ABSTRACT
Hypoxia poses a significant challenge to the effectiveness of radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients, and it is imperative to discover novel approaches to overcome this. In this study, we investigated the underlying mechanisms contributing to x-ray radioresistance in HPV-negative HNSCC cells under mild hypoxic conditions (1% oxygen) and explored the potential for autophagy modulation as a promising therapeutic strategy. Our findings show that HNSCC cells exposed to mild hypoxic conditions exhibit increased radioresistance, which is largely mediated by the hypoxia-inducible factor (HIF) pathway. We demonstrate that siRNA knockdown of HIF-1α and HIF-1ß leads to increased radiosensitivity in HNSCC cells under hypoxia. Hypoxia-induced radioresistance was not attributed to differences in DNA double strand break repair kinetics, as these remain largely unchanged under normoxic and hypoxic conditions. Rather, we identify autophagy as a critical protective mechanism in HNSCC cells following irradiation under mild hypoxia conditions. Targeting key autophagy genes, such as BECLIN1 and BNIP3/3L, using siRNA sensitizes these cells to irradiation. Whilst autophagy's role in hypoxic radioresistance remains controversial, this study highlights the importance of autophagy modulation as a potential therapeutic approach to enhance the effectiveness of radiotherapy in HNSCC.
Subject(s)
Autophagy , Cell Hypoxia , Radiation Tolerance , Squamous Cell Carcinoma of Head and Neck , Humans , Autophagy/radiation effects , Autophagy/genetics , Radiation Tolerance/genetics , Cell Line, Tumor , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Cell Hypoxia/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Beclin-1/metabolism , Beclin-1/genetics , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , DNA Repair/radiation effects , DNA Repair/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , X-Rays , DNA Breaks, Double-Stranded/radiation effects , Tumor Suppressor ProteinsABSTRACT
A nickel-catalyzed reductive cross-coupling of redox active N-hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted α-aryl nitriles, an important scaffold in the pharmaceutical sciences. The reaction exhibits a broad scope, and many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents. Mechanistic studies reveal that reduction and decarboxylation of the NHP ester to the reactive radical intermediate are accomplished by a combination of a chlorosilane additive and Zn dust. We demonstrate that stoichiometric chlorosilane is essential for product formation and that chlorosilane plays a role beyond activation of the metal reductant.
ABSTRACT
The XX/XY sex chromosome system is deeply conserved in therian mammals, as is the role of Sry in testis determination, giving the impression of stasis relative to other taxa. However, the long tradition of cytogenetic studies in mammals documents sex chromosome karyotypes that break this norm in myriad ways, ranging from fusions between sex chromosomes and autosomes to Y chromosome loss. Evolutionary conflict, in the form of sexual antagonism or meiotic drive, is the primary predicted driver of sex chromosome transformation and turnover. Yet conflict-based hypotheses are less considered in mammals, perhaps because of the perceived stability of the sex chromosome system. To address this gap, we catalog and characterize all described sex chromosome variants in mammals, test for family-specific rates of accumulation, and consider the role of conflict between the sexes or within the genome in the evolution of these systems. We identify 152 species with sex chromosomes that differ from the ancestral state and find evidence for different rates of ancestral to derived transitions among families. Sex chromosome-autosome fusions account for 79% of all variants whereas documented sex chromosome fissions are limited to three species. We propose that meiotic drive and drive suppression provide viable explanations for the evolution of many of these variant systems, particularly those involving autosomal fusions. We highlight taxa particularly worthy of further study and provide experimental predictions for testing the role of conflict and its alternatives in generating observed sex chromosome diversity.
Subject(s)
Mammals , Sex Chromosomes , Animals , Mammals/genetics , Sex Chromosomes/genetics , Male , Female , Meiosis , Evolution, Molecular , Biological Evolution , Y Chromosome/genetics , KaryotypeABSTRACT
OBJECTIVES: To investigate the impact of demographic and socioeconomic factors on the management of isolated meniscus tears in young patients and to identify trends in surgical management of meniscus tears based on surgeon volume. METHODS: Data from a large healthcare system on patients aged 14-44 years who underwent isolated meniscus surgery between 2016 and 2022 were analysed. Patient demographics, socioeconomic factors and surgeon volume were recorded. Patient age was categorised as 14-29 years and 30-44 years old. Area Deprivation Index (ADI), a measure of neighbourhood disadvantage with increased ADI corresponding to more disadvantage, was grouped as <25th, 25-75th and >75th percentile. Multivariate comparisons were made between procedure groups while univariate comparisons were made between surgeon groups. RESULTS: The study included 1552 patients treated by 84 orthopaedic surgeons. Older age and higher ADI were associated with higher odds of undergoing meniscectomy. Patients of older age and with non-private insurance were more likely to undergo treatment by a lower-volume knee surgeon. Apart from the year 2022, higher-volume knee surgeons performed significantly higher rates of meniscus repair compared with lower-volume knee surgeons. When controlling for surgeon volume, higher ADI remained a significant predictor of undergoing meniscectomy over meniscus repair. CONCLUSION: Significant associations exist between patient factors and surgical choices for isolated meniscus tears in younger patients. Patients of older age and with increased neighbourhood disadvantage were more likely to undergo meniscectomy versus meniscus repair. While higher-volume knee surgeons favoured meniscus repair, a growing trend of meniscus repair rates was observed among lower-volume knee surgeons. LEVEL OF EVIDENCE: Retrospective cohort study, level III.
