Search

This study examined the association between a dental implant and changes in adjacent teeth over time. Electronic health records of 1818 patients who received a dental implant were retrospectively evaluated over 14 years (2005-2019) in a university setting. The status of the adjacent tooth and vertical and horizontal distance from the implant platform to adjacent teeth were determined using digital intraoral radiographs taken at baseline and the last follow-up visit (1-14 years, median 4 years). In total, 1085 dental implants were evaluated. There were 234 instances of a change in the adjacent tooth. Decay was observed in 83 (7.6%) of adjacent teeth; the mean time to development was 4 years (range 1-14 years). Approximately 9% of adjacent teeth received direct restorations, 4.8% received indirect restorations, 1% received endodontic root canal treatment, and 5.6% were extracted. The mean horizontal distance between the implant platform and the adjacent teeth was 3.56 mm; the mean vertical distance from the contact point to the alveolar crest on the tooth side was 6.2 mm at the first time of the reported decay on X ray. These distances did not significantly influence the occurrence of caries. The prevalence of interproximal contact loss was higher on the mesial of the implant crown at 63% compared with 20% on the distal side. This large retrospective analysis identified that teeth adjacent to a dental implant were at risk of decay and changes in their condition. In addition, the implant-to-tooth distance and inadequate emergence profile may contribute as caries risk factors in addition to hygiene and a high sugar level diet. These findings appear essential for clinicians when making treatment decisions and discussing outcomes with patients.

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D 1 /D 2 receptor agonist, apomorphine, and the D 2 /D 3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14-42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D 2 receptors at postnatal day 62 revealed a modest increase in D 2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To examine the effect of local aqueous tobramycin injection adjunct to perioperative intravenous (IV) antibiotic prophylaxis in reducing fracture-related infections (FRIs) following reduction and internal fixation of open fractures., Design: Retrospective cohort study., Setting: Single academic Level I trauma center., Patients Selection Criteria: Patients with open extremity fractures treated with reduction and internal fixation with (intervention group) or without (control group) 80 mg of local aqueous (2 mg/mL) tobramycin injected during closure at the time of definitive fixation were identified from December 2018 to August 2021 based on population-matched demographic and injury characteristics., Outcome Measures and Comparisons: The primary outcome was FRI within 6 months of definitive fixation. Secondary outcomes consisted of fracture nonunion and bacterial speciation. Differences in outcomes between the 2 groups were assessed and logistic regression models were created to assess the difference in infection rates between groups, with and without controlling for potential confounding variables, such as sex, fracture location, and Gustilo-Anderson classification., Results: An analysis of 157 patients was performed with 78 patients in the intervention group and 79 patients in the control group. In the intervention group, 30 (38.5%) patients were women with a mean age of 47.1 years. In the control group, 42 (53.2%) patients were women with a mean age of 46.4 years. The FRI rate was 11.5% in the intervention group compared with 25.3% in the control group ( P = 0.026). After controlling for sex, Gustilo-Anderson classification, and fracture location, the difference in FRI rates between groups remained significantly different ( P = 0.014)., Conclusions: Local aqueous tobramycin injection at the time of definitive internal fixation of open extremity fractures was associated with a significant reduction in FRI rates when administered as an adjunct to intravenous antibiotics, even after controlling for potential confounding variables., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To determine whether scheduled low-dose, short-term ketorolac modulates cytokine concentrations in orthopaedic polytrauma patients., Design: Secondary analysis of a double-blinded, randomized controlled trial., Setting: Single Level I trauma center from August 2018 to October 2022., Patient Selection Criteria: Orthopaedic polytrauma patients between 18 and 75 years with a New Injury Severity Score greater than 9 were enrolled. Participants were randomized to receive 15 mg of intravenous ketorolac every 6 hours for up to 5 inpatient days or 2 mL of intravenous saline similarly., Outcome Measures and Comparisons: Daily concentrations of prostaglandin E2 and interleukin (IL)-1a, IL-1b, IL-6, and IL-10. Clinical outcomes included hospital and intensive care unit length of stay, pulmonary complications, and acute kidney injury., Results: Seventy orthopaedic polytrauma patients were enrolled, with 35 participants randomized to the ketorolac group and 35 to the placebo group. The overall IL-10 trend over time was significantly different in the ketorolac group ( P = 0.043). IL-6 was 65.8% higher at enrollment compared to day 3 ( P < 0.001) when aggregated over both groups. There was no significant treatment effect for prostaglandin E2, IL-1a, or IL-1b ( P > 0.05). There were no significant differences in clinical outcomes between groups ( P > 0.05)., Conclusions: Scheduled low-dose, short-term, intravenous ketorolac was associated with significantly different mean trends in IL-10 concentration in orthopaedic polytrauma patients with no significant differences in prostaglandin E2, IL-1a, IL-1b, or IL-6 levels between groups. The treatment did not have an impact on clinical outcomes of hospital or intensive care unit length of stay, pulmonary complications, or acute kidney injury., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To compare radiographic and clinical outcomes in nonoperative management of humeral shaft fractures treated initially with coaptation splinting (CS) followed by delayed functional bracing (FB) versus treatment with immediate FB., Design: Retrospective cohort study., Setting: Academic Level 1 Trauma Center., Patient Selection Criteria: Patients with closed humeral shaft fractures managed nonoperatively with initial CS followed by delayed FB or with immediate FB from 2016 to 2022. Patients younger than 18 years and/or with less than 3 months of follow-up were excluded., Outcome Measures and Comparisons: The primary outcome was coronal and sagittal radiographic alignment assessed at the final follow-up. Secondary outcomes included rate of failure of nonoperative management (defined as surgical conversion and/or fracture nonunion), fracture union, and skin complications secondary to splint/brace wear., Results: Ninety-seven patients were managed nonoperatively with delayed FB (n = 58) or immediate FB (n = 39). Overall, the mean age was 49.9 years (range 18-94 years), and 64 (66%) patients were female. The immediate FB group had less smokers ( P = 0.003) and lower incidence of radial nerve palsy ( P = 0.025), with more proximal third humeral shaft fractures ( P = 0.001). There were no other significant differences in demographic or clinical characteristics ( P > 0.05). There were no significant differences in coronal ( P = 0.144) or sagittal ( P = 0.763) radiographic alignment between the groups. In total, 33 (34.0%) humeral shaft fractures failed nonoperative management, with 11 (28.2%) in the immediate FB group and 22 (37.9%) in the delayed FB group ( P = 0.322). There were no significant differences in fracture union ( P = 0.074) or skin complications ( P = 0.259) between the groups., Conclusions: This study demonstrated that nonoperative treatment of humeral shaft fractures with immediate functional bracing did not result in significantly different radiographic or clinical outcomes compared to treatment with CS followed by delayed functional bracing. Future prospective studies assessing patient-reported outcomes will further guide clinical decision making., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Quadriceps rate of torque development (RTD) and torque steadiness are valuable metrics for assessing explosive strength and the ability to control force over a sustained period of time, which can inform clinical assessments of knee function. Despite their widespread use, there is a significant gap in standardized methodology for measuring these metrics, which limits their utility in comparing outcomes across different studies and populations. To address these gaps, we evaluated the influence of sampling rates, signal filtering, and torque onset detection on RTD and torque steadiness. Twenty-seven participants with a history of a primary anterior cruciate ligament reconstruction (N = 27 (11 male/16 female), age = 23 ± 8 years, body mass index = 26 ± 4 kg/m 2 ) and thirty-two control participants (N = 32 (13 male/19 female), age = 23 ± 7 years, body mass index = 23 ± 3 kg/m 2 ) underwent isometric quadriceps strength testing, with data collected at 2222 Hz on an isokinetic dynamometer. The torque-time signal was downsampled to approximately 100 and 1000 Hz and processed using a low-pass, zero-lag Butterworth filter with a range of cutoff frequencies spanning 10-200 Hz. The thresholds used to detect torque onset were defined as 0.1 Nm, 1 Nm, and 5 Nm. RTD between 0 and 100 ms, 0 and 200 ms, and 40-160 ms was computed, as well as absolute and relative torque steadiness. Relative differences were computed by comparing all outcomes to the "gold standard" values computed, with a sampling rate of 2222 Hz, a cutoff frequency in the low-pass filter of 150 Hz, and torque onset of 1 Nm, and compared utilizing linear mixed models. While all combinations of signal collection and processing parameters reached statistical significance ( p < 0.05), these differences were consistent between injured and control limbs. Additionally, clinically relevant differences (+/-10%) were primarily observed through torque onset detection methods and primarily affected RTD between 0 and 100 ms. Although measurements of RTD and torque steadiness were generally robust against diverse signal collection and processing parameters, the selection of torque onset should be carefully considered, especially in early RTD assessments that have shorter time epochs.

