The Impact of Neurological Disorders on Clinical and Functional Outcomes after Shoulder Arthroplasty: A Systematic Review.

BACKGROUND: Patients with pre-existing neurologic disorders present a unique set of challenges for shoulder arthroplasty (SA) surgeons due to the presence of concomitant contractures, muscle weakness, and spasticity, which may affect outcomes and complication rates after shoulder arthroplasty. The goal of this systematic review was to evaluate the clinical and functional outcomes after SA in patients pre-existing with neurologic disorders, focusing on complication and reoperation rates. METHODS: This systematic review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines outlined by Cochrane Collaboration. A search of PubMed, the Medline Library, and EMBASE from inception until September 2023 was conducted to obtain studies reporting on outcomes after SA in patients with neurological disorders. Study demographics and information on outcomes including patient-reported outcomes and complication rates were collected. The methodological quality of included primary studies was appraised using the MINORS scoring system. RESULTS: Twenty articles published between 1997 and 2023 met inclusion criteria. In total, 13,126 patients with neurological conditions with 7 different neurological disorders (Parkinson's disease (PD), epilepsy and seizures, cerebral palsy (CP), poliomyelitis, Charcot neuropathy (CN), cerebrovascular disease (CVD) and multiple sclerosis (MS)) were included. The mean patient age was 64.3 years (range, 33.0 - 75.8 years), 51.4% of patients were male, and the mean postoperative follow-up time was 5.1 years (range, 1.4 - 9.9 years). PD was the most reported neurological disorder (9 studies, 8,033 patients), followed by epilepsy (4 studies, 3,783 patients), and MS (1 study, 1,077 patients). While these patients did experience improvements in outcomes following SA, high complication and revision rates were noted. CONCLUSIONS: Patients with neurologic disorders demonstrate improvements in pain and function after SA but have higher reported complication and revision rates when compared with patients without neurologic conditions. This systematic review offers valuable data for both the surgeon and patient regarding anticipated clinical results and possible complications from SA in patients with neurologic disorders that may aid in shared decision-making when considering SA.

Combined Medial Collateral Ligament Reconstruction and Polyethylene Exchange for Valgus Instability Following Total Knee Arthroplasty.

Valgus instability can occur after total knee arthroplasty (TKA) due to traumatic medial collateral ligament (MCL) injury, component malpositioning, or progressive ligamentous laxity. Although revision TKA with exchange of the polyethylene to a varus-valgus-constrained liner can reduce laxity due to MCL insufficiency, isolated liner exchange in the setting of collateral ligament insufficiency may lead to greater strain at the cement-bone or implant-cement interface and possibly a greater rate of aseptic loosening. Anatomic MCL reconstruction can be performed in conjunction with liner exchange to restore stability and reduce strain compared with liner exchange alone. The purpose of this Technical Note is to describe a technique for MCL reconstruction and liner exchange for treatment of valgus instability after TKA.

A multicentre prospective assessment of the utility of robotic assisted total hip arthroplasty with virtual range of motion on intraoperative implant positioning.

BACKGROUND: The growing adoption of robotic-assistance during total hip arthroplasty (THA) has provided novel means through which a patient's anatomy and dynamic spinopelvic relationship can be incorporated into surgical planning. However, the impact of enhanced technologies on intraoperative decision-making and changes to component positioning has not yet been described. METHODS: A multicentre, prospective study included 105 patients (52% women) patients who underwent robotic-assisted THA with the integration of software that incorporates a patient's pelvic tilt (PT) and virtual range-of-motion (VROM) for impingement modeling. The primary outcome of the study was the percentage of patients who underwent changes to the preoperative plan for cup position after incorporating the data from the software. RESULTS: Utilising the intraoperative VROM information, the preoperative plan for cup position was changed from the default (40° inclination and 20° anteversion) in 82/105 (78%) cases. When stratifying by spinopelvic mobility, 64% were considered normal (change ⩾ 10° and ⩽30°), 27% were stiff (change < 10°), and 9% were hypermobile (change > 30°). For all cohorts, the majority of cases (78%) deviated from the 40° inclination and 20° version target. When evaluating the proportion of cases within the Lewinnek and Callanan safe zones based on spinopelvic mobility, 19% of cases within the normal group were planned outside of both zones compared to 39% of stiff cases and 10% of hypermobile cases. CONCLUSIONS: Utilising the latest version of robotic-assisted THA software, the preoperative plan for cup position was changed in the vast majority (78%) of patients, causing substantial deviations from traditional, generic cup targets.

