Hypermethylation Loci of ZNF671, IRF8, and OTX1 as Potential Urine-Based Predictive Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.

Characterization of renal masses with MRI-based radiomics: assessment of inter-package and inter-observer reproducibility in a prospective pilot study.

OBJECTIVES: To evaluate radiomics features' reproducibility using inter-package/inter-observer measurement analysis in renal masses (RMs) based on MRI and to employ machine learning (ML) models for RM characterization. METHODS: 32 Patients (23M/9F; age 61.8 ± 10.6 years) with RMs (25 renal cell carcinomas (RCC)/7 benign masses; mean size, 3.43 ± 1.73 cm) undergoing resection were prospectively recruited. All patients underwent 1.5 T MRI with T2-weighted (T2-WI), diffusion-weighted (DWI)/apparent diffusion coefficient (ADC), and pre-/post-contrast-enhanced T1-weighted imaging (T1-WI). RMs were manually segmented using volume of interest (VOI) on T2-WI, DWI/ADC, and T1-WI pre-/post-contrast imaging (1-min, 3-min post-injection) by two independent observers using two radiomics software packages for inter-package and inter-observer assessments of shape/histogram/texture features common to both packages (104 features; n = 26 patients). Intra-class correlation coefficients (ICCs) were calculated to assess inter-observer and inter-package reproducibility of radiomics measurements [good (ICC ≥ 0.8)/moderate (ICC = 0.5-0.8)/poor (ICC < 0.5)]. ML models were employed using reproducible features (between observers and packages, ICC > 0.8) to distinguish RCC from benign RM. RESULTS: Inter-package comparisons demonstrated that radiomics features from T1-WI-post-contrast had the highest proportion of good/moderate ICCs (54.8-58.6% for T1-WI-1 min), while most features extracted from T2-WI, T1-WI-pre-contrast, and ADC exhibited poor ICCs. Inter-observer comparisons found that radiomics measurements from T1-WI pre/post-contrast and T2-WI had the greatest proportion of features with good/moderate ICCs (95.3-99.1% T1-WI-post-contrast 1-min), while ADC measurements yielded mostly poor ICCs. ML models generated an AUC of 0.71 [95% confidence interval = 0.67-0.75] for diagnosis of RCC vs. benign RM. CONCLUSION: Radiomics features extracted from T1-WI-post-contrast demonstrated greater inter-package and inter-observer reproducibility compared to ADC, with fair accuracy for distinguishing RCC from benign RM. CLINICAL RELEVANCE: Knowledge of reproducibility of MRI radiomics features obtained on renal masses will aid in future study design and may enhance the diagnostic utility of radiomics models for renal mass characterization.

Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial.

PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. CONCLUSIONS: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.

Did the Comprehensive Care for Joint Replacement Bundled Payment Program Impact Sex Disparities in Total Hip and Knee Arthroplasties?

BACKGROUND: Sex disparities have been noted across various aspects of total hip/knee arthroplasty (THA/TKA). Given incentives to standardize care, bundled payment initiatives including the Comprehensive Care for Joint Replacement (CJR) program may reduce disparities. This study aimed to assess the CJR program's impact on sex disparities in THA/TKA care and outcomes. METHODS: This retrospective cohort study included 259,673 THAs (61.7% women) and 506,311 TKAs (64.0% women) from a large national database (2013 to 2017). Sex disparities were assessed for care and outcomes related to the period (1) before surgery, (2) during hospitalization for THA/TKA, and (3) after discharge. Disparities were reported as women:men ratios. Difference-in-differences analyses estimated the impact of the CJR program on pre-existing sex disparities. RESULTS: For both THA and TKA, women were less likely than men to present with a Charlson-Deyo comorbidity index >0 (women:men ratio 0.88 to 0.92), but were more likely to require blood transfusions (women:men ratio 1.48 to 1.79) and be discharged to institutional postacute care (women:men ratio 1.50 to 1.66). Difference-in-differences models demonstrated that the CJR bundled payment program reduced sex disparities in institutional postacute care discharges (THA: -2.28%; 95% confidence interval [CI] -4.20 to -0.35%, P = .02; TKA: -2.07%; 95% CI -3.93 to -0.20%; P = .03) and THA 90-day readmissions (-1.00%, 95% CI -1.88 to -0.13%, P = .02), indicating a differential impact of CJR in women versus men for some outcomes. CONCLUSIONS: While sex disparities in THA/TKA persist, the CJR program demonstrates potential to impact such differences. Future research should focus on how potential mechanisms could be leveraged to reduce disparities.