Abstract: Graham, MC, Thompson, KL, Hawk, GS, Fry, CS, and Noehren, B. Muscle fiber cross-sectional area is associated with quadriceps strength and rate of torque development after ACL injury. J Strength Cond Res 38(6): e273-e279, 2024-The purpose of this study was to investigate the relationship between muscle fiber type-specific properties of the vastus lateralis and quadriceps muscle performance in individuals after an anterior cruciate ligament (ACL) tear. 26 subjects (22.0 ± 5.4 years) were included in this cross-sectional study, and all data were collected before ACL reconstruction. Quadriceps peak torque (QPT) and early (0-100 ms) and late (100-200 ms) rate of torque development (RTD) were obtained from maximal voluntary isometric quadriceps strength testing. Muscle fiber cross-sectional area (fCSA) and percent fiber type distribution (FT%) were evaluated through immunohistochemical analysis of a muscle biopsy. Between-limb differences in fiber characteristics were assessed using paired t-tests (with α-level 0.05). Relationships between fiber-specific properties and quadriceps muscle performance were determined using separate multiple linear regression analyses for ACL-injured and noninjured limbs. There were significant differences in fCSA between ACL-injured and noninjured limbs across all fiber types, but no differences in FT%. Type 1 fCSA, type 2a fCSA, and their interaction effect were the explanatory variables with the strongest relationship to all performance outcomes for the ACL-injured limb. The explanatory variables in the ACL-injured limb had a significant relationship to QPT and late RTD, but not early RTD. These findings suggest that QPT and late RTD are more heavily influenced by fCSA than FT% in ACL-injured limbs. This work serves as a foundation for the development of more specific rehabilitation strategies aimed at improving quadriceps muscle function before ACL reconstruction or for individuals electing nonsurgical management., (Copyright © 2024 National Strength and Conditioning Association.)

Background: Female athletes lag behind their male counterparts in recovery from anterior cruciate ligament (ACL) injury. Quadriceps muscle size and strength are crucial factors for regaining function after ACL injury, but little is known about how these metrics vary due to biological sex., Hypothesis: Female patients have reduced vastus lateralis fiber cross-sectional area (CSA) and lower quadriceps strength after ACL injury than male patients., Study Design: Cross-sectional study., Level of Evidence: Level 4., Methods: A total of 60 participants with recent ACL tear were evaluated for vastus lateralis muscle fiber CSA, isometric quadriceps peak torque, and quadriceps rate of torque development. Linear mixed models were fit to determine differences across sex and limb for each variable of interest., Results: The female group averaged almost 20% atrophy between limbs ( P < 0.01), while the male group averaged just under 4% ( P = 0.05). Strength deficits between limbs were comparable between female and male groups., Conclusion: Immediately after ACL injury, female patients have greater between-limb differences in muscle fiber CSA but between-limb strength deficits comparable with those of male patients., Clinical Relevance: These results indicate that the underpinnings of strength loss differ based on biological sex, and thus individual patients could benefit from a sex-specific treatment approach to ACL injury., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Background: Rural residence has been associated with a lower incidence of inflammatory bowel disease (IBD) but higher health care utilization and worse outcomes. Socioeconomic status is intrinsically tied to both IBD incidence and outcomes. Inflammatory bowel disease outcomes have not been investigated in Appalachia: a rural, economically distressed region rife with risk factors for both increased incidence and unfavorable outcomes., Methods: Hospital inpatient discharge and outpatient services databases were utilized to assess outcomes in patients diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) in Kentucky. Encounters were classified by patient residence in Appalachian or non-Appalachian counties. Data were reported as crude and age-adjusted rates of visits per 100,000 population per year collected in 2016 to 2019. National inpatient discharge data from 2019, stratified by rural and urban classification codes, were utilized to compare Kentucky to national trends., Results: Crude and age-adjusted rates of inpatient, emergency department and outpatient encounters were higher in the Appalachian cohort for all 4 years observed. Appalachian inpatient encounters are more frequently associated with a surgical procedure (Appalachian, 676, 24.7% vs non-Appalachian, 1408, 22.2%; P = .0091). In 2019, the Kentucky Appalachian cohort had significantly higher crude and age-adjusted rates of inpatient discharges for all IBD diagnoses compared with national rural and nonrural populations (crude 55.2; 95% CI, 50.9-59.5; age-adjusted 56.7; 95% CI, 52.1-61.3)., Conclusions: There is disproportionately higher IBD health care utilization in Appalachian Kentucky compared with all cohorts, including the national rural population. There is a need for aggressive investigation into root causes of these disparate outcomes and identification of barriers to appropriate IBD care., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5-9 months) and old (18-22 months) age. Survival was monitored for at least 10 days or mice were euthanized for tissue collection at 24 or 48 h post-insult. Contrary to our expectation, PAI-1 KO mice at old age were significantly more sensitive to CS-induced sepsis compared to WT mice (24% vs. 65% survival, p = 0.0037). In comparison, loss of PAI-1 at young age had negligible effects on sepsis survival (86% vs. 88% survival, p = 0.8106) highlighting the importance of age as a biological variable. Injury to the kidney was the most apparent pathological consequence and occurred earlier in aged PAI-1 KO mice. Coagulation markers were unaffected by loss of PAI-1, suggesting thrombosis-independent mechanisms for PAI-1-mediated protection. In summary, although high PAI-1 levels are clinically associated with worse sepsis outcomes, loss of PAI-1 rendered mice more susceptible to kidney injury and death in a CS-induced model of sepsis using aged mice. These results implicate PAI-1 as a critical factor in the resolution of sepsis in old age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bruno, Mukherjee, Sturgill, Cornea, Yeh, Hawk, Saito and Starr.)

