Recognition of the antigen-presenting molecule MR1 by a Vδ3+ γδ T cell receptor.

Unlike conventional αß T cells, γδ T cells typically recognize nonpeptide ligands independently of major histocompatibility complex (MHC) restriction. Accordingly, the γδ T cell receptor (TCR) can potentially recognize a wide array of ligands; however, few ligands have been described to date. While there is a growing appreciation of the molecular bases underpinning variable (V)δ1+ and Vδ2+ γδ TCR-mediated ligand recognition, the mode of Vδ3+ TCR ligand engagement is unknown. MHC class I-related protein, MR1, presents vitamin B metabolites to αß T cells known as mucosal-associated invariant T cells, diverse MR1-restricted T cells, and a subset of human γδ T cells. Here, we identify Vδ1/2- γδ T cells in the blood and duodenal biopsy specimens of children that showed metabolite-independent binding of MR1 tetramers. Characterization of one Vδ3Vγ8 TCR clone showed MR1 reactivity was independent of the presented antigen. Determination of two Vδ3Vγ8 TCR-MR1-antigen complex structures revealed a recognition mechanism by the Vδ3 TCR chain that mediated specific contacts to the side of the MR1 antigen-binding groove, representing a previously uncharacterized MR1 docking topology. The binding of the Vδ3+ TCR to MR1 did not involve contacts with the presented antigen, providing a basis for understanding its inherent MR1 autoreactivity. We provide molecular insight into antigen-independent recognition of MR1 by a Vδ3+ γδ TCR that strengthens an emerging paradigm of antibody-like ligand engagement by γδ TCRs.

Glenohumeral morphological predictors of recurrent shoulder instability following arthroscopic Bankart repair.

PURPOSE: The purpose of this study was to evaluate glenohumeral morphological features on a magnetic resonance arthrogram (MRA) to determine risk factors for recurrence of anterior shoulder instability following arthroscopic Bankart repair (ABR). METHODS: A retrospective review of patients who underwent ABR between 2012 and 2017 was performed to identify patients who had recurrence of instability following stabilisation (Group 1). These were pair-matched in a 2:1 ratio for age, gender and sport with a control (Group 2) who underwent ABR without recurrence. Preoperative MRAs were evaluated for risk factors for recurrence, with glenoid bone loss and Hill-Sachs lesions also measured. Multilinear and multilogistic regression models were used to evaluate factors affecting recurrence. RESULTS: Overall, 72 patients were included in this study, including 48 patients without recurrence and 24 patients with recurrent instability. There was a significant difference between the two groups in mean glenoid bone loss (Group 1: 7.3% vs. Group 2: 5.7%, p < 0.0001) and the rate of off-track Hill-Sachs lesions (Group 1: 20.8% vs. Group 2: 0%, p = 0.0003). Of the variables analysed in logistic regression, increased glenoid anteversion (p = 0.02), acromioclavicular (AC) degeneration (p = 0.03) and increased Hill-Sachs width were associated with increased risk of failure. Increased chondral version (p = 0.01) and humeral head diameter in the anteriorposterior view were found to be protective and associated with a greater likelihood of success. CONCLUSION: Glenoid anteversion was a risk factor for recurrent instability, whereas increased chondral version and humeral head diameter were associated with higher rates of success following ABR. Glenoid bone loss, presence of an off-track Hill-Sachs lesion, increased Hill-Sachs width and AC degeneration were also associated with failure. These findings should be used by surgeons to stratify risk for recurrence following ABR. LEVEL OF EVIDENCE: Level III.

Stable Clinical and Radiological Outcomes at Medium and over 5 Year Follow Up of Calcaneus Fracture Open Reduction Internal Fixation Using a Sinus Tarsi Approach.

