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Background: Rotator cuff repair (RCR) is a well-studied procedure. However, the impact of patient sex on outcomes after RCR has not been well studied. Purpose: To conduct a systematic review and meta-analysis of sex-based differences in outcomes after RCR and to record what proportion of studies examined this as a primary or secondary purpose. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed using multiple databases according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were included if they were written in English, performed on humans, consisted of patients who underwent RCR, evaluated at least 1 of the selected outcomes based on patient sex, and had statistical analysis available for their sex-based claim. Excluded were case reports, review studies, systematic reviews, cadaveric studies, and studies that did not report at least 1 sex-specific outcome or included certain other injuries associated with a rotator cuff injury. Results: Of 9998 studies screened and 1283 full-text studies reviewed, 11 (0.11%) studies with 2860 patients (1549 male and 1329 female) were included for quantitative analysis. None of these 11 studies examined the impact of patient sex on outcomes after RCR as a primary outcome. Postoperative Constant-Murley scores were analyzed for 7 studies. Male patients had a postoperative Constant-Murley score of 76.77 ± 15.94, while female patients had a postoperative Constant-Murley score of 69.88 ± 17.02. The random-effects model showed that male patients had significantly higher scores than female patients, with a mean difference of 7.33 (95% CI, 5.21-9.46; P < .0001). Analysis of retear rates in 5 studies indicated that there was no difference in the retear rate between sexes (odds ratio, 0.91 [95% CI, 0.49-1.67]). Conclusion: Female patients had lower postoperative Constant-Murley scores compared with male patients, but there was no difference in the retear rate. However, these results were based on an analysis of only 11 studies. The paucity of studies examining the impact of sex suggests that more research is needed on the impact of patient sex on outcomes after RCR.

Background: Despite the significant difference between men and women in incidence of anterior cruciate ligament (ACL) injuries, there is a paucity of consistent information on the influence of patient sex on outcomes after ACL reconstruction. A previous meta-analysis has demonstrated that female patients have worse outcomes with regard to laxity, revision rate, Lysholm score, and Tegner activity score and are less likely to return to sports (RTS). Purpose: To conduct a systematic review and meta-analysis to evaluate and compare sex-specific outcomes after ACL reconstruction. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed using PubMed, PubMed Central, Embase, OVID, and Cochrane databases per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The following search terms were used: “anterior cruciate ligament reconstruction” OR “ACL reconstruction” OR “anterior cruciate ligament” OR “ACL” AND “gender” OR “sex” OR “male” OR “female” AND “outcome” AND “2015-Present” to gather all relevant articles between 2015 and 2020. A risk-of-bias assessment and quality assessment was conducted on included studies. Results: Of 9594 studies initially identified, 20 studies with 35,935 male and 21,455 female patients were included for analysis. The 7 studies reporting International Knee Documentation Committee (IKDC) scores showed that male patients had statistically significantly higher postoperative scores (mean difference, 3.02 [95% CI, 1.19-4.84]; P< .01; I 2 = 66%), and 7 studies that reported the rate of ACL revision showed there was no significant difference between male and female patients (odds ratio, 0.85 [95% CI, 0.45-1.60]; P = .61; I 2 = 94%). The 7 studies that reported rates of rerupture showed that males were significantly more likely than females to have a graft rerupture (odds ratio, 1.35 [95% CI, 1.22-1.50]; P < .01; I 2 = 0%). Male patients reported a higher RTS rate than did their female counterparts (59.82% compared with 42.89%); however, no formal statistical analysis could be done because of the variability in reporting techniques. Conclusion: Male and female patients with ACL injuries demonstrated similar outcomes regarding their rates of revision; however, male patients were found to have statistically significantly higher postoperative IKDC scores but at the same time higher rerupture rates. Our findings suggest that sex-based differences in outcomes after ACL reconstruction vary based on which metric is used. These results must be considered when counseling patients with ACL injuries.

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtfpoison protein and a Wtfantidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4poison, but only the spores that inherit wtf4 receive a dose of Wtf4antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4poison transcript. This dual transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers.Author SummaryKiller meiotic drivers are one type of selfish DNA sequence. When only one copy of a killer meiotic driver is found in a genome, the driver is expected to be transmitted to only half of the gametes (e.g. eggs or sperm). Killer meiotic drivers, however, kill developing gametes that do not inherit them, giving the driver a transmission advantage into the next generation. The molecular mechanisms used by these killers are not well understood. In this work, we analyzed how one killer meiotic driver, wtf4 from fission yeast, ensures targeted gamete (spore) killing. Previous work showed that wtf meiotic drivers encode a poison protein that is transmitted to all spores and an antidote protein that rescues only spores that inherit the locus. Here, we show that different timing of the expression of the two proteins, combined with differential inclusion of the proteins in developing spores, both contribute to targeted spore killing. We also demonstrate that wtf4 exploits an essential gene expression pathway, making it difficult for the genome to prevent this locus from being expressed and killing. This extends our knowledge both of how these genetic parasites act and how they are equipped to evade host suppression mechanisms.