Knotless Tensionable Anchors: Versatility, Tips, and Tricks.

Arthroscopic surgery, including implants and advanced techniques, continues to advance in the field of orthopaedics. The evolution of suture anchors has undergone design changes, passing from first-generation metal anchors, biodegradable materials, different plastic polymers, to all-suture constructs. Knotless technology also has been found to be a more reproducible method and have comparable outcomes with those found using knotted anchors. This Technical Note describes the advantages and different ways this tensionable anchor can be used in arthroscopic procedures. This implant and its understanding will be useful in the sports medicine area by simplifying procedures and making them more reproducible. The aim of the present Technical Note is to detail the simplicity and versatility of the anchor and discuss different scenarios in which this technology can be used to address common hip pathologies.

Displaced Posterior Cruciate Avulsion Fracture Fixation With Medial Collateral Ligament and Lateral Meniscus Injury Using Combined Open and Arthroscopic Methods.

Tibial-sided posterior cruciate ligament avulsion fractures are challenging injuries that often occur concomitantly in the setting of multiligament knee and other soft-tissue injuries. There is no consensus on the optimal surgical approach or timing of treatment for these injuries. This Technical Note describes the fixation of a displaced posterior cruciate ligament avulsion fracture with concomitant grade 3 medial collateral ligament injuries and bucket-handle lateral meniscus tears using open and arthroscopic techniques. This method allows the surgeon to address multiple pathologies in a single stage, although it requires strategic planning and rehabilitation considerations.

Patellar Instability Current Concepts and Controversies.

Recurrent patellar instability can significantly impact patients' quality of life and function. A large amount of research on patellar instability has been conducted in the past two decades, and a number of traditionally held principles of treatment have been challenged. This review addresses three current concepts and controversies in the treatment of patellar instability, specifically what factors lead to an increased tibial tubercle-trochlear groove distance and how to address them, when to add a tibial tubercle osteotomy to a medial patellofemoral ligament (MPFL) reconstruction, and which medial patellar stabilizers should be reconstructed. Based on current evidence, there are a few recommendations that can be made at this time. While trochleoplasty does have concerns with regard to reproducibility and complication risk, surgeons should consider this technique especially in cases with Dejour D trochlear dysplasia given high failure rates with other techniques. When evaluating whether to concomitantly perform a tibial tubercle osteotomy (TTO) with a MPFL, a TTO does appear to improve outcomes in the presence of maltracking or a positive J sign even with a tibial tuberosity-trochlear grove distance (TT-TG) of 18 to 20 mm, whereas patients without maltracking with a TT-TG of up to 25 mm may do well with an isolated MPFL reconstruction. Lastly, while MPFL reconstruction continues to have the most robust data supporting favorable outcomes, a number of biomechanical studies and short-term clinical studies have suggested promising results with medial quadriceps tendon femoral ligament and hybrid techniques.

Editorial Commentary: Bridging Graft Techniques Improve Short-Term Outcomes for Irreparable Rotator Cuff Tear Repair.