Impact of Facility Dog and Certified Child Life Specialist Dyad on Children's Pain and Anxiety During Needlestick Procedures in a Pediatric Hematology Oncology Clinic Setting.

BACKGROUND: Pediatric Hematology Oncology patients undergo frequent needlestick procedures, often leading to negative outcomes including pain and anxiety. Animal-assisted therapy has been shown to minimize pediatric patient distress; however, its utilization by a Certified Child Life Specialist (CCLS) to reduce patient distress has not been widely studied. METHODS: Pediatric patients receiving needlesticks in the Hematology Oncology Clinic were enrolled between March 2018 and May 2021. Patients who had scheduled visits when the facility dog was present were assigned to the intervention group. Patients were assigned to the control group if the facility dog was not present. The primary objective was to use the Children's Anxiety and Pain Scale to determine whether the CCLS and facility dog dyad minimized patient pain and anxiety during procedures. RESULTS: A total of 285 patients, 5 to 17 years of age, were enrolled. One hundred forty-three patients were assigned the intervention and received procedural support from the CCLS and facility dog; 142 patients were assigned the control group and received support from the CCLS only. Patient-reported pain scores were significantly lower among patients who received the intervention ( P =0.033). CONCLUSIONS: Utilization of a CCLS and facility dog dyad during painful needlestick procedures decreases patient-reported pain compared with utilization of CCLS support alone.

HCC screening with ultrasound: assessment of quality using ultrasound LI-RADS score.

PURPOSE: To describe ultrasound (US) quality for hepatocellular carcinoma (HCC) screening/surveillance using the US LI-RADS scoring system, and to assess predictive factors of worse US quality scores. METHODS: This retrospective study included adult patients (n = 470; M/F 264/206, median age 59y) at risk for HCC that underwent US for HCC screening/surveillance. US examinations were independently reviewed by 2 radiologists that assigned a visualization score (A: no/minimal, B: moderate, C: severe limitation) and US diagnostic category (US LI-RADS 1: negative, US LI-RADS 2: subthreshold, US LI-RADS 3: positive) to each study. A generalized linear mixed model was used to assess the predictive factors of worse visualization score using OR (odds ratio) statistics. Simple Kappa coefficient (K) assessed inter-reader agreement. RESULTS: For readers 1 and 2, 295/320 (62.8%/68.1%) cases were scored A, 153/134 (32.6%/28.5%) were scored B, and 22/16 (4.6%/3.4%) were scored C, respectively. There was moderate inter-reader agreement for US LI-RADS visualization score (K = 0.478) and 100% concordance for US diagnostic category (K = 1), with 30 (6.4%) cases scored as positive (US LI-RADS 3). Cirrhosis and obesity were significant independent predictors of worse visualization scores (B/C) (cirrhosis: OR 10.4 confidence intervals: [4.25-25.48], p < 0.001; obesity: OR 3.61 [2.11-6.20], p < 0.001). Of the 30 lesions scored as US LI-RADS 3, 9 were characterized as probable or definite HCC on confirmatory CT/MRI, yielding a PPV of 30% (9/30) and a false-positive rate of 70% (21/30). CONCLUSION: Moderate to severe limitations in quality of US performed for HCC screening/surveillance was observed in approximately one-third of patients. Patients with cirrhosis and/or elevated BMI have poorer quality US studies and may benefit from other screening modalities such as CT or MRI.

Epidemiology of Hand and Wrist Injuries in Collegiate-Level Athletes in the United States.

