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1.
World Neurosurg ; 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38503403

ABSTRACT

OBJECTIVE: The aim of this study is to gauge the current social climate in neurosurgical residency training and attitudes regarding sexual orientation and gender identity. METHODS: We conducted a cross-sectional study through a 35-question questionnaire distributed to roughly 1700 residents at all U.S. neurosurgical residency programs. RESULTS: A total of 107 responses were obtained. Seventeen residents (16%) identified as being an LGBTQ+ individual. The majority (76%) of LGBTQ+ residents were concerned about how their sexual orientation would be perceived while applying to programs, and 47% endorsed purposefully concealing sexual orientation at work for fear of rejection or reprisal. More than half (56%) of those surveyed have witnessed homophobic/transphobic remarks by patients. While at work, 29% of LGBTQ+ individuals stated they are uncomfortable being open with their sexual orientation, and 3 LGBTQ+ individuals admitted being the target of direct homophobic/transphobic comments. CONCLUSIONS: This is the first study to our knowledge that has been conducted assessing the presence, perception, and treatment of LGBTQ+ trainees in neurosurgical residency. Our study outlines the challenges LGBTQ+ individuals face when applying to neurosurgical programs, which involves the perception of their sexual orientation, their witnessed instances of homophobic and transphobic comments by coworkers and patients, and their hesitation with discussing their social lives compared with their non-LGBTQ+ peers at work for fear of judgment or reprisal. Ongoing research is needed to address these issues to obtain workplace respect and fairness in this population and thus create an accepting atmosphere and achieve social justice in neurosurgery training.

2.
Chemistry ; 30(21): e202400239, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38251309

ABSTRACT

DNA-encoded libraries (DELs) have become a leading technology for hit identification in drug discovery projects as large, diverse libraries can be generated. DELs are commonly synthesised via split-and-pool methodology; thus, chemical transformations utilised must be highly efficient, proceeding with high conversions. Reactions performed in DEL synthesis also require a broad substrate scope to produce diverse, drug-like libraries. Many pharmaceutical compounds incorporate multiple C-N bonds, over a quarter of which are synthesised via reductive aminations. However, few on-DNA reductive amination procedures have been developed. Herein is reported the application of the micelle-forming surfactant, TPGS-750-M, to the on-DNA reductive amination of DNA-conjugated amines, yielding highly efficient conversions with a broad range of aldehydes, including medicinally relevant heterocyclic and aliphatic substrates. The procedure is compatible with DNA amplification and sequencing, demonstrating its applicability to DEL synthesis.


Subject(s)
Amines , Micelles , Amination , Amines/chemistry , DNA/chemistry , DNA Replication
3.
Elife ; 122023 Dec 18.
Article in English | MEDLINE | ID: mdl-38108810

ABSTRACT

The enteric nervous system (ENS), a collection of neural cells contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the neural crest and remains largely unchanged thereafter. Here, we show that the lineage composition of maturing ENS changes with time, with a decline in the canonical lineage of neural-crest derived neurons and their replacement by a newly identified lineage of mesoderm-derived neurons. Single cell transcriptomics and immunochemical approaches establish a distinct expression profile of mesoderm-derived neurons. The dynamic balance between the proportions of neurons from these two different lineages in the post-natal gut is dependent on the availability of their respective trophic signals, GDNF-RET and HGF-MET. With increasing age, the mesoderm-derived neurons become the dominant form of neurons in the ENS, a change associated with significant functional effects on intestinal motility which can be reversed by GDNF supplementation. Transcriptomic analyses of human gut tissues show reduced GDNF-RET signaling in patients with intestinal dysmotility which is associated with reduction in neural crest-derived neuronal markers and concomitant increase in transcriptional patterns specific to mesoderm-derived neurons. Normal intestinal function in the adult gastrointestinal tract therefore appears to require an optimal balance between these two distinct lineages within the ENS.


Subject(s)
Enteric Nervous System , Glial Cell Line-Derived Neurotrophic Factor , Adult , Humans , Gastrointestinal Motility , Gene Expression Profiling , Mesoderm
4.
Clin Shoulder Elb ; 26(4): 380-389, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37957884