The sinus tarsi approach is increasingly growing in popularity for open reduction internal fixation of calcaneus fractures. Multiple studies have demonstrated favorable short-term results compared to the traditional extensile L incision, however long-term data over 5 years is currently limited to a single retrospective case series. Following local ethical approval, all patients who had completed a minimum 5 years from time of operation were contacted with a Standardized Telephone Questionnaire completed. This followed a previous retrospective chart review, with follow up telephone or clinic consultation performed by Davey et al. of this cohort at mean 35 months. Thirty-four fractures (31 patients) completed minimum 5 year follow up from the eligible group of 54 fractures (49 patients). Regarding functional outcomes, a significant improvement in mean Maryland Foot Score was observed between short- (mean 35.8 months) and medium-term (mean 81.9 months) of 77.6 (SD 15.0) to 86 (SD 7.9) (p = .0082). There was no significant difference in postoperative and long term radiographic Bohler's angle (p = .9683). Eleven feet (32%) proceeded to require reoperation, with removal of metal performed in 10 (29%), fusion in 2 (6%), and skin grafting following wound breakdown for 1 (3%). Four feet (12.9%) experienced post operative wound complications, including 3 (9.68%) cases of infection and 2 (6.45%) of delayed wound healing. This study demonstrated stable clinical and radiographic outcomes over 5 years following Calcaneus Fracture Open Reduction Internal Fixation using a sinus tarsi approach, supporting its continued usage when treating intraarticular calcaneus fractures for which operative intervention is indicated.

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe coronavirus disease 2019 (COVID-19) in a small proportion of infected individuals. The immune system plays an important role in the defense against SARS-CoV-2, but our understanding of the cellular immune parameters that contribute to severe COVID-19 disease is incomplete. Here, we show that populations of effector γδ T cells are associated with COVID-19 in unvaccinated patients with acute disease. We found that circulating CD27neg CD45RA+ CX3CR1+ Vδ1effector cells expressing Granzymes (Gzms) were enriched in COVID-19 patients with acute disease. Moreover, higher frequencies of GzmB+ Vδ2+ T cells were observed in acute COVID-19 patients. SARS-CoV-2 infection did not alter the γδ T cell receptor repertoire of either Vδ1+ or Vδ2+ subsets. Our work demonstrates an association between effector populations of γδ T cells and acute COVID-19 in unvaccinated individuals.

Mucosal-Associated Invariant T Cell Effector Function Is an Intrinsic Cell Property That Can Be Augmented by the Metabolic Cofactor α-Ketoglutarate.

Mucosal-associated invariant T (MAIT) cells are an innate-like population of unconventional T cells that respond rapidly to microbial metabolite Ags or cytokine stimulation. Because of this reactivity and surface expression of CD45RO+, CD45RA-, and CD127+, they are described as effector memory cells. Yet, there is heterogeneity in MAIT cell effector response. It is unclear what factors control MAIT cell effector capacity, whether it is fixed or can be modified and if this differs based on whether activation is TCR dependent or independent. To address this, we have taken a systematic approach to examine human MAIT cell effector capacity across healthy individuals in response to ligand and cytokine stimulation. We demonstrate the heterogenous nature of MAIT cell effector capacity and that the ability to produce an effector response is not directly attributable to TCR clonotype or coreceptor expression. Global gene transcription analysis revealed that the MAIT cell effector capacity produced in response to TCR stimulation is associated with increased expression of the epigenetic regulator lysine demethylase 6B (KDM6B). Addition of a KDM6B inhibitor did not alter MAIT cell effector function to Ag or cytokine stimulation. However, addition of the KDM6B cofactor α-ketoglutarate greatly enhanced MAIT cell effector capacity to TCR-dependent stimulation in a partially KDM6B-dependent manner. These results demonstrate that the TCR-dependent effector response of MAIT cells is epigenetically regulated and dependent on the availability of metabolic cofactors.

Arthroscopic Rotator Cuff Repair Results in Improved Clinical Outcomes and Low Revision Rates at 10-Year Follow-Up: A Systematic Review.

PURPOSE: To study the literature to evaluate the functional outcomes, radiologic outcomes, and revision rates following arthroscopic rotator cuff repair (ARCR) at a minimum of 10-years follow-up. METHODS: Two independent reviewers performed a literature search of PubMed, Embase, and Scopus using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Only studies reporting on outcomes of ARCR with a minimum 10-year follow-up were considered for inclusion. Patient demographics, satisfaction, and clinical, radiologic, and surgical outcomes were evaluated. RESULTS: Our search found 9 studies including 455 shoulders in 448 patients (51.6% male patients), with age at time of surgery ranging from 45 to 90 years met our inclusion criteria. Overall follow-up ranged from 10 to 18 years. At final follow-up, the ranges of American Shoulder & Elbow Surgeons, age- and sex-adjusted Constant-Morley, and University of California Los Angeles scores were reported in 5, 6, and 3 studies, respectively, as 79.4 to 93.2, 73.2 to 94, and 26.5 to 33, respectively. Of the included studies, satisfaction rates varied in 6 studies from 85.7% to 100% in the long-term. Additionally, the overall radiologic retear rate ranged from 9.5% to 63.2%. The overall surgical revision rates ranged in 6 studies from 3.8% to 15.4%, with from 0% to 6.7% requiring revision ARCR and from 1.0% to 3.6% requiring revision subacromial decompression in 6 and 2 studies, respectively, at minimum 10-years' follow-up. CONCLUSIONS: In this study, we found that ARCR results in high rates of patient satisfaction, satisfactory clinical outcomes with respect to patient-reported functional outcomes and range of motion, and low revision rates at minimum 10-years' follow-up. However, an overall 30% retear rate was observed in asymptomatic patients. LEVEL OF EVIDENCE: Level IV, systematic review of Level II-IV studies.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition).

