Antigen preparations in the form of detergent-solubilized cell lysates could, in principle, render membrane proteins (MPs) compatible with in vitro antibody engineering technologies. To this end, detergent-solubilized cell lysates were coupled with the yeast surface display platform to affinity mature an anti-transferrin receptor (TfR) single-chain antibody (scFv). Lysates were generated from TfR-expressing HEK293 cells by solubilization with detergent-containing buffer after undergoing plasma membrane-restricted biotinylation. Lysate-resident TfR was then combined with a mutagenic anti-TfR scFv library in a competitive, dissociation rate screen, and scFvs were identified with up to 4-fold improved dissociation rates on the surface of yeast. Importantly, although the lysates contained a complex mixture of biotinylated proteins, the engineered scFvs retained their TfR binding specificity. When secreted by yeast as soluble proteins, mutant scFvs bound to cell surface TfR with 3-7-fold improvements in equilibrium binding affinity. Although a known MP antigen was targeted for purposes of this study, employing biotin tagging as a means of antigen detection makes the lysate-based approach particularly flexible. We have previously shown that yeast display can be used to identify lead antibodies using cell lysate-resident MP antigens, and combined with this work showing that antibodies can also be quantitatively engineered using cell lysates, these approaches may provide a high-throughput platform for generation and optimization of antibodies against MPs.
Background: Open fractures are debilitating injuries for athletes. No prior studies have investigated open fractures in National Football League (NFL) players. Purpose: To compare outcomes after open fracture in NFL players in terms of (1) time to return to sport (RTS), (2) postinjury career length and games played per season, (3) postinjury performance, and (4) postinjury performance compared with matched controls. Study Design: Retrospective comparative series; Level of evidence, 3. Methods: Publicly available records were used to identify NFL players who had sustained an open fracture between 1970 and 2018. Controls were matched to injured players by age, experience, position, and preinjury performance. RTS was defined as playing in at least 1 NFL game after open fracture. Comparisons between injured and control players were made using the paired-samples Student t test. Results: Injuries in 37 players were analyzed (age, 27.2 ± 3.6 years; experience, 4.4 ± 3.6 seasons). The 3 most common locations for open fracture were the tibia/fibula (n = 16), hand/finger (n = 12), and forearm/wrist (n = 3). A total of 30 (81%) players had a mean time of RTS of 9.3 ± 8.2 months after open fracture; of these players, 4 (13.3%) who sustained hand/finger open fracture did not undergo surgical treatment. There was no difference in postinjury career length or games played per season between control and injured players. Postinjury performance was similar to preinjury performance in injured players, and postinjury performance scores were similar between injured and control players. There were significant differences between players who sustained upper extremity and lower extremity open fractures in RTS time (4.0 ± 4.8 vs 14.6 ± 7.4 months, respectively; P = .00007) and postinjury performance (6.4 ± 4.3 vs 3.3 ± 2.1, respectively; P = .03). Conclusion: RTS after open fracture among NFL players was high. Players who sustained an open fracture had similar games played per season, career length, and performance compared with matched controls. Players who sustained an upper extremity open fracture had a faster RTS time, higher RTS rate, and improved postinjury performance compared with players who sustained a lower extremity open fracture.
Background Dislocation after primary total hip arthroplasty (THA) has an incidence of 2–3%. Approximately 77% of dislocations occur within the first year after surgery. The SuperPATH technique is a minimally invasive approach for THA that preserves soft tissue attachments. The purpose of this study is to describe the dislocation rate at 1 year after SuperPATH primary THA. Methods All elective primary THAs performed by the senior author using the SuperPATH approach. Exclusion criteria were acute femoral neck fracture, revision surgery, or malignancy. There were 214 of 279 eligible patients available for telephone interviews (76.7%). Medical records were reviewed for secondary outcomes including early and late complications, cup positioning, distance ambulated on postoperative day one, discharge destination, and blood transfusions. Results Mean age at surgery was 64 ± 10.8 years and mean time to telephone follow up was 773 ± 269.7 days. There were 104 female and 110 male patients. There were zero dislocations reported. Blood transfusions were performed in 3.7% of patients, and 75.7% were discharged to home at an average of 2.3 ± 1.0 days. Cup position averaged 43.6 ± 5.2° abduction and 20.9 ± 6.2° anteversion, with an average leg length discrepancy of 3.6 ± 3.32 mm. Complications included three intraoperative calcar fractures, one periprosthetic femur fracture, one early femoral revision, three superficial infections, and one instance of wound necrosis. Conclusion SuperPATH approach is safe for use in primary THA resulting in a low dislocation rate.