ABSTRACT

BACKGROUND: Total shoulder arthroplasty (TSA) with a nonspherical humeral head component and inlay glenoid is a successful bone-preserving treatment for glenohumeral arthritis. This study aimed to describe the 90-day complication profile of TSA with this prosthesis and compare major and minor complication and readmission rates between inpatient- and outpatient-procedure patients. METHODS: A retrospective review was performed of a consecutive cohort of patients undergoing TSA with a nonspherical humeral head and inlay glenoid in the inpatient and outpatient settings by a single surgeon between 2017 and 2022. Age, sex, body mass index, American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), and 90-day complication and readmission rates were compared between inpatient and outpatient groups. RESULTS: One hundred eighteen TSAs in 111 patients were identified. Mean age was 64.9 years (range, 39-90) and 65% of patients were male. Ninety-four (80%) and 24 (20%) patients underwent outpatient and inpatient procedures, respectively. Four complications (3.4%) were recorded: axillary nerve stretch injury, isolated ipsilateral arm deep venous thrombosis (DVT), ipsilateral arm DVT with pulmonary embolism requiring readmission, and gastrointestinal bleed requiring readmission. There were no reoperations or other complications. Outpatients were younger with lower ASA and CCI scores than inpatients; however, there was no difference in complications (1/24 vs. 3/94, P=1.00) or readmissions (1/24 vs. 1/94, P=0.37) between these two groups. CONCLUSIONS: TSA with a nonspherical humeral head and inlay glenoid can be performed safely in both inpatient and outpatient settings. Rates of early complications and readmissions were low with no difference according to surgical setting. Level of evidence: IV.

5.
Orthop J Sports Med ; 11(10): 23259671231198025, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37840903

ABSTRACT

Background: Shoulder instability encompasses a spectrum of glenohumeral pathology ranging from subluxation to dislocation. While dislocation frequently leads to removal from play, athletes are often able to play through subluxation. Previous research on glenohumeral instability among athletes has largely focused on missed-time injuries, which has likely disproportionately excluded subluxation injuries and underestimated the overall incidence of shoulder instability. Purpose: To describe the epidemiology of shoulder instability injuries resulting in no missed time beyond the date of injury (non-missed time injuries) among athletes in the National Football League (NFL). Study Design: Descriptive epidemiology study. Methods: The NFL's electronic medical record was retrospectively reviewed to identify non-missed time shoulder instability injuries during the 2015 through 2019 seasons. For each injury, player age, player position, shoulder laterality, instability type, instability direction, injury timing, injury setting, and injury mechanism were recorded. For injuries that occurred during games, incidence rates were calculated based on time during the season as well as player position. The influence of player position on instability direction was also investigated. Results: Of the 546 shoulder instability injuries documented during the study period, 162 were non-missed time injuries. The majority of non-missed time injuries were subluxations (97.4%), occurred during games (70.7%), and resulted from a contact mechanism (91.2%). The overall incidence rate of game-related instability was 1.6 injuries per 100,000 player-plays and was highest during the postseason (3.5 per 100,000 player-plays). The greatest proportion of non-missed time injuries occurred in defensive secondary players (28.4%) and offensive linemen (19.8%), while kickers/punters and defensive secondary players had the highest game incidence rates (5.5 and 2.1 per 100,000 player-plays, respectively). In terms of direction, 54.3% of instability events were posterior, 31.9% anterior, 8.5% multidirectional, and 5.3% inferior. Instability events were most often anterior among linebackers and wide receivers (50% and 100%, respectively), while posterior instability was most common in defensive linemen (66.7%), defensive secondary players (58.6%), quarterbacks (100.0%), running backs (55.6%), and tight ends (75.0%). Conclusion: The majority of non-missed time shoulder instability injuries (97.4%) were subluxations, which were likely excluded from or underreported in previous shoulder instability studies due to the inherent difficulty of detecting and diagnosing shoulder subluxation.

6.
Am J Trop Med Hyg ; 109(4): 752-760, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37604474

ABSTRACT

Antimalarial medications are recommended for chemoprevention as part of malaria control programs to decrease the morbidity and mortality related to more than 200 million infections each year. We sought to evaluate patient and provider acceptability of malaria chemoprevention in a long-acting formulation. We administered questionnaires to patients and providers in malaria endemic districts in Kenya and Zambia. Questions explored preferences and concerns around long-acting antimalarial formulations compared with oral formulations. We recruited 202 patient respondents (Kenya, n = 102; Zambia, n = 100) and 215 provider respondents (Kenya, n = 105; Zambia, n = 110). Long-acting injection was preferred to oral pills, whereas oral pills were preferred to implant or transdermal administration by patient respondents. Of 202 patient respondents, 80% indicated that they 'definitely would try' malaria chemoprevention offered by injection instead of oral pills. Of parents or guardians, 84% of 113 responded that they 'definitely would' have their child age < 12 years and 90% of 88 'definitely would' have their child ≥12 years receive an injection for malaria prevention. Provider respondents indicated that they would be more likely to prescribe a long-acting injectable product compared with an oral product for malaria chemoprevention in adults (70%), adolescents ages 12 years and older (67%), and children <12 years (81%). Potential for prolonged adverse effects with long-acting products was the highest concern for patient respondents, while higher medication-related cost was cited as the most concerning barrier to implementation by providers. Overall, these findings indicate enthusiasm for the development of long-acting injectable antimalarials to provide individual delivery method options across age groups.