Subject(s)
Meniscectomy , Socioeconomic Factors , Tibial Meniscus Injuries , Humans , Adolescent , Tibial Meniscus Injuries/surgery , Young Adult , Meniscectomy/statistics & numerical data , Male , Adult , Female , Age Factors , Retrospective Studies , Residence CharacteristicsABSTRACT
PURPOSE: To determine the comparative accuracy and precision of routine magnetic resonance imaging (MRI) versus magnetic resonance (MR) arthrogram in measuring labral tear size as a function of time from a shoulder dislocation. METHODS: We retrospectively evaluated consecutive patients who underwent primary arthroscopic stabilization between 2012 and 2021 in a single academic center. All patients completed a preoperative MRI or MR arthrogram of the shoulder within 60 days of injury and subsequently underwent arthroscopic repair within 6 months of imaging. Intraoperative labral tear size and location were used as standards for comparison. Three musculoskeletal radiologists independently interpreted tear extent using a clock-face convention. Accuracy and precision of MR labral tear measurements were defined based on location and size of the tear, respectively. Accuracy and precision were compared between MRI and MR arthrogram as a function of time from dislocation. RESULTS: In total, 32 MRIs and 65 MR arthrograms (total n = 97) were assessed. Multivariate analysis demonstrated that intraoperative tear size, early imaging, and arthrogram status were associated with increased MR accuracy and precision (P < .05). Ordering surgeons preferred arthrogram for delayed imaging (P = .018). For routine MRI, error in accuracy increased by 3.4° per day and error in precision increased by 2.3° per day (P < .001) from time of injury. MR arthrogram, however, was not temporally influenced. Significant loss of accuracy and precision of MRI compared with MR arthrogram occurred at 2 weeks after an acute shoulder dislocation. CONCLUSIONS: Compared with MR arthrogram, conventional MRI demonstrates time-dependent loss of accuracy and precision in determining shoulder labral tear extent after dislocation, with statistical divergence occurring at 2 weeks. LEVEL OF EVIDENCE: Level II, retrospective radiographic diagnostic study.
Subject(s)
Magnetic Resonance Imaging , Shoulder Dislocation , Humans , Retrospective Studies , Male , Female , Adult , Shoulder Dislocation/diagnostic imaging , Shoulder Dislocation/surgery , Arthroscopy , Middle Aged , Arthrography/methods , Young Adult , Time Factors , Shoulder Injuries/diagnostic imagingABSTRACT
PURPOSE: The purpose of this study was to identify risk factors for subsequent meniscal surgery following anterior cruciate ligament (ACL) reconstruction (ACLR) in patients without recurrent ACL injury. METHODS: Patients aged ≥14 years who underwent primary ACLR with minimum 1-year follow-up and without recurrent ACL injury were retrospectively reviewed. Patient demographics and surgical data at the time of ACLR were collected. Postoperative radiographs were used to measure femoral and tibial tunnel position, and posterior tibial slope. Univariate and multivariate analyses were performed to identify risk factors for subsequent meniscal surgery. RESULTS: Of 629 ACLRs that fulfilled the inclusion criteria, subsequent meniscal surgery was performed in 65 [10.3%] patients. Multivariate analysis revealed that medial meniscal repair at the time of ACLR, younger age, anterior femoral tunnel position and distal femoral tunnel position were significantly associated with subsequent meniscal surgery (p < 0.001, p = 0.016, p = 0.015, p = 0.035, respectively). The frequency of femoral tunnel placement >10% outside of the literature-established anatomic position was significantly higher in those who underwent subsequent meniscal surgery compared to those who did not (38.3% vs. 20.3%, p = 0.006). Posterior tibial slope and ACL graft type were not significantly associated with subsequent meniscal surgery. CONCLUSION: Medial meniscal repair at the time of ACLR, younger age and nonanatomic femoral tunnel placement were risk factors for subsequent meniscal surgery in patients without recurrent ACL injury. Femoral tunnel placement <10% outside of the native anatomic position is important to reduce the risk of subsequent meniscal surgery. LEVEL OF EVIDENCE: Level IV.
