Decreased Prevalence of New-Onset Adhesive Capsulitis in Patients Prescribed Angiotensin Receptor Blockers.

BACKGROUND: Angiotensin receptor blockers (ARBs) are commonly prescribed antihypertensive agents that have well-known antifibrotic properties. The purpose of this study was to examine the association between ARB use and the rates of new-onset adhesive capsulitis as well as adhesive capsulitis requiring operative treatment. METHODS: Using a large national insurance database, a randomly generated cohort of patients with at least 3 continuous months of ARB use between January 2010 and December of 2019 (n=1,000,000) was compared to a separate randomly generated cohort without ARB use (n=3,000,000) . Rates of newly diagnosed adhesive capsulitis and associated manipulation under anesthesia and/or arthroscopic capsulotomy were calculated over a one- and two-year period following the completion of at least 3 continuous months of ARB therapy. Rates were compared using multivariable logistic regression to control for demographics and comorbidities. Both unadjusted and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated and reported for each comparison. Statistical significance was set at P<0.05. RESULTS: The mean age in the ARBs cohort was 61.8 years (SD = 10.0), while in the control cohort, it was 54.8 years (SD = 12.3) (p < 0.001). The ARBs cohort had significantly lower rates of newly diagnosed adhesive capsulitis compared to the control cohort at both one year (0.15% vs. 0.55%, p < 0.001) and two years (0.3% vs. 0.78%, p < 0.001). Similar findings were observed for the arthroscopic capsular release/MUA cohort associated with adhesive capsulitis. After adjusting for confounding factors, the lower rates of adhesive capsulitis and arthroscopic capsular release/MUA associated with adhesive capsulitis in the ARBs cohort remained statistically significant (p < 0.001). CONCLUSION: Patients prescribed ARBs experienced a decrease rate of newly diagnosed adhesive capsulitis, as well as adhesive capsulitis requiring surgical intervention when compared to a control cohort. These findings suggest a potential protective effect of ARBs against the development of adhesive capsulitis. Further investigations are warranted to elucidate the underlying mechanisms and establish a causal relationship.

Social deprivation index affects time to MRI after knee injury in pediatric patients and is predicted by patient demographics.

OBJECTIVES: This study aims to characterize the association between the timing of MRI ordering and completion for pediatric knee injuries and Social Deprivation Index (SDI), which is a comprehensive, validated, county-level, measure of socioeconomic variation in health outcomes based upon combining geography, income, education, employment, housing, household characteristics, and access to transportation. METHODS: A retrospective chart review was completed of patients 21 years old and younger from our institution with a history of knee sports injury (ligamentous/soft tissue injury, structural abnormality, instability, inflammation) evaluated with MRI between 5/26/2017 and 12/28/2020. Patients were from three states and attended to by physicians associated with an urban academic institution. Patients were assigned SDI scores based on their ZIP code. Excluded from the study were patients with a non-knee related diagnosis (hip, foot, or ankle), patients from ZIP codes with unknown SDI, and non-sports medicine diagnoses (tumor, infection, fracture). RESULTS: In a multivariate regression analysis of 355 patients, increased SDI was independently associated with increased time from clinic visit to MRI order (p = 0.044) and from clinic visit to MRI completion (p = 0.047). Each 10-point increase in SDI (0-100) was associated with a delay of 7.2 days on average. SDI itself was found to be associated with a patient's race (p < 0.001), ethnicity (p < 0.001), and insurance category (p < 0.001). CONCLUSION: Increased SDI is independently associated with longer time from clinic visit to knee MRI order and longer time from clinic visit to knee MRI completion in our pediatric population. Recognizing potential barriers to orthopedic care can help create the change necessary to provide the best possible care for all individual patients.

Apirhabdus apintestini gen. nov., sp. nov., a member of a novel genus of the family Enterobacteriaceae, isolated from the gut of the western honey bee Apis mellifera.