Subject(s)
Antimalarials , Malaria , Child , Adult , Adolescent , Humans , Antimalarials/therapeutic use , Malaria/epidemiology , Chemoprevention/methods , Zambia , Injections
7.
Arthrosc Sports Med Rehabil ; 5(3): e833-e838, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37388867

ABSTRACT

Purpose: The purpose of this study was to compare patient-reported outcomes and return to play (RTP) rates following ulnar collateral ligament reconstruction (UCLR) in patients with and without posteromedial elbow impingement (PI) treated with concomitant arthroscopic posteromedial osteophyte resection. Methods: Baseball players who underwent UCLR performed by the senior surgeon with minimum follow-up of 2 years were surveyed in this retrospective cohort study. Primary outcomes included Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow (KJOC) score, Andrews-Timmerman score, and RTP rate. Secondary outcomes included patient satisfaction scores. Results: 35 baseball players were included. Eighteen had no preoperative impingement (mean age: 19.06 ± 3.28 years), while 17 had PI treated with concomitant arthroscopic osteophyte resection (mean age: 20.06 ± 2.68 years). Following surgery, there was no difference in mean Andrews-Timmerman score (no impingement = 91.67 ± 8.04 vs PI = 92.06 ± 7.92, P = .89) nor KJOC score (no impingement = 83.36 ± 11.72 vs PI = 79.88 ± 12.35, P = .40), but there was a decreased mean KJOC throwing control sub-score in the PI group (7.65 ± 2.40 vs 9.11 ± 1.32, P = .04). There was no difference in RTP rate between the groups (no impingement = 72.22%, PI = 94.12%, χ2 = 1.28; P = .26). There was significantly higher mean satisfaction score in the no impingement group (96.67 ± 4.58 vs 90.12 ± 11.91; P = .04), and those patients were also more likely to pursue surgical treatment again (94.44% vs 52.94%, χ2 = 7.88; P = .005). Conclusions: There was no difference in RTP rate following ulnar collateral ligament reconstruction in baseball players with and without posteromedial impingement treated with arthroscopic resection. Outcomes on the KJOC and Andrews-Timmerman scores were good to excellent in both groups. Players in the posteromedial impingement group were less satisfied with their outcome, however, and less likely to elect for surgery if they were to sustain the injury again. Additionally, players in the posteromedial impingement group were found to have decreased throwing control on the KJOC questionnaire, which may suggest that the presence of posteromedial osteophytes represent adaptive changes to stabilize the elbow while throwing. Level of Evidence: Level III, retrospective cohort study.

8.
Orthop J Sports Med ; 11(3): 23259671221147921, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36970322

ABSTRACT

Background: Ulnar collateral ligament (UCL) reconstruction has received a unique level of attention in the press and social media. There has also been an increasing use of the internet by patients to seek medical information. Concern exists regarding the quality and comprehensibility of online information when used for patient education. Purpose: To evaluate the quality and comprehensibility of the most-viewed YouTube videos related to the diagnosis and management of UCL injuries. Based on our new evidence-based scoring rubrics, we hypothesized that the quality and comprehensibility of these videos would be poor. Study Design: Cross-sectional study. Methods: The YouTube platform was searched on September 7, 2021, with the terms "UCL injury," "ulnar collateral ligament injury," "UCL surgery," "ulnar collateral ligament surgery," and "Tommy John surgery," and the 50 most-viewed videos from each search were compiled, yielding 250 videos. After removal of duplicates and application of exclusion criteria, the 100 most-viewed videos remained. Basic attributes, including duration of video and number of views, were recorded. Each video was then analyzed by 2 independent reviewers and evaluated for 4 key parameters (quality of diagnostic content [QAR-D], quality of treatment content [QAR-T], presence of inaccurate information, and comprehensibility) and graded on a novel scale from 1 to 4 (4 being the most appropriate for patient education). Results: The mean QAR-D was 4.83 ± 3.41 (fair quality), and the mean QAR-T was 2.76 ± 3.26 (poor quality). Physician-led educational videos had both the highest mean QAR-D (6.37) and the highest mean QAR-T (4.34). No correlation was observed between video quality and views/likes. A total of 12 videos included ≥1 inaccuracy. The mean comprehensibility score was 2.66 ± 1.12, with 39 videos falling below the acceptable comprehensibility threshold (score <3). Conclusion: The overall quality of UCL injury-related YouTube content was low. In addition, the absence of correlation between video quality and views/likes suggests that patients are not preferentially utilizing the limited high-quality content that does exist on the YouTube platform. In addition, inaccurate videos were prevalent (12%), and almost half of all videos were deemed inappropriate for patient education in terms of comprehensibility, as defined by our comprehensibility parameter.