γδ T cells are resident in visceral adipose tissue (VAT) where they show an age-associated increase in numbers and contribute to local and systemic chronic inflammation. However, regulation of this population and mechanisms for the age-dependent accumulation are not known. In this study, we identified a progressive trend of γδ T cell accumulation in VAT over the lifespan in mice and explored physiological mechanisms contributing to accumulation. Using isochronic parabiotic pairs of wild-type (WT) and T cell receptor delta knockout (TCRδ KO) mice at young and old age, we confirmed that VAT γδ T cells are predominately a tissue-resident population which is sustained in aging. Migration of peripheral γδ T cells into VAT was observed at less than 10%, with a decreasing trend by aging, suggesting a minor contribution of recruitment to γδ T cell accumulation with aging. Since tissue-resident T cell numbers are tightly regulated by a balance between proliferation and programmed cell death, we further explored these processes. Using in vivo EdU incorporation and the proliferation marker Ki67, we found that the absolute number of proliferating γδ T cells in VAT is significantly higher in the aged compared to young and middle-aged mice, despite a decline in the proportion of proliferating to non-proliferating cells by age. Analysis of apoptosis via caspase 3/7 activation revealed that VAT γδ T cells show reduced apoptosis starting at middle age and continuing into old age. Further, induction of apoptosis using pharmacological inhibitors of Bcl2 family proteins revealed that VAT γδ T cells at middle age are uniquely protected from apoptosis via a mechanism independent of traditional anti-apoptotic Bcl2-family proteins. Collectively, these data indicate that protection from apoptosis at middle age increases survival of tissue-resident γδ T cells resulting in an increased number of proliferative cells from middle age onward, and leading to the age-associated accumulation of γδ T cells in VAT. These findings are important to better understand how adipose tissue dysfunction and related changes in the immune profile contribute to inflammaging among the elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mukherjee, Bruno, Oakes, Hawk, Stromberg, Cohen and Starr.)

Purpose: To determine whether the utilization of psychological treatments changes after arthroscopic rotator cuff repair (RCR) for patients with preoperative depression and/or anxiety., Methods: The Truven Healthcare Marketscan database was used to identify patients who underwent arthroscopic RCR between January 2009 and December 2016. We included all patients with diagnosis codes associated with either depression or anxiety before RCR. Patients were excluded if they did not have complete insurance coverage for 1 year before or after surgery, or if they had arthroscopic RCR in the year before the index surgical procedure. We compared the proportion of patients with preoperative depression or anxiety who filled a prescription and had psychotherapy procedural codes in the year before and the year after arthroscopic RCR., Results: A total of 170,406 patients who underwent RCR were identified, of which depression and/or anxiety was found in 46,737 patients (43.7% male). Of the 46,737 patients, 19.6% filled a prescription for a depression/anxiety medication at least once in the year before surgery. Of this subset of patients, 41.5% did not fill a prescription for depression or anxiety medication after surgery, whereas 32.6% continued medication use but demonstrated a median 30-day reduction in the number of days' worth of medication. Similarly, 13.1% of patients were attending psychotherapy sessions preoperatively, but 76.6% of those patients either stopped or reduced the amount of psychotherapy sessions in the year following RCR., Conclusions: The number of prescriptions and psychotherapy sessions decreased in the year after RCR for patients with preoperative diagnoses of depression and/or anxiety., Level of Evidence: Level IV, case series., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic osteoarthritis (PTOA). Growth differentiation factor 8 (GDF8) has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. We investigated GDF8 levels in ACL-injured human skeletal muscle and serum and tested a humanized monoclonal GDF8 antibody against a placebo in a mouse model of PTOA (surgically induced ACL tear). In patients, muscle GDF8 was predictive of atrophy, weakness, and periarticular bone loss 6 months following surgical ACL reconstruction. In mice, GDF8 antibody administration substantially mitigated muscle atrophy, weakness, and fibrosis. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated PTOA severity and deficits in periarticular bone microarchitecture. Furthermore, GDF8 genetic deletion neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal recovery and mitigate the severity of PTOA after injury.