PURPOSE: Hand and wrist injuries are common among competitive athletes and can have a substantial impact on playing time and future participation. The purpose of this study was to provide epidemiological data from the National Collegiate Athletic Association Injury Surveillance Program to correlate injury diagnosis with the need for surgery and time loss. METHODS: Using the National Collegiate Athletic Association Injury Surveillance Program, this retrospective study extracted data of hand and wrist injuries for all 25 National Collegiate Athletic Association sports from the academic years 2004-2005 to 2013-2014. The "severe" category was defined as injuries resulting in the following: (1) surgery, (2) season-ending status, or (3) more than 30 days of playing time loss. The epidemiologic data included injury rate per 100,000 athlete exposures (defined as 1 athlete participating in 1 practice or competition) based on diagnoses and demographic information such as sports and sex. We used a Poisson regression model to estimate the incidence rate and 95% confidence interval. RESULTS: Overall, 4,851 hand injuries were identified, with an injury rate of 41.2 per 100,000 athlete exposures. The most common diagnoses were metacarpal or phalangeal fractures (19.9%), lacerations or contusions (15.4%), and wrist sprains (14.7%). The surgical rate was 9.6%, and the season-ending rate was 5.8%. Severe injuries occurred in 17.5% of the hand and wrist injuries; within this subset, the most common diagnoses included metacarpal or phalangeal fractures (43.8%), scaphoid fractures (12.8%), and thumb ulnar collateral ligament tears (8.7%). Scaphoid fractures and metacarpal or phalangeal fractures had the highest surgical rate and season-ending rate among all the injuries. CONCLUSIONS: The injury rate of hand and wrist injuries is comparable with those of other common sports injuries. Approximately one fifth of the injuries were considered severe, which led to a high surgical rate, and these had a considerable impact on the athletes' ability to finish the season. TYPE OF STUDY/LEVEL OF EVIDENCE: Outcome research level II.

Surgical Scheduling Impacts Hospital Length of Stay and Associated Healthcare Costs for Patients Undergoing Total Hip and Knee Arthroplasty.

Background: Surgical scheduling, specifically the day of the week on which surgery is performed, has been associated with various postoperative outcomes in patients undergoing lower extremity joint arthroplasty. Purpose: We sought to investigate surgical scheduling as a potential modifiable factor for patient quality metrics and related costs. Methods: In a retrospective prognostic study, all total knee and total hip arthroplasty (TKA/THA) cases that took place in 2017 to 2018 at a multihospital academic health system were queried. Patients were separated by the day of the week the surgery was performed, with Monday/Tuesday compared to Thursday/Friday. Outcomes included length of stay (LOS) (extended LOS defined as 3 days or longer), cost, and complications. Multivariable regression models measured associations between scheduling of surgery and outcomes; odds ratios (OR) and 95% confidence intervals (CIs) are reported. Results: Overall, 1,571 TKA and 992 THA patients were included (65% and 35%, respectively, performed on Monday/Tuesday and 70% and 30%, respectively, performed on Thursday/Friday). Patients undergoing TKA on Monday/Tuesday versus Thursday/Friday had higher American Society of Anesthesiologists scores (42% vs 33% with score of 3 or higher) but less often an extended LOS (31% vs 54%; adjusted OR: 2.76, 95% CI: 2.22-3.46), lower skilled nursing facility costs (unadjusted mean, $12,515 vs $14,154) and lower home health aide costs (unadjusted mean, $3,793 vs $4,192). Similar patterns were observed in THA patients. Conclusion: These results from institutional data suggest that surgical scheduling is a modifiable factor possibly associated with postoperative outcomes. Furthermore, more rigorous study is warranted.

Racial Differences in Care and Outcomes After Total Hip and Knee Arthroplasties: Did the Comprehensive Care for Joint Replacement Program Make a Difference?