9.
Proc Natl Acad Sci U S A ; 120(4): e2217687120, 2023 01 24.
Article in English | MEDLINE | ID: mdl-36649430

ABSTRACT

The heart develops in a synchronized sequence of proliferation and differentiation of cardiac progenitor cells (CPCs) from two anatomically distinct pools of cells, the first heart field (FHF) and second heart field (SHF). Congenital heart defects arise upon dysregulation of these processes, many of which are restricted to derivatives of the FHF or SHF. Of the conserved set of signaling pathways that regulate development, the Wnt signaling pathway has long been known for its importance in SHF development. The source of such Wnts has remained elusive, though it has been postulated that these Wnts are secreted from ectodermal or endodermal sources. The central question remains unanswered: Where do these Wnts come from? Here, we show that CPCs autoregulate SHF development via Wnt through genetic manipulation of a key Wnt export protein (Wls), scRNA-seq analysis of CPCs, and use of our precardiac organoid system. Through this, we identify dysregulated developmental trajectories of anterior SHF cell fate, leading to a striking single ventricle phenotype in knockout embryos. We then applied our findings to our precardiac organoid model and found that Wnt2 is sufficient to restore SHF cell fate in our model of disrupted endogenous Wnt signaling. In this study, we provide a basis for SHF cell fate decision-proliferation vs. differentiation-autoregulated by CPCs through Wnt.


Subject(s)
Heart Defects, Congenital , Heart , Humans , Heart/physiology , Cell Differentiation , Wnt Signaling Pathway , Wnt Proteins/genetics , Wnt Proteins/metabolism , Gene Expression Regulation, Developmental
10.
Differentiation ; 130: 7-15, 2023.
Article in English | MEDLINE | ID: mdl-36527791

ABSTRACT

Fibroblast growth factors (Fgfs) have long been implicated in processes critical to embryonic development, such as cell survival, migration, and differentiation. Several mouse models of organ development ascribe a prosurvival requirement specifically to FGF8. Here, we explore the potential role of prosurvival FGF8 signaling in kidney development. We have previously demonstrated that conditional deletion of Fgf8 in the mesodermal progenitors that give rise to the kidney leads to renal aplasia in the mutant neonate. Deleterious consequences caused by loss of FGF8 begin to manifest by E14.5 when massive aberrant cell death occurs in the cortical nephrogenic zone in the rudimentary kidney as well as in the renal vesicles that give rise to the nephrons. To rescue cell death in the Fgf8 mutant kidney, we inactivate the genes encoding the pro-apoptotic factors BAK and BAX. In a wild-type background, the loss of Bak and Bax abrogates normal cell death and has minimal effect on renal development. However, in Fgf8 mutants, the combined loss of Bak and Bax rescues aberrant cell death in the kidneys and restores some measure of kidney development: 1) the nephron progenitor population is greatly increased; 2) some glomeruli form, which are rarely observed in Fgf8 mutants; and 3) kidney size is rescued by about 50% at E18.5. The development of functional nephrons, however, is not rescued. Thus, FGF8 signaling is required for nephron progenitor survival by regulating BAK/BAX and for subsequent steps involving, as yet, undefined roles in kidney development.


Subject(s)
Kidney , Nephrons , Mice , Animals , Female , Pregnancy , bcl-2-Associated X Protein/metabolism , Nephrons/metabolism , Apoptosis , Cell Differentiation , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factor 8/metabolism
11.
Biol Open ; 11(9)2022 09 15.
Article in English | MEDLINE | ID: mdl-36017733

ABSTRACT

Recent genetic lineage tracing studies reveal heterogeneous origins of vascular endothelial cells and pericytes in the developing brain vasculature, despite classical experimental evidence for a mesodermal origin. Here we provide evidence through a genetic lineage tracing experiment that cephalic paraxial mesodermal cells give rise to endothelial cells and pericytes in the developing mouse brain. We show that Hepatic leukemia factor (Hlf) is transiently expressed by cephalic paraxial mesenchyme at embryonic day (E) 8.0-9.0 and the genetically marked E8.0 Hlf-expressing cells mainly contribute to the developing brain vasculature. Interestingly, the genetically marked E10.5 Hlf-expressing cells, which have been previously reported to contain embryonic hematopoietic stem cells, fail to contribute to the vascular cells. Combined, our genetic lineage tracing data demonstrate that a transient expression of Hlf marks a cephalic paraxial mesenchyme contributing to the developing brain vasculature. This article has an associated First Person interview with the first author of the paper.


