Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8+ T Cell Killing.

UNLABELLED: Simian immunodeficiency virus (SIV)-specific CD8(+) T cells kill SIV-infected CD4(+) T cells in an major histocompatibility complex class I (MHC-I)-dependent manner. However, they are reportedly less efficient at killing SIV-infected macrophages. Since the viral accessory protein Nef has been shown to downregulate MHC-I molecules and enhance cytotoxic T lymphocyte (CTL) evasion in human immunodeficiency virus type 1 (HIV-1)-infected CD4(+) T cells, we examined whether Nef played a role in protecting SIV-infected macrophages from killing by SIV-specific CD8(+) T cells. To explore the role of Nef in CD8(+) T cell evasion, we compared the ability of freshly sorted SIV-specific CD8(+) T cells to readily suppress viral replication or eliminate CD4(+) T cells or monocyte-derived macrophages infected with SIV variants containing wild-type (WT) or mutated nef genes. As expected, SIV-specific CD8(+) T cells suppressed viral replication and eliminated the majority of SIV-infected CD4(+) T cells, and this killing was enhanced in CD4(+) T cells infected with the nef variants. However, macrophages infected with nef variants that disrupt MHC-I downregulation did not promote rapid killing by freshly isolated CD8(+) T cells. These results suggest that mechanisms other than Nef-mediated MHC-I downregulation govern the resistance of SIV-infected macrophages to CD8(+) T cell-mediated killing. This study has implications for viral persistence and suggests that macrophages may afford primate lentiviruses some degree of protection from immune surveillance. IMPORTANCE: Myeloid cells are permissive for HIV/SIV replication in vitro and may contribute to viral persistence in vivo. While many studies have been geared to understanding how CD8(+) T cells control viral replication in CD4(+) T cells, the role of these cells in controlling viral replication in macrophages is less clear. Primary, unstimulated CD8(+) T cells insignificantly suppress viral replication or eliminate SIV-infected macrophages. Since the viral Nef protein downregulates MHC-I and provides infected cells some degree of protection from CD8(+) T cell-mediated effector functions, we evaluated whether Nef may be contributing to the resistance of macrophages to CD8(+) T cell suppression. Our results suggest that Nef is not involved in protecting infected macrophages from CD8(+) T cell killing and suggest that other mechanisms are involved in macrophage evasion from CD8 surveillance.

Management and subsequent outcomes of patellar sleeve injuries: A retrospective case series of 90 pediatric and adolescent patients.

Purpose: This study aims to report the epidemiology of patellar sleeve injuries, describe diagnostic findings and treatment, and assess functional outcomes following different treatments. Methods: A medical database was queried from 1990 to 2016 to identify patients ≤18 years presenting to a single pediatric institution with a patellar sleeve injury. Patients with significant comorbidities or previously operatively treated for ipsilateral knee injuries were excluded. Standard demographic data, mechanism of injury, skeletal maturity, injury-related radiographic parameters, along with treatment paradigms, post-treatment clinical and radiographic findings, and patient-reported outcomes were collected. Results: A total of 90 patients, mean age of 10.7 years (range: 7-17) was included, of which 69 (77%) were male. Seventy-three percent of all injuries occurred while playing sports (particularly football/basketball/soccer), with "direct blow" or "landing" being the most prevalent mechanisms of injury. Twenty-six (29%) underwent operative treatment, with transosseous suture fixation being the most popular surgical technique (73%). Of the 64 (71%) non-operatively treated patients, 18 (39%) were placed in a hinged knee brace locked in extension with the remainder split between casting and standard knee immobilizer. Compared to the non-operative cohort, a higher percentage of the operative group had a pre-treatment extensor lag (p < 0.001) and greater fragment displacement (p < 0.001) with patella alta (p < 0.001) on imaging. There was no difference in outcome scores (Pedi-IKDC/Lysholm) or patella alta on radiographs between groups. Post-treatment surveys indicated no difference in residual pain or ability to return to sport. Conclusion: This large case series provides valuable epidemiologic, clinical, and radiographic data describing patellar sleeve fractures, along with outcomes following non-operative and operative treatments. Level of evidence: IV.

Interfacility Transfer Patients With Pelvic, Acetabular, and Lower Extremity Fractures Are at Higher Risk for Major Complications and Readmissions.

