Quantum pBac: An effective, high-capacity piggyBac-based gene integration vector system for unlocking gene therapy potential.

Recent advances in gene therapy have brought novel treatment options for cancer. However, the full potential of this approach has yet to be unlocked due to the limited payload capacity of commonly utilized viral vectors. Virus-free DNA transposons, including piggyBac, have the potential to obviate these shortcomings. In this study, we improved a previously modified piggyBac system with superior transposition efficiency. We demonstrated that the internal domain sequences (IDS) within the 3' terminal repeat domain of hyperactive piggyBac (hyPB) donor vector contain dominant enhancer elements. Plasmid-free donor vector devoid of IDS was used in conjunction with a helper plasmid expressing Quantum PBase™ v2 to generate an optimal piggyBac system, Quantum pBac™ (qPB), for use in T cells. qPB outperformed hyPB in CD20/CD19 CAR-T production in terms of performance as well as yield of the CAR-T cells produced. Furthermore, qPB also produced CAR-T cells with lower donor-associated variabilities compared to lentiviral vector. Importantly, qPB yielded mainly CD8+ CAR-TSCM cells, and the qPB-produced CAR-T cells effectively eliminated CD20/CD19-expressing tumor cells both in vitro and in vivo. Our findings confirm qPB as a promising virus-free vector system with an enhanced payload capacity to incorporate multiple genes. This highly efficient and potentially safe system will be expected to further advance gene therapy applications.

Evaluation of the safety of tranexamic acid use in pediatric patients undergoing spinal fusion surgery: a retrospective comparative cohort study.

BACKGROUND: Pediatric spinal fusion may be associated with significant intraoperative blood loss, leading to complications from transfusion, hypoperfusion and coagulopathy. One emerging strategy to mediate these risks is by utilization of the anti-fibrinolytic agent tranexamic acid (TXA). However, concerns regarding potential adverse reactions, specifically postoperative seizures and thrombotic events, still exist. To assess these risks, we examined the perioperative morbidity of TXA use in a large national database. METHODS: Retrospective data from pediatric patients (age 18 years or younger), discharged between January 2013 to December 2015, who underwent primary or revision posterior spinal fusions, was collected from the Premier Perspective database (Premier, Charlotte, NC). Patients were stratified by TXA use and records were assessed for complications of new onset seizures, strokes, pulmonary embolisms (PE) or deep vein thromboses (DVT) occurring during the perioperative period. RESULTS: In this cohort of 2,633 pediatric patients undergoing posterior spinal fusions, most often to treat adolescent idiopathic scoliosis, 15% received TXA. Overall, adverse events were rare in this patient population. The incidence of seizure, stoke, PE, or DVT in the control group was 0.54% (95% CI, 0.31% to 0.94%) and not significantly different from the TXA group. There was no significant difference in the incidence of DVTs, and no incidences of stroke in either group. There were no new-onset seizures or PEs in patients who received TXA. CONCLUSIONS: The use of TXA was not associated with an increased risk of adverse events including seizure, stroke, PE, and DVT. Our findings support the safety of TXA use in pediatric patients undergoing spinal fusion surgery.

Defining Features of Hand Anomalies in Severe Thumb Hypoplasia: A Classification Modification.

PURPOSE: To investigate morphologic hand anomalies in children with severe but unclassifiable forms of thumb hypoplasia and radial-sided hand deficiency. METHODS: We identified 15 extremities in 13 patients with severe thumb hypoplasia and associated absent radial-sided digits through the Congenital Upper Limb Differences registry. All patients had forearm involvement. Medical records, clinical photographs, and radiographs were evaluated. Radial longitudinal deficiency (RLD) and thumb hypoplasia were classified according to the Bayne and Klug classification and modified Blauth classification, respectively. Unusual or defining associated hand characteristics were identified and categorized. RESULTS: The most common type of forearm abnormality was absence of the radius (Bayne and Klug type IV), which was present in 10 extremities in the cohort. All 15 extremities had absent thumbs with loss of additional digits. In 6 patients, RLD was part of a syndrome (46%). CONCLUSIONS: Severe forms of thumb hypoplasia in RLD are uncommon. We propose a further modification of the Blauth classification of thumb hypoplasia, type VI, for improved communication regarding this severe type of radial deficiency involving the hand. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

The American Shoulder and Elbow Surgeons score highly correlates with the Simple Shoulder Test.