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.

Evaluation of factors associated with successful 5-year outcomes following arthroscopic Bankart repair in athletes.

PURPOSE: The purpose of this study was to evaluate the outcomes of athletes 5-years post-operatively following arthroscopic Bankart repair, and to evaluate factors associated with satisfaction and shoulder function, as defined by subjective shoulder value. METHODS: A retrospective review of athletes who underwent arthroscopic Bankart repair, with a minimum of 5-year follow-up was performed. Recurrence, Visual Analogue Scale (VAS) score, Subjective Shoulder Value (SSV), satisfaction, and whether they would undergo the same surgery again, and rate, level and timing of return to play, and Shoulder Instability-Return to Sport after Injury (SIRSI) score were evaluated. Multi-linear regression models were used to evaluate factors affecting postoperative Satisfaction, and SSV level. RESULTS: Overall, 144 athletes who underwent arthroscopic Bankart repair were included, with a mean age of 26.9 years (SD: 8.1), 132 (91.7%) were males, and mean follow-up of 75.7 months. At final follow up, 82.6% were satisfied/very satisfied, and the mean SSV was 85.8 (SD: 14.4). Overall, the rate of return to play was 80.5%, with 63.9% returning at the same level at a mean of 6.2 months (SD: 2.7). Overall, there was 18 (12.5%) had recurrent instability, and a further procedure was performed in 15 (10.4%) patients. Linear regression revealed that the SIRSI score (p < 0.0001), SSV (p < 0.0001), VAS (p < 0.0031), no sleep trouble (p = 0.0129) was associated with satisfaction. Logistic regression revealed whether a patient required revision surgery (p = 0.0029), or had re-dislocation (p = 0.0031) was also associated with satisfaction. Linear regression revealed that the SIRSI score (p < 0.0001), VAS score (p < 0.0001), and no sleep trouble (p < 0.0001), were associated with SSV score. CONCLUSION: There was a high rate of satisfaction at 5-year follow-up, with excellent patient-reported outcomes and a high rate of return to play among athletes. However, there was a moderate rate of recurrent instability and further revision surgery. This study identified that the SIRSI score, VAS score, no sleep trouble and ability to return to play at the same level were associated with both satisfaction and SSV score. LEVEL OF EVIDENCE: III.

Analysis of patients unable to return to play following arthroscopic Bankart repair.

PURPOSE: The purpose of this study was to analyze patients that did not return to play (RTP) following arthroscopic Bankart repair (ABR) compared to those who did RTP, and analyze factors associated with not returning to play. METHODS: A retrospective review of patients who underwent ABR, and subsequently did not RTP after a minimum of 24-month follow-up was performed. Additionally, these were pair matched in a 3:1 ratio for age, gender, sport and level of pre-operative play with a control group who RTP. Patients were evaluated for their psychological readiness to return to sport using the SIRSI score. Multivariate regression models were used to evaluate factors affecting RTP. RESULTS: The study included a total of 52 patients who were unable to RTP and 156 who returned to play. Ten patients (19.2 %) who did not RTP passed the SIRSI benchmark of 56 with a mean overall score of 39.8 ± 24.6, in those who returned 73.0 % passed the SIRSI benchmark of 56 with a mean overall score of 68.9 ± 22.0 (p < 0.0001 for both). The most common primary reasons for not returning were 27 felt physically unable to return, whilst 21 felt it was a natural end to their career or their lifestyle had changed. Multi-logistic regression revealed that 4 of the 12 components of the SIRSI score (p < 0.05 for all) and SSV (p = 0.0049), were the factors that were associated with RTP. CONCLUSION: Following ABR, those that do not return to play exhibit poor psychological readiness to return to play, with multi-linear regression revealing the SIRSI questions associated with fear of re-injury were associated with a lower rate of RTP. Additionally, functional limitations were found to be associated with a lower rate of RTP. LEVEL OF EVIDENCE: Level III; Retrospective Comparative Cohort Study.

