Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation.

Aims: The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease. Methods and results: Interleukin-6-overexpressing (IL-6OE) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6OE mice) overexpressing the cytokine in myeloid cells. Eight- to 12-week-old LysM-IL-6OE mice spontaneously developed inflammatory colitis and significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS) formation, and vascular dysfunction in resistance vessels. The latter phenotype was associated with decreased survival. Vascular dysfunction was accompanied by a significant accumulation of neutrophils, monocytes, and macrophages in the aorta, increased myeloid cell reactivity (elevated ROS production), and vascular fibrosis associated with phenotypic changes in vascular smooth muscle cells. In addition to elevated Mcp1 and Cxcl1 mRNA levels, aortae from LysM-IL-6OE mice expressed higher levels of inducible NO synthase and endothelin-1, thus partially accounting for vascular dysfunction, whereas systemic blood pressure alterations were not observed. Bone marrow (BM) transplantation experiments revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner. Conclusion: Mice with conditional overexpression of IL-6 in myeloid cells show systemic and vascular inflammation as well as endothelial dysfunction. A decrease in circulating IL-6 levels by replacing IL-6-producing myeloid cells in the BM improved vascular dysfunction in this model, underpinning the relevant role of IL-6 in vascular disease.

Changes in cortical grey matter volume with Cognitive Orientation to daily Occupational Performance intervention in children with developmental coordination disorder.

Introduction: Cognitive Orientation to daily Occupational Performance (CO-OP) is a cognitive-based, task-specific intervention recommended for children with developmental coordination disorder (DCD). We recently showed structural and functional brain changes after CO-OP, including increased cerebellar grey matter. This study aimed to determine whether CO-OP intervention induced changes in cortical grey matter volume in children with DCD, and if these changes were associated with improvements in motor performance and movement quality. Methods: This study is part of a randomized waitlist-control trial (ClinicalTrials.gov ID: NCT02597751). Children with DCD (N = 78) were randomized to either a treatment or waitlist group and underwent three MRIs over 6 months. The treatment group received intervention (once weekly for 10 weeks) between the first and second scan; the waitlist group received intervention between the second and third scan. Cortical grey matter volume was measured using voxel-based morphometry (VBM). Behavioral outcome measures included the Performance Quality Rating Scale (PQRS) and Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). Of the 78 children, 58 were excluded (mostly due to insufficient data quality), leaving a final N = 20 for analyses. Due to the small sample size, we combined both groups to examine treatment effects. Cortical grey matter volume differences were assessed using a repeated measures ANOVA, controlling for total intracranial volume. Regression analyses examined the relationship of grey matter volume changes to BOT-2 (motor performance) and PQRS (movement quality). Results: After CO-OP, children had significantly decreased grey matter in the right superior frontal gyrus and middle/posterior cingulate gyri. We found no significant associations of grey matter volume changes with PQRS or BOT-2 scores. Conclusion: Decreased cortical grey matter volume generally reflects greater brain maturity. Decreases in grey matter volume after CO-OP intervention were in regions associated with self-regulation and motor control, consistent with our other studies. Decreased grey matter volume may be due to focal increases in synaptic pruning, perhaps as a result of strengthening networks in the brain via the repeated learning and actions in therapy. Findings from this study add to the growing body of literature demonstrating positive neuroplastic changes in the brain after CO-OP intervention.

Cortical grey matter volume differences in children with developmental coordination disorder compared to typically developing children.