ABSTRACT
PURPOSE: To describe rates of conversion to unicompartmental or total knee arthroplasty (KA) in patients over the age of 40 years (at initial surgery) after partial meniscectomy (ME) or meniscal repair (MR). METHODS: Patients over the age of 40 undergoing isolated ME or MR between 2016 and 2018 were extracted from a single healthcare provider database. Data on patient characteristics, type of initial surgery, number of returns to the operating room, as well as performed procedures, including conversion to KA, were recorded. Comparative group statistics as well as a Kaplan-Meier survival rate analysis were performed. RESULTS: A total of 3638 patients (47.8% female) were included, with 3520 (96.8%) undergoing ME and 118 (3.2%) MR. Overall, 378 (10.4%) patients returned to the OR at an average of 22.7 ± 17.3 months postoperatively. Conversion to KA was performed more frequently in patients after primary ME (n = 270, 7.7%) compared to those with MR (2.5%, n = 3, odds ratio [OR]: 3.2, p = 0.03). Compared to ME (2.3%, n = 82), two times as many patients undergoing MR returned for subsequent meniscus surgery (MR: 5.9%, n = 7, OR: 2.6, p = 0.02). Time from primary surgery to KA (ME: 22 ± 17 months, MR: 25 ± 15 months, p = 0.96) did not differ between the treatment groups. Survivorship was 95% for ME and 98.2% for MR after 24 months (p = 0.76) and 92.5% and 98.2% after 60 months (p = 0.07), respectively. CONCLUSION: The overall reoperation rate after meniscal surgery was 10.4% in patients over the age of 40 years. Patients treated with primary ME have over three times higher odds to undergo subsequent KA compared to those treated with MR. However, patients with primary MR have a higher rate of subsequent meniscus surgery compared to those undergoing primary ME. This information is important when considering and treating a patient over the age of 40 and meniscal injury. LEVEL OF EVIDENCE: Level III study.
Subject(s)
Arthroplasty, Replacement, Knee , Meniscectomy , Reoperation , Humans , Female , Male , Middle Aged , Reoperation/statistics & numerical data , Adult , Aged , Tibial Meniscus Injuries/surgery , Age Factors , Menisci, Tibial/surgery , Retrospective Studies , Kaplan-Meier EstimateABSTRACT
PURPOSE: To retrospectively compare strength outcomes of individuals undergoing postoperative rehabilitation following quadriceps tendon (QT) autograft anterior cruciate ligament reconstruction (ACLR) with and without blood flow restriction therapy. METHODS: A retrospective review of consecutive patients undergoing ACLR with QT autograft with a minimum of two quantitative postoperative isometric strength assessments via an electromechanical dynamometer (Biodex) was included. Demographics, surgical variables and strength measurement outcomes were compared between patients undergoing blood flow restriction therapy as part of postoperative rehabilitation versus those who did not. RESULTS: Eighty-one (81) patients met the inclusion criteria. No differences were found in demographic and surgical characteristics between those who received blood flow restriction compared with those who did not. While both groups had improvements in quadriceps peak torque and limb symmetry index (LSI; defined as peak torque of the operative limb divided by the peak torque of the nonoperative limb) over the study period, the blood flow restriction group had significantly lower mean peak torque of the operative limb at first Biodex strength measurement (95.6 vs. 111.2 Nm; p = 0.03). Additionally, the blood flow restriction group had a significantly lower mean LSI than those with no blood flow restriction at the second Biodex measurement timepoint (81% vs. 90%; p = 0.02). No other significant differences were found between the strength outcomes measured. CONCLUSIONS: Results of this study show that the 'real world' clinical implementation of blood flow restriction therapy to the postoperative rehabilitation protocol following QT autograft ACLR did not result in an increase in absolute or longitudinal changes in quadriceps strength measurements. A better understanding and standardisation of the use of blood flow restriction therapy in the rehabilitation setting is necessary to delineate the true effects of this modality on strength recovery after QT autograft ACLR. LEVEL OF EVIDENCE: Level III.
Subject(s)
Anterior Cruciate Ligament Reconstruction , Autografts , Muscle Strength , Quadriceps Muscle , Humans , Retrospective Studies , Anterior Cruciate Ligament Reconstruction/rehabilitation , Anterior Cruciate Ligament Reconstruction/methods , Male , Female , Quadriceps Muscle/blood supply , Quadriceps Muscle/physiology , Muscle Strength/physiology , Adult , Young Adult , Tendons/transplantation , Regional Blood Flow/physiology , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Injuries/rehabilitation , Transplantation, Autologous , TorqueABSTRACT
A chronic cough, gag, or retch is a common presenting clinical complaint in dogs. Those refractory to conservative management frequently undergo further diagnostic tests to investigate the cause, including CT examination of their head, neck, and thorax for detailed morphological assessment of their respiratory and upper gastrointestinal tract. This case series describes five patients with CT characteristics consistent with an intracranial and jugular foraminal mass of the combined glossopharyngeal (IX), vagus (X), and accessory (XI) cranial nerves and secondary features consistent with their paresis. The consistent primary CT characteristics included an intracranial, extra-axial, cerebellomedullary angle, and jugular foraminal soft tissue attenuating, strongly enhancing mass (5/5). Secondary characteristics included smooth widening of the bony jugular foramen (5/5), mild hyperostosis of the petrous temporal bone (3/5), isolated severe atrophy of the ipsilateral sternocephalic, cleidocephalic, and trapezius muscles (5/5), atrophy of the ipsilateral thyroarytenoideus and cricoarytenoideus muscles of the vocal fold (5/5), and an ipsilateral "dropped" shoulder (4/5). Positional variation of the patient in CT under general anesthesia made the "dropped" shoulder of equivocal significance. The reported clinical signs and secondary CT features reflect a unilateral paresis of the combined cranial nerves (IX, X, and XI) and are consistent with jugular foramen syndrome/Vernet's syndrome reported in humans. The authors believe this condition is likely chronically underdiagnosed without CT examination, and this case series should enable earlier CT diagnosis in future cases.