BACKGROUND/HYPOTHESIS: There is no consensus to which patient-determined shoulder outcome scores should be considered when analyzing patient outcomes for either clinical or research purposes. The use of multiple outcome scores may be redundant and cause increased responder burden. The hypothesis of this study is that the American Shoulder and Elbow Surgeons score (ASES) will highly correlate with the Simple Shoulder Test (SST) for rotator cuff repair and total shoulder arthroplasty and have comparable responsiveness. If determined to be highly correlated, the use of these scores simultaneously may be redundant and one score may be eliminated. METHODS: A retrospective review of the senior author's database of patients undergoing rotator cuff repair and total shoulder arthroplasty was reviewed in which the ASES was recorded simultaneously with the SST. Correlations were determined using the Pearson correlation coefficient (r > 0.7 excellent; r = 0.61-0.7 strong-moderate; r = 0.31-0.6 moderate; r = 0.2-0.3 poor) for all interactions between the 2 scores. Subgroup analysis was performed to determine if correlations differed in (1) preoperative outcome and (2) postoperative outcome determinations. Responsiveness was determined by calculating the standardized response mean and the effect size of both scores. RESULTS: There were a total of 1810 simultaneous measurements (both rotator cuff repair and total shoulder arthroplasty) of the ASES and SST. The correlation was excellent for the ASES and SST for all patients (n = 1810; r = 0.81; P < .0001). The correlation of preoperative scores was strong-moderate (n = 1191; r = 0.60; P < .0001), and the correlation of postoperative scores was excellent (n = 619; r = 0.78; P < .0001). Both scores were determined to be highly responsive, but both the standardized response mean (2.8 vs. 2.1) and the effect size (2.2 vs. 1.8) of the ASES were greater than those of the SST. CONCLUSION: In general, there was an excellent correlation between the ASES and the SST for all patients undergoing arthroscopic rotator cuff repair and total shoulder arthroplasty. Because there is an excellent correlation between the 2 scores, including these 2 scores simultaneously in tracking patient-determined outcomes appears to be redundant and therefore unnecessary. Because there is superior responsiveness of the ASES score compared with the SST, the authors recommend utilization of the ASES over the SST in patients undergoing rotator cuff repair and total shoulder arthroplasty.

Do patients who smoke tobacco have success with primary arthroscopic rotator cuff repair? A comparison with nonsmokers.

BACKGROUND: It is recommended that patients cease smoking before rotator cuff repair. However, not all patients want to or are able to successfully cease smoking. This raises the question if these patients should be advised to pursue surgical intervention or if surgery should be contraindicated until patients successfully cease smoking. METHODS: A retrospective analysis of patients undergoing rotator cuff repair was performed to examine the effects of smoking tobacco on patient-determined outcomes (Western Ontario Rotator Cuff Index [WORC], American Shoulder and Elbow Surgeons score [ASES], Simple Shoulder Test [SST], and Single Assessment Numeric Evaluation [SANE]). Patients who smoked tobacco at the time of surgery were compared with patients who were not smoking to determine if differences in (1) severity of preoperative and postoperative symptoms and (2) the postoperative improvements were statistically significant. RESULTS: Thirty-one patients were smokers and 205 were nonsmokers. Preoperative scores were worse for smokers compared with nonsmokers: WORC (32 vs. 43; P = .0002), ASES (32 vs. 43; P = .001), SST (3.5 vs. 4.6; P = .04), and SANE (34 vs. 38; P = .35). Postoperative scores were worse for smokers compared with nonsmokers: WORC (79 vs. 89; P = .001), ASES (82 vs. 89; P = .04), SST (9.0 vs. 10.2; P = .02), and SANE (84 vs. 89; P = .09). There were no significant differences in change in scores over time or percentage of patients achieving the minimal clinically important difference of the score between groups. CONCLUSIONS: From examining the patients' subjective patient-determined outcome scores, it does not appear that rotator cuff repair should be strictly contraindicated in active smokers. Postoperative improvements in smokers were similar to nonsmokers. Smokers have lower baseline preoperative and postoperative outcome scores compared with nonsmokers.