There is a growing need for nonarthroplasty treatment options for irreparable rotator cuff tears. Options include superior capsular reconstruction (SCR), tendon transfers, subacromial balloon spacer, bridge grafting, biological tuberoplasty, and partial rotator cuff repair with or without augmentation. In our experience, repair with marginal convergence techniques is superior to SCR; if there is enough tissue, repair is the preferred strategy. In an effort to improve outcomes after repair, there has been increased interest in the use of interposition or bridging graft (BG) techniques, in which an allograft or autograft is secured on the humerus laterally and to the remnant tendon medially. Interposition or bridging grafts can be used to supplement partial repair in an effort to replace the patient's own missing tissues, and restore the biomechanical force couple of the rotator cuff and create a humeral head-depressing spacer effect in the subacromial space. These techniques show promising results compared to superior capsular reconstruction. Various graft options for BG are available, including human dermal allograft, fascia lata autograft, and tenotomized biceps autograft. Multiple animal studies have demonstrated that interposition grafts can improve the biomechanical properties of the repair construct, and histological studies in animal models have shown evidence of tissue in-growth into the BG, which could lead to increased repair strength over time. Finally, recent studies suggest that a bridging graft may improve short-term outcomes compared to partial repair alone. It remains to be seen whether this difference is clinically meaningful and durable.

No Difference in Patient-Reported Outcomes for Periacetabular Osteotomy and Hip Arthroscopy With Capsular Plication in the Setting of Borderline Hip Dysplasia: A Propensity-Matched Multicenter Study With Minimum 5-Year Follow-Up.

PURPOSE: To compare minimum 5-year patient-reported outcome measures after hip arthroscopy (HA) and periacetabular osteotomy (PAO) for borderline hip dysplasia. METHODS: Hips with a lateral center-edge angle (LCEA) between 18° and less than 25° that underwent either PAO or HA were selected from 2 institutions. The exclusion criteria were as follows: LCEA less than 18°, Tönnis osteoarthritis grade greater than 1, prior hip surgical procedures, active inflammatory disease, Workers' Compensation, and concomitant surgery. Patients underwent propensity matching based on age, sex, body mass index, and Tönnis osteoarthritis grade. Patient-reported outcome measures included the modified Harris Hip Score, as well as calculation of the minimal clinically important difference, patient acceptable symptom state, and maximum outcome improvement satisfaction threshold. Preoperative radiographic predictors included comparison of the Femoro-epiphyseal Acetabular Roof index and ligamentum teres lesions. RESULTS: A total of 28 PAO patients underwent propensity matching to 49 HA patients. The 2 groups were similar in terms of mean age, sex, preoperative body mass index, and LCEA. The PAO group had a longer mean follow-up period (95.8 months vs 81.3 months, P = .001). The mean Femoro-epiphyseal Acetabular Roof index was significantly lower preoperatively in the HA group (P < .001). The 2 groups showed similar and significant improvements in the mean modified Harris Hip Score from preoperatively to latest follow-up (P < .001). The relative risk of subsequent surgery in the PAO group was 3.49 (P = .024), mostly attributed to hardware removal (25%). The revision rate was 3.6% in the PAO group and 8.2% in the HA group (P = .65). One patient in the PAO group required revision HA for intra-articular adhesions. Three of the patients requiring revision in the HA group underwent PAO because of persistent pain, and one underwent revision HA alone. Conversion to total hip arthroplasty was required in 1 patient in the HA group and no patients in the PAO group. CONCLUSIONS: Both PAO and HA with capsular plication provide borderline hip dysplasia patients with clinically significant improvements and low revision rates at a minimum of 5 years postoperatively. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic trial.

Concomitant open distal clavicle excision is associated with greater improvement in range of motion without increased risk of acromial stress fracture after reverse total shoulder arthroplasty: a retrospective cohort study.