Subject(s)
Dog Diseases , Glossopharyngeal Nerve , Jugular Foramina , Tomography, X-Ray Computed , Vagus Nerve , Animals , Dogs , Female , Accessory Nerve/diagnostic imaging , Cranial Nerve Neoplasms/veterinary , Cranial Nerve Neoplasms/diagnostic imaging , Dog Diseases/diagnostic imaging , Glossopharyngeal Nerve/diagnostic imaging , Jugular Foramina/diagnostic imaging , Tomography, X-Ray Computed/veterinary , Vagus Nerve/diagnostic imaging , Vagus Nerve Diseases/veterinary , Vagus Nerve Diseases/diagnostic imaging , Vagus Nerve Diseases/diagnosis , Vagus Nerve Diseases/pathology , Retrospective StudiesABSTRACT
Heterocycles are the backbone of modern medical chemistry and drug development. The derivatization of "an olefin" inside aromatic rings represents an ideal approach to access functionalized saturated heterocycles from abundant aromatic building blocks. Here, we report an operationally simple, efficient, and practical method to selectively access hydrosilylated and reduced N-heterocycles from bicyclic aromatics via a key diradical intermediate. This approach is expected to facilitate complex heterocycle functionalizations that enable access to novel medicinally relevant scaffolds.
Subject(s)
Quinolines , Isoquinolines , Molecular Structure , Catalysis , Drug DevelopmentABSTRACT
PURPOSE: The purpose of this study was to compare rates of recurrent dislocation and postsurgical outcomes in patients undergoing arthroscopic Bankart repair for anterior shoulder instability immediately after a first-time traumatic anterior dislocation versus patients who sustained a second dislocation event after initial nonoperative management. METHODS: A retrospective chart review was performed of patients undergoing primary arthroscopic stabilization for anterior shoulder instability without concomitant procedures and minimum 2-year clinical follow-up. Primary outcome was documentation of a recurrent shoulder dislocation. Secondary clinical outcomes included range of motion, Visual Analog Scale (VAS), American Shoulder and Elbow Surgeons Shoulder Score (ASES), and Shoulder Activity Scale (SAS). RESULTS: Seventy-seven patients (mean age 21.3 years ± 7.3 years) met inclusion criteria. Sixty-three shoulders underwent surgical stabilization after a single shoulder dislocation, and 14 underwent surgery after 2 dislocations. Average follow-up was 35.9 months. The rate of recurrent dislocation was significantly higher in the 2-dislocation group compared to single dislocations (42.8% vs 14.2%, P = .03). No significant difference was present in range of motion, VAS, ASES, and SAS scores. The minimal clinically important difference (MCID) was 1.4 for VAS and 1.8 for SAS scores. The MCID was met or exceeded in the primary dislocation group in 31/38 (81.6%) patients for VAS, 23/31 (74.1%) for ASES, and 24/31 for SES (77.4%) scores. For the second dislocation cohort, MCID was met or exceeded in 7/9 (77.8%) for VAS, 4/7 (57.1%) for ASES, and 5/7 for SES (71.4%) scores. CONCLUSION: Immediate arthroscopic surgical stabilization after a first-time anterior shoulder dislocation significantly decreases the risk of recurrent dislocation in comparison to those who undergo surgery after 2 dislocation events, with comparable clinical outcome scores. These findings suggest that patients who return to activities after a primary anterior shoulder dislocation and sustain just 1 additional dislocation event are at increased risk of a failing arthroscopic repair. STUDY DESIGN: Retrospective comparative study; Level of evidence, 3.