Patient-determined outcomes after arthroscopic rotator cuff repair with and without biceps tenodesis utilizing the PITT technique.

HYPOTHESIS AND BACKGROUND: The percutaneous intra-articular transtendon technique (PITT) is a simple, rapid, and low-cost method of performing a biceps tenodesis. Few studies exist that examine the patient-determined outcomes of this technique in general or in patients undergoing arthroscopic rotator cuff repair (RCR) with and without biceps tenodesis. We hypothesized that patients undergoing an isolated arthroscopic RCR would have equivalent outcomes to those undergoing RCRs with PITT biceps tenodesis. METHODS: We compared preoperative, patient-determined outcomes scores on patients undergoing primary arthroscopic RCR with and without a PITT biceps tenodesis with postoperative scores at a minimum of 2 years. These scores included the Western Ontario Rotator Cuff score (WORC), American Shoulder and Elbow Surgeons score (ASES), Single Assessment Numeric Evaluation (SANE), Simple Shoulder Test (SST), and Shoulder Activity Level (SAL). Indication for a concomitant biceps tenodesis was a partial long head biceps tendon tear or biceps instability/subluxation. RESULTS: A total of 153 patients underwent an isolated RCR and 131 patients underwent RCR with biceps tenodesis (RCRBT). Both groups had improvements in WORC, ASES, SANE, and SST (P < .0001) and deteriorations in the SAL (P ≤ .005). There was no difference in the change in outcome scores between the groups (RCRBT vs. RCR, respectively) for WORC (46 vs. 47; P = .85), ASES (46 vs. 47; P = .82), SANE (53 vs. 51; P = .35), SST (5.8 vs. 5.8; P = .93), and SAL (-0.9 vs. -1.4; P = .46). There was no difference between the groups in complications that required revision surgery (1.5% vs. 1.3%; P = .91). CONCLUSIONS: Arthroscopic PITT RCRBT is safe and effective with equivalent patient-determined outcomes compared with patients undergoing RCR without biceps tenodesis.

Does arthroscopic rotator cuff repair improve patients' activity levels?

BACKGROUND: Rotator cuff repair decreases pain, improves range of motion, and increases strength. Whether these improvements translate to an improvement in a patient's activity level postoperatively remains unknown. The Shoulder Activity Level is a valid and reliable outcomes survey that can be used to measure a patient's shoulder-specific activity level. Currently, there are no studies that examine the effect of rotator cuff repair on shoulder activity level. METHODS: Preoperative patient-determined outcomes scores collected prospectively on patients undergoing rotator cuff repair were compared with postoperative scores at a minimum of 2 years. These scores included the Shoulder Activity Level, Western Ontario Rotator Cuff Index, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, and simple shoulder test. Inclusion criteria were patients undergoing arthroscopic rotator cuff repair. RESULTS: Included were 281 shoulders from 273 patients with a mean follow-up of 3.7 years. The postoperative median Western Ontario Rotator Cuff Index (42 vs. 94), American Shoulder and Elbow Surgeons (41 vs. 95), Single Assessment Numeric Evaluation (30 vs. 95), and simple shoulder test (4 vs. 11) scores were statistically significantly improved compared with preoperative scores (P < .0001). The postoperative median Shoulder Activity Level score decreased compared with the preoperative score (12 vs. 11; P < .0001). CONCLUSIONS: Patients reported a statistically significant deterioration of their Shoulder Activity Level score after rotator cuff repair compared with their preoperative scores, although disease-specific and joint-specific quality of life scores all had statistically significantly improvement. This study suggests that patients generally have (1) significant improvements in their quality of life and (2) small deteriorations in activity level after arthroscopic rotator cuff repair.