BACKGROUND: The purpose of this study was to evaluate the effect of concomitant open distal clavicle excision (DCE) on postoperative clinical outcomes and incidence of acromial and scapular stress fractures (ASFs) in patients with symptomatic acromioclavicular joint osteoarthritis (ACJ OA) undergoing reverse total shoulder arthroplasty (RTSA). METHODS: A single-surgeon retrospective cohort study was conducted including patients who underwent primary elective RTSA with or without DCE from 2015 to 2019 with a minimum 6-month follow-up period. Shoulder active range of motion (AROM) and visual analog scale (VAS) pain were recorded preoperatively and postoperatively. ASFs and other adverse events were identified using postoperative notes and/or radiographs. Characteristics and outcomes were compared between the RTSA and RTSA-DCE groups. RESULTS: Forty-six RTSA patients (mean age, 67.9±8.7 years; 60.9% male; mean follow-up, 24.9±16.6 months) and 70 RTSA-DCE patients (mean age, 70.2±8.9 years; 20.0% male; mean follow-up, 22.7±12.9 months) were included. There were no significant intergroup differences in rates of ASF (RTSA, 0.0% vs. RTSA-DCE, 1.4%; P=1.00), stress reactions (RTSA, 8.7% vs. RTSA-DCE, 11.4%; P=0.76), reoperation, revision, or infection (all P>0.05), or in pre-to-postoperative reduction in VAS pain (P=0.17) at latest follow-up. However, the RTSA-DCE group had greater pre-to-postoperative improvement in flexion AROM (RTSA, 43.7°±38.5° vs. RTSA-DCE, 59.5°±33.4°; P=0.03) and internal rotation (IR) AROM (P=0.02) at latest follow-up. CONCLUSIONS: Concomitant DCE in RTSA improves shoulder flexion and IR AROM, alleviates shoulder pain, and does not increase the risk of ASFs. Level of evidence: III.

Evaluation of Pre-emptive Analgesia in Total Knee Arthroplasty During Early Post-operative Periods.

INTRODUCTION: Pre-emptive analgesia is expected to decrease post-operative pain. The degree of soft tissue release is directly related to preoperative deformity; we presume the severity of pain has a similar correlation in patients undergoing total knee arthroplasty (TKA). The main purpose of this research was to evaluate the effects of pre-emptive analgesia of different drugs in TKA with different degrees of preoperative genu varus. METHODS: In this prospective observational study, 67 patients were enrolled with different degrees of genu varus deformity. They were subdivided into two groups: those with ≥15° and those with <15° varus deformities of the knee. Etoricoxib 60 mg and pregabalin 75 mg were administered orally in all the patients as pre-emptive analgesia two hours before surgery. Parameters such as the amount of soft tissue release, visual analog score (VAS), knee range of motion, complications, etc. were documented from the pre-operative period to 72 hours post-TKA. RESULTS: With pre-emptive analgesia in post-TKA patients, the VAS score demonstrated a statistically significant difference at 24, 48, and 72 hours. The comparison of intraoperative flexion between <15° and ≥15° showed a statistically significant difference with pre-emptive analgesia in post-TKA patients. CONCLUSION: The use of etoricoxib 60 mg and pregabalin 75 mg, two hours before surgery reduced the pain scores in patients undergoing TKA with different degrees of genu varus and correlated with intraoperative parameters associated with soft medial tissue release for genu varus.

Hip morphology on initial ultrasound predicts hip morphology at one year in developmental dysplasia of the hip.

Purpose: This study aimed to determine whether point-of-care ultrasound performed during the Pavlik method treatment of developmental dysplasia of the hip predicts acetabular morphology at 12 months of age. Methods: We reviewed the medical records, ultrasounds, and radiographs of patients treated successfully with the Pavlik method between 2017 and 2019. We performed sonographic measurements on point-of-care ultrasound at the initial presentation, the Pavlik discontinuation, and an additional sonographic follow-up. We measured the acetabular index on a plain anteroposterior radiograph of the pelvis obtained at a minimum of 12 months of age. Spearman's rank correlation coefficient was used to analyze for correlation between sonographic measurements and the acetabular index. Results: A total of 72 patients were included in the final analysis. There were no residual or late dysplasia cases at the last radiographic follow-up (mean age = 14.8 ± 2.7 months). Sonographic parameters at the initial presentation significantly correlated with the acetabular index at the final radiographic follow-up (p < 0.001). Patients with worsening degrees of developmental dysplasia of the hip based on stability on sonographic testing (stable, unstable, or dislocated) had higher acetabular indices at the final radiographic follow-up (p < 0.05). Conclusion: Point-of-care ultrasound at initial presentation and the Pavlik discontinuation significantly correlate with acetabular morphology at 1-1.5 years of age. At initial presentation, hips that were unstable or dislocated on point-of-care ultrasound had significantly greater acetabular indices than stable hips at the final follow-up. Level of evidence: level IV case series.