This study compared perceived social support among women of all body mass index (BMI) categories with an attempt to assess the efficacy of the BumptUp® mobile application to improve social support for exercise during pregnancy and postpartum. Thirty-five pregnant women living in Southern United States were included in the sample. The intervention group received access to the BumptUp® mobile application that was designed to promote physical activity during pregnancy and postpartum. The control group received an evidence-based educational brochure. Perceived social support for exercise was assessed at four-time points using the social support and exercise survey. Outcomes were evaluated at 23-25, 35-37 gestational weeks, and 6 and 12 weeks postpartum. Based on their pre-pregnancy weight and height, BMI was computed to categorize participants into lean, overweight, and obese groups. Social support across BMI categories and between control and intervention groups were compared using linear mixed-effect models. Women grouped in the overweight and obese BMI categories reported receiving significantly lower levels of social support for exercise than women in the lean category throughout pregnancy and postpartum during mid-pregnancy, late pregnancy, and at 12 weeks postpartum (p < 0.05). Although the intervention group received higher social support than the control group throughout all four assessment points, the difference was not statistically significant (p > 0.05). Women with a pre-pregnancy BMI of overweight and obese received lower social support for exercise during pregnancy and postpartum. The efficacy of BumptUp® to improve perceived social support for exercise in pregnancy and postpartum was not evident in the results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Purpose: It remains unknown if cephalomedullary nail (CMN) length has an impact on pain and opioid use following fixation. Given the lack of level I evidence favoring a specific CMN length to prevent adverse surgical outcomes, we investigated if CMN length impacts acute postoperative pain and opioid use. The authors hypothesize that the use of longer CMNs results in increased pain scores and morphine milligram equivalents (MME) intake during the 0-24 h (h) and 24-36 h postoperative period., Methods: A retrospective chart review was performed from 2010 to 2020 of patients ≥ 65 years-old who underwent CMN for IT fractures and fractures with subtrochanteric extension (STE). We compared patients who received short and long CMNs using numeric rating scale (NRS) pain scores and MME intake at 0-24 h and 24-36 h postoperatively., Results: 330 patients receiving short (n = 155) and long (n = 175) CMNs met criteria. CMN length was found to not be associated with higher pain scores in the early postoperative phase. However, patients with long CMNs received higher MME from 0-24 h (25.4% estimated mean increase, p value = 0.02) and 24-36 h (22.3% estimated mean increase, p value = 0.04) postoperatively, even after adjusting for covariates, gender, and age., Conclusion: Patients with long CMNs received greater MME postoperatively. Additionally, differences in pain and MME were not significantly different between patients with and without STE, suggesting our findings were not influenced by this pattern. These results suggest longer CMNs are associated with higher acute postoperative opioid intake among patients with IT fractures., Level of Evidence: Therapeutic level III., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Objective: To determine whether scheduled low-dose, short-term ketorolac is associated with reduced length of stay, opioid use, and pain in orthopaedic polytrauma patients., Design: Double-blinded, randomized controlled trial., Setting: One Level 1 trauma center., Patients: From August 2018 to October 2022, 70 orthopaedic polytrauma patients between 18-75 years-old with a New Injury Severity Score (NISS) > 9 were randomized. 70 participants were enrolled, with 35 randomized to the ketorolac group and 35 to the placebo group., Intervention: 15 mg of intravenous (IV) ketorolac every 6 hours for up to 5 inpatient days or 2 mL of IV saline in a similar fashion., Main Outcome Measurements: Length of Stay (LOS), Morphine Milligram Equivalents (MME), Visual Analogue Scale (VAS), and Complications., Results: Study groups were not significantly different with respect to age, BMI, and NISS (p>0.05). Median LOS was 8 days (interquartile range [IQR], 4.5 to 11.5) in the ketorolac group compared to 7 days (IQR, 3 to 10) in the placebo group (p = 0.275). Over the 5-day treatment period, the ketorolac group experienced a 32% reduction in average MME (p = 0.013) and a 12-point reduction in baseline-adjusted mean VAS (p = 0.037) compared to the placebo group. There were no apparent short-term adverse effects in either group., Conclusion: Scheduled low-dose, short-term IV ketorolac was associated with significantly reduced inpatient opioid use and pain in orthopaedic polytrauma patients with no significant difference in LOS and no apparent short-term adverse effects. The results support the use of scheduled low-dose, short-term IV ketorolac for acute pain control among orthopaedic polytrauma patients. Further studies are needed to delineate lasting clinical effects and potential long-term effects, such as fracture healing., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Conflicts of Interest and Source of Funding: This project was aided by a grant from the Orthopaedic Trauma Association. The authors declare no conflicts of interest relevant to the submitted work., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Preoperative mood disorders influence postoperative outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR), but the prevalence and risk factors associated with postoperative depression/anxiety development remain unknown. The purposes of this study were to quantify the prevalence of postoperative diagnoses of depression or anxiety following ACLR in patients under the age of 25 and assess the interplay between patient sex and ACL reoperation on the prevalence of a depression or anxiety diagnosis following ACLR., Methods: ACLR patients under the age of 25 years old were identified in the Truven Healthcare Marketscan database. Patients with incomplete coverage +/- one year of the index surgical procedure were excluded. Patients were categorized by the presence of preoperative, postoperative, or no depression/anxiety using the International Classification of Diseases, Ninth Revision (ICD-9) codes. We compared patient demographics and reoperation rates following the index ACLR between the depression and anxiety categories. Additionally, logistic regression was fit to assess the interaction between sex and either ipsilateral or contralateral ACL surgery on postoperative depression/anxiety diagnosis., Results: Of the 42,174 patients, 10.7% had a new depression/anxiety diagnosis after ACLR. Postoperative depression/anxiety was nearly twice as prevalent for females (F: 14.4%, M: 7.6%) despite having similar rates of secondary ACLR (F: 15.5%, M: 13.0%). Those with postoperative depression/anxiety had a considerably greater prevalence of reoperation (18.8%) than those without depression/anxiety (13.7%) and those with pre-existing preoperative depression/anxiety (12.9%). Sex and reoperation were independently associated with postoperative depression/anxiety diagnosis., Conclusion: Female sex and secondary ACL surgery are independently associated with an increased prevalence of postoperative depression/anxiety. Nearly one in seven young females are diagnosed with depression/anxiety after ACLR. Similarly, a greater proportion of patients who suffer a secondary ACL surgery are subsequently diagnosed with depression/anxiety. The orthopedic community must be cognizant of the increased risk of postoperative depression/anxiety for females and those who suffer a secondary ACL surgery, and screening for depression/anxiety in these at-risk populations with referrals to mental health professionals may be warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Conley et al.)