Does total shoulder arthroplasty improve patients' activity levels?

BACKGROUND: Total shoulder arthroplasty (TSA) decreases pain, improves range of motion, and increases strength. Whether these improvements translate to improvements in activity levels postoperatively remains unknown. The Shoulder Activity Level (SAL) is a valid and reliable outcomes survey that measures the patient's activity level. Currently, no studies have specifically examined the effect of TSA on SAL. METHODS: A prospective collection of preoperative, patient-determined outcomes on patients undergoing TSA was compared with postoperative scores at a minimum of 2 years. These scores included the SAL, Western Ontario Osteoarthritis of the Shoulder Index (WOOS), American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment, Single Assessment Numeric Evaluation (SANE), and the Simple Shoulder Test (SST). Inclusion criteria were patients undergoing primary anatomic TSA or reverse TSA. RESULTS: A mean follow-up of 3.7 years was available for 80 anatomic and 42 reverse TSAs. Anatomic TSAs had improvements from median preoperative scores to median postoperative scores for WOOS (34 to 89; P < .0001), ASES (30 to 87; P < .0001), SST (2 to 9; P < .0001), and SANE scores (23 to 90; P < .0001). The SAL improved from 7 to 8 but did not quite reach statistical significance (P = .07). Reverse TSAs had improvements from median preoperative scores to median postoperative scores for WOOS (31 to 83; P < .0001), ASES (29 to 82; P < .0001), SST (2 to 7; P < .0001), and SANE scores (20 to 85; P < .0001). The SAL improved from 4.5 to 6, but this did not reach statistical significance (P = .38). However, when anatomic and reverse TSAs were analyzed together, a statistically significant improvement was found postoperatively in the SAL (from 6 to 8; P = .006). CONCLUSIONS: Anatomic TSA and reverse TSA improved activity levels. In addition, disease-specific and joint-specific quality of life scores all had statistically significant improvements. This study suggests that after shoulder arthroplasty patients in general have (1) significant improvements in their quality of life and (2) have small improvements in activity level. This study shows that most patients do not have to decrease their activity levels to diminish symptoms to an acceptable range.

An Analysis of the Financial Burden Associated with the Residency Match at the University of South Dakota Sanford School of Medicine.

OBJECTIVE: The application process for residency positions is a costly endeavor. This study aims to quantify the financial expenses incurred by University of South Dakota Sanford School of Medicine (USD SSOM) class of 2016. Our hope is that this study will prepare future students of USD and other smaller programs for the financial burdens associated with the match. This data should be used to guide financial decision making by medical students from USD or by regional students from medical programs that desire to apply to residency programs not offered at their home institution. METHODS: A 10-item online survey was administered in April of 2016 via the USD Sanford School of Medicine email listserv to the graduating MD class of 2016. The survey asked respondents about the number and cost of away-rotations completed, interviews attended, second-look days attended after the interview, preferences for interviewing during an away-rotation, the specialty the applicant matched into, and number on each applicant's rank list that he/she matched. RESULTS: The survey had a 68.3 percent response rate. The mean number of away-rotations completed, interviews attended, and second-look days attended were 1.3, 12.1, and 0.1 per applicant respectively. The mean costs of attendance to away-rotations, interviews, and second-look days were $1,690.63, $4,881.88, and $24 per applicant, respectively. The total mean collective cost of away-rotations, interviews, and second-look days was $6,596.51 per applicant. CONCLUSIONS: The process of applying to residencies among the graduating MD class of 2016 is a costly endeavor. Attendance of interviews for residency positions is the most costly part of the residency application process. Although the financial burden associated with applying to residency programs is high, increasing competition for graduate medical education positions may only drive the cost further.

Quadrilateral Space Syndrome Treated with Ultrasound-Guided Corticosteroid Injection: A Case of Isolated Teres Minor Atrophy and Review of the Literature.