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtfpoison protein and a Wtfantidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4poison, but only the spores that inherit wtf4 receive a dose of Wtf4antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4poison transcript. This transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers.

Category: Ankle; Sports; Trauma Introduction/Purpose: Tibiofibular syndesmotic injuries occur in association with fractures or in isolation, often referred to as 'high ankle sprains'. Dynamic instability of the syndesmosis in the high-level athlete is difficult to diagnose, requiring a high index of suspicion for the identification and surgical stabilization to prevent late adverse sequelae, such as recurrent ankle pain, anterolateral soft tissue impingement, local synovitis, and chronic instability of distal syndesmosis. Both CT and MRI have been helpful in identifying syndesmotic injuries, but are static, non-weight bearing imaging modalities that cannot demonstrate dynamic instability, which may miss the unstable nature of some injuries. We present a novel imaging technique utilizing weight-bearing CT with syndesmotic stress in which a case is presented to illustrate it's utility in the elite athlete. Methods: Cone beam weight bearing computed tomography (WBCT) is a well-described imaging modality for evaluation of foot and ankle injuries. We have found it highly beneficial to teach our CT technologists about syndesmosis injuries and the importance of augmented physiologic stress applied across the ankle joint (in addition to the standard WBCT) to better demonstrate instability or motion, particularly at the tibiofibular syndesmosis. To perform an augmented stress weight bearing CT, the patient is positioned in the WBCT scanner and initial images are acquired in the standing weight bearing position with feet directed forward and weight distributed equally. A second image acquisition is then performed (augmented stress), where the patient is coached to firmly plant both feet on the ground and internally rotate the shin and knee. This places an external rotational moment on the TFS due to the planted foot and ankle. Results: Our case is of a 21-year-old male collegiate football player, wide receiver, that sustained an eversion injury to his left ankle during game play. He subsequently was unable to bear weight, with pain anteriorly over the distal tibiofibular joint. Pain was reproduced with dorsiflexion and eversion stress; however, he had a negative 'squeeze test' on examination. Initial weight bearing radiographs were negative. An MRI was obtained which did not reveal evidence of syndesmotic injury. Subsequently, weight- bearing CT stress examination of the syndesmosis was obtained and found to have 8 mm widening of the tibiofibular syndesmosis, 4 mm increased when compared to his contralateral, uninjured, ankle. This was also compared with a neutral WBCT without stress that did not illustrate the unstable nature of the injury. The coronal images also demonstrate increased uncovering of the talus underneath the tibial plafond. Conclusion: Tibiofibular syndesmotic injuries have historically been detected with standard x-ray, stress plain films, standard CT, and MRI. In cases where injury and stability are not obvious by these diagnostic studies, more subtle injuries may be frequently missed leading to increased morbidity, chronic instability, and increased return to play times. The addition of a stress view on weight-bearing CT can allow further identification of instability of the syndesmosis. We propose this technique for diagnosing otherwise unrecognized, subtle dynamically unstable syndesmosis injuries where clinical suspicion persists despite negative imaging, particularly in the elite athlete.

Category: Sports; Ankle; Other Introduction/Purpose: A uniform criterion has not been established for return to sport (RTS) testing which is complicated by the lack of a standardized definition of the term RTS. Most commonly, RTS is defined as playing in at least one game of the athletes' respective sport, or the first game played after treatment.1 However, the timeline from the injury and/or treatment date to RTS varies amongst each physician or institution. Regarding the ankle, there is an enormous paucity of functional testing research. Therefore, the purpose of this project is to review current literature for joint-specific and global lower extremity testing to determine the most valid functional test that can be utilized to prevent re-injury as athletes RTS. Methods: A systematic search of PubMed, PubMed Central, Cochrane Library, OVID, and Embase databases was conducted to identify clinical studies that included evaluation of a return to sport test or functional test (single test or test battery) for the lower extremities. Both operative and non-operative treatments included in this review. Only studies that had patients between the ages of 14 years old and 40 years old were included. Specfici rehab protocik or treatment plan, non-English publications, non- human or cadaver studies, and studies that did not evaluate return to sport test or function test were excluded. Results: Of 8,705 studies, 65 (0.7%) studies published through October of 2021 met inclusion criteria and were analyzed. 52 out of 65 (80%) articles discussed RTS for the knee. Furthermore, 50 out of the 52 (96%) specifically analzyed RTS following ACLR. With this said, we did not abandon ankle and hip RTS cases. Discussed herein, are numerous RTS tests including the most common, isokinetic dynamometry testing which is seen in 38 out of the 52 (73%) of the knee RTS cases. Unfortunately, only 4 out of 65 (6.2%) studies analyzed RTS for the hip and 1 out of the 65 (1.5%) barely touched on the ankle. The remaining studies analyzed healthy participants only. Conclusion: More research is clearly required to identify the most valid functional test batteries for joint-specific RTS lower extremity testing. Even with the enormous amount of literature that exists regarding ACL injuries and testing there is no standardized criterion for RTS clearance. As seen in this review, the research available for the hip and ankle is substantially scarcer in regards functional testing. We hope that the suggested test batteries from this review can serve as a framework for future research and validation for joint-specific RTS functional testing.