Introduction: The cause of Developmental Coordination Disorder (DCD) is unknown, but neuroimaging evidence suggests that DCD may be related to altered brain development. Children with DCD show less structural and functional connectivity compared to typically developing (TD) children, but few studies have examined cortical volume in children with DCD. The purpose of this study was to investigate cortical grey matter volume using voxel-based morphometry (VBM) in children with DCD compared to TD children. Methods: This cross-sectional study was part of a larger randomized-controlled trial (ClinicalTrials.gov ID: NCT02597751) that involved various MRI scans of children with/without DCD. This paper focuses on the anatomical scans, performing VBM of cortical grey matter volume in 30 children with DCD and 12 TD children. Preprocessing and VBM data analysis were conducted using the Computational Anatomy Tool Box-12 and a study-specific brain template. Differences between DCD and TD groups were assessed using a one-way ANOVA, controlling for total intracranial volume. Regression analyses examined if motor and/or attentional difficulties predicted grey matter volume. We used threshold-free cluster enhancement (5,000 permutations) and set an alpha level of 0.05. Due to the small sample size, we did not correct for multiple comparisons. Results: Compared to the TD group, children with DCD had significantly greater grey matter in the left superior frontal gyrus. Lower motor scores (meaning greater impairment) were related to greater grey matter volume in left superior frontal gyrus, frontal pole, and right middle frontal gyrus. Greater grey matter volume was also significantly correlated with higher scores on the Conners 3 ADHD Index in the left superior frontal gyrus, superior parietal lobe, and precuneus. These results indicate that greater grey matter volume in these regions is associated with poorer motor and attentional skills. Discussion: Greater grey matter volume in the left superior frontal gyrus in children with DCD may be a result of delayed or absent healthy cortical thinning, potentially due to altered synaptic pruning as seen in other neurodevelopmental disorders. These findings provide further support for the hypothesis that DCD is related to altered brain development.

naRNA-LL37 composite DAMPs define sterile NETs as self-propagating drivers of inflammation.

Neutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs). NETs counteract microbes but are also linked to inflammation in atherosclerosis, arthritis, or psoriasis by unknown mechanisms. Here, we report that NET-associated RNA (naRNA) stimulates further NET formation in naive PMNs via a unique TLR8-NLRP3 inflammasome-dependent pathway. Keratinocytes respond to naRNA with expression of psoriasis-related genes (e.g., IL17, IL36) via atypical NOD2-RIPK signaling. In vivo, naRNA drives temporary skin inflammation, which is drastically ameliorated by genetic ablation of RNA sensing. Unexpectedly, the naRNA-LL37 'composite damage-associated molecular pattern (DAMP)' is pre-stored in resting neutrophil granules, defining sterile NETs as inflammatory webs that amplify neutrophil activation. However, the activity of the naRNA-LL37 DAMP is transient and hence supposedly self-limiting under physiological conditions. Collectively, upon dysregulated NET release like in psoriasis, naRNA sensing may represent both a potential cause of disease and a new intervention target.

Effect of BMI on Complications Following Total Shoulder Arthroplasty: A Population-Wide Analysis.

BACKGROUND: Evidence regarding the effect of body mass index (BMI) on complications following anatomic shoulder arthroplasty (aTSA) and reverse shoulder arthroplasty (rTSA) remains controversial. This high-powered study examines the effect of BMI on surgical and medical complications following anatomic shoulder arthroplasty (aTSA) and reverse shoulder arthroplasty (rTSA). METHODS: This retrospective cohort study was conducted using the Premier Healthcare Database (PHD) to query all adult patients who underwent primary, elective TSA (aTSA, rTSA) from 2016 to 2020. Patients eligible for inclusion were identified using ICD-10 and CPT codes for primary TSA. Patients were stratified into three subgroups based on BMI (BMI <30 kg/m2, BMI 30-35 kg/m2, BMI > 35 kg/m2). The primary endpoints assessed were 90-day risks of postoperative complications, revisions, and readmissions among the three BMI groups undergoing primary TSA. RESULTS: A total of 32,645 patients were analyzed; 10,951 patients underwent aTSA and 21,694 patients underwent rTSA. Patient populations for aTSA and rTSA differed significantly across all BMI categories in terms of age, sex, cost of care, and insurance status. After multivariate regression analysis, there was no increased risk of surgical complications in the aTSA and rTSA cohorts with BMI 30-35 kg/m2 and BMI > 35 kg/m2. In the aTSA cohort, rates of acute respiratory failure (adjusted Odds Ratio (aOR) 2.65) was all significantly higher in the BMI > 35 kg/m2 group. As for rTSA cohort, acute respiratory failure (aOR 1.67) and acute renal failure (aOR 1.53) were significantly higher in the BMI > 35 kg/m2 group. CONCLUSION: While we found no increased risk of immediate postoperative surgical risks, patients with a BMI > 35 kg/m2 demonstrated greater risk of medical complications after rTSA. Given this trend, providers should exercise caution in patient selection for TSA and counsel obese patients as to these increased risks. Future studies should aim to provide a more comprehensive picture of the effect of BMI on functional outcomes after TSA.