Quadrilateral space syndrome (QSS) is a rare orthopedic condition caused by compression, entrapment, or injury to the axillary nerve or posterior humeral circumflex artery as they arise from the quadrilateral space. QSS can present with point tenderness over the quadrilateral space and weakness and paresthesia in the axillary nerve distribution. It is commonly associated with repetitive overhead activities and is seen in athletes engaging in such activities. Here we report a case of QSS in a 42-year-old male weight lifter who presented with pain and soreness in the posterior aspect of his right shoulder radiating around his arm as well as slight weakness of his right shoulder of a few weeks duration. MRI results of his shoulder demonstrated moderate atrophy and fatty infiltration of the teres minor. His diagnosis of QSS was confirmed with electro diagnostic testing which showed axillary neuropathy. He was treated with ultrasound guided corticosteroid injections and gained relief from this treatment. His axillary neuropathy was shown to be resolving on repeat electro diagnostic testing at six-months follow-up. Here we report a case of QSS and provide a brief review of the literature.

Posaconazole tablet pharmacokinetics: lack of effect of concomitant medications altering gastric pH and gastric motility in healthy subjects.

Posaconazole oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new posaconazole tablet formulation has demonstrated improved bioavailability over the oral suspension in healthy adults in a fasting state. This study evaluated the effects of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and gastric motility (metoclopramide) on the pharmacokinetics of posaconazole tablets. This was a prospective open-label 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg dose (4 100-mg tablets) of posaconazole was administered alone or with 20 ml antacid (2 g of aluminum hydroxide and 2 g of magnesium hydroxide), ranitidine (150 mg), esomeprazole (40 mg), or metoclopramide (15 mg). There was a ≥ 10-day washout between treatment periods. Posaconazole exposure, time to maximum concentration of drug in serum (Tmax), and apparent terminal half-life (t1/2) were similar when posaconazole was administered alone or with medications affecting gastric pH and gastric motility. Geometric mean ratios (90% confidence intervals [CIs]) of the area under the concentration-time curve from time zero to infinity (AUC0-inf) (posaconazole with medications affecting gastric pH and gastric motility versus posaconazole alone) were 1.03 (0.88-1.20) with antacid, 0.97 (0.84-1.12) with ranitidine, 1.01 (0.87-1.17) with esomeprazole, and 0.93 (0.79-1.09) with metoclopramide. Geometric mean ratios (90% CIs) of the maximum concentration of drug in serum (Cmax) were 1.06 (0.90-1.26) with antacid, 1.04 (0.88-1.23) with ranitidine, 1.05 (0.89-1.24) with esomeprazole, and 0.86 (0.73-1.02) with metoclopramide. In summary, in healthy volunteers, the pharmacokinetics of a single 400-mg dose of posaconazole tablets was not altered to a clinically meaningful extent when posaconazole was administered alone or with medications affecting gastric pH or gastric motility.

Habb-e-Asgand, polyherbal Unani formulation, protects liver and antioxidative enzymes against paracetamol induced hepatotoxicity.

Abstract Context: Habb-e-Asgand, a polyherbal Homeopathy/Unani drug from Hamdard Wakf Laboratory, India, used in arthritis, gout and joint pain, is a mixture of many herbal medicinal plants. Scientific attempts to test and validate its efficacy are meager. Objective: To evaluate the hepatoprotective and antioxidative potential of Habb-e-Asgand against paracetamol toxicity. Materials and methods: Swiss albino male mice (n = 5/group) were treated with Habb-e-Asgand (250 mg/kg, body weight (b.w.) in normal saline orally for 14 days followed by a single dose of paracetamol (400 mg/kg b.w./normal saline) intraperitoneally 24 h before euthanization. We estimated liver function (LFTs) using diagnostic kits, while antioxidant enzymes, cytochrome P450 (CYP) and lipid peroxidation (LPO) were measured using spectrophotometric methods. Results: Paracetamol alone induced LFTs enzymes significantly (p < 0.05 and p < 0.01, 0.001), serum glutamate pyruvate transaminase (SGPT, ∼70%), serum glutamate oxaloacetate transaminase (SGOT, ∼20%), alkaline phosphatase (ALP, ∼20%), total bilirubin (∼30%), CYP activity (∼50%) and LPO (∼45%), while it significantly inhibited the activity of antioxidant enzymes glutathione reductase (GR, ∼35%), glutathione peroxidase (GPx, ∼40%), glutathione S-tranferase (GST, ∼16%), catalase (CAT, ∼84%) and glutathione (GSH, ∼30%) contents. Habb-e-Asgand alone and in combination of paracetamol significantly (p < 0.05, 0.01, 0.001) decreased LFT levels (20-25%), CYP activity (∼45%) and LPO level (∼25%), while it induced antioxidant enzyme activity (GR, ∼15%; GPx, ∼17%; GST, ∼20% and CAT, ∼60%). Discussion: Paracetamol metabolites may be mediating production of reactive oxidant species (ROS) and liver injury, which are attenuated by Habb-e-Asgand antioxidant constituents. Conclusion: Habb-e-Asgand may be used as a prophylaxis for ROS related liver injury.

Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.

CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.

Surgical Pearls and Pitfalls for Anatomic Acromioclavicular/Coracoclavicular Ligament Reconstruction.

Injuries to the acromioclavicular (AC) joint are common shoulder injuries in contact/collision athletes. There are a number of different surgical options that can be used to treat these injuries. The majority of these injuries can be treated nonoperatively with an early return to play for type I and II injuries. Surgical intervention and AC/CC (coracoclavicular) ligament reconstruction have excellent postoperative outcomes if complications can be avoided. This review will focus on the pearls and pitfalls for anatomic AC and CC ligament reconstruction for high-grade AC joint injuries.

Validity of Research Based on Publicly Obtained Data in Sports Medicine: A Quantitative Assessment of Concussions in the National Football League.

CONTEXT: Numerous researchers have leveraged publicly available internet sources to publish clinical research concerning incidence and recovery from injuries in National Football League (NFL) players. OBJECTIVE: This study aims to (1) provide a comprehensive systematic review of all publicly obtained data studies (PODS) regarding concussions in NFL athletes and (2) quantify the percentage of injuries identified by these studies in comparison with published concussion data from the NFL injury database. STUDY SELECTION: A systematic review was conducted in accordance with PRISMA guidelines to identify all published studies utilizing publicly obtained data regarding concussions in NFL athletes. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Manuscript details, factors related to the athletes of interest (eg, study period, positions included), and results (eg, concussion rate, number of total concussions, return-to-play data) were extracted independently by 2 authors. Results were compared with incident concussions reported from 2015 to 2019 by each medical staff member to the NFL database linked to the League's electronic health record (EHR). RESULTS: A total of 20 concussion-focused manuscripts based on PODS were identified from 2014 to 2020. PODS captured between 20% and 90% of concussions (mean, 70%) reported by medical staff to the injury database. PODS reported that 55% of concussions occurred on offensive plays, 45% on defensive plays and <1% occurred during special teams plays, compared with 44%, 37%, and 18%, respectively, as indicated by published data from the NFL injury database. When analyzed by position groups, running backs and quarterbacks comprised the most over-represented positions concussed in PODS, while offensive linemen, defensive backs, and linebackers comprised the most under-represented positions. CONCLUSION: PODS captured approximately 70% of concussions reported by NFL medical staff to the NFL injury database. There is heterogeneity in the degree to which PODS were able to identify concussions, with a bias toward concussions among players at higher profile positions.

Small residual fracture gaps delay time to union in length stable femur fractures treated with intrameduallary fixation.