BACKGROUND: There is a paucity of literature on racial differences across a full total joint arthroplasty (TJA) "episode of care" and beyond. Given various incentives, the Comprehensive Care for Joint Replacement (CJR) program in the U.S. may have impacted preexisting racial differences across this care continuum. The purposes of the present study were (1) to assess trends in racial differences in care/outcome characteristics before, during, and after TJA surgery and (2) to assess if the CJR program coincided with reductions in these racial differences. METHODS: This retrospective cohort study includes data on 1,483,221 TJAs (based on Medicare claims data, 2013 to 2018). Racial differences between Black and White patients were assessed for (1) preoperative characteristics (Deyo-Charlson comorbidity index, patient sex, and age), (2) characteristics during hospitalization (length of stay, blood transfusions, and combined complications), and (3) postoperative characteristics (90 and 180-day readmission rates and institutional post-acute care). Additionally, Medicare payments for each period were assessed. Racial differences (Black versus White patients) were expressed in terms of odds ratios (ORs) and 95% confidence intervals (CIs) per year. A "difference-in-differences" analysis (comparing before and after CJR implementation, with non-CJR hospitals being used as controls) estimated the association of the CJR program with changes in racial differences. RESULTS: In both 2013 and 2018, Black patients (n = 74,390; 5.0%) were more likely than White patients to have a higher Deyo-Charlson comorbidity index (score of >0) (OR = 1.32 [95% CI = 1.28 to 1.36] and OR = 1.32 [95% CI = 1.28 to 1.37]), to require more transfusions (OR = 1.55 [95% CI = 1.49 to 1.62] and OR = 1.77 [95% CI = 1.56 to 2.01]), to be discharged to institutional post-acute care (OR = 1.40 [95% CI = 1.36 to 1.44] and OR = 1.49 [95% CI = 1.43 to 1.56]), and to be readmitted within 90 days (OR = 1.38 [95% CI = 1.32 to 1.44] and OR = 1.21 [95% CI = 1.13 to 1.29]) (p < 0.05 for all). Adjusted difference-in-differences analyses demonstrated that the CJR program coincided with reductions in racial differences in 90-day readmission (-1.24%; 95% CI, -2.46% to -0.03%) and 180-day readmission (-1.28%; 95% CI, -2.52% to -0.03%) (p = 0.044 for both). CONCLUSIONS: Racial differences persist among patients managed with TJA. The CJR program coincided with reductions in some racial differences, thus identifying bundle design as a potential novel strategy to target racial disparities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Neutralizing Anti-Granulocyte Macrophage-Colony Stimulating Factor Autoantibodies Recognize Post-Translational Glycosylations on Granulocyte Macrophage-Colony Stimulating Factor Years Before Diagnosis and Predict Complicated Crohn's Disease.

BACKGROUND & AIMS: Anti-granulocyte macrophage-colony stimulating factor autoantibodies (aGMAbs) are detected in patients with ileal Crohn's disease (CD). Their induction and mode of action during or before disease are not well understood. We aimed to investigate the underlying mechanisms associated with aGMAb induction, from functional orientation to recognized epitopes, for their impact on intestinal immune homeostasis and use as a predictive biomarker for complicated CD. METHODS: We characterized using enzyme-linked immunosorbent assay naturally occurring aGMAbs in longitudinal serum samples from patients archived before the diagnosis of CD (n = 220) as well as from 400 healthy individuals (matched controls) as part of the US Defense Medical Surveillance System. We used biochemical, cellular, and transcriptional analysis to uncover a mechanism that governs the impaired immune balance in CD mucosa after diagnosis. RESULTS: Neutralizing aGMAbs were found to be specific for post-translational glycosylation on granulocyte macrophage-colony stimulating factor (GM-CSF), detectable years before diagnosis, and associated with complicated CD at presentation. Glycosylation of GM-CSF was altered in patients with CD, and aGMAb affected myeloid homeostasis and promoted group 1 innate lymphoid cells. Perturbations in immune homeostasis preceded the diagnosis in the serum of patients with CD presenting with aGMAb and were detectable in the noninflamed CD mucosa. CONCLUSIONS: Anti-GMAbs predict the diagnosis of complicated CD long before the diagnosis of disease, recognize uniquely glycosylated epitopes, and impair myeloid cell and innate lymphoid cell balance associated with altered intestinal immune homeostasis.

The involvement of PacIRA system of Stenotrophomonas maltophilia in the uptake of Pseudomonas aeruginosa pyochelin and intraspecies competition for iron acquisition.

BACKGROUND: Stenotrophomonas maltophilia, a species of highly genetic diversity, has emerged as an important nosocomial pathogen. S. maltophilia and Pseudomonas aeruginosa are often co-isolated from pneumonia patients. In our previous study, we have demonstrated that the pacIRA cluster present in some but not all clinical S. maltophilia isolates. Proteins encoded by pacIRA operon are an extracytoplasmic function (ECF) sigma factor, a transmembrane anti-sigma regulator, and a TonB-dependent receptor. This study aimed to elucidate PacIRA system function and its significance to S. maltophilia. METHODS: The pacI, pacR, and pacA genes were individually or totally deleted from the chromosome of KJΔEnt, a pacIRA-positive and siderophore-null strain. Growth promotion assay was performed to examine the implication of pacIRA system in iron utilization. Gene expression was quantified by quantitative real time PCR (qRT-PCR). Growth competition assay was executed to investigate the significance of pacIRA operon to S. maltophilia. RESULTS: PacIRA system contributed to utilize ferri-pyochelin of P. aeruginosa as iron sources for growth in an iron-depleted condition, but hardly utilized ferric citrate, hemin, ferri-stenobactin, and ferri-pyoverdine. PacIRA was founded to belong to Fur regulon and upregulated in response to iron-depleted stress. Growth competition assay demonstrated that pacIRA-positive S. maltophilia had a superiority over pacIRA-negative S. maltophilia in iron acquisition when they were co-cultured in P. aeruginosa ferri-pyochelin-supplemented medium. CONCLUSIONS: PacIRA system of S. maltophilia is a xenosiderophore uptake implement, involving in the acquisition of pyochelin of P. aeruginosa.

