancy and suggest methods that can potentially allow for a more targeted orthopaedic application experience.

An Early Look at Operative Orthopaedic Injuries Associated with Electric Scooter Accidents: Bringing High-Energy Trauma to a Wider Audience.

BACKGROUND: There is a new method of transportation that started in our community in late 2017- rideshare electric scooters (e-scooters). These scooters have proven immensely popular and can now be found in many cities around the world. Despite the pervasiveness of e-scooters, their associated injury patterns are poorly understood. The purpose of this study was to describe our department's experience at the epicenter of the e-scooter phenomenon that is sweeping the globe and to characterize operative orthopaedic injuries that are related to e-scooter accidents. METHODS: We performed a retrospective chart review of all of the operative orthopaedic cases and trauma consults at 2 trauma centers (a level-I center and a level-II center) between September 2017 and August 2019. We identified all operative injuries in which the cause of injury was an e-scooter accident. Data that included demographics, mechanism of injury, diagnosis, and treatment were collected. RESULTS: Seventy-five operative injuries were identified in 73 patients during the study period. The mean patient age was 35.4 years (range, 14 to 74 years), and the median age was 32 years. There were 4 pediatric patients (14, 15, 15, and 17 years old). Thirty-two patients (43.8%) sustained upper-extremity injuries, and 42 patients (57.5%) sustained lower-extremity injuries; 1 of these patients had both upper and lower-extremity injuries. Nine patients (12.3%) had open fractures. There were 7 hip fractures in patients with an average age of 42.4 years (range, 28 to 68 years). Seventy-one (97.3%) of 73 patients were e-scooter riders, and 2 (2.7%) were pedestrians who were struck by e-scooter riders. CONCLUSIONS: E-scooters can cause serious injury. Seventy-three patients required operative treatment in just the first 2 years of e-scooter use in our community. Operative injuries occurred throughout the skeletal system, and several were injuries that are typically associated with high-energy trauma. Although, as a rule, e-scooter use is limited to adults and banned in high pedestrian-traffic areas in our city, the inclusion of 4 underage riders and 2 pedestrians in our cohort suggests that these rules are not always followed. As e-scooters continue to increase in popularity, additional steps should be taken to regulate their use and protect riders and the public.

Glenohumeral Dislocation Arthropathy: Etiology, Diagnosis, and Management.

Dislocation arthropathy describes the development of progressive degenerative changes of the glenohumeral joint in the setting of instability. Although the specific etiology remains unclear, the trauma of a single dislocation, repetitive injury associated with recurrent dislocations, changes in shoulder biomechanics, and complications associated with instability surgery have all been implicated in its development. Pain and restricted range of motion are the most common patient complaints. Conservative management, consisting of pain control, activity modification, and physical therapy, is the first-line treatment after the development of arthropathy. If conservative management fails, multiple surgical options exist. Arthroscopic débridement can be attempted in young, active patients and in those patients with mild-to-moderate arthropathy. Open subscapularis lengthening and capsular release can be done in patients with prior instability repairs that are overly tight. In young patients with minimal bone loss and glenoid wear, surface replacement arthroplasty and hemiarthroplasty are surgical options. In older patients with moderate-to-severe arthropathy, total shoulder or reverse shoulder arthroplasty is the preferred treatment option. Further study is needed to better predict which patients will develop dislocation arthropathy and will thus benefit from early surgical intervention.

Assessment of Vertebral Curves Using the Manual Post-It Technique.

STUDY DESIGN: A prospective study of a new technique. OBJECTIVE: The aims of this study were to report a manual technique for measuring vertebral curves on digital spine radiographs, and to assess the agreement of this technique with that of digital software for measuring vertebral curves. SUMMARY OF BACKGROUND DATA: Modern picture archiving and communication systems (PACS) typically include software for evaluating radiographic measurements. However, in the outpatient spine setting, patients may present with radiographs stored on a physical disc, which may not include software for measuring vertebral curves. Certain smartphone applications may be used to determine curve magnitude; however, the need exists for an accurate manual technique to measure vertebral curves on digital radiographs in the absence of available analytic software or smartphone technology. METHODS: We prospectively reviewed anteroposterior and lateral spine radiographs of 24 spinal deformity patients. Two independent observers measured Cobb angles for: (1) the major coronal curve; (2) the thoracic kyphosis (T2-T12); and (3) the lumbar lordosis (T12-S1). Measurements were made: (1) digitally using our institution's PACS; and (2) by a manual technique, which involves placement of an adhesive Post-It note directly on the computer screen, transcribing the angle onto the Post-It note with a pencil, and measuring the angle with a handheld goniometer. Intraclass correlation coefficients (ICCs) were calculated to determine the agreement between the 2 methods. RESULTS: For both observers, the agreement between the digital PACS and manual Post-It techniques was graded as excellent for both coronal and sagittal plane curves (all ICCs>0.9). Interobserver reliability between the 2 observers was also graded as excellent for both the PACS and Post-It techniques (all ICCs>0.9). CONCLUSIONS: The Post-It technique for measuring Cobb angles demonstrated excellent agreement with the PACS system in our series of spinal deformity patients. Curves on digital radiographs can be accurately measured using a convenient manual technique.