Subject(s)
Endothelial Cells , Leukemia , Animals , Brain , Humans , Leukemia/metabolism , Mesoderm , Mice , Stem Cells
12.
Cartilage ; 13(3): 19476035221098164, 2022.
Article in English | MEDLINE | ID: mdl-35819020

ABSTRACT

OBJECTIVE: The objective of this study was to identify and describe the existing literature on criteria used for return to play (RTP) following surgical management of osteochondral defects of the knee. DESIGN: A systematic review was performed to evaluate the surgical management of osteochondral defects of the knee in skeletally mature patients with a minimum of 2-year follow-up using Level I to IV studies in PubMed EMBASE from January 1998 to January 2016. RESULTS: Twelve studies with at least one explicitly stated criterion for RTP were identified from a review of 253 published articles. The majority of included studies were Levels II and IV (33%, respectively). Autologous chondrocyte implantation (ACI) was exclusively evaluated in 33.3% of papers and 16.7% evaluated osteochondral allograft transplantation (OCA). Eight different RTP criteria were used alone or in combination across the reviewed studies and time was the most often utilized criterion (83.3%). Minimum time to RTP ranged from 3 to 18 months. CONCLUSIONS: This systematic review identifies current criteria used in the available literature to dictate RTP. Time from surgery was the most commonly employed criterion across the reviewed studies. Given the complex biological processes inherent to the healing of cartilaginous defects, further research is needed to design more comprehensive guidelines for RTP that are patient-centered and utilize multiple functional and psychological domains relevant to the process of returning to sport.


Subject(s)
Cartilage Diseases , Cartilage, Articular , Intra-Articular Fractures , Cartilage Diseases/surgery , Cartilage, Articular/surgery , Humans , Knee , Knee Joint/surgery , Return to Sport
13.
J Am Acad Orthop Surg ; 30(12): 563-572, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35653280

ABSTRACT

Anterior shoulder instability is a common orthopaedic condition that often involves damage to the bony architecture of the glenohumeral joint in addition to the capsulolabral complex. Patients with recurrent shoulder dislocations are at increased risk for glenohumeral bone loss, as each instability event leads to the accumulation of additional glenoid and/or humeral head bone defects. Depending on the degree of bone loss, successful treatment may need to address bony lesions in addition to injured soft-tissue structures. As such, a thorough understanding of methods for evaluating bone loss preoperatively, in terms of location, size, and significance, is essential. Although numerous imaging modalities can be used, three-dimensional imaging has proven particularly useful and is now an integral component of preoperative planning.


Subject(s)
Joint Instability , Shoulder Dislocation , Shoulder Joint , Humans , Humeral Head/pathology , Joint Instability/etiology , Joint Instability/pathology , Joint Instability/surgery , Shoulder/pathology , Shoulder Dislocation/diagnostic imaging , Shoulder Dislocation/surgery , Shoulder Joint/diagnostic imaging , Shoulder Joint/pathology , Shoulder Joint/surgery
14.
Dev Dyn ; 251(5): 877-884, 2022 05.
Article in English | MEDLINE | ID: mdl-34719815

ABSTRACT

BACKGROUND: Fibroblast growth factors (Fgfs) are required for survival and organ formation during embryogenesis. Fgfs often execute their functions redundantly. Previous analysis of Fgf3 mutants revealed effects on inner ear formation and embryonic survival with incomplete penetrance. RESULTS: Here, we show that presence of a neomycin resistance gene (neo) replacing the Fgf3 coding region leads to reduced survival during embryogenesis and an increased penetrance of inner ear defects. Fgf3neo/neo mutants showed reduced expression of Fgf4, which is positioned in close proximity to the Fgf3 locus in the mouse genome. Conditional inactivation of Fgf4 during inner ear development on a Fgf3 null background using Fgf3/4 cis mice revealed a redundant requirement between these Fgfs during otic placode induction. In contrast, inactivation of Fgf3 and Fgf4 in the pharyngeal region where both Fgfs are also co-expressed using a Foxg1-Cre driver did not affect development of the pharyngeal arches. However, these mutants showed reduced perinatal survival. CONCLUSIONS: These results highlight the importance of Fgf signaling during development. In particular, different members of the Fgf family act redundantly to guarantee inner ear formation and embryonic survival.