Cerebrovascular Reactivity Following Spinal Cord Injury.

Background: Spinal cord injuries (SCI) often result in cardiovascular issues, increasing the risk of stroke and cognitive deficits. Objectives: This study assessed cerebrovascular reactivity (CVR) using functional magnetic resonance imaging (fMRI) during a hypercapnic challenge in SCI participants compared to noninjured controls. Methods: Fourteen participants were analyzed (n = 8 with SCI [unless otherwise noted], median age = 44 years; n = 6 controls, median age = 33 years). CVR was calculated through fMRI signal changes. Results: The results showed a longer CVR component (tau) in the grey matter of SCI participants (n = 7) compared to controls (median difference = 3.0 s; p < .05). Time since injury (TSI) correlated negatively with steady-state CVR in the grey matter and brainstem of SCI participants (RS = -0.81, p = .014; RS = -0.84, p = .009, respectively). Lower steady-state CVR in the brainstem of the SCI group (n = 7) correlated with lower diastolic blood pressure (RS = 0.76, p = .046). Higher frequency of hypotensive episodes (n = 7) was linked to lower CVR outcomes in the grey matter (RS = -0.86, p = .014) and brainstem (RS = -0.89, p = .007). Conclusion: Preliminary findings suggest a difference in the dynamic CVR component, tau, between the SCI and noninjured control groups, potentially explaining the higher cerebrovascular health burden in SCI individuals. Exploratory associations indicate that longer TSI, lower diastolic blood pressure, and more hypotensive episodes may lead to poorer CVR outcomes. However, further research is necessary to establish causality and support these observations.

NCAA football players are at higher risk of upper extremity injury after first-time concussion.

BACKGROUND: Previous research has demonstrated that concussions increase the risk of subsequent lower extremity musculoskeletal injury in athletes. However, the risk of upper extremity injury in athletes' post-concussion is poorly understood. METHODS: All concussed football players within a National Collegiate Athletic Association (NCAA) Division I conference athletic database were identified between 2017 and 2021. After exclusions, each athlete experiencing their first concussion was then retrospectively reviewed for upper extremity injuries in the year prior to their concussion and in the year beginning at 90 days after their concussion. All upper extremity injuries were identified and the odds ratio, 95% confidence interval, and statistical significance between groups were calculated in Microsoft Excel. RESULTS: 160 de-identified football players from a single conference who were first diagnosed with concussions in the seasons from 2017 through 2021 met inclusion criteria. In these athletes the odds of upper extremity injury in year following first diagnosed concussion were 2.36 times higher than in the year prior (95% CI 1.13-4.95, p = 0.02). Shoulder was the most common site of injury with 57.7% of injuries compared to 19.2% in the hand, 15.4% in the elbow, 7.7% in the forearm, and 0% in the wrist. CONCLUSION: This study demonstrates that collegiate football players are at a 2.36 times greater risk of upper extremity injury in the year following their first diagnosed concussion compared to the year preceding it. The most common site of upper extremity injury after concussion was the shoulder. LEVEL OF EVIDENCE: III.