A Gram-negative, motile, rod-shaped bacterial strain, CA-0114T, was isolated from the midgut of a western honey bee, Apis mellifera. The isolate exhibited ≤96.43 % 16S rRNA gene sequence identity (1540 bp) to members of the families Enterobacteriaceae and Erwiniaceae. Phylogenetic trees based on genome blast distance phylogeny and concatenated protein sequences encoded by conserved genes atpD, fusA, gyrB, infB, leuS, pyrG and rpoB separated the isolate from other genera forming a distinct lineage in the Enterobacteriaceae. In both trees, the closest relatives were Tenebrionicola larvae YMB-R21T and Tenebrionibacter intestinalis BIT-L3T, which were isolated previously from Tenebrio molitor L., a plastic-eating mealworm. Digital DNA-DNA hybridization, orthologous average nucleotide identity and average amino acid identity values between strain CA-0114T and the closest related members within the Enterobacteriaceae were ≤23.1, 75.45 and 76.04 %, respectively. The complete genome of strain CA-0114T was 4 451669 bp with a G+C content of 52.12 mol%. Notably, the apparent inability of strain CA-0114T to ferment d-glucose, inositol and l-rhamnose in the API 20E system is unique among closely related members of the Enterobacteriaceae. Based on the results obtained through genotypic and phenotypic analysis, we propose that strain CA-0114T represents a novel species and genus within the family Enterobacteriaceae, for which we propose the name Apirhabdus apintestini gen. nov., sp. nov. (type strain CA-0114T=ATCC TSD-396T=DSM 116385T).

Itaconate stabilizes CPT1a to enhance lipid utilization during inflammation.

One primary metabolic manifestation of inflammation is the diversion of cis-aconitate within the tricarboxylic acid (TCA) cycle to synthesize the immunometabolite itaconate. Itaconate is well established to possess immunomodulatory and metabolic effects within myeloid cells and lymphocytes, however, its effects in other organ systems during sepsis remain less clear. Utilizing Acod1 knockout mice that are deficient in synthesizing itaconate, we aimed to understand the metabolic role of itaconate in the liver and systemically during sepsis. We find itaconate aids in lipid metabolism during sepsis. Specifically, Acod1 KO mice develop a heightened level of hepatic steatosis when induced with polymicrobial sepsis. Proteomics analysis reveals enhanced expression of enzymes involved in fatty acid oxidation in following 4-octyl itaconate (4-OI) treatment in vitro. Downstream analysis reveals itaconate stabilizes the expression of the mitochondrial fatty acid uptake enzyme CPT1a, mediated by its hypoubiquitination. Chemoproteomic analysis revealed itaconate interacts with proteins involved in protein ubiquitination as a potential mechanism underlying its stabilizing effect on CPT1a. From a systemic perspective, we find itaconate deficiency triggers a hypothermic response following endotoxin stimulation, potentially mediated by brown adipose tissue (BAT) dysfunction. Finally, by use of metabolic cage studies, we demonstrate Acod1 KO mice rely more heavily on carbohydrates versus fatty acid sources for systemic fuel utilization in response to endotoxin treatment. Our data reveal a novel metabolic role of itaconate in modulating fatty acid oxidation during polymicrobial sepsis.

Statistical Fragility Analysis of Open Reduction Internal Fixation vs Primary Arthrodesis to Treat Lisfranc Injuries: A Systematic Review.