OBJECTIVES: The purpose of this study was to investigate whether residual fracture gapping and translation at time of intramedullary nail (IMN) fixation for diaphyseal femur fractures were associated with delayed healing or nonunion. DESIGN: Retrospective cohort study SETTING: Level 1 trauma hospital, quaternary referral center PATIENTS/PARTICIPANTS/INTERVENTION: Length stable Winquist type 1 and 2 diaphyseal femur fractures treated with IMN at a single Level I trauma center were retrospectively reviewed. MAIN OUTCOME MEASURE: The largest fracture gap and translation were evaluated on immediate anteroposterior (AP) and lateral postoperative radiographs. Radiographic healing was assessed using Radiographic Union Score in Femur (RUSF) scores at each follow-up. Radiographic union was defined as a RUSF score ≥8 and consolidation of at least 3 cortices. ANOVA and student's t-tests were used to evaluate the influence of fracture gap parameters on time to union (TTU) and nonunion rate. Patients were stratified to measured average gap and translation distances <1mm, 1-3mm and >3mm for portions of the analysis. RESULTS: Sixty-six patients who underwent IMN with adequate follow-up were identified. A total of 93.9% of patients achieved union at an average of 2.8 months. Fractures with average AP/lateral gaps of <1mm, 1-2.9 mm, and >3mm had an average TTU of 70.1, 91.7, and 111.9 days respectively; fractures with larger residual gap sizes had a significantly longer TTU (p=0.009). Fractures with an average gap of 1-2.9mm and >3 mm had a significantly higher nonunion rate (1.5% and 4.5% respectively) compared to 0% nonunion in the <1 mm group (p=0.003). CONCLUSION: Residual gapping following intramedullary fixation of length stable diaphyseal femur fractures is associated with a significant increase in likelihood of nonunion. SUMMARY: Residual displacement of length stable femoral shaft fractures following intramedullary nailing can have a significantly negative impact on fracture healing. An average 3 mm AP/lateral residual fracture gap or a total of 6 mm of the AP + lateral fracture gap appeared to be a critical gap size with increased rates of nonunion and time to union. Therefore, we suggest minimizing the sum of the residual AP and lateral fracture gap to less than a total of 6 mm.

Utility of Talus Osteochondral Allograft Augmentation for Varying Hill-Sachs Lesion Sizes: A Cadaveric Study.

Background: Humeral head reconstruction with fresh osteochondral allografts (OCA) serves as a potential treatment option for anatomic reconstruction. More specifically, talus OCA is a promising graft source because of its high congruency with a dense cartilaginous surface. Purpose: To analyze the surface geometry of the talus OCA plug augmentation for the management of shoulder instability with varying sizes of Hill-Sachs lesions (HSLs). Study Design: Controlled laboratory study. Methods: Seven fresh-frozen cadaveric shoulders were tested in this study. The humeral heads were analyzed using actual patients' computed tomography scans. Surface laser scan analysis was performed on 7 testing states: (1) native state; (2) small HSL; (3) talus OCA augmentation for small HSL; (4) medium HSL; (5) talus OCA augmentation for medium HSL; (6) large HSL; and (7) talus OCA augmentation for large HSL. OCA plugs were harvested from the talus allograft and placed in the most medial and superior aspect of each HSL lesion. Surface congruency was calculated as the mean absolute error and the root mean squared error in the distance. A 1-way repeated-measures analysis of variance was performed to evaluate the effects of the difference in the HSL size and associated talus OCA plugs on surface congruency and the HSL surface area. Results: The surface area analysis of the humeral head with the large (1469 ± 75 mm2), medium (1391 ± 81 mm2), and small (1230 ± 54 mm2) HSLs exhibited significantly higher surface areas than the native state (1007 ± 88 mm2; P < .001 for all sizes). The native state exhibited significantly lower surface areas as compared with after talus OCA augmentation for large HSLs (1235 ± 63 mm2; P < .001) but not for small or medium HSLs. Talus OCA augmentation yielded improved surface areas and congruency after treatment in small, medium, and large HSLs (P < .001). Conclusion: Talus OCA plug augmentation restored surface area and congruency across all tested HSLs, and the surface area was best improved with the most common HSLs-small and medium. Clinical Relevance: Talus OCA plugs may provide a viable option for restoring congruity of the shoulder in patients with recurrent anterior glenohumeral instability and an HSL.

Sternoclavicular Joint Reconstruction With Gracilis Tendon Autograft.