Subjective Causes for Failure to Return to Sport After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

CONTEXT: While current literature has explored the outcomes of athletes who return to sport (RTS) after anterior cruciate ligament (ACL) injuries, less is known about the outcomes of those who are unsuccessful in returning to sport. OBJECTIVE: To determine the rate of athletes who did not RTS after primary ACL reconstruction (ACLR) and to identify the specific subjective reasons for failure to RTS. DATA SOURCES: A comprehensive search of the PubMed/MEDLINE, Scopus, and Web of Science databases was conducted through April 2021. STUDY SELECTION: Eligible studies included those explicitly reporting the rate of failure for RTS after ACLR as well as providing details on reasons for athletes' inability to return; 31 studies met the inclusion criteria. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 2 to 4. DATA EXTRACTION: The reasons for failure to RTS referred to in our study are derived from those established previously in the studies included. Data were collected on the number of athletes, mean age, mean follow-up time, type of sport played, failure to RTS rate, and specific reasons for failure to return. RESULTS: The weighted rate of failure to RTS after ACLR was 25.5% (95% CI, 19.88-31.66). The estimated proportion of psychosocial-related reasons cited for failure to RTS was significantly greater than knee-related reasons for failure RTS (55.4% vs 44.6%, P < 0.01). The most cited reason for failure to RTS was fear of reinjury (33.0%). CONCLUSION: This study estimates the rate of failure to RTS after ACLR to be 25.5%, with the majority of athletes citing fear of reinjury as the major deterrent for returning to sports. We highlight how factors independent of surgical outcomes may impact an athlete's ability to return to play given that the predominant reason for no RTS after ACLR was unrelated to the knee.

Cracking the NLRP3 code: Pioneering precision medicine for inflammation.

Precisely diagnosing and effectively treating cryopyrin-associated periodic syndrome (CAPS), an inflammatory condition linked to gain-of-function NLRP3 inflammasome mutations, poses challenges. A novel classification approach may help inform therapeutic decisions and offer valuable insights into broader inflammatory conditions (Cosson et al. J. Exp. Med. 2024. https://doi.org/10.1084/jem.20231200).

Outcomes of multiligament knee injury treated with versus without internal brace suture augmentation.

PURPOSE: To compare the postoperative outcomes between Internal Brace (IB) and non-IB patients who underwent surgical management of multiple-ligament knee injuries (MLKI). METHODS: Patients who underwent surgical management of MLKI at two institutions between 2010 and 2020 were identified and offered participation in the study via the collection of postoperative functional outcomes for MLKI; Lysholm Knee score, Multiligament Quality of Life (ML-QOL), Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT), Pain Interference (PI), Physical Function (PF), and Mobility instruments (MI). The postoperative outcomes and reoperation rates were compared between the IB group and non-IB group. RESULTS: One hundred and twenty-six patients were analyzed; 89 were included in the IB group (31.5% female; age 35.6 ± 1.4 years), and 37 were included in the non-IB group (25.7% female; age 38.8 ± 2.4 years). Mean follow-up time of the entire cohort was 37.9 ± 4.7 months [IB: 21.8 + 1.63; non-IB: 76.4 ± 6.2, p < 0.001). The IB group achieved similar PROMIS CAT [PROMIS Pain (51.8 + 1.1 vs. 52.1 + 1.6, p = 0.8736), Physical Function (46.6 + 1.2 vs. 46.4 + 1.8, p = 0.9168), Mobility (46.0 + 1.0 vs. 43.7 + 1.6, p = 0.2185)], ML-QOL [ML-QOL Physical Impairment (36.6 + 2.5 vs. 43.5 ± 4.2, p = 0.1485), Emotional Impairment (42.5 + 2.9 vs. 48.6 ± 4.6, p = 0.2695), Activity Limitation (34.5 + 2.8 vs. 36.2 ± 4.3, p = 0.7384), Societal Involvement (39.1 + 3.0 vs. 41.7 + 4.2, p = 0.6434)] and Lysholm knee score (64.9 + 2.5 vs. 60.4 + 4.0, p = 0.3397) postoperatively compared the non-IB group, but the differences were not significant. CONCLUSION: In this cohort of patients with MLKI treated with versus without IB, outcomes and reoperation rates trended toward favoring IB, but the study was not sufficiently powered to reach statistical significance. Internal bracing could be useful in the management of MLKI. In the future, matched patient cohorts with more patients are warranted to further evaluate the clinical impact of the internal brace in MLKI.