BACKGROUND: There is a lack of consensus in the use of open reduction internal fixation (ORIF) vs primary arthrodesis (PA) in the management of Lisfranc injuries. Statistical fragility represents the number of events needed to flip statistical significance and provides context to interpret P values of outcomes from conflicting studies. The current study evaluates the statistical fragility of existing research with an outcome-specific approach to provide statistical clarity to the ORIF vs PA discussion. We hypothesized that statistical fragility analysis would offer clinically relevant insight when interpreting conflicting outcomes regarding ORIF vs PA management of Lisfranc injuries. METHODS: All comparative studies, RCTs, and case-series investigating ORIF vs PA management of Lisfranc injuries published through October 5, 2023, were identified. Descriptive characteristics, dichotomous outcomes, and continuous outcomes were extracted. Fragility index and continuous fragility index were calculated by the number of event reversals needed to alter significance. Outcomes were categorized by clinical relevance, and median FI and CFI were reported. RESULTS: A total of 244 studies were screened. Ten studies and 67 outcomes (44 dichotomous, 23 continuous) were included in the fragility analysis. Of the 10 studies, 4 studies claimed PA to correlate with superior outcomes compared to ORIF with regard to functional scores and return to function outcomes. Of these 4 studies, 3 were statistically robust. Six studies claimed PA and ORIF to have no differences in outcomes, in which only 2 studies were statistically robust. CONCLUSION: The overall research regarding ORIF vs PA is relatively robust compared with other orthopaedic areas of controversy. Although the full statistical context of each article must be considered, studies supporting PA superiority with regard to functional scores and return to function metrics were found to be statistically robust. Outcome-specific analysis revealed moderate fragility in several clinically relevant outcomes such as functional score, return to function, and wound complications.

Characteristics of Femoral Shaft Fractures That Predict Ipsilateral Femoral Neck Fractures.

INTRODUCTION: This study aims to characterize radiographic features and fracture characteristics in femoral shaft fractures with associated femoral neck fractures, with the goal of establishing predictive indicators for the presence of ipsilateral femoral neck fractures (IFNFs). METHODS: A retrospective cohort was collected from the electronic medical record of three level I trauma centers over a 5-year period (2017 to 2022) by current procedural terminology (CPT) codes. Current CPT codes for combined femoral shaft and IFNFs were identified to generate our study group. CPT codes for isolated femur fractures were identified to generate a control group. RESULTS: One hundred forty patients comprised our IFNF cohort, and 280 comprised the control cohort. On univariate, there were significant differences in mechanism of injury (P < 0.001), Orthopedic Trauma Association (OTA)/Arbeitsgemeinshaft fur Osteosynthesefragen (AO) classification (P = 0.002), and fracture location (P < 0.001) between cohorts. On multivariate, motor vehicle crashes were more commonly associated with IFNFs compared with other mechanism of injuries. OTA/AO 32A fractures were more commonly associated with IFNFs when compared with OTA/AO 32B fractures (adjusted odds ratio = 0.36, P < 0.001). Fractures through the isthmus were significantly more commonly associated with IFNFs than fractures more proximal (adjusted odds ratio = 2.52, P = 0.011). DISCUSSION: Detecting IFNFs in femoral shaft fractures is challenging. Motor vehicle crashes and motorcycle collisions, OTA/AO type 32A fractures, and isthmus fractures are predictive of IFNFs.

Global heterogeneity in folic acid fortification policies and implications for prevention of neural tube defects and stroke: a systematic review.

Background: Folic acid (pteroylmonoglutamic acid) supplements are highly effective for prevention of neural tube defects (NTD) prompting implementation of mandatory or voluntary folic acid fortification for prevention of NTDs. We used plasma folate levels in population studies by country and year to compare effects of folic acid fortification types (mandatory or voluntary folic acid fortification policies) on plasma folate levels, NTD prevalence and stroke mortality rates. Methods: We conducted systematic reviews of (i) implementation of folic acid fortification in 193 countries that were member states of the World Health Organization by country and year, and (ii) estimated population mean plasma folate levels by year and type of folic acid fortification. We identified relevant English language reports published between Jan 1, 1990 and July 31, 2023 using Google Scholar, Medline, Embase and Global Health. Eligibility criteria were observational or interventional studies with >1000 participants. Studies of pregnant women or children <15 years were excluded. Using an ecological study design, we examined the associations of folic acid fortification types with NTD prevalence (n = 108 studies) and stroke mortality rates (n = 3 countries). Findings: Among 193 countries examined up to 31 July 2023, 69 implemented mandatory folic acid fortification, 47 had voluntary fortification, but 77 had no fortification (accounting for 32%, 53% and 15% of worldwide population, respectively). Mean plasma folate levels were 36, 21 and 17 nmol/L in populations with mandatory, voluntary and no fortification, respectively (and proportions with mean folate levels >25 nmol/L were 100%, 15% and 7%, respectively). Among 75 countries with NTD prevalence, mean (95% CI) prevalence per 10,000 population were 4.19 (4.11-4.28), 7.61 (7.47-7.75) and 9.66 (9.52-9.81) with mandatory, voluntary and no folic acid fortification, respectively. However, age-standardised trends in stroke mortality rates were unaltered by the introduction of folic acid fortification. Interpretation: There is substantial heterogeneity in folic acid fortification policies worldwide where folic acid fortification are associated with 50-100% higher population mean plasma folate levels and 25-50% lower NTD prevalence compared with no fortification. Many thousand NTD pregnancies could be prevented yearly if all countries implemented mandatory folic acid fortification. Further trials of folic acid for stroke prevention are required in countries without effective folic acid fortification policies. Funding: Medical Research Council (UK) and British Heart Foundation.