Editorial Commentary: Outcome After Ipsilateral Hip Arthroscopy Predicts Outcomes on the Contralateral Side, Regardless of Time Between Surgeries.

Surgical predictability is a multifactorial methodology of coordinated actions backed by clinical expertise and historical tracking. Recent research shows outcome after ipsilateral hip arthroscopy predicts outcomes on the contralateral side, regardless of time between surgeries. This is based on research by experienced surgeons who have achieved reproducibility, predictability, and consistency of their outcomes. To patients at time of scheduling, this translates to, "Trust us, we know what we're doing." This research may not be generalizable to low volume or inexperienced hip arthroscopists.

No difference in clinical outcomes between operative and nonoperative management of minimally retracted proximal hamstring ruptures.

PURPOSE: The indications for surgical treatment of proximal hamstring ruptures are continuing to be refined. The purpose of this study was to compare patient-reported outcomes (PROs) between patients who underwent operative or nonoperative management of proximal hamstring ruptures. METHODS: A retrospective review of the electronic medical record identified all patients who were treated for a proximal hamstring rupture at our institution from 2013 to 2020. Patients were stratified into two groups, nonoperative or operative management, which were matched in a 2:1 ratio based on demographics (age, gender, and body mass index), chronicity of the injury, tendon retraction, and number of tendons torn. All patients completed a series of PROs including the Perth Hamstring Assessment Tool (PHAT), Visual Analogue Scale for pain (VAS), and the Tegner Activity Scale. Statistical analysis was performed using multi-variable linear regression and Mann-Whitney testing to compare nonparametric groups. RESULTS: Fifty-four patients (mean age = 49.6 ± 12.9 years; median: 49.1; range: 19-73) with proximal hamstring ruptures treated nonoperatively were successfully matched 2:1 to 27 patients who had underwent primary surgical repair. There were no differences in PROs between the nonoperative and operative cohorts (n.s.). Chronicity of the injury and older age correlated with significantly worse PROs across the entire cohort (p < 0.05). CONCLUSIONS: In this cohort of primarily middle-aged patients with proximal hamstring ruptures with less than three centimeters of tendon retraction, there was no difference in patient-reported outcome scores between matched cohorts of operatively and nonoperatively managed injuries. LEVEL OF EVIDENCE: Level III.

Multiple Sleep Latency Test/Maintenance of Wakefulness Test and Central Hypersomnias: Evolving Diagnostic and Therapeutic Approaches.

SUMMARY: Central disorders of hypersomnolence include a spectrum of conditions, such as narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome, in which excessive daytime sleepiness is the primary feature. Subjective testing with tools, such as sleep logs and sleepiness scales, are often helpful in the evaluation of these disorders but do not necessarily correlate well with objective testing, such as polysomnography and multiple sleep latency test and maintenance of wakefulness test. The most recent International Classification of Sleep Disorders-Third Edition has incorporated biomarkers, such as cerebrospinal fluid hypocretin level, into the diagnostic criteria and have restructured the classification of conditions based on our evolved understanding of their underlying pathophysiologic mechanisms. Therapeutic approaches largely consist of behavioral therapy, with a focus on optimizing sleep hygiene, optimizing opportunity for sleep, and strategic napping, along with judicious use of analeptic and anticataleptic agents when necessary. Emerging therapy has revolved around hypocretin-replacement therapy, immunotherapy, and nonhypocretin agents, with the goal of better targeting the underlying pathophysiology of these disorders rather than addressing symptoms. The most novel treatments have targeted the histaminergic system (pitolisant), dopamine reuptake transmission (solriamfetol), and gamma-aminobutyric acid modulation (flumazenil and clarithromycin) to promote wakefulness. Continued research is required for a more solid understanding of the biology of these conditions to develop a more robust armamentarium of therapeutic options.

Arthroscopic Peripheral Compartment Iliopsoas Release for Iliopsoas Impingement After Primary Total Hip Arthroplasty.