Differential survival of Staphylococcal species in macrophages.

Staphylococcus aureus is considered an extracellular pathogen, yet the bacterium is able to survive within and escape from host cells. An agr/sae mutant of strain USA300 is unable to escape from macrophages but can replicate and survive within. We questioned whether such "non-toxic" S. aureus resembles the less pathogenic coagulase-negative Staphylococcal (CoNS) species like S. epidermidis, S. carnosus, S. lugdunensis, S. capitis, S. warneri, or S. pettenkoferi. We show that the CoNS are more efficiently killed in macrophage-like THP-1 cells or in human primary macrophages. Mutations in katA, copL, the regulatory system graRS, or sigB did not impact bacterial survival in THP-1 cells. Deletion of the superoxide dismutases impaired S. aureus survival in primary macrophages but not in THP-1 cells. However, expression of the S. aureus-specific sodM in S. epidermidis was not sufficient to protect this species from being killed. Thus, at least in those cells, better bacterial survival of S. aureus could not be linked to higher protection from ROS. However, "non-toxic" S. aureus was found to be insensitive to pH, whereas most CoNS were protected when phagosomal acidification was inhibited. Thus, species differences are at least partially linked to differences in sensitivity to acidification.

Does preoperative screening VCUG affect the outcomes and complications of pyeloplasty in patients with ureteropelvic junction obstruction?

INTRODUCTION: The role of voiding cystourethrogram (VCUG) in evaluating vesicoureteral reflux (VUR) in patients with known ureteropelvic junction obstruction (UPJO) remains unclear. While VCUG is frequently performed, the incidence of concomitant VUR and UPJO is low, and VUR is often low-grade with high rates of spontaneous regression. OBJECTIVE: To analyze the clinical relevance of VCUG in patients with UPJO by determining its incidence and studying the difference in clinical outcomes between patients with known, unknown, and negative VUR. STUDY DESIGN: Retrospective review of patients with UPJO who underwent pyeloplasty from 2012 to 2020 with <18 years-old, unilateral UPJO, postoperative follow-up of ≥2 months and had at least 1 renal ultrasound (US) after pyeloplasty. Results were compared among 3 groups: patients who underwent VCUG before pyeloplasty and were found to have VUR (group 1), patients who underwent VCUG before pyeloplasty without VUR (group 2), and patients who did not have a VCUG before pyeloplasty (group 3). RESULTS: A total of 275 patients met the inclusion criteria, of which 21 patients were classified in group 1, 166 patients in group 2, and 88 patients in group 3 (Table). The age at preoperative VCUG was 14.7 ± 32.9 months in group 1 and 15.17 ± 35.8 months in group 2 (p = 0.960). Overall, the incidence of concomitant UPJO and VUR was 11.2%. In group 1 the initial VUR grade was 5 in 2 patients, 4 in 3, 3 in 5, 2 in 7, and 1 in 4 patients. Of these, only 1 patient required ureteral reimplantation after pyeloplasty. Post-pyeloplasty, no significant differences were observed in complications (p = 0.7436), length of follow up (p = 0.3212), SFU grade 4 hydronephrosis (p = 0.2247), postoperative UTIs (p = 0.1047) and pyeloplasty success rate (p = 0.4206) among the 3 groups. Despite the use of antibiotic prophylaxis being significantly different amongst the three groups (p < 0.001), it was not associated with a lower incidence of postoperative UTIs (group 1 p = 0.068, group 2 p = 0.486, group 3 p = 1). In patients with reflux, an increase in age was associated with a decrease in the rates of complications (p = 0.019). CONCLUSION: We found no significant difference in the outcomes in patients who had a preoperative VCUG as compared to those who did not. The preoperative diagnosis of VUR by VCUG changed the management in less than 1% of the study population and thus its role in patients with UPJO should be reevaluated.