Subject(s)
Joint Dislocations , Joint Instability , Shoulder Dislocation , Shoulder Joint , Humans , Young Adult , Adult , Shoulder Dislocation/surgery , Shoulder Dislocation/complications , Joint Instability/surgery , Shoulder Joint/surgery , Retrospective Studies , Recurrence , Joint Dislocations/surgery , Arthroscopy/methodsABSTRACT
PURPOSE: This study aimed to evaluate posterolateral tibial plateau impaction fractures and how they contribute to rotatory knee laxity using quantitative pivot shift analysis. It was hypothesised that neither the presence of nor the degree of involvement of the plateau would affect rotatory knee laxity in the ACL-deficient knee. METHODS: A retrospective review of prospectively collected data on 284 patients with complete anterior cruciate ligament (ACL) injuries was conducted. Posterolateral tibial plateau impaction fractures were identified on preoperative MRI. The patients were divided into two cohorts: "fractures" or "no fractures". The cohort with fractures was further categorised based on fracture morphology: "extra-articular", "articular-impaction", or "displaced-articular fragment". All data were collected during examination under anaesthesia performed immediately prior to ACL reconstruction. This included a standard pivot shift test graded by the examiner and quantitative data including anterior tibial translation (mm) via Rolimeter, quantitative pivot shift (QPS) examination (mm) via PIVOT tablet technology, and acceleration (m/sec2) during the pivot shift test via accelerometer. Quantitative examinations were compared with the contralateral knee. RESULTS: There were 112 patients with posterolateral tibial plateau impaction fractures (112/284, 39%). Of these, 71/112 (63%) were "extra-articular", 28/112 (25%) "articular-impaction", and 13/112 (12%) "displaced-articular". Regarding the two groups with or without fractures, there was no difference in subjective pivot shift (2 ± 0 vs 2 ± 0, respectively, n.s.), QPS (2.4 ± 1.6 mm vs 2.7 ± 2.2 mm, respectively, n.s.), anterior tibial translation measurements (6 ± 3 mm vs 5 ± 3 mm, respectively, n.s.), or acceleration of the knee during the pivot (1.7 ± 2.3 m/s2 vs 1.8 ± 3.1 m/s2, respectively, n.s.). When the fractures were further subdivided, subgroup analysis revealed no significant differences noted in any of the measured examinations between the fracture subtypes. CONCLUSION: This study showed that the posterolateral tibial plateau impaction fractures are commonly encountered in the setting of ACL tears; however, contrary to previous reports, they do not significantly increase rotatory knee laxity. This suggests that this type of concomitant injury may not need to be addressed at the time of ACL reconstruction. LEVEL OF EVIDENCE: Level III.
Subject(s)
Anterior Cruciate Ligament Injuries , Joint Instability , Tibial Fractures , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Anterior Cruciate Ligament Injuries/complications , Anterior Cruciate Ligament Injuries/diagnosis , Anterior Cruciate Ligament Injuries/surgery , Tibial Fractures/complications , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery , Tibia , Joint Instability/diagnosisABSTRACT
PURPOSE: The purpose of this study was to evaluate whether harvesting a second graft from the ipsilateral extensor mechanism adversely affects clinical outcomes in revision anterior cruciate ligament (ACL) reconstruction. METHODS: A retrospective review of 34 patients undergoing revision anterior cruciate ligament (ACL) reconstruction with either quadriceps tendon (QT) autograft or bone-tendon-bone (BTB) autograft was conducted. Patients with two grafts (BTB+QT) from the extensor mechanism were matched based on age, laterality, and sex to patients who had primary reconstruction with hamstring (HS) autograft followed by revision with either BTB or QT autograft (HS+QT/BTB). Return of quadriceps function was assessed with time to return to jogging in a standardized rehab protocol or time to regain 80% quadriceps strength. Secondary outcomes included International Knee Documentation Committee (IKDC) and Marx scores at 12-month follow-up and return to sport. RESULTS: There were no significant differences in return to jogging or 80% quadriceps strength (HS 149.5 ± 38.2 days, BTB+QT 131.7 ± 40.1 days, n.s.), number able to return to sport (HS 62%, BTB+QT 93%, n.s.), months to return to sport (HS 10.6 ± 1.4, BTB+QT 10.5 ± 2.3, n.s.), return to pre-injury level of competition (HS 62%, BTB+QT 73%, n.s.), or IKDC (HS 77.2 ± 16.4, BTB+QT 74.8 ± 23.9, n.s.) and Marx scores (HS 9.2 ± 5.3, BTB+QT 8.0 ± 3.7, n.s.) at one-year follow-up. CONCLUSION: The main finding of the present study was that outcomes for patients who underwent revision ACL reconstruction with a second extensor mechanism autograft were comparable to those seen for patients who underwent revision ACL reconstruction with extensor mechanism autograft after primary ACL reconstruction with hamstring autograft. By better understanding the consequences of harvesting a second graft from the extensor mechanism, surgeons can better decide what graft to use in revision ACL reconstruction. LEVEL OF EVIDENCE: Level III.
Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Hamstring Tendons , Humans , Autografts/transplantation , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Injuries/etiology , Anterior Cruciate Ligament Reconstruction/methods , Tendons/transplantation , Anterior Cruciate Ligament/surgery , Hamstring Tendons/transplantation , Transplantation, AutologousABSTRACT
Peer review is an essential process to ensure that scientific articles meet high standards of methodology, ethics and quality. The peer-review process is a part of the academic mission for physicians in the university setting. The work of reviewers is of great value for authors, as it gives constructive criticism and improves manuscript quality before publication. Often, however, reviews are of suboptimal quality. Usually, reviewers do not receive formal training either on how to perform a review or on the peer-review process. In addition, it is generally believed that experienced authors are great reviewers, but this may not always be true. The overarching goal of a review is to make the manuscript better; to help the authors. The purpose of this article is to offer relevant suggestions and provide a checklist on how to perform a useful review.
Subject(s)
Checklist , Peer Review , Humans , Peer Review, Research/methodsABSTRACT
PURPOSE: To compare failure rates and outcomes after transosseous equivalent (TOE) double row (DR) knotted suture bridge versus knotless suture tape bridge repair techniques for rotator cuff tears. METHODS: A consecutive series of 272 shoulders in 256 patients who underwent arthroscopic, double row, TOE repair for full-thickness tears of the supraspinatus tendon were reviewed. Eighty-four shoulders were repaired using knotted suture bridge (KSB) technique, and 188 shoulders were repaired using all knotless suture tape bridge (KTB) technique. Revision procedures and concomitant subscapularis tendon repairs were excluded from analysis. The minimum follow-up was 12 months. Primary outcome was failure of surgical repair, defined as either confirmed retear on MRI and/or need for revision surgery. Secondary clinical outcome measures were assessed including range of motion, strength, visual analog scale (VAS), operative time, subjective shoulder value (SSV), Patient-Reported Outcomes Measurement Information System (PROMIS) mental and physical health, American Shoulder and Elbow Surgeons Shoulder Score (ASES), Brophy shoulder activity scores, and need for manipulation under anesthesia (MUA). RESULTS: A total of 127 shoulders (38 KSB and 89 KTB) met inclusion criteria for the study. No significant difference in demographic variables were present between the groups at baseline. Supraspinatus tear size and average follow-up time did not differ significantly between groups. Failure rates were similar between the KSB and KTB repairs (13.1 vs 7.9%, n.s.). There was no significant difference in functional outcomes including strength, range of motion in forward flexion and external rotation, as well as patient reported outcomes including VAS, SSV, PROMIS, ASES, and Brophy scores between the groups. There was also no difference in post-operative stiffness requiring MUA. CONCLUSION: Both KSB and KTB repair techniques demonstrate low retear rates with excellent functional outcomes when compared to pre-operative examination. Both KSB and KTB techniques are viable options for achieving a successful rotator cuff repair. LEVEL OF EVIDENCE: Level III.
Subject(s)
Rotator Cuff Injuries , Rotator Cuff , Humans , Rotator Cuff/surgery , Treatment Outcome , Rotator Cuff Injuries/surgery , Shoulder , Arthroscopy/methodsABSTRACT
PURPOSE: To investigate the potential use of large language models (LLMs) in orthopaedics by presenting queries pertinent to anterior cruciate ligament (ACL) surgery to generative pre-trained transformer (ChatGPT, specifically using its GPT-4 model of March 14th 2023). Additionally, this study aimed to evaluate the depth of the LLM's knowledge and investigate its adaptability to different user groups. It was hypothesized that the ChatGPT would be able to adapt to different target groups due to its strong language understanding and processing capabilities. METHODS: ChatGPT was presented with 20 questions and response was requested for two distinct target audiences: patients and non-orthopaedic medical doctors. Two board-certified orthopaedic sports medicine surgeons and two expert orthopaedic sports medicine surgeons independently evaluated the responses generated by ChatGPT. Mean correctness, completeness, and adaptability to the target audiences (patients and non-orthopaedic medical doctors) were determined. A three-point response scale facilitated nuanced assessment. RESULTS: ChatGPT exhibited fair accuracy, with average correctness scores of 1.69 and 1.66 (on a scale from 0, incorrect, 1, partially correct, to 2, correct) for patients and medical doctors, respectively. Three of the 20 questions (15.0%) were deemed incorrect by any of the four orthopaedic sports medicine surgeon assessors. Moreover, overall completeness was calculated to be 1.51 and 1.64 for patients and medical doctors, respectively, while overall adaptiveness was determined to be 1.75 and 1.73 for patients and doctors, respectively. CONCLUSION: Overall, ChatGPT was successful in generating correct responses in approximately 65% of the cases related to ACL surgery. The findings of this study imply that LLMs offer potential as a supplementary tool for acquiring orthopaedic knowledge. However, although ChatGPT can provide guidance and effectively adapt to diverse target audiences, it cannot supplant the expertise of orthopaedic sports medicine surgeons in diagnostic and treatment planning endeavours due to its limited understanding of orthopaedic domains and its potential for erroneous responses. LEVEL OF EVIDENCE: V.