Anterior iliopsoas (IP) impingement after total hip arthroplasty is an underrecognized and continued cause for postoperative pain. There are multiple etiologies for this impingement from cup positioning and sizing to changes in the leg length, and offset must be evaluated to confirm no need for implant revision. Additionally, tension of the IP tendon can be increased in patients with diminished spinal mobility, either from prior fusion or with increasing age. Managing this surgically after failing conservative treatment options is best done arthroscopically to prevent additional large, open procedures that place the arthroplasty at unnecessary risk of infection and potential instability. In this article, we describe an arthroscopic technique using fluoroscopy to guide the release of the iliopsoas tendon from the peripheral compartment.

Telemedicine: An Effective Tool for Patient-Physician Communication.

The purpose of this study was to evaluate the effectiveness of telemedicine appointments in a tertiary orthopedic hip clinic during the COVID-19 pandemic, as a substitute for traditional in-person visits. One hundred sixty-three patients had a telemedicine visit from March to September 2020. Patients were divided into two cohorts. The presurgical group included all patients who had not undergone any prior surgical hip procedures. The pre-surgical group was further subdivided into two groups based on the purpose of the visit: conservative treatment and imaging review. Patients who were indicated for surgical treatment from these two groups were identified to assess their compliance with the surgical indication. The effectiveness was measured by assessing whether patients required an in-person visit before the scheduled follow-up after the telemedicine visit for further medical assessment. Fifty (30.7%) men and 113 (69.3%) women had a telemedicine visit during the 6-month period. The mean age was 43.68 (±16.95) years. There were 92 (56.4%) patients in the presurgical group, of whom 41% followed up after indication for conservative treatment and 59% visited to review imaging. From these groups, 27% were indicated for surgical treatment. The postsurgical group contained 71 (43.6%) patients, divided into three groups based on their surgery date: 0 to 3 months (27%), 4 to 12 months (59%), and more than 12 months (14%). All patients were compliant with the scheduled follow-up after their telemedicine visit. This study showed that telemedicine can be an effective tool for patient-physician communication, obviating the need for subsequent follow-up beyond regularly scheduled visits. [Orthopedics. 2023;46(3):e173-e178.].

Simplified biplanar classification for heterotopic ossification is more predictive of patient-reported outcomes than the Brooker classification after anterior total hip arthroplasty.

BACKGROUND: Heterotopic ossification (HO) commonly occurs after total hip arthroplasty (THA) and can adversely impact clinical outcomes. The purpose of this study is to propose a more reliable HO grading method that is better predictive of patient-reported outcomes (PROs) after THA than the Brooker classification. METHODS: 513 THAs (62 ± 10 years old) were reviewed. The incidence and grade of HO was evaluated using the Brooker grading system and a simplified biplanar classification system (grade 1: ⩾1 cm between bone on both anteroposterior and lateral views, grade 2: <1 cm between bone on either view). The modified Harris Hip Score (mHHS), Forgotten Joint Score (FJS), and visual analogue scale (VAS) for pain were collected at minimum of 2 years after surgery and were compared between HO grades using multiple regression models. RESULTS: The incidence of HO varied by Brooker grade (grade 1, 23.4%; grade 2, 22.4%; grade 3, 7.2%; grade 4, 0%) and biplanar grade (grade 1: 45.6%; grade 2: 7.4%). The biplanar classification demonstrated higher interobserver reliability than the Brooker classification (κ = 0.95 and 0.91, respectively). Brooker grade 3 HO decreased the mHHS by 6.5 (standard error: 2.7) but did not have a significant effect on FJS or VAS. Biplanar grade 2 HO decreased the mHHS by 9.9 (standard error: 2.7), the FJS by 12.9 (standard error: 4.51) and increased the VAS pain score by 0.81 (standard error: 0.35). The Cox test was used to compare the fit of regression models and determined the biplanar classification was a significantly better predictor than the Brooker classification (p < 0.001). CONCLUSIONS: Biplanar grade 2 HO had a significant negative influence on PROs. Contrary to previous literature, these results show clinical significance of non-bridging HO. Compared with the Brooker classification, the biplanar classification has greater interobserver reliability and is more predictive of outcomes after THA.