Subject(s)
Ear, Inner , Fibroblast Growth Factors , Animals , Ectoderm/metabolism , Female , Fibroblast Growth Factor 3/genetics , Fibroblast Growth Factor 3/metabolism , Fibroblast Growth Factor 4 , Fibroblast Growth Factors/metabolism , Forkhead Transcription Factors/genetics , Mice , Multigene Family , Nerve Tissue Proteins/genetics , Pregnancy
15.
Am J Sports Med ; 50(4): 1157-1165, 2022 03.
Article in English | MEDLINE | ID: mdl-34181472

ABSTRACT

BACKGROUND: Injury to the ulnar collateral ligament of the elbow is common among overhead throwing athletes and can result in significant functional limitations. While surgical reconstruction offers high rates of return to competition, there are no validated or universally accepted guidelines for determining when an athlete can safely resume play. PURPOSE: To assess the existing scientific literature for return-to-competition criteria utilized after ulnar collateral ligament reconstruction. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: The PubMed database was searched for clinical investigations of ulnar collateral ligament reconstruction in overhead throwing athletes published between January 2000 and June 2020. Only studies that had a minimum follow-up of 1 year and included at least 1 specific return-to-competition criterion were considered. RESULTS: A total of 15 studies were included in the final analysis, encompassing 1156 patients with an average age of 20.7 years (SD, 2.0 years). Baseball players composed 96.3% of patients for whom sport was specified, and 92.4% of baseball players were pitchers. The most common return-to-competition criterion, identified in 87% of studies, was completion of a return-to-throwing program, which started on average 16.7 weeks (range, 12-18 weeks) after surgery. A return-to-mound program was utilized in 53% of studies, starting on average 7.4 months (range, 6-9 months) postoperatively. Minimum time from surgery was used in 73% studies, with players waiting 7 to 12 months (mean, 9.7; SD, 1.4 months) after surgery before return-to-competition consideration. The overall rate of return to competition at the preinjury level or higher was 85.7% (SD, 8.5%) at an average of 12.2 months (SD, 0.6 months). CONCLUSION: In general, we observed a paucity of literature describing the return-to-competition process after ulnar collateral ligament reconstruction in overhead throwing athletes. Only 3 explicit return-to-competition criteria were identified across all studies: completion of a return-to-throwing program, completion of a return-to-mound program for pitchers, and minimum time from surgery. Increased transparency regarding postoperative rehabilitation protocols and further research are necessary to identify and validate sport-specific return-to-competition criteria, which will ultimately help athletes return to play in a safe and timely fashion after ulnar collateral ligament reconstruction.


Subject(s)
Baseball , Collateral Ligament, Ulnar , Collateral Ligaments , Elbow Injuries , Elbow Joint , Ulnar Collateral Ligament Reconstruction , Adult , Baseball/injuries , Collateral Ligament, Ulnar/injuries , Collateral Ligament, Ulnar/surgery , Collateral Ligaments/injuries , Collateral Ligaments/surgery , Elbow/surgery , Elbow Joint/surgery , Humans , Ulnar Collateral Ligament Reconstruction/methods , Young Adult
16.
Chem Sci ; 12(27): 9475-9484, 2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34349922

ABSTRACT

DNA encoded libraries (DELs) represent powerful new technology for finding small molecule ligands for proteins and are increasingly being applied to hit finding in medicinal chemistry. Crucial to the synthesis of high quality DELs is the identification of chemical reactions for their assembly that proceed with very high conversion across a range of different substrates, under conditions compatible with DNA-tagged substrates. Many current chemistries used in DEL synthesis do not meet this requirement, resulting in libraries of low fidelity. Amide couplings are the most commonly used reaction in synthesis of screening libraries and also in DELs. The ability to carry out highly efficient, widely applicable amide couplings in DEL synthesis would therefore be highly desirable. We report a method for amide coupling using micelle forming surfactants, promoted by a modified linker, that is broadly applicable across a wide range of substrates. Most significantly, this works exceptionally well for coupling of DNA-conjugated carboxylic acids (N-to-C) with amines in solution, a procedure that is currently very inefficient. The optimisation of separate procedures for coupling of DNA-conjugated acids and amines by reagent screening and statistically driven optimisation is described. The generality of the method is illustrated by the application to a wide range of examples with unprecedented levels of conversion. The utility of the (N-to-C) coupling of DNA-conjugated acids in DEL synthesis is illustrated by the three cycle synthesis of a fully DNA-encoded compound by two cycles of coupling of an aminoester, with intermediate ester hydrolysis, followed by capping with an amine. This methodology will be of great utility in the synthesis of high fidelity DELs.