Peroneus Longus Tendon Autograft May Present a Viable Alternative for Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To examine the available literature to better understand the objective and patient-reported outcomes using peroneus longus tendon (PLT) autograft compared with more commonly used autografts, such as the quadrupled hamstring tendons (HT), in patients undergoing primary for anterior cruciate ligament reconstruction (ACLR). METHODS: A comprehensive search of published literature in PubMed, Web of Science, Cochrane Library, Ovid, and EMBASE databases was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included patients undergoing ACLR with PLT autograft, inclusion of patient-recorded outcome measures, and availability in English language. Publications that included only biomechanical analysis or ACLR with use of allograft or combination grafts were excluded. RESULTS: A total of 16 studies (Level of Evidence range: I-IV) met inclusion criteria, with follow-up ranging from 3 months to 5 years. In the available case series, patient-reported outcomes ranged from Lysholm = 80.7 to 95.1, International Knee Documentation Committee 78.1 to 95.7. In prospective cohorts and randomized controlled trials, PLT performance was comparable with HT autografts (PLT/HT: Lysholm = 88.3-95.1/86.5-94.9, International Knee Documentation Committee = 78.2-92.5/87.4-93.4). The majority of PLT grafts diameters were equal or greater than HT counterparts with a mean of >8 mm (PLT/HT: 7.0-9.0 mm/7.65-8.5 mm). There was minimal donor-site morbidity associated with PLT harvest. CONCLUSIONS: Although limitations exist within the available literature, existing evidence suggests that PLT autograft routinely produces adequately sized grafts with comparable early outcomes to HT autograft and low risk of donor-site morbidity. However, the PLT autograft is yet to demonstrate superiority to any of the more-traditional autograft selections. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.

Postoperative Angiotensin Receptor Blocker Use is Associated With Decreased Rates of Manipulation Under Anesthesia, Arthroscopic Lysis of Adhesions, and Prosthesis-Related Complications in Patients Undergoing Total Knee Arthroplasty.

BACKGROUND: The cellular mechanisms underlying excess scar tissue formation in arthrofibrosis following total knee arthroplasty (TKA) are well-described. Angiotensin receptor blockers (ARB), particularly losartan, is a commonly prescribed antihypertensive with demonstrated antifibrotic properties. This retrospective study aimed to assess the rates of 1- and 2-year postoperative complications in patients who filled prescriptions for ARBs during the 90 days after TKA. METHODS: Patients undergoing primary TKA were selected from a large national insurance database, and the impact of ARB use after TKA on complications was assessed. Of the 1,299,106 patients who underwent TKA, 82,065 had filled at least a 90-day prescription of losartan, valsartan, or olmesartan immediately following their TKA. The rates of manipulation under anesthesia (MUA), arthroscopic lysis of adhesions (LOA), aseptic loosening, periprosthetic fracture, and revision at 1 and 2 years following TKA were analyzed using multivariable logistic regressions to control for various comorbidities. RESULTS: ARB use was associated with decreased rates of MUA (odds ratio [OR] = 0.94, 95% confidence interval (CI), 0.90 to 0.99), arthroscopy/LOA (OR = 0.86, 95% CI, 0.77 to 0.95), aseptic loosening (OR = 0.71, 95% CI, 0.61 to 0.83), periprosthetic fracture (OR = 0.58, 95% CI, 0.46 to 0.71), and revision (OR = 0.79, 95% CI, 0.74 to 0.85) 2 years after TKA. CONCLUSIONS: ARB use throughout the 90 days after TKA is associated with a decreased risk of MUA, arthroscopy/LOA, aseptic loosening, periprosthetic fracture, and revision, demonstrating the potential protective abilities of ARBs. Prospective studies evaluating the use of ARBs in patients at risk for postoperative stiffness would be beneficial to further elucidate this association.