Subscapularis management during open Latarjet procedure: does subscapularis split versus tenotomy matter? A systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to systematically review the literature to ascertain the clinical outcomes of the open Latarjet (OL) procedure using either a subscapularis-split (SS) or subscapularis tenotomy (ST) via a deltopectoral (DP) approach. METHODS: Two independent reviewers performed a literature search using the PubMed, Embase, and Scopus databases according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Only studies reporting on outcomes of the OL procedure via a DP approach comparing both SS and ST were considered for inclusion. Meta-analysis to compare clinical outcomes was performed using RevMan software. RESULTS: Our search found 5 studies that met our inclusion criteria, including 615 shoulders (80.8% male patients), with an average age of 27.8 ± 12.6 years (range, 15-79 years) and mean follow-up period of 50.1 ± 29.4 months (range, 12-180 months). A total of 410 shoulders and 205 shoulders underwent the OL procedure via a DP approach using the ST technique and the SS technique, respectively, with both techniques resulting in significant increases in the Rowe score postoperatively (P < .0001 for both). Additionally, significantly higher postoperative Constant scores were observed in patients who underwent the OL procedure via an SS technique vs. those in the ST group (91.8 ± 7.2 vs. 79.6 ± 16.1, P < .0001). However, meta-analysis showed nonsignificantly higher postoperative Rowe and American Shoulder and Elbow Surgeons scores in patients who underwent the OL procedure via an SS technique vs. those in the ST group (96.1 ± 2.6 vs. 86.4 ± 7.6 [P = .57] and 91.6 ± 1.3 vs. 80.6 ± 25.5 [P = .47], respectively). Furthermore, meta-analysis showed that significantly more patients in the ST group had positive lift-off test results (10.0%) when compared with the SS group at final follow-up (2.7%, P = .01). However, meta-analysis indicated that the rate of recurrent instability was trending toward significance in favor of the SS group (0% vs. 11.7%, P = .07). CONCLUSION: Our systematic review established that in cases of OL procedures being carried out via a DP approach, the SS technique results in significantly better functional outcome measures and significantly lower rates of subscapularis insufficiency when compared with an L-shaped ST technique at medium-term follow-up. Furthermore, there were lower rates of recurrent instability that were trending toward significance in favor of the SS technique.

Athletes with primary glenohumeral instability demonstrate lower rates of bone loss than those with recurrent instability and failed prior stabilization.

BACKGROUND: The purpose of this study was to compare the preoperative magnetic resonance arthrography findings in patients who underwent glenohumeral stabilization with a history of primary instability, recurrent instability, or failed stabilization. METHODS: All patients who presented with glenohumeral instability and underwent stabilization performed by a single surgeon in our institution between 2008 and 2020 were considered for inclusion in this study. The magnetic resonance arthrography findings of all patients were recorded. Imaging findings were compared between patients with primary instability, those with recurrent instability, and those with failed prior stabilization. P < .05 was considered statistically significant. RESULTS: Overall, 871 patients were included, of whom 814 (93.5%) were male patients; the mean age was 23.1 years (range, 13-57 years). There were 200 patients with primary instability, 571 with recurrent instability, and 100 who required revision stabilization surgery, with no significant differences in demographic characteristics between the groups. A significantly higher amount of glenoid bone loss was noted in patients with recurrent instability (43.4%) and failed prior stabilization (56%) than in those with primary instability (26.5%) (P < .0001). Additionally, a significantly higher number of Hill-Sachs lesions were observed in patients with recurrent instability (70.1%) and failed prior stabilization (89%) than in those with primary instability (67.5%) (P < .0001). We found no significant differences between the groups regarding articular cartilage damage, glenolabral articular disruption, anterior labral periosteal sleeve avulsion, humeral avulsion of the glenohumeral ligaments, or superior labral anterior-posterior tears (P > .05). CONCLUSION: Patients presenting for stabilization with recurrent instability or following a failed stabilization procedure have higher rates of glenohumeral bone loss than those with primary instability. Therefore, stabilization of primary instability, particularly in high-functioning athletes with a view to preventing recurrence, may reduce the overall progression of glenohumeral bone loss and potential subsequent inferior clinical outcomes.