Category: Midfoot/Forefoot; Trauma Introduction/Purpose: The Lisfranc joint is the interface between the midfoot and forefoot and forms a strong connection due to its bony architecture and ligamentous attachments in the foot. An unstable Lisfranc injury has traditionally been defined as displacement >2 mm between the 1st and 2nd metatarsal bases or between the medial cuneiform and the second metatarsal base, when compared to the contralateral side on imaging modalities. Classically, Lisfranc injuries have been detected with standard X- ray, stress plain films, standard CT, MRI and ultrasound. We describe an imaging technique that may be used to further assist in the diagnosis and management of subtle Lisfranc injuries, and include a case to demonstrate its use in athletes. Methods: Cone beam weight bearing computed tomography (WBCT) is a well-described imaging modality for evaluation of foot and ankle injuries. We have found it highly beneficial to teach our CT technologists about Lisfranc injuries and the importance of augmented physiologic stress applied across the midfoot (in addition to the standard WBCT) to better demonstrate instability or motion, particularly at the second TMT joint. To perform an augmented stress weight bearing CT, the patient is positioned in the WBCT scanner and initial images are acquired in the standing weight bearing position with feet directed forward and weight distributed equally. A second image acquisition is then performed (augmented stress), where the patient is coached to lift both heels from the scanner platform symmetrically, in a calf-raise type exercise. It is important that the patient distributes weight as evenly as possible between the feet so the affected side is stressed sufficiently. Results: We present here a 22-year-old male collegiate football player who is an offensive lineman. While blocking during a game, his foot was plantarflexed, and he 'felt a pop' in his midfoot. On exam, the player was tender to palpation over the medial midfoot, at the Lisfranc joint. He had pain with forced pronation and abduction as well as axial load through the first webspace. Initial weight bearing radiographs did not show evidence of widening between the medial cuneiform and second metatarsal base. Due to his concerning examination, an MRI was ordered, which revealed a small bony avulsion off the plantar aspect of the second metatarsal base with an otherwise intact Lisfranc ligament. He then underwent weightbearing CT stress views of the foot, which revealed greater than 2 mm of widening between the first and second metatarsals when compared to the contralateral side, indicating instability of the Lisfranc joint. Conclusion: We present the augmented stress weightbearing CT technique of the midfoot to evaluate for subtle Lisfranc injury. The need for this imaging modality has proven useful in the elite athlete with subtle injury to the midfoot, otherwise not found on conventional imaging techniques. Timely diagnosis and treatment is imperiative to these players due to the morbidity associated with missed Lisfranc injuries. We propose this technique for diagnosing otherwise unrecognized, subtle Lisfranc injuries in patients where clinical suspicion persists despite negative imaging because this technique stresses the joint and we believe makes the weightbearing CT more sensitive for this injury.