17.
JSES Int ; 5(4): 692-698, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34223417

ABSTRACT

BACKGROUND: Machine learning has shown potential in accurately predicting outcomes after orthopedic surgery, thereby allowing for improved patient selection, risk stratification, and preoperative planning. This study sought to develop machine learning models to predict nonhome discharge after total shoulder arthroplasty (TSA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent elective TSA from 2012 to 2018. Boosted decision tree and artificial neural networks (ANN) machine learning models were developed to predict non-home discharge and 30-day postoperative complications. Model performance was measured using the area under the receiver operating characteristic curve (AUC) and overall accuracy (%). Multivariate binary logistic regression analyses were used to identify variables that were significantly associated with the predicted outcomes. RESULTS: There were 21,544 elective TSA cases identified in the National Surgical Quality Improvement Program registry from 2012 to 2018 that met inclusion criteria. Multivariate logistic regression identified several variables associated with increased risk of nonhome discharge including female sex (odds ratio [OR] = 2.83; 95% confidence interval [CI] = 2.53-3.17; P < .001), age older than 70 years (OR = 3.19; 95% CI = 2.86-3.57; P < .001), American Society of Anesthesiologists classification 3 or greater (OR = 2.70; 95% CI = 2.41-2.03; P < .001), prolonged operative time (OR = 1.38; 95% CI = 1.20-1.58; P < .001), as well as history of diabetes (OR = 1.56; 95% CI = 1.38-1.75; P < .001), chronic obstructive pulmonary disease (OR = 1.71; 95% CI = 1.46-2.01; P < .001), congestive heart failure (OR = 2.65; 95% CI = 1.72-4.01; P < .001), hypertension (OR = 1.35; 95% CI = 1.20-1.52; P = .004), dialysis (OR = 3.58; 95% CI = 2.01-6.39; P = .002), wound infection (OR = 5.67; 95% CI = 3.46-9.29; P < .001), steroid use (OR = 1.43; 95% CI = 1.18-1.74; P = .010), and bleeding disorder (OR = 1.84; 95% CI = 1.45-2.34; P < .001). The boosted decision tree model for predicting nonhome discharge had an AUC of 0.788 and an overall accuracy of 90.3%. The ANN model for predicting nonhome discharge had an AUC of 0.851 and an overall accuracy of 89.9%. For predicting the occurrence of 1 or more postoperative complications, the boosted decision tree model had an AUC of 0.795 and an overall accuracy of 95.5%. The ANN model yielded an AUC of 0.788 and an overall accuracy of 92.5%. CONCLUSIONS: Both the boosted decision tree and ANN models performed well in predicting nonhome discharge with similar overall accuracy, but the ANN had higher discriminative ability. Based on the findings of this study, machine learning has the potential to accurately predict nonhome discharge after elective TSA. Surgeons can use such tools to guide patient expectations and to improve preoperative discharge planning, with the ultimate goal of decreasing hospital length of stay and improving cost-efficiency.

18.
Orthop J Sports Med ; 9(6): 23259671211016340, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34262981

ABSTRACT

BACKGROUND: Online video-sharing platforms such as YouTube have become popular sources of medical information for patients. However, concern exists regarding the quality of such non-peer reviewed content. In fact, a previous investigation found the majority of YouTube information related to femoroacetabular impingement (FAI) to be of poor quality. PURPOSE: To provide an updated assessment of the quality of FAI-related videos available on YouTube. STUDY DESIGN: Cross-sectional study. METHODS: The terms FAI, femoroacetabular impingement, and hip impingement were searched on YouTube, and exclusion criteria were applied to the first 100 results for each term. The diagnostic and treatment content of each video was graded and assigned a quality assessment rating based on a previously used rubric. Video characteristics (e.g. duration, views, "likes") were compared using both quality assessment rating and video source. RESULTS: A total of 142 videos were included in the final analysis. The most common video source was educational (48.6%), followed by physician-sponsored (30.3%). The majority of videos were graded as "somewhat useful" for both diagnostic and treatment content (59.4% and 61.6%, respectively); however, treatment content was rated "not useful" more often than diagnostic information (20.3% vs. 8.7%, respectively). Videos rated as "somewhat useful" received the most views per day on average, while educational videos were the most viewed by source (views and views per day). Educational videos had more views and likes on average than physician-sponsored videos (P < .05), but all other comparisons of video characteristics by source were not significant. Video duration was the only characteristic found to vary significantly by quality assessment rating (P < .001 for both diagnostic and treatment analyses), with higher-quality videos tending to be longer. Videos rated as "excellent" and "very useful" had mean durations >30 minutes but were viewed the least. CONCLUSION: The overall quality of FAI-related content on YouTube remains low. Clinicians should be familiar with medical information available to patients on the internet, as it can influence patients' perspectives and shared decision-making processes. This review substantiates the need for more publicly available, high-quality video content regarding the diagnosis and treatment of FAI.