Purpose: To evaluate the epidemiology of concussions in pediatric baseball and softball players. We hypothesized that head-to-ball injuries would be the most common cause of concussions., Methods: The National Electronic Injury Surveillance System (NEISS) database was used to gather data. Concussions occurring during baseball and softball participation in pediatric patients (4-17 years old) from 2012 to 2021 was gathered. Concussion mechanisms were grouped into 5 categories: head-to-player, head-to-ball, head-to-surface (ground, walls, railings), head-to-bat, and unknown. Linear regression models were used to assess changes in yearly concussion rates over the study period. Results from these models were reported using parameter estimates and the estimated Pearson correlation coefficient., Results: A weighted total of 54,978 baseball and softball related concussion injuries were analyzed. The average weighted age of our cohort at the time of injury was 13.1 years, with 54.1% (n = 29,761) of concussions occurring in males. The national estimated incidence of concussion injuries decreased non-significantly over the study period (slope estimate = -311 concussions/year, r = -0.625, p-value = 0.054). The majority of weighted national estimate concussions were due to head-to-ball injuries (n = 34,650; 63.0%), followed by head-to-player (n = 8501; 15.5%), head-to-surface (n = 5347; 9.7%), and head-to-bat (n = 5089; 9.3%). On sub-analysis, individuals were grouped into 3 age brackets: 4-8, 9-13, and 14-17 years. The most common mechanism of concussions in children of all ages was head-to-ball. The incidence of head-to-player and head-to-surface injuries increased throughout each age group, while head-to-bat decreased., Conclusion: The incidence of concussions in pediatric baseball and softball athletes has been decreasing non-significantly over our 10-year study period. The most common mechanism of concussions in our study was head-to-ball injuries., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The anterior cruciate ligament (ACL) is commonly injured in elite-level female athletes, which usually requires ACL reconstruction (ACLR)., Purpose: To analyze return to play (RTP) and changes in performance of players in the National Women's Soccer League (NWSL) after ACLR., Study Design: Descriptive epidemiology study., Methods: NWSL players who sustained an ACL tear and underwent surgery between the 2013 and 2020 seasons were identified by multiple online resources. Players were classified as forwards, defenders, midfielders, and goalkeepers. RTP was assessed according to games played, games started, percentage of minutes played, plus/minus net per 90 minutes (a measure of a player's contribution to their team's performance while on the field), goals scored, and assists. A subanalysis was performed based on the median age at the time of the injury (≤24 vs ≥25 years). Nonparametric testing methods were used throughout the analysis., Results: A total of 30 NWSL athletes were included. Midfielders had the highest percentage of injuries (n = 11; 36.7%), followed by forwards (n = 10; 33.3%). Overall, 27 players returned to the NWSL at a median of 12.1 months (IQR, 10.9-14.3 months), constituting a 90.0% RTP rate. There was a significant decrease in the percentage of minutes played from 1 year before the injury to 1 year after the injury (median, 87.9% [IQR, 80.7%-90.6%] vs 25.1% [IQR, 16.3%-57.2%], respectively; P = .031). Forwards and midfielders had a significant decrease in the number of assists from 1 year before the injury to 1 year after the injury (median, 3.0 [IQR, 1.0-3.0] vs 0.0 [IQR, 0.0-1.0], respectively; P = .037) as well as the number of goals scored when averaging across 2 seasons before the injury to 2 seasons after the injury (median, 3.0 [IQR, 1.5-5.5] vs 1.0 [IQR, 0.5-3.5], respectively; P = .031). On subanalysis, older players started in significantly more games (median, 12.0 [IQR, 3.8-18.5] vs 3.0 [IQR, 0.5-6.0], respectively; P = .048) and had a higher percentage of minutes played (median, 63.0% [IQR, 18.8%-77.3%] vs 14.9% [IQR, 2.0%-21.2%], respectively; P = .046) at 1 year after the injury versus younger players., Conclusion: There was a 90.0% RTP rate after ACLR in the NWSL. Players who returned to the NWSL had a lower percentage of minutes played in their first year after RTP, with older players starting in more games and having a greater percentage of minutes played. Compared with preinjury performance, forwards and midfielders had a significant decrease in the number of assists at 1 year after the injury as well as the number of goals scored at 2 years after the injury., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: D.J. has received consulting fees from Xiros and Smith & Nephew, nonconsulting fees from Smith & Nephew, royalties from Smith & Nephew, and hospitality payments from Linvatec. A.V.S. has received grant support from Arthrex; education payments from Arthrex, Smith & Nephew, and Stryker; and nonconsulting fees from Smith & Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Purpose: To evaluate the epidemiology of concussions in youth ice hockey players., Methods: The National Electronic Injury Surveillance System (NEISS) database was used to gather data. Concussions occurring during ice hockey participation in youth patients (4-21 years old) from 2012 to 2021 was gathered. Concussion mechanisms were grouped into 7 categories: head-to-player, head-to-puck, head-to-ice, head-to-board/glass, head-to-stick, head-to-goal post, and unknown. Hospitalization rates were also tabulated. Linear regression models were used to assess changes in yearly concussion and hospitalization rates over the study period. Results from these models were reported using parameter estimates [with 95% confidence intervals (CI)] and the estimated Pearson correlation coefficient. Additionally, logistic regression was used to model the risk of hospitalization across the different cause categories., Results: A total of 819 ice hockey related concussions were analyzed between 2012 and 2021. The average age of our cohort was 13.4 years, with 89.3% (n = 731) of concussions occurring in males. The incidence of head-to-ice, head-to-board/glass, head-to-player, and head-to-puck concussion mechanisms decreased significantly over the study period (slope estimate = -2.1 concussions/year [CI: (-3.9, -0.2)], r = -0.675, p = 0.032), (slope estimate = -2.7 concussions/year [CI: (-4.3, -1.2)], r = -0.816, p = 0.004), (slope estimate = -2.2 concussions/year [CI: (-3.4, -1.0)], r = -0.832, p = 0.003), and (slope estimate = -0.4 concussions/year [CI: (-0.62, -0.09)], r = -0.768, p = 0.016), respectively. Majority of patients were discharged from the emergency department (ED) to their home, as only 20 people (2.4%) were hospitalized over our study period. The majority of concussions were due to head-to-ice (n = 285, 34.8%), followed by head-to-board/glass (n = 217, 26.5%) and head-to-player (n = 207, 25.3%). The most common cause for hospitalizations due to concussions was head-to-board/glass (n = 7, 35%), followed by head-to-player (n = 6, 30%) and head-to-ice (n = 5, 25%)., Conclusion: The most common mechanism of youth ice hockey concussions was head-to-ice in our 10-year study period, while head-to-board/glass was the most common cause of hospitalizations. IRB: This project did not require review by the institutional review board., Competing Interests: Declaration of Competing Interest All authors declare that there are no financial conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To determine which preoperative factors are associated with prolonged opioid use after medial patellofemoral ligament reconstruction (MPFLR)., Methods: The M151Ortho PearlDiver database was queried for patients who underwent MPFLR between 2010 and 2020. Inclusion criteria included patients who underwent MPFLR using Current Procedural Terminology codes 27420, 27422, and 27427 and had a patellar instability diagnosis. Prolonged opioid use was defined as opioid use greater than 1 month after surgery. Postoperative opioid use from 1 month to 6 months was assessed. Multivariable logistic regression was used to evaluate the association between patient-related risk factors (age, sex, Charlson Comorbidity Index, anxiety, depression, substance use disorder, osteoarthritis, tibial tubercle osteotomy [TTO], and previous opioid use within 3 months to 1 week of surgery) with prolonged postoperative opioid use. Odds ratios (OR) and their associated 95% confidence intervals (CI) were calculated for each risk factor., Results: A total of 23,249 patients were included. There was a higher proportion of female patients compared to male patients (67.8% vs 32.2%) in our cohort, as well as a large proportion of patients who had preoperative opioid use (23.9%). In total, 14.3% of patients had a concomitant TTO. Three months post-MPFLR, male patients were at a decreased risk of opioid usage (OR 0.75; CI 0.67-0.83; P ≤ .001). Older age (OR 1.01, CI 1.00-1.01; P ≤ .001), patients with pre-existing anxiety (OR 1.30, CI 1.15-1.47; P ≤ .001), substance use disorder (OR 2.04, CI 1.80-2.31; P ≤ .001), knee osteoarthritis (OR 1.70, CI 1.49-1.94; P ≤ .001), concomitant TTO (OR 1.91, CI 1.67-2.17; P ≤ .001), and opioid familiarity (OR 7.68, CI 6.93-8.52; P ≤ .001) were at a significantly increased risk of postoperative opioid usage., Conclusions: Older age, female sex, anxiety, substance use disorder, osteoarthritis, tibial tubercle osteotomy, and opioid familiarity are risk factors for prolonged opioid use following MPFLR., Level of Evidence: Level III, retrospective cohort study., (© 2023 The Authors.)

Background: A Lisfranc injury can occur to either the ligament or bone, which causes instability when attempting to perform strength and balance maneuvers., Purpose/hypothesis: The study's aims were to (1) analyze the return-to-play (RTP) rate and performance level of players in the National Football League (NFL) after Lisfranc injury and (2) determine the economic and financial impact of Lisfranc injuries to the NFL. We hypothesized that there would be a low RTP rate following Lisfranc injury in the NFL., Study Design: Case series; Level of evidence, 4., Methods: Multiple online public records were used to identify NFL players with Lisfranc injuries between the 2009 and 2020 seasons. Players were assessed according to their RTP statistics: snap count, approximate value (AV), games played, and games started. Nonparametric methods were used to compare player statistics before and after injury. Also, player salaries while injured were calculated (in 2022 US dollars after adjusting for inflation) to approximate economic loss for those players who returned to play., Results: A total of 33 NFL athletes sustained a Lisfranc injury during the study period. Most Lisfranc injuries were experienced by offensive linemen (n = 8; 24.2%), followed by running backs (n = 7; 21.2%). Overall 27 players (81.8%) returned to play after injury at a median of 11.0 months (IQR, 10.2-11.8 months). There were no significant differences between pre- and postinjury snap counts or number of games played and started. In terms of player performance, there was a statistically significant decrease in AV at 1 year postinjury (median [IQR], 6.0 [4.0-10.0] preinjury vs 5.0 [2.5-7.5] postinjury; P = .022). The overall cost of recovery amounted to $104.7 million, with quarterbacks (n = 4) accounting for the greatest cost at $32.6 million. The next 2 most expensive positions were offensive and defensive linemen (n = 5 each) at $19.4 million each., Conclusion: Our results did not support the hypothesis, as the RTP rate for NFL athletes sustaining Lisfranc injuries was 81.8%. This injury was associated with a significant decrease in AV 1 year postinjury. In terms of economic impact, quarterbacks accounted for almost one-third of expenses while constituting only 14.8% of injuries., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.V.S. has received grant support from Arthrex; education payments from Arthrex, Legacy Ortho, Smith & Nephew, and Stryker; nonconsulting fees from Smith & Nephew; and hospitality payments from Wright Medical. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Purpose: To evaluate the content and quality of YouTube videos concerning patellar dislocations., Methods: "Patellar dislocation" and "kneecap dislocation" were searched on the YouTube library. The Uniform Resource Locator of the first 25 suggested videos was extracted, for a total of 50 videos. The following variables were collected for each video: number of views, duration in minutes, video source/uploader, content type, days since upload, view ratio (views/day), and number of likes. Video source/uploader was categorized as academic, physician, nonphysician, medical source, patient, commercial, and other. The Journal of the American Medical Association (JAMA), Global Quality Scale (GQS), Patellar Dislocation Specific Score (PDSS), and DISCERN scores were used to assess each video. A series of linear regression models were used to explore relationships between each of these scores and the aforementioned variables., Results: The median video length was 4.11 minutes (interquartile range 2.07-6.03, range 0.31-53.56), and the total number of views for all 50 videos was 3,697,587 views. The mean overall JAMA benchmark score ± standard deviation was 2.56 ± 0.64, GQS: 3.54 ± 1.05, total PDSS: 5.76 ± 3.42. Physicians were the most common video source/uploader (42%). Academic sources had the greatest mean JAMA benchmark score (3.20), whereas nonphysician and physician sources had the greatest mean GQS scores (4.09 and 3.95, respectively). Videos uploaded by physicians had the greatest PDSS scores (7.5)., Conclusions: The overall transparency, reliability, and content quality of YouTube videos on patellar dislocation measured by the JAMA benchmark score and PDSS, respectively, are poor. Additionally, the overall educational and video quality, as assessed by the GQS, was intermediate., Clinical Relevance: It is important to understand the quality of information patients receive on YouTube so providers can guide patients to greater-quality sources., (© 2023 The Authors.)