Shoulder arthroplasty for inflammatory arthritis is associated with higher rates of medical and surgical complications: a nationwide matched cohort analysis from 2016-2020.

BACKGROUND: Inflammatory arthritis (IA) represents a less common indication for anatomic and reverse total shoulder arthroplasty (TSA) than osteoarthritis (OA). The safety and efficacy of anatomic and reverse TSA in this population has not been as well studied compared to OA. We analyzed the differences in outcomes between IA and OA patients undergoing TSA. METHODS: Patients who underwent primary anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) from 2016-2020 were identified in the Premier Healthcare Database. Inflammatory arthritis (IA) patients were identified using International Classification of Diseases, Tenth Revision, diagnosis codes and compared to osteoarthritis controls. Patients were matched in a 1:8 fashion by age (±3 years), sex, race, and presence of pertinent comorbidities. Patient demographics, hospital factors, and patient comorbidities were compared. Multivariate regression was performed following matching to account for any residual confounding and 90-day complications were compared between the 2 cohorts. Descriptive statistics and regression analysis were employed with significance set at P < .05. RESULTS: Prior to matching, 5685 IA cases and 93,539 OA controls were identified. Patients with IA were more likely to be female, have prolonged length of stay and increased total costs (P < .0001). After matching and multivariate analysis, 4082 IA cases and 32,656 controls remained. IA patients were at increased risk of deep wound infection (OR 3.14, 95% CI 1.38-7.16, P = .006), implant loosening (OR 4.11, 95% CI 1.17-14.40, P = .027), and mechanical complications (OR 6.34, 95% CI 1.05-38.20, P = .044), as well as a decreased risk of postoperative stiffness (OR 0.36, 95% CI 0.16-0.83, P = .002). Medically, IA patients were at increased risk of PE (OR 2.97, 95% CI 1.52-5.77, P = .001) and acute blood loss anemia (OR 1.27, 95% CI 1.12-1.44, P < .0001). DISCUSSION AND CONCLUSION: Inflammatory arthritis represents a distinctly morbid risk profile compared to osteoarthritis patients with multiple increased surgical and postoperative medical complications in patients undergoing aTSA and rTSA. Surgeons should consider these potential complications and employ a multidisciplinary approach in preoperative risk stratification of IA undergoing shoulder replacement.

Evaluation of spin in reviews of biodegradable balloon spacers for massive irreparable rotator cuff tears.

HYPOTHESIS: Clinical studies are often at risk of spin, a form of bias where beneficial claims are overstated while negative findings are minimized or dismissed. Spin is often more problematic in abstracts given their brevity and can result in the misrepresentation of a study's actual findings. The goal of this study is to aggregate primary and secondary studies reporting the clinical outcomes of the use of subacromial balloon spacers in the treatment of massive irreparable rotator cuff tears to identify the incidence of spin and find any significant association with study design parameters. MATERIALS AND METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Independent searches were completed on 2 databases (PubMed and Embase) for primary studies, systematic and current concepts reviews, and meta-analyses and the results were compiled. Two authors independently screened the studies using a predetermined inclusion criteria and aggregated data including titles, publication journals and years, authors, study design, etc. Each study was independently assessed for the presence of 15 different types of spin. Statistical analysis was conducted to identify associations between study characteristics and spin. RESULTS: Twenty-nine studies met the inclusion criteria for our analysis, of which 10 were reviews or meta-analyses and 19 were primary studies. Spin was identified in every study except for 2 (27/29, 93.1%). Type 3 spin, "Selective reporting of or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention" and type 9 spin, "Conclusion claims the beneficial effect of the experimental treatment despite reporting bias" were most frequently noted in our study, both observed in 12/29 studies (41.4%). Date of publication, and adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses or "The International Prospective Register of Systematic Reviews" were study characteristics associated with a higher rate of certain types of spin. There was a statistically significant association between disclosure of external study funding source and the presence of spin type 4, but none of the other forms of spin. CONCLUSION: Spin is highly prevalent in the abstracts of primary studies, systematic reviews, and meta-analyses discussing the use of subacromial balloon spacer technology in the treatment of massive irreparable rotator cuff tears. Our findings revealed that spin in the abstract tended to favor the balloon spacer intervention. Further efforts are required in the future to mitigate spin within the abstracts of published manuscripts.