Return to play following open Bankart repair in collision athletes aged 18 years or less.

HYPOTHESIS: The purpose of this study was to evaluate clinical outcomes, return to play (RTP), and recurrence rates in patients aged 18 years or less who underwent open Bankart repair (OBR) for anterior shoulder instability. METHODS: A retrospective review of collision athletes under 18 years old who underwent OBR by 2 surgeons between the years 2010 and 2019 was carried out. An OBR using a subscapularis split was performed in all patients. Recurrent instability, rate of RTP, and time to RTP were recorded. The Shoulder Instability Return to Sport after Injury score, Subjective Shoulder Value score, and visual analog scale scores were also evaluated. RESULTS: The study included 34 male collision athletes with a mean age of 16.5 ± 1.3 years (range, 15-18 years). The mean follow-up for patients was 49.5 ± 30.7 months. A total of 30 patients (88.2%) returned to full sport at a mean time of 5.8 ± 2.2 months, with 27 (90%) managing to return at their preinjury level of participation. The mean Subjective Shoulder Value score for patients at the final follow-up was 86.8 ± 17.5, the mean Shoulder Instability Return to Sport after Injury score was 86.3 ± 22.6, and the mean visual analog scale score was 1.6 ± 1.8. Eight patients (23.5%) re-dislocated their shoulder, with 4 of them requiring a further surgery. Two patients (5.8%) reported having incidents of subluxation that did not require reduction. CONCLUSION: This study found high rates of patient-reported satisfaction, excellent functional outcomes, and high rates of RTP in the medium term among young collision athletes aged 18 years or less who underwent OBR for anterior shoulder instability. However, there were high rates of recurrence with moderate rates of revision surgical stabilization in the medium term.

Telemedicine in Orthopedic Surgery: A Systematic Review of Current Evidence.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has triggered transformative changes in how clinicians interact with patients. There has been a shift toward virtual consultations. The evidence to support this change in practice is unclear. The aim of this study was to systematically review the evidence base for virtual consultations for orthopedics. Materials and Methods: Two independent reviewers performed a literature search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing the MEDLINE, EMBASE, and Scopus databases. Only studies reporting outcomes following the use of telemedicine for diagnosis, consultation, rehabilitation, and follow-up were included. Outcomes analyzed were: (1) patient and clinician satisfaction, (2) clinical outcome measures, and (3) cost analysis of traditional versus teleconsultation. Results: A total of 41 studies were included. Fifteen studies compared clinical outcomes of telemedicine against a matched traditional cohort. Of these 15 studies, 2 demonstrated noninferiority, 9 showed no statistically significant difference, and 4 found telemedicine to be superior. Eleven studies recorded patient reported outcomes, which demonstrated high patient satisfaction. Nine studies reported decreased costs when telemedicine was compared to traditional care. The remaining six studies had varied aims and methodologies that didn't fit well with any of these subheadings. Discussion: While the available evidence is limited, the studies assessed here show that telemedicine can deliver high quality health care with good clinical outcomes and high patient satisfaction in a cost-effective manner. Our team thinks what this has highlighted is that communication technology is advancing rapidly and that we as a community of surgeons need to be able to adapt rapidly and adopt innovative technology to continue to improve patient experience and outcomes.

Tourniquet Use During Open Reduction and Internal Fixation of Ankle Fractures - A Systematic Review and Meta-Analysis.

The intra-operative use of tourniquet in open reduction and internal fixation (ORIF) of ankle fractures remains a topic of debate. The purpose of this study was to perform a systematic review and meta-analysis of randomized control trials (RCTs) comparing clinical outcomes of patients undergoing ankle ORIF with tourniquet use versus a control group where no tourniquet was used. A systematic review was performed with reference to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines of the Pubmed, Scopus, Embase, and Cochrane Library databases. Studies were included if they were an RCT comparing tourniquet and no-tourniquet in ankle ORIF. Meta-analysis was performed using RevMan, and p-value <.05 was considered to be statistically significant. On completion of the literature search, a total of 4 RCTs including 350 ankles (52.6% males), with a mean age of 47.1 ± 5.7 years were included. There were 173 patients in the tourniquet group (T), versus 177 patients in the no tourniquet control group (NT), with nonsignificant differences between the groups for age, gender and body mass index demographics (all p > .05). There were significantly shorter duration of surgery, with significantly higher patient-reported rates of pain levels at day 2 postoperatively (both p < .001) in the T group. Additionally, there were significantly greater ranges of ankle motion at 6 weeks postoperatively (p = .03), with nonsignificant differences reported incidence of wound infections and deep vein thrombosis (p = .056 and p = .130 respectively) between the groups. In conclusion, current evidence suggests that although intraoperative tourniquet usage in cases of ankle ORIF results in significant reductions in duration of surgery, this may be at the expense of higher patient-reported pain scores and reduced range of motion postoperatively.