Subject(s)
Orthopedic Procedures , Orthopedic Surgeons , Orthopedics , Humans , Anterior Cruciate Ligament , LanguageABSTRACT
PURPOSE: To perform a systematic review and meta-analysis to investigate the rate of stiffness after multi-ligament knee injury (MLKI) surgery and identify potential risk factors associated with postoperative stiffness. METHODS: This study was conducted in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Registration was done on the PROSPERO International Prospective Register of Systematic Reviews (CRD42022321849). A literature search of PubMed, Ovid, Embase, and Cochrane Library databases was conducted in October 2022 for clinical studies reporting postoperative stiffness after MLKI surgery. A quality assessment was performed using the Methodological Index of Non-Randomized Studies (MINORS) grading system. The following variables were extracted from studies for correlation to postoperative stiffness: study characteristics, cohort demographics, Schenk classification, neurovascular injury, mechanism of injury, external fixator placement, timing of surgery, and concomitant knee injuries. RESULTS: Thirty-six studies comprising 4,159 patients who underwent MLKI surgery met the inclusion criteria, including two Level-II, fourteen Level-III, and twenty Level-IV studies. The average MINOR score of the studies was 14. The stiffness rate after MLKI was found to be 9.8% (95% CI 0.07-0.13; p < 0.01; I2 = 87%), and the risk of postoperative stiffness was significantly lower for patients with two ligaments injured compared to patients with ≥ 3 ligaments injured (OR = 0.45, 95% CI (0.26-0.79), p = 0.005; I2 = 0%). The results of the pooled analysis showed early surgery (< 3 weeks) resulted in significantly increased odds of postoperative stiffness compared with delayed surgery (≥ 3 weeks) (OR = 2.18; 95% CI 1.11-4.25; p = 0.02; I2 = 0%). However, age, gender, body mass index, energy of injury, and neurovascular injury were not associated with an increased risk of postoperative stiffness (n.s.). CONCLUSION: Performing surgery within the first 3 weeks following MLKI, or concomitant injury of ≥ 3 ligaments, are significantly associated with increased risk of postoperative stiffness. These findings can be utilized by surgeons to decide the timing of surgery for MLKI surgeries especially in which ≥ 3 ligaments are injured. LEVEL OF EVIDENCE: Level IV.
Subject(s)
Anterior Cruciate Ligament Injuries , Knee Injuries , Soft Tissue Injuries , Vascular System Injuries , Humans , Knee Injuries/surgery , Knee Injuries/complications , Ligaments/injuries , Risk Factors , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Injuries/complicationsABSTRACT
PURPOSE: Quantitative pivot shift (QPS) testing using PIVOT technology can detect high- and low-grade rotatory knee instability following anterior cruciate ligament injury or reconstruction (ACLR). The aim of this project was to determine if preoperative QPS correlates with postoperative knee kinematics in the operative and contralateral, healthy extremity following ACLR with or without lateral extraarticular tenodesis (LET) using a highly precise in vivo analysis system. A positive correlation between preoperative QPS and postoperative tibial translation and rotation following ACLR with or without LET in the operative and healthy, contralateral extremity was hypothesized. METHODS: Twenty patients with ACL injury and high-grade rotatory knee instability were randomized to undergo anatomic ACLR with or without LET as part of a prospective randomized trial. At 6 and 12 months postoperatively, in vivo kinematic data were collected using dynamic biplanar radiography superimposed with high-resolution computed tomography scans of patients' knees during downhill running. Total anterior-posterior (AP) tibial translation and internal-external tibial rotation were measured during the gait cycle. Spearman's rho was calculated for preoperative QPS and postoperative kinematics. RESULTS: In the contralateral, healthy extremity, a significant positive correlation was seen between preoperative QPS and total AP tibial translation at 12 months postoperatively (rs = 0.6, p < 0.05). There were no additional significant correlations observed between preoperative QPS and postoperative knee kinematics at 6 and 12 months postoperatively in the operative and contralateral, healthy extremity for combined isolated ACLR and ACLR with LET patients as well as isolated ACLR patients or ACLR with LET patients analyzed separately. DISCUSSION: The main finding of this study was that there was a significant positive correlation between preoperative QPS and total AP tibial translation at 12 months postoperatively in the contralateral, healthy extremity. There were no significant correlations between preoperative QPS and postoperative in vivo kinematics at 6 and 12 months following ACLR with or without LET. This suggests that QPS as measured with PIVOT technology does correlate with healthy in vivo knee kinematics, but QPS does not correlate with in vivo kinematics following ACLR with or without LET.