OBJECTIVE: To compare the adverse event profile and patient comorbidity profile of lower extremity orthopaedic trauma patients admitted via interfacility transfer (IT) to direct admission (DA) patients from home. METHODS: A total of 39,497 patients from 2012 to 2019 were identified in the American College of Surgeon National Surgical Quality Improvement Program database. DA patients were compared with IT patients for differences in preoperative comorbidities, adverse events, length of stay, and readmissions in the 30-day postoperative period. Student t tests were used to assess continuous variables. Pearson χ 2 test and odds ratios (ORs) were used for categorical variables. RESULTS: The IT group comprised 7167 patients, and the DA group comprised 32,330 patients. IT patients were on average older (65.5 vs. 58.8 years, P < 0.01), more likely to be American Society of Anesthesiologists Status >2 ( P < 0.01), and had a worse comorbidity profile for numerous preoperative risk factors. IT patients had significantly higher rates of mortality [3.3% vs. 1.4%; odds ratio (OR) 2.29; 95% confidence interval (CI), 1.96-2.77], major complications (10.2% vs. 6.1%; OR 1.74; 95% CI, 1.60-1.91), significantly higher readmission rates (5.8% vs. 4.8%, P < 0.01, OR 1.22 95% CI, 1.09-1.36), and more infectious complications (7% vs. 4.7%; OR 1.54; 95% CI, 1.38-1.71) than DA patients. Transfer remained a significant factor predicting major adverse events in regression analysis controlling for patient characteristics and fracture type ( P < 0.01; B 1.197; 95% CI, 1.09-1.32). CONCLUSIONS: This study revealed that IT patients undergoing operative management of pelvic, acetabular, and lower extremity fractures are at a significantly increased risk of major complications, readmission, and have a higher morbidity burden than DA patients. As healthcare transitions to value-based care and bundled payments, hospitals that accept a high volume of ITs will face exposure to added risk and financial penalties without adequate policy protections. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Posterior Tibiotalar Impingement After Pediatric Ankle Fracture Surgical Fixation: A Case Report.

CASE: A 13-year-old healthy, nearly skeletally mature, female patient presented to an outpatient clinic after sustaining a bimalleolar ankle fracture-dislocation, which was subsequently treated with open reduction and internal fixation and casting. Postoperatively, the patient had significant limitations to ankle range of motion. Imaging revealed posterior tibiotalar impingement. The patient underwent arthroscopic debridement and osteoplasty, and she was able to return to previous levels of activity. CONCLUSIONS: Complications from pediatric ankle fractures are rare, so further diagnostic workup is warranted for patients with persistent pain and limitations.

Implant Removal Matrix for the upper Extremity Orthopedic Surgeon.

Orthopedic implant removal is a commonly performed procedure. While implant removal can be associated with improved symptoms, risks of the surgery are notable. Stripped screws, broken and retained hardware, and morbidity associated with soft tissue compromise during difficult removal are all common. Familiarity with the instruments is critical to procedure success. The purpose of this study is to assist removal of unfamiliar screws in upper extremity surgery by offering a reference for screw and driver compatibility across manufacturers. Inclusion of device manufacturers was determined by market share. Screw size, drive configuration, and screw removal system compatibility data was collected and recorded. Screw, guide-wire, and screwdriver compatibility was assessed and compared to two commonly utilized universal implant-removal sets. Eight upper extremity implant vendors were included. The data was compiled in table format according to manufacturer and sub-categorized to facilitate screw identification according to radiographically identifiable characteristics. The diversity of orthopaedic implants in upper extremity surgery requires careful preoperative planning to identify the appropriate equipment for implant removal. The goal of this work is to provide a centralized reference of commonly implanted screws, guide-wires, and drivers for the upper extremity to facilitate removal.

Consideration of medial anatomical structures at risk when placing quadricortical syndesmotic fixation: A cadaveric study.

BACKGROUND: Surgical fixation of syndesmotic instability using quadricortical fixation, whether screws or suture-button devices, places structures on the medial side of the tibia at iatrogenic risk. This study aims to radiographically map the anatomic course of structures on the medial aspect of the distal tibia to be able to at-risk zones (ARZs) for syndesmotic fixation. METHODS: Eighteen fresh-frozen cadaveric ankle specimens were dissected. The saphenous neurovascular bundle (SNVB) and the posterior tibial tendon (PTT) were identified and marked with copper wiring. Standardized and calibrated lateral radiographs of the distal tibia and fibula were analyzed using a grid system consisting of 3 columnar zones from anterior to posterior and five 1-cm rows to chart the anatomic course of the SNVB and the PTT. RESULTS: The SNVB was located in the more anterior zones (1, 2, or anterior to Zone 1) in 97.3% of specimens. The SNVB traversed from posterior to anterior as it descended proximal to distal. The PTT was found in Zone 3 (most posterior zone) for all specimens. The PTT was noted to pass behind (radiographically overlap) the tibia in 83.3% (15 of 18) of specimens between 1 and 3 cm above the tibiotalar joint. CONCLUSIONS: Placement of quadricortical syndesmotic fixation places structures on the medial ankle at risk. The SNVB is at considerable risk along the anterior course of the distal tibial while the PTT is only at risk in zone 3 at the distal extent of the tibia.