Introduction: Perioperative hypothermia (PH) is common in patients undergoing total joint arthroplasty (TJA). A previous study at our institution identified the largest drop in core body temperature between preoperative holding and induction of anesthesia. This study evaluates the effect of preoperative warming measures on PH in TJA patients. Methods: A retrospective review was conducted of 672 patients undergoing TJA at our institution between April 1 and October 31, 2017. Under the new normothermia protocol, patients received warmed intravenous fluids and forced-air warming gowns in the preoperative holding area. Time and temperature data for the perioperative period were collected from the electronic health record. Chi-square and paired t-tests were used to compare between total knee arthroplasty and total hip arthroplasty patients and between new and old protocols. Results: In the new protocol, 173 of 672 (26%) patients were hypothermic at incision compared with 140 of 383 (37%) patients in the previous protocol (P < 0.05). The largest drop in core body temperature occurred between preoperative holding and induction of anesthesia. The duration of time from operating room entry to incision was less for normothermic than for hypothermic patients. The duration of hypothermia was similar between new and old protocols overall, but markedly fewer total hip arthroplasty patients remained hypothermic for the entire surgery under the new protocol. Conclusion: Adding forced-air warming preoperatively to our warming protocol reduced the rate of PH by approximately 30%. The time from entry into the operating room to the start of surgery should be minimized because patients are vulnerable to PH during this interval.
Background: Methodological quality and author internationality are increasing in orthopaedic surgery. The purpose of this study was to evaluate the methodological quality and author geography trends from 1994 to 2019 in high-quality foot and ankle journals. Methods: Analyses of 1,242 foot and ankle publications in Foot and Ankle International , American Journal of Bone and Joint Surgery , and American Journal of Sports Medicine were done for 1994, 1999, 2004, 2009, 2014, and 2019. Articles were classified according to study type, level of evidence (LOE), and author's country of publication. Results: The most common clinical study was therapeutic (65.4). Significant increases were noted in the proportion of therapeutic ( P < 0.01) and prognostic ( P < 0.01) articles. The average LOE increased from 3.96 ± 1.01 to 3.19 ± 0.97 ( P < 0.01). The proportion of Level I ( P = 0.29) and level IV articles ( P = 0.21) remained constant, level II ( P < 0.01) and level III ( P < 0.01) articles increased, and level V ( P < 0.01) articles decreased. United States authorship decreased from 78.1% in 1994 to 44.8% in 2009, then remained constant through 2019 ( P < 0.01). Conclusion: This study demonstrated an improvement in LOE of foot and ankle publications across a 25-year period in three high-quality orthopaedic journals. Increasing internationality was also observed.
ObjectivesTo determine which outcome scores physicians are using in hip preservation surgery, as well as when they are administered, who administers them and on what platform.MethodsA cross-sectional survey was conducted to examine which patient-reported outcome (PRO) scores are being used by hip preservation surgeons, including hip joint–specific, lower extremity limb–specific, disease-specific, general health, quality of life, pain, activity, spine and psychiatric wellness scores. Descriptive statistics were calculated. Heterogeneity was assessed using I2 statistics.ResultsFifty-six surgeons responded (mean 169 arthroscopic, 65 open hip preservation surgeries per year; mean 13 years experience). 13% of surgeons did not collect any patient outcome scores. A total of 25 different PROs were reported. Of 13 possible hip joint–specific outcome scores, the modified Harris Hip Score was most frequently collected (46%), followed by International Hip Outcome Tool−12 (41%) and Hip Outcome Score (38%). There was considerable heterogeneity in hip joint–specific PROs (I2 86%). The Short Form−12 was the most common general health score (30%). Tegner and UCLA Activity scores were collected by 11% of participants. Fifty-nine per cent collected outcomes preoperatively, 45% at 3 months, 54% at 6 months, 61% at 1 year and 32% annually. Paper collection was the most common collection platform (46%), and a dedicated research assistant was most frequently the source of data collection (34%).ConclusionThis international survey demonstrates that although most hip preservation surgeons collect hip outcome scores, there is a large amount of heterogeneity in outcome scores used and method of collection. As hip preservation evidence continues to evolve, these results should emphasise the need for an initiative to standardise outcome score collection.Level of evidenceLevel V.
Background: Medial column procedures are commonly used to treat progressive collapsing foot deformity (PCFD) reconstruction. The aim of this research is to present the clinical results of plantar plating for medial naviculocuneiform (NC) arthrodesis when NC joint pathology contributes to medial arch collapse. The authors hypothesized that lag screws with a plantar neutralization plate would result in a satisfactory NC joint fusion rate. Methods: A single-surgeon, retrospective case series was performed on patients with flexible PCFD who underwent NC arthrodesis using lag screws and a contoured neutralization plate applied plantarly across the medial NC joint as part of PCFD reconstruction. Thirteen patients (11 females, 2 males; mean age 53.1 [34-62] years) between 2016 and 2019 were identified for inclusion. Mean follow-up was 25.2 ± 12.7 months. Preoperative and postoperative anteroposterior talo–first metatarsal angle, lateral talo–first metatarsal angle, talonavicular coverage angle, and calcaneal pitch were measured. Union was evaluated radiologically. AOFAS midfoot scores were recorded at final follow-up. Results: All parameters demonstrated a significant improvement. Fusion was confirmed in 11 of 13 patients (85%) at a mean 5.7 ± 2.1 months. One patient required a revision of their NC fusion because of symptomatic nonunion. There were no cases of symptomatic plantar hardware. Conclusion: The results of this small cohort series suggest that lag screw with plantar plate NC arthrodesis yielded generally improved short-term radiographic and clinical outcomes in PCFD patients with medial arch collapse through the NC joint. Level of Evidence: Level IV, retrospective case series.
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