Increased time from injury to surgical repair in patients with proximal hamstring ruptures is associated with worse clinical outcomes at mid-term follow-up.

INTRODUCTION: Prior studies of hamstring tendon tears have reported varied findings on whether increased delay from injury to surgery is associated with worse outcomes. The purpose of this study was to determine whether increased time from injury to surgical repair is associated with worse clinical outcomes in patients with proximal hamstring ruptures. MATERIALS AND METHODS: Patients who underwent surgical repair of a proximal hamstring rupture from 2010 to 2019 were followed for a minimum of 24 months from surgery. A cutoff of 6 weeks from injury to the time of surgery was used to distinguish between acute and chronic ruptures. All patients completed patient-reported outcome measures (PROs) at the final follow-up. Multiple factors were analyzed for their effects on PROs including time to surgery, amount of tendon retraction, and demographics such as sex and age. RESULTS: Complete data sets were obtained for 38 patients at a mean follow-up of 4.9 years. All data is reported as a mean ± standard deviation. Patients who underwent acute repair of proximal hamstring ruptures had significantly greater Perth Hamstring Assessment Tool (PHAT) scores than those who underwent chronic repair (76.9 ± 18.8 vs 60.6 ± 18.2, p = 0.01). Increased time to surgery was significantly correlated with worse PHAT scores (ρ = - 0.47, p = 0.003). There was no difference in PROs based on the amount of tendon retraction, number of tendons torn, sex, smoking status, or BMI. CONCLUSIONS: This study found that acute repair performed within 6 weeks of injury appears to yield improved PROs compared to chronic repair. These data highlight the importance of timely and accurate diagnosis of proximal hamstring ruptures and early operative intervention for surgical candidates.

CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase.

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications.

Crosslinker structure modulates bulk mechanical properties and dictates hMSC behavior on hyaluronic acid hydrogels.

Synthetic hydrogels are attractive platforms due in part to their highly tunable mechanics, which impact cell behavior and secretory profile. These mechanics are often controlled by altering the number of crosslinks or the total polymer concentration in the gel, leading to structure-property relationships that inherently couple network connectivity to the overall modulus. In contrast, the native extracellular matrix (ECM) contains structured biopolymers that enable stiff gels even at low polymer content, facilitating 3D cell culture and permeability of soluble factors. To mimic the hierarchical order of natural ECM, this work describes a synthetic hydrogel system in which mechanics are tuned using the structure of sequence-defined peptoid crosslinkers, while fixing network connectivity. Peptoid crosslinkers with different secondary structures are investigated: 1) a helical, molecularly stiff peptoid, 2) a non-helical, less stiff peptoid, and 3) an unstructured, relatively flexible peptoid. Bulk hydrogel storage modulus increases when crosslinkers of higher chain stiffness are used. In-vitro studies assess the viability, proliferation, cell morphology, and immunomodulatory activity of human mesenchymal stem cells (hMSCs) on each hydrogel substrate. Matrix mechanics regulate the morphology of hMSCs on the developed substrates, and all of the hydrogels studied upregulate IDO production over culture on TCP. Softer substrates further this upregulation to a plateau. Overall, this system offers a biomimetic strategy for decoupling hydrogel storage modulus from network connectivity, enabling systematic study of biomaterial properties on hMSC behavior and enhancement of cellular functionality for therapeutic applications. STATEMENT OF SIGNIFICANCE: Various strategies to tune hydrogel mechanics have been developed to control human mesenchymal stem cell (hMSC) behavior and regulate their immunomodulatory potential. However, these strategies typically couple mechanics to network connectivity, which in turn changes other hydrogel properties such as permeability that may have unintended effects on hMSC behavior. This work presents a strategy to tune hydrogel mechanics using crosslinkers with different secondary structure and molecular rigidity. This strategy successfully decouples hydrogel moduli from crosslinker stoichiometry and mimics the hierarchical nature of the native extracellular matrix. The moduli of the developed hydrogels led to significant impacts on hMSC morphology and proliferation, and increased immunomodulatory potential, indicating that molecular rigidity is a promising avenue to control engineered ECM mechanics for therapeutic applications.