Analysis of surgery rates among 25 national collegiate athletic association sports.

OBJECTIVES: While injuries among collegiate athletes are common and well-studied, there have been no studies comparing which sports and injury types have the highest operation rates. This information would be valuable for athlete governing bodies and providers to improve player safety. Our hypothesis was the surgery incidence rates vary substantially between sports and injury types, with football and knee injuries representing the sport and injury type with the highest respective surgery rates. METHODS: This was a descriptive epidemiology study of all injuries requiring surgery as recorded in the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) for academic years 2004-2005 to 2013-2014. Surgery incidence rates (and 95% confidence intervals, CI) were calculated for each sport (per 10,000 athletic exposures [AE]) and for the most common injury types, by academic year. In addition, absolute numbers of performed surgeries were calculated as well as rates of return to sport. RESULTS: Sports with the highest surgery incidence rate (per 10,000 AEs) were women's gymnastics (8.9; 95% CI 7.2-10.9), men's football (6.1; 95% CI 5.8-6.4), and men's wrestling (5.3; 95% CI 4.5-6.3). Absolute numbers of injury-related surgeries performed were greatest for men's football (n = 31,043), women's basketball (6,625), and men's basketball (5,717). Anterior cruciate ligament tears had the greatest surgery incidence rate per 100,000 AEs for all sports combined (7.95; 95% CI = 7.5 to 8.5), and also represented the injuries with the lowest rate of return to sport. CONCLUSION: Women's gymnastics, men's football, and men's and women's basketball are NCAA sports with an elevated risk of injury requiring of surgery. The results from this study can guide the NCAA and providers regarding which sports should be the focus of future research, new injury prevention strategies, and healthcare personnel allocation during events.

Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

Long-term follow-up of perianchor cyst formation after rotator cuff repair.

BACKGROUND: Perianchor cyst formation (PCF) can occur after arthroscopic rotator cuff repair with poly-L-lactic acid (PLLA) anchors; however, little is known about PCF after all-suture anchor (ASA) use. METHODS: We reviewed patients who underwent double-row arthroscopic rotator cuff repair from 2012 to 2017 with ASAs implanted in the medial row and PLLA anchors in the lateral row. We evaluated PCF (graded on magnetic resonance imaging) and compared physical examination and functional surveys between patients with PCF (WC) and without PCF (WoC) at long-term follow-up. RESULTS: Among twenty-two patients (23 shoulders), 93% of PLLA anchors (vs. 79% ASA) displayed a grade 0 PCF, P = .100. No PLLA anchors had a grade 3 or 4 PCF, compared to 11% of ASAs, P = .158. At a mean postoperative follow-up time of 113 weeks, there was no significant difference between WC and WoC cohorts with regard to range of motion, rotator cuff strength, American Shoulder and Elbow Surgeons survey scores, or retear rates. However, the WoC cohort had a significantly higher University of California at Los Angeles shoulder survey score at final follow-up (34.3 WoC vs. 30.9 WC, P = .024). CONCLUSION: No difference was found in PCF between ASAs and PLLA anchors. At long-term follow-up, WoC patients had significantly improved functional outcome scores, based on the University of California at Los Angeles survey, but equivalent range of motion and rotator cuff strength examinations compared with WC patients.

Care disruptions among patients with lung cancer: A COVID-19 and cancer outcomes study.