Introduction Affecting more than 30 million adults annually, osteoarthritis (OA) is the most common joint disorder in the United States. A variety of management options for knee OA exists, including physical therapy, weight loss, intra-articular corticosteroid injections, and total joint arthroplasty. With many treatments available, patients often utilize the internet to educate themselves about their condition and management options. The purpose of this study was to evaluate the quality, transparency, and readability of online information for the treatment of knee OA. Methods The search terms "knee," "arthritis," and "treatment" were entered into an incognito mode Google browser. Websites were classified by type (commercial, academic, nonacademic medical practice, government/patient advocacy, and other) and graded on content quality, transparency, and readability using the following scores, respectively: modified DISCERN, Journal of American Medical Association (JAMA) Benchmark, and Flesch-Kincaid (FK) grade level. Results Of the 95 websites evaluated, commercial (mean, 38.2) and academic (37.3) sites had the highest total DISCERN scores, which were significantly greater than nonacademic medical practice (31.8) and government/patient advocacy sites (33.4) (p≤0.035). Nonacademic medical practice sites had the lowest mean total DISCERN (31.8) and JAMA (1.47) scores and the highest FK grade level readability (9.5). There was a significant positive correlation between mean total DISCERN and JAMA scores (r=0.46, p<0.001). Conclusion The mean overall quality of websites regarding the treatment of OA was good as evidenced by greater modified DISCERN scores. However, website quality ranged from poor to excellent, indicating that some websites are still missing key information patients may find useful when assessing treatment options online., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sullivan et al.)

To combat maternal morbidity and mortality, interventions designed to increase physical activity levels during and after pregnancy are needed. Mobile phone-based interventions show considerable promise, and BumptUp ® has been carefully developed to address the lack of exercise among pregnant and postpartum women. The primary goal of this pilot study was to test the potential efficacy of BumptUp ® for improving physical activity among pregnant and postpartum women. A randomized controlled clinical trial was performed (N = 35) with women either receiving access to the mhealth app or an educational brochure. Physical activity and self-efficacy for exercise data were collected at baseline (in mid-pregnancy) and at three additional timepoints (late pregnancy, 6 and 12 weeks postpartum). For moderate-to-vigorous physical activity, a clear trend is observed as the mean estimated difference between groups increases from -0.35 (SE: 1.75) in mid-pregnancy to -0.81 (SE: 1.75) in late pregnancy. For self-efficacy for exercise, the estimated difference of means (control-intervention) changed from 0.96 (SE: 6.53) at baseline to -7.64 (SE: 6.66) in late pregnancy and remained at -6.41 (SE: 6.79) and -6.70 (SE: 6.96) at 6 and 12 weeks postpartum, respectively. When assessing the change in self-efficacy from mid-to -ate pregnancy only, there was a statistically significant difference between groups ( p = 0.044). BumptUp ® (version 1.0 (3)) shows potential for efficacy. Pilot data suggest key refinements to be made and a larger clinical trial is warranted., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

The mechanisms through which oral commensal bacteria mitigates uncontrolled inflammatory responses of the oral mucosa remain unknown. Here, we show that representative oral bacterial species normally associated with oral health [S. gordonii ( Sg ), V. parvula ( Vp ), A. naeslundii ( An ), C. sputigena ( Cs ), and N. mucosa ( Nm )] enhanced differential chemokine responses in oral epithelial cells (OECs), with some bacteria ( An, Vp, and Nm ) inducing higher chemokine levels (CXCL1, CXCL8) than others ( Sg, Cs ). Although all bacterial species (except Cs ) increased CCL20 mRNA levels consistent with protein elevations in cell lysates, only An, Vp , and Nm induced higher CCL20 secretion, similar to the effect of the oral pathogen F. nucleatum (Fn) . In contrast, most CCL20 remained associated with OECs exposed to Sg and negligible amounts released into the cell supernatants. Consistently, Sg attenuated An -induced CCL20. MiR-4516 and miR-663a were identified as Sg -specifically induced miRNAs modulating validated targets of chemokine-associated pathways. Cell transfection with miR-4516 and miR-663a decreased An - and Fn -induced CCL20. MiRNA upregulation and attenuation of An -induced CCL20 by Sg were reversed by catalase. Up-regulation of both miRNAs was specifically enhanced by oral streptococci H 2 O 2 -producers. These findings suggest that CCL20 levels produced by OECs in response to bacterial challenge are regulated by Sg -induced miR-4516 and miR-663a in a mechanism that involves hydrogen peroxide. This type of molecular mechanism could partly explain the central role of specific oral streptococcal species in balancing inflammatory and antimicrobial responses given the critical role of CCL20 in innate (antimicrobial) and adaptive immunity (modulates Th17 responses).