19.
Orthop J Sports Med ; 9(5): 23259671211007743, 2021 May.
Article in English | MEDLINE | ID: mdl-33997084

ABSTRACT

BACKGROUND: Shoulder instability is a common and potentially debilitating injury among collision sport athletes that can lead to long-term damage of the glenohumeral joint. Limited data exist regarding instability among elite athletes in the National Football League (NFL). PURPOSE: To describe the epidemiology of shoulder instability in the NFL from 2012 through 2017. STUDY DESIGN: Descriptive epidemiology study. METHODS: The NFL's injury database was reviewed for shoulder instability injuries resulting in missed time during the study inclusion dates. Injuries were classified by type and direction, as well as timing, setting, and mechanism. Median missed time was determined for the different types and directions of instability. Incidence rates for game-related injuries were calculated based on timing during the season and player position. Finally, the relationship between player position and instability direction was assessed. RESULTS: During the 6-year study period, 355 players sustained 403 missed-time shoulder instability injuries. Most injuries occurred during games (65%) via a contact mechanism (85%). The overall incidence rate of game-related instability was 3.6 injuries per 100,000 player-plays and was highest during the preseason (4.9 per 100,000 player-plays). The defensive secondary position accounted for the most injuries, but quarterbacks had the highest incidence rate in games (5.5 per 100,000 player-plays). Excluding unspecified events (n = 128; 32%), 70% (n = 192) of injuries were subluxations and 30% (n = 83) were dislocations; 75% of dislocations were anterior, while subluxations were more evenly distributed between the anterior and posterior directions (45% vs 52%, respectively). Players missed substantially more time after dislocation compared with subluxation (median, 47 days vs 13 days, respectively). When instability direction was known, the majority of instability events among quarterbacks and offensive linemen were posterior (73% and 53%, respectively), while anterior instability was most common for all other positions. CONCLUSION: Shoulder instability is a common injury in the NFL and can result in considerable missed time. Dislocations occur less frequently than subluxations but lead to greater time lost. While most dislocations are anterior, more than half of subluxations are posterior, which is likely the result of repetitive microtrauma to the posterior capsulolabral complex sustained during sport-specific motions such as blocking. The risk of instability varies by player position, and position may also influence instability direction.

20.
J Orthop Trauma ; 35(10): 535-541, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-33993177

ABSTRACT

OBJECTIVE: To determine the association between surgical timing and short-term morbidity and mortality in elderly patients who sustain hip fractures using a national trauma database (OTA/AO 31A1-3, 31B1-3). DESIGN: Retrospective cohort study. SETTING: Level I-IV trauma centers in the United States. PATIENTS/PARTICIPANTS: All patients ≥65 years of age who underwent surgery for hip fracture from 2011 to 2013. INTERVENTION: Time to surgery of <24, 24-48, and >48 hours from admission. MAIN OUTCOME MEASUREMENTS: Primary outcome was mortality by hospital discharge. Secondary outcomes were complications of myocardial infarction, cardiac arrest, acute respiratory distress syndrome (ARDS), unplanned reintubation, pneumonia, stroke, severe sepsis, and intensive care unit length of stay. RESULTS: Twenty-seven thousand fifty-eight patients were included in the study. Relative to the <24 hours cohort, patients in the >48 hours cohort were at increased risk for mortality (OR 1.89, 95% CI 1.52-2.33, P < 0.001), ARDS (OR 2.57, 95% CI 1.94-3.39, P < 0.001 for ARDS), myocardial infarction (OR 2.19, 95% CI 1.64-2.94, P < 0.0001), pneumonia (OR 2.04, 95% CI 1.71-2.44, P < 0.001), severe sepsis (OR 2.34, 95% CI 1.52-3.58, P = 0.003), and intensive care unit stay (OR 2.48, 95% CI 2.25-2.74, P < 0.0001). A subgroup analysis showed that healthier patients (modified Charlson Comorbidity Index less than 5) who had surgery >48 hours were not at increased risk of mortality. CONCLUSIONS: For elderly patients with hip fractures, delaying surgery for more than 48 hours may be associated with increased short-term morbidity and mortality. This association may be pronounced for patients with more medical comorbidities. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Hip Fractures , Aged , Databases, Factual , Hip Fractures/surgery , Hospitalization , Humans , Retrospective Studies , Trauma Centers , United States/epidemiology
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