Early complications of acromioclavicular joint reconstruction requiring reoperation.

PURPOSE: Prior studies have reported high complication rates with acromioclavicular joint reconstruction (ACJR). However, many of these reports have suffered from small sample sizes and inclusion of older surgical techniques. The purpose of this study was to determine the rates of early complications requiring reoperation in patients treated with ACJR. METHODS: From 2007 to 2011, patients who were treated with ACJR were identified using the PearlDiver database, a large insurance database in the USA. The following reoperations were then queried from this patient cohort: irrigation and debridement within 30 days of index surgery, manipulation under anaesthesia (MUA) of the shoulder joint within 3 months of index surgery, and revision ACJR, distal clavicle excision, and removal of hardware within 6 months of index surgery. RESULTS: In total, 2106 patients treated with ACJR were identified. The reoperation rates for irrigation and debridement, MUA, revision ACJR, distal clavicle excision, and removal of hardware were 2.6, 1.3, 4.2, 2.8, and 6.2 %, respectively. Patients ≥35 years of age and females more likely to undergo a reoperation after ACJR. Specifically, patients ≥35 years of age were more likely to undergo MUA and revision ACJR, while patients ≥50 years of age were more likely to undergo an irrigation and debridement. Females were more likely than males to undergo revision ACJR and distal clavicle excision. CONCLUSIONS: Older patients and females were more likely to experience postoperative complications requiring reoperations, including revision ACJR, distal clavicle excision, and irrigation and debridement. By analysing a large cohort of patients across multiple centres and providers, this study provides valuable insight into the recent complication profiles of ACJR, allowing surgeons to appropriately counsel patients on the risks of these procedures. LEVEL OF EVIDENCE: IV.

Utilization of Platelet-Rich Plasma for Musculoskeletal Injuries: An Analysis of Current Treatment Trends in the United States.

BACKGROUND: Platelet-rich plasma (PRP) has emerged as a popular biologic treatment for musculoskeletal injuries and conditions. Despite numerous investigations on the efficacy of PRP therapy, current utilization of this treatment within the United States is not widely known. PURPOSE: To investigate the national utilization of PRP, including the incidence and conditions for which it is used in the clinical setting, and to determine the current charges associated with this treatment. STUDY DESIGN: Descriptive epidemiology study. METHODS: Using a national database (PearlDiver) of private insurance billing records, we conducted a comprehensive search using Current Procedural Terminology (CPT) codes to identify patients who received PRP injections over a 2-year period (2010-2011). Associated International Classification of Diseases, 9th Revision (ICD-9) codes were identified to determine the specific conditions the injection was used to treat. The aggregate patient data were analyzed by yearly quarter, practice setting, geographic region, and demographics. PRP therapy charges were calculated and reported as per-patient average charges (PPACs). RESULTS: A total of 2571 patients who received PRP injections were identified; 51% were male and 75% were older than 35 years. The overall incidence ranged from 5.9 to 7.9 per 1000 patients over the study period. PRP was most commonly administered in hospitals (39%) and ambulatory surgical centers (37%) compared with in private offices (26%). The most common conditions treated were knee meniscus/plica disorders, followed by unspecified shoulder conditions, rotator cuff injuries, epicondylitis, and plantar fasciitis. Further evaluation revealed that 25% of all patients received injections for cartilage-related conditions, 25% meniscus, 25% unspecified, 12% tendon, 8% glenoid labrum, and 5% ligament. The PPAC for PRP treatment was US$1755 per injection. CONCLUSION: Despite a lack of consensus regarding PRP indications and efficacy, we observed widespread application of this treatment for a myriad of musculoskeletal injuries. Most treated patients were older than 35 years, and the most commonly treated conditions included cartilage and meniscus disorders. Given the current controversy surrounding this treatment, further studies are necessary to guide clinicians on the value of this therapy for each clinical diagnosis.