Arm health in elite collegiate summer league baseball players assessed by the Kerlan-Jobe Orthopaedic Clinic score.

CONTEXT: Collegiate baseball players with professional aspirations often participate in summer leagues, foremost among them is the Cape Cod Baseball League (CCBL). Injuries acquired during the college baseball season can be carried into the CCBL season and vice versa. OBJECTIVE: To assess throwing arm injury history and current functionality in mid-season CCBL players. DESIGN: Cross-sectional study. SETTING: Online questionnaire. PATIENTS OF OTHER PARTICIPANTS: 123 CCBL players participated. Qualifying athletes were ≥18 years old and a rostered CCBL player with remaining collegiate eligibility. MAIN OUTCOME MEASURES: After collecting background information, the Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow questionnaire was employed to assess throwing arm injury history and current functionality. The maximum KJOC score is 100.0; higher scores correspond to greater functionality. RESULTS: The mean KJOC score was 86.6 ± 14.5 (n = 92). 24.5% (23/94) of players reported a prior diagnosis of throwing arm injury other than a strain/sprain. Forty-nine (49/96, 51.0%) players had undergone rehabilitation for a throwing arm injury, and seven (7/96, 7.3%) had experienced a medical procedure. Players with no prior treatment (n = 41, 88.9 ± 19.0) more frequently demonstrated KJOC scores ≥ 90 than players with previous treatment (n = 55, 80.9 ± 17.1; P < .001). The 18 players with time-loss arm injury in the last year (71.3 ± 20.0) had lower mean KJOC scores than players with no injury or time loss (90.3 ± 9.8; P < .001). Similarly, players who reported current arm trouble (n = 15) had lower KJOC scores (71.6 ± 17.5) than players with healthy arms (89.5 ± 11.9; P < .001). CONCLUSIONS: CCBL players report an average KJOC score below 90, with particularly low scores in cases of prior arm injury and treatment.

Evaluating Measurement Properties of Patient-Reported Outcome Measures in Glaucoma: A Systematic Review.

TOPIC: The purpose of the current study was to systematically identify and evaluate existing patient-reported outcome measures (PROMs) for clinical glaucoma practice. CLINICAL RELEVANCE: Understanding and incorporating patient preferences into decision-making is now recognized as critical for optimal resource allocation, especially in technologically advancing areas, such as minimally invasive surgeries. Patient-reported outcome measures are instruments designed to evaluate the health outcomes that are most important to patients. Despite their recognized importance, especially in the era of patient-centered care, their routine use in clinical settings remains low. METHODS: A systematic literature search was conducted in 6 databases (EMBASE, MEDLINE, PsycINFO, Scopus, BIOSIS, and Web of Science) from the date of inception. Studies were included in the qualitative review if they reported measurement properties of PROMs in adult patients with glaucoma. COnsensus-based Standards for the selection of health Measurement INstruments guidelines were used to assess the included PROMs. The study protocol is registered with PROSPERO (registration number: CRD42020176064). RESULTS: The literature search yielded 2661 records. After deduplication, 1259 studies entered level 1 screening, and based on title and abstract review, 164 records proceeded to full-text screening. In 48 included studies, 70 instrument reports discuss 43 distinct instruments in 3 major categories: glaucoma-specific, vision-specific, and general health-related quality of life. Most used measures were glaucoma-specific (Glaucoma Quality of Life [GQL] and Glaucoma Symptom Scale [GSS]) and vision-specific (National Eye Institute Visual Function Questionnaire [NEI VFQ-25]). All 3 have sufficient validity (especially construct), with GQL and GSS having sufficient internal consistency, cross-cultural validity, and reliability, with reports suggesting high methodological quality. CONCLUSION: The GQL, GSS, and NEI VFQ-25 are the 3 most used questionnaires in a research setting, having considerable validation in a patient population with glaucoma. Limited reports on interpretability, responsiveness, and feasibility in all 43 identified instruments make identifying a single optimal questionnaire for clinical use challenging and highlight the need for further studies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Diagnosis of Vitamin D Deficiency Is Associated With Increased Rates of Anterior Cruciate Ligament Tears and Reconstruction Failure.