Subject(s)
Anterior Cruciate Ligament Injuries , Joint Instability , Tenodesis , Humans , Tenodesis/methods , Biomechanical Phenomena , Prospective Studies , Knee Joint/surgery , Anterior Cruciate Ligament Injuries/surgery , Joint Instability/etiology , Joint Instability/surgeryABSTRACT
PURPOSE: To compare various nonarthroplasty treatment options for massive, irreparable rotator cuff tears, including allograft bridging/augmentation, debridement, partial repair, superior capsule reconstruction (SCR), subacromial balloon spacer, and tendon transfer. METHODS: A comprehensive search was conducted through the PubMed, MEDLINE, and EMBASE databases for all articles pertaining to nonarthroplasty treatment options for irreparable rotator cuff tears. Inclusion criteria included manuscripts published between 2009 and 2020 with at least 1 year follow-up and Level I-IV evidence. Articles were separated into six groups: debridement, arthroscopic and open repair, allograft bridging/augmentation, SCR, subacromial balloon spacer, and tendon transfer. Data points included range of motion (external rotation, abduction, forward flexion, and internal rotation), visual analog scale (VAS) pain score, American Shoulder and Elbow Surgeons (ASES) score, Constant score, rate of revision surgery, and rate of conversion to arthroplasty. RESULTS: A total of 83 studies and 3363 patients were included. All treatment options had statistically significant improvements in postoperative range of motion and patient-reported outcomes. Debridement had statistically significantly greater postoperative abduction and forward flexion range of motion, as well as better VAS pain scores, compared to the other treatment options. The SCR subgroup had the greatest improvement in ASES scores postoperatively. The overall revision rate was 7.2% among all surgical options, with the allograft bridging/augmentation group having the lowest rate of revision at 0-8.3%. The overall rate of conversion to arthroplasty was 7.2%, with debridement having the greatest rate of conversion at 15.4%. CONCLUSION: All six nonarthroplasty treatment options for irreparable rotator cuff tears resulted in statistically significant improvements in range of motion and patient-reported outcomes at 1 year follow-up or more, with low rates of revision and conversion to arthroplasty. Debridement had statistically significantly greater postoperative abduction and forward flexion range of motion, as well as better VAS pain scores, compared to the other treatment options. However, these conclusions should be interpreted with caution due to the heterogeneous nature of the data, lack of prospective randomized control trials, and short-term follow-up. The findings of this study highlight the complexity of irreparable, massive rotator cuff tears, and the need for an individualized approach when treating these patients. LEVEL OF EVIDENCE: Level IV.
Subject(s)
Rotator Cuff Injuries , Humans , Rotator Cuff Injuries/surgery , Rotator Cuff/surgery , Treatment Outcome , Range of Motion, Articular , PainABSTRACT
PURPOSE: Variations in femoral and tibial bony morphology have been associated with higher clinical grading and increased quantitative tibial translation, but not tibial acceleration, during the pivot shift test following anterior cruciate ligament (ACL) injury. The purpose of this study was to determine the impact of femoral and tibial bony morphology, including a measurement influenced by both parameters (the Lateral Tibiofemoral Articular Distance (LTAD)), on the degree of quantitative tibial acceleration during the pivot shift test and rates of future ACL injury. METHODS: All patients who underwent primary ACL reconstruction from 2014 to 2019 by a senior orthopedic surgeon with available quantitative tibial acceleration data were retrospectively reviewed. All patients underwent a pivot shift examination under anesthesia with a triaxial accelerometer. Measurements of femoral and tibial bony morphology were performed by two fellowship-trained orthopedic surgeons using preoperative magnetic resonance imaging and lateral radiographs. RESULTS: Fifty-one patients were included at a mean follow-up of 4.4 years. The mean quantitative tibial acceleration during the pivot shift was 13.8 m/s2 (range: 4.9-52.0 m/s2). A larger Posterior Condylar Offset Ratio (r = 0.30, p = 0.045), smaller medial-to-lateral width of the medial tibial plateau (r = - 0.29, p = 0.041), lateral tibial plateau (r = - 0.28, p = 0.042), and lateral femoral condyle (r = - 0.29, p = 0.037), and a decreased LTAD (r = - 0.53, p < 0.001) significantly correlated with increased tibial acceleration during the pivot shift. Linear regression analysis demonstrated an increase in tibial acceleration of 1.24 m/s2 for every 1 mm decrease in LTAD. Nine patients (17.6%) sustained ipsilateral graft rupture and 10 patients (19.6%) sustained contralateral ACL rupture. No morphologic measurements were associated with rates of future ACL injury. CONCLUSION: Increased convexity and smaller bony morphology of the lateral femur and tibia were significantly associated with increased tibial acceleration during the pivot shift. Additionally, a measurement, termed the LTAD, was found to have the strongest association with increased tibial acceleration. Based on the results of this study, surgeons can utilize these measurements to preoperatively identify patients at risk of increased rotatory knee instability. LEVEL OF EVIDENCE: Level IV.