Ten Pearls for Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) reconstruction is a common orthopaedic procedure that has continued to evolve. Since it is a complex procedure, it carries a risk of a range of complications. To ensure optimal results, there are many important considerations to take such as the choice of graft, tunnel positioning, graft preparation, and many others. In this technical note, we elucidate our top 10 pearls to consider for a successful ACL reconstruction.

Management of Hand and Wrist Injuries in NCAA Division I Football Players From a Single Institution: Factors Associated With Epidemiology, Surgical Intervention, and Return to Play.

Background: Upper extremity injuries account for approximately 16.9% of football injuries in the National Collegiate Athletic Association (NCAA). Purpose: To determine the epidemiology, management, and outcomes of hand/wrist injuries in collegiate football athletes so as to identify factors associated with surgical intervention and delayed return to play (RTP). Study Design: Descriptive epidemiology study. Methods: We retrospectively reviewed hand/wrist injuries that occurred within a single NCAA Division I football team from January 1, 2003, to December 31, 2020. Data analyzed included player position, college seniority, injury characteristics, injury management, surgical procedures performed, and timing of RTP. A univariate analysis was performed to identify factors associated with increased risk for surgical intervention and delayed (>21 days) RTP after hand and wrist injury in this cohort. Results: Overall, 124 patients with 168 hand/wrist injuries were identified (9.9 wrist/hand injuries per year). Sprain of the thumb metacarpophalangeal (MCP) joint ulnar collateral ligament (UCL) was the most common diagnosis (19.6%). Surgery was required in 22% of injuries, with injury of the UCL of the thumb MCP joint (8/37) being the most common indication. Injuries occurring during competitive games (odds ratio = 4.29; 95% CI, 1.2-15.9) were associated with an increased risk for surgery. Most (70%) injuries did not lead to time missed from football, whereas the remaining 30% resulted in an average of 33 ± 36 days missed. Conclusion: Over 17 athletic seasons, the annual incidence of hand and wrist injury in these NCAA Division I football players was 9.9 injuries per year, with 22% requiring surgical treatment. Injury to the UCL of the thumb MCP joint was the most common injury and indication for surgery, and 30% of injuries resulted in approximately 1 month lost. Injuries sustained in games were associated with operative management and delayed RTP.

Tissue Augmentation Techniques in the Management of Ligamentous Knee Injuries.

Despite early reports of high failure rates in knee ligament repair techniques resulting in favor of reconstruction, newer advances in surgical technology have shifted the attention back to repair with the addition of various tissue augmentation techniques. Ligament repair preserves proprioceptors in the native ligament and avoids autograft tendon harvest, minimizing the complications associated with donor site ruptures in reconstruction techniques. Tissue augmentation has been successfully used in knee ligamentous and tendon repair procedures, as well as in some upper extremity procedures. This study provides a clinical update on the surgical techniques, biomechanics, and outcomes with the application of various tissue augmentation techniques in the ligaments surrounding the knee joint.

Seasonal Variation in Serum Testosterone Levels: Evidence from 2 Large Institutional Databases.