Objective: To identify the prevalence of mood disorder diagnoses in patients undergoing cartilage transplantation procedures and determine the relationship between mood disorders, opioid usage, and postoperative health care costs., Design: Patients with current procedural terminology (CPT) codes for osteochondral autograft transplantation (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI) were identified in the Truven Health Marketscan database (January 2009-September 2014). Patients were grouped based on having a preoperative mood disorder diagnosis (preMDD). Preoperative opioids, postoperative opioids ≥90 days, and health care costs within the year postoperative were compared for those with and without mood disorders. Costs were analyzed, adjusting for preoperative cost, sex, age, and opioid usage, for those with and without mood disorders., Results: A total of 3,682 patients were analyzed (ACI: 690, OAT: 1,294, OCA: 1,698). A quarter of patients had preMDD (ACI: 25.4%, OAT: 20.6%, OCA: 22.7%). Postoperative opioid use was more prevalent in preMDD patients (OAT: 37.1% vs. 24.1%, P < 0.001; OCA: 30.4% vs. 24.8%, P = 0.032; ACI: 33.7% vs. 26.2%, P = 0.070) (odds ratio [OR] ranged from 1.29 to 1.86). First-year postoperative log-transformed costs were significantly greater for preMDD patients (ACI: $7,733 vs. $5,689*, P = 0.012; OAT: $5,221 vs. $3,823*, P < 0.001; OCA: $6,973 vs. $3,992*, P < 0.001; *medians reported). The estimated adjusted first postoperative year cost increase for preMDD OCA patients was 41.7% ( P < 0.001) and 28.0% for OAT patients ( P = 0.034). There was no statistical difference for ACI patients ( P = 0.654)., Conclusion: Cartilage transplantation patients have a high prevalence of preoperative mood disorders. Opioid use and health care costs were significantly greater for patients with preoperative mood disorder diagnoses., Level of Evidence: Level III, retrospective therapeutic study.

Background: Alzheimer's disease (AD) is a progressive age-dependent disorder whose risk is affected by genetic factors. Better models for investigating early effects of risk factors such as apolipoprotein E (APOE) genotype are needed., Objective: To determine whether APOE genotype produces neuropathologies in an AD-susceptible neural system, we compared effects of human APOE ɛ3 (E3) and APOE ɛ4 (E4) alleles on the mouse olfactory epithelium., Methods: RNA-Seq using the STAR aligner and DESeq2, immunohistochemistry for activated caspase-3 and phosphorylated histone H3, glucose uptake after oral gavage of 2-[1,2-3H (N)]-deoxy-D-glucose, and Seahorse Mito Stress tests on dissociated olfactory mucosal cells., Results: E3 and E4 olfactory mucosae show 121 differentially abundant mRNAs at age 6 months. These do not indicate differences in cell type proportions, but effects on 17 odorant receptor mRNAs suggest small differences in tissue development. Ten oxidoreductases mRNAs important for cellular metabolism and mitochondria are less abundant in E4 olfactory mucosae but this does not translate into differences in cellular respiration. E4 olfactory mucosae show lower glucose uptake, characteristic of AD susceptibility and consistent with greater expression of the glucose-sensitive gene, Asns. Olfactory sensory neuron apoptosis is unaffected at age 6 months but is greater in E4 mice at 10 months., Conclusion: Effects of human APOE alleles on mouse olfactory epithelium phenotype are apparent in early adulthood, and neuronal loss begins to increase by middle age (10 months). The olfactory epithelium is an appropriate model for the ability of human APOE alleles to modulate age-dependent effects associated with the progression of AD.

Purpose: In this study, we investigated whether patients undergoing arthroscopic treatment of femoral acetabular impingement syndrome (FAIS) seek health care for treatment of comorbid depression and anxiety in the year following hip arthroscopy., Methods: Using the Truven Health Marketscan database, FAIS patients who underwent hip arthroscopy between January 2009 and December 2016 were identified. Claims related to depression or anxiety filed during the year before surgery were required for inclusion. Using claims for pharmaceutical and psychological therapy treatments for mental health disorders, four groups of patients were analyzed on the basis of preoperative anxiety/depression treatment: medication only, therapy only, medication + therapy, and no treatment. Number of opioid pain prescriptions within 180 days prior to surgery and >90 days after hip arthroscopy were also compared., Results: Depression and anxiety claims were identified in 5,208/14,830 (35.1%) patients. Preoperative treatment for depression and anxiety included medication only ( n  = 648, 12.4%), therapy only ( n  = 899, 17.3%), medication + therapy ( n  = 252, 4.8%), and no treatment ( n  = 3,409, 65.5%). Of the 900 patients who filled an anxiety/depression-related prescription prior to surgery, 422 (46.9%) patients did not fill a similar prescription in the postoperative year. Of the 1,151 patients receiving anxiety/depression-related therapy prior to surgery, 549 (47.7%) did not receive therapy in the postoperative year. Preoperative opioid prescriptions were filled for 393 patients (60.6%) in medication-only group, 275 (30.6%) in therapy-only group, 156 (61.9%) in medication + therapy group, and 1,059 (31.1%) in the group receiving no treatment. Opioid prescriptions >90 days postoperatively were filled for 330 (50.9%), 225 (25.0%), 120 (47.6%), and 861 (25.3%) patients, respectively., Conclusion: Hip arthroscopy for FAIS is associated with a decreased postoperative use of health care resources for the treatment of depression and anxiety. Clinicians should also be aware of the potential interplay between preoperative psychotropic medication use and prolonged opioid use when counseling patients., Level of Evidence: IV, therapeutic case series., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Purpose: To identify factors predictive of a large labral tear at the time of shoulder instability surgery., Methods: As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients undergoing open or arthroscopic shoulder instability surgery for a labral tear were evaluated. Patients with >270° tears were defined as having large labral tears. To build a predictive logistic regression model for large tears, the Feasible Solutions Algorithm was used to add significant interaction effects., Results: After applying exclusion criteria, 1235 patients were available for analysis. There were 222 females (18.0%) and 1013 males (82.0%) in the cohort, with an average age of 24.7 years (range 12 to 66). The prevalence of large tears was 4.6% (n = 57), with the average tear size being 141.9°. Males accounted for significantly more of the large tears seen in the cohort (94.7%, P = .01). Racquet sports (P = .01), swimming (P = .02), softball (P = .05), skiing (P = .04), and golf (P = .04) were all associated with large labral tears, as was a higher Western Ontario Shoulder Instability Index (WOSI; P = .01). Age, race, history of dislocation, and injury during sport were not associated with having a larger tear. Using our predictive logistic regression model for large tears, patients with a larger body mass index (BMI) who played contact sports were also more likely to have large tears (P = .007)., Conclusions: Multiple factors were identified as being associated with large labral tears at the time of surgery, including male sex, preoperative WOSI score, and participation in certain sports including racquet sports, softball, skiing, swimming, and golf., Level of Evidence: I, prognostic study., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: Hearing loss (HL) and apolipoprotein E ε4 (ApoE4) allele are both dementia risk factors. No research has investigated the association of these variables regarding dementia, specifically Alzheimer's disease. Our goal was to evaluate HL and ApoE4 allele positivity toward degree of Alzheimer's neurodegeneration., Study Design: Retrospective., Setting: Academic., Patients: Alzheimer's neuropathology obtained from brain tissue databank. Documented demographics, subjective hearing status, cognition, and ApoE4. Subjects divided into four groups based on hearing status and ApoE4 positivity., Main Outcome Measures: Differences in cognition (clinical dementia rating, mini mental state examination (MMSE), geriatric depression score) and Alzheimer's neuropathology staging (Braak, CERAD) between groups., Results: Two-hundred and fifty-nine subjects. No significant difference between groups, with regard to hearing status or ApoE4 positivity, in premorbid cognition, including scores for clinical dementia rating and MMSE (p = 0.2332). HL subjects had less severe neuropathology, as compared with normal hearing subjects. For example, high grade Braak stage was present in 27.1 and 51.0% of HL and normal hearing subjects, respectively (p = 0.0263). This finding was in context of equivocal clinical cognition between groups. ApoE4+ individuals had more severe neurodegeneration; for example, 65.7 and 33.5% with high grade Braak stage for ApoE4+ and ApoE4- subjects, respectively (p < 0.0001)., Conclusion: Subjective HL subjects had less severe neuropathology with no difference in cognition, suggesting an additive effect of HL to cognitive burden of Alzheimer's neuropathology. HL appeared to increase cognitive burden, but wasn't manifested by greater neurodegeneration. This is clinically relevant in that treating HL could slow Alzheimer's disease progression.