PURPOSE: To characterize the association between a diagnosis of hypovitaminosis D and primary anterior cruciate ligament (ACL) tear, primary anterior cruciate ligament reconstruction (ACLR), and revision ACLR in different sex and age cohorts. METHODS: In this retrospective cohort study of the PearlDiver claims database, records were queried between January 1, 2011, and October 31, 2018 for all patients aged 10 to 59 years who received a diagnosis of hypovitaminosis D. Rates of primary ACL tears, primary reconstruction, and revision reconstruction were calculated for sex- and age-specific cohorts and compared with a control of patients without a diagnosis of hypovitaminosis D. Incidence rates for primary ACL injuries were calculated, and multivariable logistic regression was used to compare rates of ACL injury, primary reconstruction, and revision reconstruction while controlling for age, sex, Charlson Comorbidity Index, and several other comorbidities. RESULTS: Among the 328,011 patients (mean age 41.9 ± 12.6 years, 65.8% female) included in both the hypovitaminosis D and control cohorts, the incidence of ACL tears was 115.2 per 100,000 person-years (95% confidence interval [CI] 107.2-123.7) compared with 61.0 (95% CI 55.2-67.2) in the demographic- and comorbidity-matched control cohort. The study cohort was significantly more likely to suffer an ACL tear over a 1- (aOR 1.67, 95% CI 1.41-1.99, P < .001) and 2-year (aOR 1.81, 95% CI 1.59-2.06, P < .001) period. This trend remained for both male patients at the 1- (aOR 1.66, 95% CI 1.29-2.14, P < .001) and 2-year (aOR 1.68, 95% CI 1.37-2.06, P < .001) mark and female patients at the 1- (aOR 1.69, 95% CI 1.33-2.14, P < .001) and 2-year (aOR 1.80, 95% CI 1.51-2.14, P < .001) mark. Finally, patients with vitamin D deficiency had a significantly increased likelihood of undergoing a revision ACLR within 2 years of a primary reconstruction (aOR 1.28, 95% CI 1.05-1.55, P = .012). CONCLUSIONS: This study reports an association between patients previously diagnosed with hypovitaminosis D and significantly increased rates of both index ACL tears (81% increase within 2 years of diagnosis) and revision ACLR (28% within 2 years). These results identify a population with increased odds of injury and provide valuable knowledge as we expand our understanding of the relationship between vitamin D and musculoskeletal health. LEVEL OF EVIDENCE: Level III, retrospective database study.

A Diagnosis of Vitamin D Deficiency Is Associated With Increased Rates of Primary Patellar Instability and Need for Recurrent Surgical Stabilization.