Return to Play Following COVID-19 Infection-A Systematic Review of Current Evidence.

CONTEXT: The COVID-19 pandemic has had catastrophic impact on a global scale, affecting people from all walks of life including elite athletes. OBJECTIVES: The purpose of this study was to evaluate the reported rates of return to play (RTP) in conjunction with the expert-derived guidelines previously recommended to enable safe RTP post COVID-19 infection. EVIDENCE ACQUISITION: Two independent reviewers searched the literature based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, utilizing the MEDLINE, Embase, and Scopus databases. Only studies that reported rates of RTP and/or recommended guidelines for safe RTP were included. EVIDENCE SYNTHESIS: Overall, 17 studies (3 level III and 14 level V) were included. A total of 3 studies reported rates of RTP in a total of 1255 athletes and 623 officials; 72 (30 symptomatic) were infected with COVID-19, 100% of whom were able to RTP post COVID-19 infection. Of the 14 studies recommending guidelines for safe RTP, 3 and 9 studies recommended 7 and 14 days of rest in isolation respectively for asymptomatic patients with COVID-19 infection, prior to safe RTP. In contrast, 7 studies recommended 3 to 6 months of rest (following 14 d isolation) in cases of COVID-19-induced myocarditis as a safe timeframe for safe RTP. Of the 11 studies reporting on whether blanket testing prior to RTP was recommended, only 7 studies recommended a negative test result as mandatory prior to RTP for athletes previously infected with COVID-19. CONCLUSIONS: Although excellent rates of RTP have been reported for elite athletes post COVID-19 infection, discrepancies in recommended rest periods, requirement for mandatory negative test results, and the magnitude of screening investigations required continue to exist in the literature, with a need for further standardized international guidelines required in future. LEVEL OF EVIDENCE: Level V; systematic review of all forms of evidence.

Our evolving understanding of the role of the γδ T cell receptor in γδ T cell mediated immunity.

The γδ T cell immune cell lineage has remained relatively enigmatic and under-characterised since their identification. Conversely, the insights we have, highlight their central importance in diverse immunological roles and homeostasis. Thus, γδ T cells are considered as potentially a new translational tool in the design of new therapeutics for cancer and infectious disease. Here we review our current understanding of γδ T cell biology viewed through a structural lens centred on the how the γδ T cell receptor mediates ligand recognition. We discuss the limited knowledge of antigens, the structural basis of such reactivities and discuss the emerging trends of γδ T cell reactivity and implications for γδ T cell biology.

Recasting Human Vδ1 Lymphocytes in an Adaptive Role.

γδ T cells are unconventional lymphocytes commonly described as 'innate-like' in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αß T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges. Concomitantly, they differentiate from a Vδ1 T cell naïve (Tnaïve) to a Vδ1 T cell effector (Teffector) phenotype, marked by the downregulation of lymphoid homing receptors and upregulation of peripheral homing receptors and effector markers. This suggests that an adaptive paradigm applies to Vδ1 T cells, likely involving TCR-dependent but MHC-unrestricted responses to microbial and non-microbial challenges.

The use of radiomic analysis of magnetic resonance imaging in predicting distant metastases of rectal carcinoma following surgical resection: A systematic review and meta-analysis.