Purpose: To (1) quantify the prevalence of mood disorders in patients undergoing arthroscopic rotator cuff repair (RCR) by use of a large claims database and (2) compare opioid use and medical costs in the year before and the year after RCR between patients with and without comorbid mood disorders., Methods: A large claims database was queried to identify patients who underwent arthroscopic RCR (Current Procedural Terminology code 29827) between October 2010 and December 2015. All patients were then screened for insurance claims relating to either anxiety or depression. We compared net costs and opioid use both 1 year preoperatively and 1 year postoperatively between patients with and without mood disorders by use of an analysis of covariance., Results: A total of 170,329 patients (97,427 male patients [57.2%] and 72,902 female patients [42.8%]) undergoing arthroscopic RCR were identified. Of the 170,329 patients, 46,737 (27.4%) had comorbid anxiety or depression, and after adjustment for preoperative cost, sex, age, and both preoperative and postoperative opioid use, the 1-year postoperative cost was 7.05% higher for those with a preoperative mood disorder than for those without a mood disorder. In addition, opioid use both in the 180 days prior to surgery (36.7% vs 26.9%) and more than 90 days after surgery (33.0% vs 27.2%) was substantially greater in the group with comorbid depression or anxiety., Conclusions: In patients with comorbid mood disorders, opioid use and health care costs were increased both preoperatively and postoperatively. The increased cost in this patient population is estimated at $62.3 million annually. In an effort to provide high-quality, value-based care, treatment strategies should be developed to identify these patients preoperatively and provide the appropriate resources needed to improve the probability of a successful surgical outcome., Level of Evidence: Level III, retrospective, comparative therapeutic study., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4 + T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To determine if opioid use and health care costs in the year before and following hip arthroscopy for femoroacetabular impingement (FAI) differ between those with or without depression or anxiety., Methods: Using the Truven Health Marketscan database, FAI patients who underwent hip arthroscopy between October 2010 and December 2015 were identified (Current Procedural Terminology codes 29914 [femoroplasty], 29915 [acetabuloplasty], and/or 29916 [labral repair]). Patients were excluded if they had incomplete coverage for 1 year either before or following surgery. The number of patients with 1 or more claims related to depression or anxiety during the year before surgery was quantified (International Statistical Classification Diseases and Related Health-9 codes 296, 298, 300, 309, 311). Health care costs in the year before and following hip arthroscopy were compared between those with or without depression or anxiety. We also compared the number of patients in each group who filled a narcotic pain prescription within 180 days before surgery as well as >60 or >90 days after hip arthroscopy., Results: Depression or anxiety claims were seen in 5,208/14,830 patients (35.1%) before surgery. A significantly greater proportion of those with preoperative depression or anxiety filled opioid-related prescriptions in the 6 months before surgery (36.2% vs 25.6%, P < .0001) and both >60 days (31.3% vs 24.7%, P < .0001) and >90 days after surgery (29.5% vs 23.4%, P < .0001). The group with preoperative depression or anxiety had significantly greater health care costs both before ($8,775 vs $5,674, P < .0001) and following surgery ($5,287 vs $3,908, P < .0001)., Conclusions: Both before and following hip arthroscopy, opioid use and health care costs were significantly greater for FAI patients with comorbid depression or anxiety., Level of Evidence: Level III, retrospective comparative therapeutic study., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

There is a lack of vapor intrusion (VI) models that reliably account for weather conditions and building characteristics, especially at sites where active alternative pathways, such as sewer connections and other preferential pathways, are present. Here, a method is presented to incorporate freely-available models, CONTAM, and CFD0, to estimate site-specific building air exchange rates (AERs) and indoor air contaminant concentrations by accounting for weather conditions and building characteristics at a well-known VI site with a land drain preferential pathway. To account for uncertainty in model input parameters that influence indoor air chlorinated volatile organic compound (CVOC) concentration variability, this research incorporated Monte Carlo simulations and compared model results with retrospective field data collected over approximately 1.5 years from the study site. The results of this research show that mass entry rates for TCE are likely influenced by indoor air pressures that can be modeled as a function of weather conditions (over seasons) and building characteristics. In addition, the results suggest that temporal variability in indoor air TCE concentrations is greatest (modeled and measured) due to the existence of a land drain, which acts as a preferential pathway, from the subsurface to the granular fill beneath the floor slab. The field data and modeling results are in good agreement and provide a rare comparison of field data and modeling results for a VI site. The modeling approach presented here offers a useful tool for decision makers and VI practitioners as they assess these complex and variable processes that have not been incorporated within other VI models.

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed., Competing Interests: AO, SP, JS, BB, SM, GH, AS, NK, MK, AR, TB, KE, CP, MS, HS No competing interests declared, (© 2019, Owen et al.)

Objective: The relationship between hearing loss and cognitive decline is of great importance with growing evidence of hearing loss as an independent modifiable risk factor for dementia. Our goal was to evaluate for differences in dementia neuropathology between subjective normal hearing and hearing loss subjects, as well as subjects who wore hearing aids., Study Design: Retrospective database., Setting: Tertiary academic center., Patients: Brain tissue analyzed from our Center on Aging. Demographics, subjective hearing status, hearing aid use, cognitive status, and dementia neuropathology documented., Interventions: Dementia neuropathology analyzed in brains of normal hearing and hearing loss subjects., Main Outcome Measures: Differences in dementia neuropathology between hearing groups. Groups were compared using logistic regression and analysis of covariance (ANCOVA)., Results: Two-hundred and seventy-three subjects were included, 189 normal hearing and 84 subjective hearing loss subjects. No significant difference demonstrated in Alzheimer's disease neuropathology (p > 0.05) or pathologic stage (p = 0.2471). No significant difference observed in neuropathology of other major dementia types, specifically, presence of Lewy bodies (p > 0.05), Lewy body disease pathologic stage (p = 0.9778), or presence of micro-infarcts, macro-infarcts, or arteriosclerosis (p > 0.05). Hearing aid-wearing subjects had a lower prevalence of clinical dementia (39.1% versus 57.9%; p = 0.0208) with no significant difference in dementia neuropathology (p > 0.05)., Conclusion: Subjective hearing loss was not found to be associated with significantly different dementia neuropathology, which counters hypotheses on hearing loss causing permanent neurodegeneration and cognitive decline. Hearing aid users were found to have a lower prevalence of dementia for similar levels of neurodegeneration, suggesting a potential neuroprotective effect of hearing aids.