BACKGROUND: Vitamin D has been proven experimentally to affect musculoskeletal health. The purpose of this study was to identify the relationship between vitamin D deficiency and patellar instability. HYPOTHESIS: Vitamin D deficiency is associated with an increased risk of experiencing primary patellar instability and recurrent patellar dislocation after primary surgical stabilization. STUDY DESIGN: Retrospective comparative study. LEVEL OF EVIDENCE: Level 3. METHODS: A 1:1 matched retrospective study of 328,011 patients diagnosed with vitamin D deficiency was performed using the PearlDiver database. Incidence of primary patellar instability was calculated according to sex and age. Rates of primary patellar instability and surgical stabilization for recurrent dislocation were calculated with sex- and age-specific stratifications. Multivariable logistic regression was used to compare the rates of primary injury and recurrent stabilization while controlling for demographics and medical comorbidities. RESULTS: A total of 656,022 patients were analyzed. The overall 1-year incidence rate of patellar instability in patients with vitamin D deficiency was 82.6 per 100,000 person-years (95% CI, 73.2-92.9), compared with 48.5 (95% CI, 41.4-56.5) in the matched control. Women were significantly more likely to experience primary patellar instability within 1 (adjusted odds ratio [aOR] = 1.45; 95% CI, 1.12-1.88) and 2 years (aOR, 1.31; 95% CI, 1.07-1.59) of hypovitaminosis D diagnosis. Patients aged 10 to 25 years with hypovitaminosis D were at greater risk of requiring recurrent patellar stabilization for both men (aOR, 2.48; 95% CI, 1.06-5.80) and women (aOR, 1.77; 95% CI, 1.04-3.02). CONCLUSION: Patients diagnosed with vitamin D deficiency experienced higher rates of primary patellar instability and have greater risk of requiring recurrent surgical stabilization for subsequent dislocations. CLINICAL RELEVANCE: These results suggest that monitoring and proactively treating vitamin D deficiency in the physically active patient may lower the risk of suffering primary patellar instability or recurrence after surgical stabilization.

Application of a CRISPR Sequence-Based Method for a Large-Scale Assessment of Salmonella Serovars in Ontario Poultry Production Environments.

Accurate detection of all Salmonella serovars present in a sample is important in surveillance programs. Current detection protocols are limited to detection of a predominant serovar, missing identification of less abundant serovars in a sample. An alternative method, called CRISPR-SeroSeq, serotyping by sequencing of amplified CRISPR spacers, was employed to detect multiple serovars in a sample without the need of culture isolation. The CRISPR-SeroSeq method successfully detected 34 most frequently reported Salmonella serovars in pure cultures and target serovars at 104 CFU/mL in 27 Salmonella-negative environmental enrichment samples post-spiked with one of 15 different serovars, plus 2 additional serovars at 1 log CFU/mL higher abundance. When the method was applied to 442 naturally contaminated environmental samples collected from 192 poultry farms, 25 different serovars were detected from 430 of the samples. In 73.1% of the samples, 2 to 7 serovars were detected, with Salmonella Kiambu (55.7%), Salmonella Infantis (48.4%), Salmonella Kentucky (27.1%), Salmonella Livingstone (26.6%), and Salmonella Mbandaka/Montevideo (23.4%) being the most prevalent on the farms. Single isolates from 384 samples were also analyzed using a traditional serotyping method, and the same serovar identified by culture was detected by CRISPR-SeroSeq in 96.1% (369/384) of samples, with the former missing detection of additional and sometimes critical serovars. The surveillance data obtained via CRISPR-SeroSeq revealed a significant emergence of Salmonella Kiambu and Salmonella Rissen on poultry farms in Ontario. The results highlight the effectiveness of the CRISPR-SeroSeq approach in detecting multiple Salmonella serovars in poultry environmental samples under applied conditions, providing updated surveillance information on Salmonella serovars on poultry farms in Ontario. IMPORTANCE The CRISPR-SeroSeq method represents an alternative molecular tool to the traditional culture-based serotyping method that can detect multiple Salmonella serovars in a sample and provide rapid serovar results without the need of selective enrichment and culture isolation. The evaluation results can facilitate implementation of the method in routine Salmonella surveillance on poultry farms and in outbreak investigations. The application of the method can increase the accuracy of current serovar prevalence information. The results highlight the effectiveness of the validated method and the need for monitoring Salmonella serovars in poultry environments to improve current surveillance programs. The updated surveillance data provide timely information on emergence of different Salmonella serovars on poultry farms in Ontario and support on-farm risk assessment and risk management of Salmonella.

Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.

Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and interleukin-1ß (IL-1ß) secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves crista ultrastructure, and attenuates mitochondrial reactive oxygen species (ROS) production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. Our study suggests a non-canonical role of mitochondrial PDHK in promoting mitochondrial stress and supporting NLRP3 inflammasome activation during acute inflammation.

Association of topical glaucoma medications with lacrimal drainage obstruction and eyelid malposition.

BACKGROUND/OBJECTIVES: Adverse effects of topical glaucoma medications (TGMs) may include development of ocular adnexal disorders. We undertook a study to determine the effect of TGMs on the risk of developing lacrimal drainage obstruction (LDO) and eyelid malposition. SUBJECTS/METHODS: All patients 66 years of age and older in Ontario, Canada initiating TGM and all patients diagnosed with glaucoma/suspected glaucoma but not receiving TGM from 2002 to 2018 were eligible for inclusion in this retrospective cohort study. Using validated healthcare administrative databases, cohorts were identified with TGM and no TGM patients matched 1:2 on sex and birth year. The effect of TGM treatment on risk of surgery for LDO and lid malpositions was estimated using Kaplan-Meier and Cox proportional hazards models. RESULTS: Cohorts included 122,582 patients in the TGM cohort and 232,336 patients in the no TGM cohort. Among the TGM cohort there was decreased event-free survival for entropion (log-rank P < 0.001), trichiasis (P < 0.001), and LDO (P = 0.006), and increased ectropion-free survival (P = 0.007). No difference in ptosis-free survival was detected (P = 0.78). For the TGM cohort there were increased hazards for entropion (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.12-1.37; P < 0.001), trichiasis (HR 1.74, 95% CI 1.57-1.94; P < 0.001), and LDO (at 15 years: HR 2.39, 95% CI 1.49-3.85; P = 0.004), and a decreased hazard for ectropion (HR 0.89, 95% CI 0.81-0.97; P = 0.008). No association between TGM treatment and ptosis hazard was detected (HR 0.99, 95% CI 0.89-1.09; P = 0.78). CONCLUSIONS: TGMs are associated with an increased risk of undergoing surgery for LDO, entropion, and trichiasis.

Evolution of first-line glaucoma therapy, 2007-2018: a population-based analysis.

OBJECTIVE: To evaluate the long-term evolution of first-line glaucoma therapy (FLGT) initiated by ophthalmologists and optometrists. DESIGN: Retrospective population-based study using validated provincial health care databases. PARTICIPANTS: 194,759 Ontario residents, 66 years of age or older, who received FLGT between 2007 and 2018. METHODS: A total of 194,759 individuals from 12 annual cohorts were enrolled, and rates of first-line medical treatment (prostaglandin analogue [PGA], beta-blocker, alpha-2-agonist, and carbonic anhydrase inhibitor) and laser trabeculoplasty (LT) were calculated. Provider (ophthalmologist or optometrist) rates also were assessed. RESULTS: Across the entire study period, of the 194,759 enrolled individuals who received FLGT, 60.2% initially received medical treatment and 39.8% underwent LT. Approximately 94.6% were treated by ophthalmologists. PGA therapy was the most common therapy prior to 2010, whereupon LT became the most common FLGT. By 2015, LT exceeded the total of all medications as FLGT. The annual rate of initial medication prescriptions by optometrists rose to 101.4 per 100,000 population between 2011 and 2018. In 2018, PGA and non-PGA prescription rates by ophthalmologists were 2.6 and 5.0 times higher, respectively, than prescription rates by optometrists. CONCLUSION: LT therapy has become the most common FLGT for Ontario residents 66 years of age or older. PGAs remain the most frequently prescribed glaucoma medication. While ophthalmologists continue to provide the majority of FLGT, optometrists now provide a small but growing fraction of FLGT following the introduction of glaucoma medication prescribing privileges.