OBJECTIVE: Seasonal variations in testosterone levels have been reported in some studies, but the results are inconsistent. In this study, we aimed to determine if clinically relevant seasonal variability in testosterone levels exists using a large cohort of men from 2 different institutions, 1 located in an area with seasons (Pittsburgh, Pa) and 1 without seasons (Miami, Fla). METHODS: Using 2 institutional databases, testosterone levels were obtained for men ages 18-99 from 2010 to 2021 who had at least 2 morning testosterone levels drawn within a 2-year period. All samples were analyzed with liquid chromatography with tandem mass spectrometry. To avoid potential confounding by testosterone altering medications patients who were currently or previously on exogenous testosterone, endogenous testosterone-stimulating medications, testosterone-suppressing medications, and aromatase inhibitors were excluded from the study. RESULTS: There were 9495 and 16171 total testosterone levels measured from Miami and Pittsburgh, respectively, with all men having 2 or more levels. There was no statistically significant variation in testosterone levels for the overall cohort in Pittsburgh or Miami, respectively. Additionally, when stratified by age group, no individual groups were found to have significant seasonal variability. CONCLUSION: Our findings suggest that although there is differing total testosterone levels between men who reside in 2 different climates, there is no significant variability in testosterone levels between seasons. Therefore, testosterone levels can be checked and interpreted without the need to account for the season during which they were drawn.

The Impact of Obesity on Sperm Parameters in Young Adult Males: A Retrospective Study of Sperm Donors.

OBJECTIVE: To utilize a large cohort of healthy sperm bank donors to evaluate the association between body mass index and individual sperm parameters. METHODS: Sperm parameters from donors across the United States were obtained between 2013 and 2022. Donors were healthy men aged 18-46years old. Semen samples were analyzed in a certified lab following guidelines by the World Health Organization. A multivariable interaction model between age, body mass index, and sperm parameters was conducted. RESULTS: There were 117,357 sperm donations included in our study. In our sample, 98,397 (83.84%) men were classified as young donors (ages 18-32years) and 18,960 (16.16%) were classified as old donors (ages 33-46years). We identified 1032 (0.88%) men as underweight, 76,635 (65.30%) as normal weight, 36,686 (31.26%) as overweight, and 3004 (2.56%) as obese. Participants had a median total motile sperm count (TMSC) of 186 (interquartile ranges [IQR]: 128 million), volume of 3.36 (IQR: 1.82 mL), sperm concentration of 56 (IQR: 34 million/mL) and a progressive motility of 59.84% (IQR: 16.95%). Older obese donor had lower TMSC (ß = -22.98 ±â€¯4.66, P < .001), semen volumes (ß = -0.85 ±â€¯0.06, P < .001), and progressive motility (ß = -3.94 ±â€¯0.56, P < .001) compared to younger, healthy weight donors. CONCLUSION: We observed lower TMSC, semen volumes, and progressive motility in older obese donors. Although these values are within the normal expected ranges for individual sperm parameters, our ability to detect differences within this healthy population highlights the importance of maintaining a healthy diet and exercise regimen for preserving high sperm counts.

Crystal structures of human and mouse ketohexokinase provide a structural basis for species- and isoform-selective inhibitor design.

A molecular understanding of the proteins involved in fructose metabolism is essential for controlling the current spread of fructose-related obesity, diabetes and related adverse metabolic states in Western populations. Fructose catabolism starts with the phosphorylation of D-fructose to fructose 1-phosphate by ketohexokinase (KHK). KHK exists in two alternatively spliced isoforms: the hepatic and intestinal isoform KHK-C and the peripheral isoform KHK-A. Here, the structure of apo murine KHK (mKHK), which differs from structures of human KHK in overall conformation, is reported. An isoform-selective ligand, which offers a 50-fold higher potency on mKHK and human KHK-A compared with KHK-C, is further characterized. In mKHK, large-scale conformational changes are observed upon ligand binding. The structures suggest a combined strategy for the design of species- and isoform-selective KHK inhibitors.