Meiotic drivers are parasitic loci that force their own transmission into greater than half of the offspring of a heterozygote. Many drivers have been identified, but their molecular mechanisms are largely unknown. The wtf4 gene is a meiotic driver in Schizosaccharomyces pombe that uses a poison-antidote mechanism to selectively kill meiotic products (spores) that do not inherit wtf4. Here, we show that the Wtf4 proteins can function outside of gametogenesis and in a distantly related species, Saccharomyces cerevisiae. The Wtf4poison protein forms dispersed, toxic aggregates. The Wtf4antidote can co-assemble with the Wtf4poison and promote its trafficking to vacuoles. We show that neutralization of the Wtf4poison requires both co-assembly with the Wtf4antidote and aggregate trafficking, as mutations that disrupt either of these processes result in cell death in the presence of the Wtf4 proteins. This work reveals that wtf parasites can exploit protein aggregate management pathways to selectively destroy spores., eLife digest Meiotic drivers are genes that break the normal rules of inheritance. Usually, a gene has a 50% chance of passing on to the next generation. Meiotic drivers force their way into the next generation by poisoning the gametes (the sex cells that combine to form a zygote) that do not carry them. Harnessing the power of genetic drivers could allow scientists to spread beneficial genes across populations. One group of meiotic drivers found in fission yeast is called the 'with transposon fission yeast', or 'wtf' gene family. The wtf drivers act during the production of spores, which are the fission yeast equivalent of sperm, and they encode both a poison that can destroy the spores and its antidote. The poison spreads through the sac holding the spores, and can affect all of them, while the antidote only protects the spores that make it. This means that the spores carrying the wtf genes survive, while the rest of the spores are killed. To understand whether it is possible to use the wtf meiotic drivers to spread other genes, perhaps outside of fission yeast, scientists must first establish exactly how the proteins coded for by genes behave. To do this, Nuckolls et al. examined a member of the wtf family called wtf4. Attaching a fluorescent label to the poison and antidote proteins produced by wtf4 made it possible to see what they do. This revealed that the poison clumps, forming toxic aggregates that damage yeast spores. The antidote works by mopping up these aggregates and moving them to the cell's main storage compartment, called the vacuole. Mutations that disrupted the ability of the antidote to interact with the poison or its ability to move the poison into storage stopped the antidote from working. Nuckolls et al. also showed that if genetic engineering was used to introduce wtf4 into a distantly related species of budding yeast the effects of this meiotic driver were the same. This suggests that the wtf genes may be good candidates for future genetic engineering experiments. Engineered systems known as 'gene drives' could spread beneficial genetic traits through populations. This could include disease-resistance genes in crops, or disease-preventing genes in mosquitoes. The wtf genes are small and work independently of other genes, making them promising candidates for this type of system. These experiments also suggest that the wtf genes could be useful for understanding why clumps of proteins are toxic to cells. Future work could explore why clumps of wtf poison kill spores, while clumps of poison plus antidote do not. This could aid research into human ailments caused by protein clumps, such as Huntington’s or Alzheimer’s disease.

To analyze the literature to compare outcomes and complications following primary lateral ankle ligament repair compared with lateral ankle ligament reconstruction and the suture tape augmentation in patients with lateral ankle instability.Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria, a systematic literature review using the PubMed/Ovid Medline database was performed (October 11, 1947, to October 1, 2019). Clinical trials that included all the following criteria were considered eligible; published in the English language; patients undergoing primary lateral ankle repair or reconstruction with/without autograft or allograft (anterior talofibular ligament, anterior talofibular ligament + calcaneofibular ligament) or suture tape augmentation; a follow-up at least 1 year; reported least 1 of the measured outcomes (The American Orthopaedic Foot Ankle Score, Karlsson Score, return to sport [RTS], complications, skin wound complications, reoperation). Surgical techniques were evaluated, and studies were subdivided by the following categories: primary repair (PR), reconstruction with graft (GR), and suture tape augmentation (STA). Complications, radiographic outcomes, functional outcome scores, and RTS were analyzed.A total of 41 of 1,991 studies met the criteria for final analysis. This included 1,920 patients who underwent surgical intervention for chronic lateral instability with at least a 1-year follow-up. There were 350 patients who had GR, 1,486 who underwent the PR, and 84 who had STA. GR group appeared to have the lowest rate of complications: GR 3.1% (11 of 350), PR 4.2% (63 of 1486), and STA 10.7% (9 of 84). Postoperative American Orthopaedic Foot Ankle Score ranged from 89.0 to 95.1 for GR and 90.0 to 98.8 for PR. Postoperative Karlsson scores ranged from 80.9 to 94.4 for GR and from 89.2 to 94.1 for PR. Anterior drawer postoperative scores ranged from 1.4 to 30.3 mm for GR, 2.7 to 8.6 mm for PR, and 4.1 to 4.2 mm for STA. Postoperative talar tilt ranged from 2.4 to 7.3° for GR, 1.9 to 6.0° for PR, and 3.6 to 4.5° for STA. RTS ranged from 9.5 to 20.4 weeks for the PR group; one study reported a RTS of 10.6 weeks for STA.Excellent outcomes were noted across all intervention groups. Current literature may suggest there is no difference in functional outcomes between patients treated with PR versus GR. However, there may be a potential improvement in functional outcomes with PR versus STA.Level IV, systematic review of Level I to Level IV studies.