Clinical instability of the sternoclavicular (SC) joint is a challenging problem. Recurrent subluxation and pain can lead to significant functional limitations. Although many patients respond positively to conservative treatment, chronic dislocations often require operative intervention. The complex anatomy of the diarthrodial SC joint and the existence of concomitant SC joint degenerative changes compounded with close-by neurovascular structures present a surgical challenge. The purpose of this Technical Note is to describe a technique for the open management of symptomatic sternoclavicular joint instability using a figure-of-8 reconstruction with a gracilis autograft. The present authors believe this technique provides a technically safe and reproducible method for reconstructing the SC joint without compromising biomechanical strength.

Midterm Outcomes of Posterior Medial Meniscus Root Tear Repair: A Systematic Review.

BACKGROUND: Whereas there has been growing interest in surgical repair of posterior medial meniscus root tears (PMMRTs), our understanding of the medium- and long-term results of this procedure is still evolving. PURPOSE: To report midterm clinical outcomes from PMMRT repairs. STUDY DESIGN: Systematic review. METHODS: A literature review for this systematic analysis was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We identified studies that reported the results of arthroscopic repair of PMMRTs. Functional and imaging outcomes were reviewed and summarized. RESULTS: In total, 28 studies with a total of 994 patients (83% female) with an overall mean age of 57.1 were included in this review. Clinical outcomes (Lysholm, International Knee Documentation Committee, Hospital for Special Surgery, and Tegner scores) were improved at final follow-up in all studies. Of patients, 49% had radiographic progression of at least 1 grade in the Kellgren-Lawrence scale at a mean follow-up of 4.0 years in 11 studies. Cartilage degeneration had progressed at least 1 grade on magnetic resonance imaging scans in 23% of patients at a mean follow-up of 31.6 months in 4 studies. CONCLUSION: PMMRT repairs provide a functional benefit with consistent improvements in clinical outcome scores. There is some evidence that PMMRT repair slows the progression of osteoarthritis but does not prevent it at midterm follow-up.

Mechanical and Microstructural Properties of Meniscus Roots Vary by Location.

BACKGROUND: Despite the growing awareness of the clinical significance of meniscus root tears, there are relatively limited biomechanical and microstructural data available on native meniscus roots that could improve our understanding of why they are injured and how to best treat them. PURPOSE/HYPOTHESIS: The purpose of the study was to measure the material and microstructural properties of meniscus roots using mechanical testing and quantitative polarized light imaging. The hypothesis was that these properties vary by location (medial vs lateral, anterior vs posterior) and by specific root (anteromedial vs anterolateral, posteromedial vs posterolateral). STUDY DESIGN: Descriptive laboratory study. METHODS: Anterior and posterior meniscus roots of the medial and lateral meniscus were isolated from 22 cadavers (10 female, 12 male; mean ± SD age, 47.1 ± 5.1 years) and loaded in uniaxial tension. Quantitative polarized light imaging was used to measure collagen fiber organization and realignment under load. Samples were subjected to preconditioning, stress-relaxation, and a ramp to failure. Time-dependent relaxation behavior was quantified. Modulus values were computed in the toe and linear regions of the stress-strain curves. The degree of linear polarization (DoLP) and angle of polarization-measures of the strength and direction of collagen alignment, respectively-were calculated during the stress-relaxation test and at specific strain values throughout the ramp to failure (zero, transition, and linear strain). RESULTS: Anterior roots had larger moduli than posterior roots in the toe (P = .007) and linear (P < .0001) regions and larger average DoLP values at all points of the ramp to failure (zero, P = .016; transition, P = .004; linear, P = .002). Posterior roots had larger values across all regions in terms of standard deviation angle of polarization (P < .001). Lateral roots had greater modulus values versus medial roots in the toe (P = .027) and linear (P = .014) regions. Across all strain points, posterolateral roots had smaller mean DoLP values than posteromedial roots. CONCLUSION: Posterior meniscus roots have smaller modulus values and more disorganized collagen alignment at all strain levels when compared with anterior roots. Posterolateral roots have lower strength of collagen alignment versus posteromedial roots. CLINICAL RELEVANCE: These data findings may explain at least in part the relative paucity of anterior meniscus root tears and the predominance of traumatic posterolateral roots tears as compared with degenerative posteromedial root tears.