AIM: Estimating prognosis in rectal carcinoma (RC) is challenging, with distant recurrence (DR) occurring in up to 30% of cases. Radiomics is a novel field using diagnostic imaging to investigate the tumour heterogeneity of cancers and may have the potential to predict DR. The aim of the study was to perform a systematic review of the current literature evaluating the use of radiomics in predicting DR in patients with resected RC. METHODS: A systematic review was performed as per PRISMA guidelines to identify studies reporting radiomic analysis of magnetic resonance imaging (MRI) to predict DR in patients diagnosed with RC. Sensitivity and specificity of radiomic analyses were included for meta-analysis. RESULTS: A total of seven studies including 1497 patients (998 males) were included, seven, five and one of whom reported radiomics, respectively. The overall pooled rate of DR from all included studies was 17.1% (256/1497), with 15.6% (236/1497), 1.3% (19/1497) and 0.2% (3/1497) of patients having hepatic, pulmonary and peritoneal metastases. Meta-analysis demonstrated that radiomics correctly predicted DR with pooled sensitivities and specificities of MRI 0.76 (95% CI: 0.73, 0.78) and 0.85 (95% CI: 0.83, 0.88), respectively. CONCLUSION: This systematic review suggests the benefit of radiomic analysis of preoperative MRI in identifying patients with resected RC at an increased risk of DR. Our findings warrant validation in larger prospective studies as modalities to predict DR is a significant unmet need in RC. Radiomics may allow for tailored therapeutic strategies for high-risk groups.

Pain Management Strategies After Anterior Cruciate Ligament Reconstruction: A Systematic Review With Network Meta-analysis.

PURPOSE: To systematically review randomized controlled trials (RCTs) evaluating various pain control interventions after anterior cruciate ligament reconstruction (ACLR) to determine the best-available evidence in managing postoperative pain and to optimize patient outcomes. METHODS: A systematic review of the literature was performed based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A study was included if it was an RCT evaluating an intervention to reduce postoperative pain acutely after ACLR in one of the following areas: (1) nerve blocks, (2) nerve block adjuncts, (3) intra-articular injections, (4) oral medications, (5) intravenous medications, (6) tranexamic acid, and (7) compressive stockings and cryotherapy. Quantitative and qualitative statistics were carried out, and network meta-analysis was performed where applicable. RESULTS: Overall, 74 RCTs were included. Across 34 studies, nerve blocks were found to significantly reduce postoperative pain and opioid use, but there was no significant difference among the various nerve blocks in the network meta-analysis. Intra-articular injections consisting of bupivacaine and an adjunct were found to reduce reported postoperative pain scores up to 12 hours after ACLR, with significantly lower postoperative opioid use. CONCLUSIONS: Nerve blocks and regional anesthesia are the mainstay treatment of postoperative pain after ACLR, with the commonly used nerve blocks being equally efficacious. Intra-articular injections consisting of bupivacaine and an adjunct were found to reduce reported postoperative pain scores up to 12 hours after ACLR, with significantly lower postoperative opioid use. There was promising evidence for the use of some oral and intravenous medications, tranexamic acid, and nerve block adjuncts, as well as cryotherapy, to control pain and reduce postoperative opioid use. LEVEL OF EVIDENCE: Level II, systematic review and meta-analysis of RCTs.

Open Latarjet Procedure in Athletes Following Failed Prior Instability Surgery Results in Lower Rates of Return to Play.

PURPOSE: The purpose of this study was to compare the outcomes of open Latarjet (OL) in competitive athletes with primary shoulder instability versus those with recurrent instability versus those undergoing OL for failed prior instability surgery. METHODS: A retrospective review of patients who underwent OL with a minimum of 24-month follow-up was performed. Additionally, these were pair-matched in a 1:2:1 ratio for age, gender, sport, level of preoperative play, and follow-up length for primary instability, recurrent instability and failed prior instability surgery. Return to sport, the level of return and the timing of return were assessed. Additionally, recurrence, Visual Analogue Scale for pain (VAS), Subjective Shoulder Value (SSV), Rowe score, Shoulder Instability-Return to Sport after Injury (SIRSI) score, satisfaction, and whether they would undergo the same surgery again were compared. RESULTS: After pair-matching, a total of 200 patients were included, with a mean age of 22.7 years and a mean follow-up of 38.8 months. Overall, there was no significant difference in any of the clinical outcome scores (VAS, Rowe, SIRSI, SSV) used for the 3 groups (P > 0.05 for all). However, there was a significantly lower rate of return to play for those undergoing OL because of failed prior instability surgery (88% vs 91% vs 64%, P < 0.0001) and for return at the same or a higher level (66% vs 78% vs 56%, P = 0.02). There was no significant difference in the rate of recurrent instability among the 3 groups (6% vs 5% vs 6%, P = 0.95). CONCLUSION: OL results in excellent clinical outcomes and low recurrence rates for those with primary shoulder instability, those with recurrent instability and those undergoing OL for failed prior instability surgery. However, in those undergoing OL for failed prior stabilization surgery, there was a lower rate of return to play. LEVEL OF EVIDENCE: Level III: Retrospective Comparative Study.