INTRODUCTION: Patients with lung cancer (LC) are susceptible to severe outcomes from COVID-19. This study evaluated disruption to care of patients with LC during the COVID-19 pandemic. METHODS: The COVID-19 and Cancer Outcomes Study (CCOS) is a prospective cohort study comprised of patients with a current or past history of hematological or solid malignancies with outpatient visits between March 2 and March 6, 2020, at two academic cancer centers in the Northeastern United States (US). Data was collected for the three months prior to the index week (baseline period) and the following three months (pandemic period). RESULTS: 313 of 2365 patients had LC, 1578 had other solid tumors, and 474 had hematological malignancies. Patients with LC were not at increased risk of COVID-19 diagnosis compared to patients with other solid or hematological malignancies. When comparing data from the pandemic period to the baseline period, patients with LC were more likely to have a decrease in in-person visits compared to patients with other solid tumors (aOR 1.94; 95% CI, 1.46-2.58), but without an increase in telehealth visits (aOR 1.13; 95% CI 0.85-1.50). Patients with LC were more likely to experience pandemic-related treatment delays than patients with other solid tumors (aOR 1.80; 95% CI 1.13-2.80) and were more likely to experience imaging/diagnostic procedure delays than patients with other solid tumors (aOR 2.59; 95% CI, 1.46-4.47) and hematological malignancies (aOR 2.01; 95% CI, 1.02-3.93). Among patients on systemic therapy, patients with LC were also at increased risk for decreased in-person visits and increased treatment delays compared to those with other solid tumors. DISCUSSION: Patients with LC experienced increased cancer care disruption compared to patients with other malignancies during the early phase of the COVID-19 pandemic. Focused efforts to ensure continuity of care for this patient population are warranted.

Chinese medicine, Gui Lu Er Xian Jiao - related serous retinal detachment 2nd to circumscribed choroidal hemangioma a case report.

PURPOSE: Circumscribed choroidal hemangioma is a rare condition where there is development of benign vascular tumors, and it generally appears in middle-aged adults. Here we report a case of Chinese medicine, Gui Lu Er Xian Jiao - related serous retinal detachment secondary to circumscribed choroidal hemangioma. OBSERVATIONS: A 55-year-old female, who had no remarkable ocular or medical history but has been taking a special Chinese compound medicine, Gui Lu Er Xian Jiao, for the past 2 years, presented with progressive blurred vision in the left eye for weeks. After serial ocular examinations, serous retinal detachment 2nd to circumscribed choroidal hemangioma was disclosed. Owing to the close timing association with medication history of Gui Lu Er Xian Jiao, we advised her to discontinue the Chinese medicine first. The serous retinal detachment resolved completely without any other management. CONCLUSIONS AND IMPORTANCE: The content of Gui Lu Er Xian Jiao has been reported to have angiogenesis effect, which possibly change the vascular permeability and induce the serous retinal detachment and therefore blurred vision in our patient. To the best of our knowledge, this is the first report on such relationship between Gui Lu Er Xian Jiao and serous retinal detachment 2nd to circumscribed choroidal hemangioma. The case report highlighted the importance of detailed history taking in the management of ocular diseases.

Epidemiology of Severe Foot Injuries in US Collegiate Athletes.

BACKGROUND: The effects of foot injuries on collegiate athletes in the United States are of interest because of the short 5-year eligibility period in the National Collegiate Athletic Association (NCAA). PURPOSE: To discuss the epidemiology of severe NCAA foot injuries sustained over 10 years in 25 sports. STUDY DESIGN: Descriptive epidemiology study. METHODS: We utilized the NCAA Injury Surveillance System, which prospectively collects deidentified injury data for collegiate athletes. Severe injuries were classified as season- or career-ending injuries, injuries with >30-day time loss, or injuries requiring operative treatment. Injury rates (IRs) were analyzed per 100,000 athlete-exposures. RESULTS: Of 3607 total foot injuries, 18.71% (n = 675) were classified as severe, with an IR of 5.73 per 100,000 athletic-exposures. For all severe injuries, the operative rate was 24.3%, the season-ending rate 37.0%, and the career-ending rate 4.4%. The proportion of recurrent injuries was 13.9%. Men's sports with the highest severe foot IRs were basketball (IR = 10.71), indoor track (IR = 7.16), and football (IR = 7.08). Women's sports with the highest severe foot IRs were cross-country (IR = 17.15), gymnastics (IR = 14.76), and outdoor track (IR = 14.65). Among all severe foot injuries, the most common was a fifth metatarsal fracture. The highest contact/noncontact injury ratios were phalangeal fracture, turf toe, and Lisfranc injury. The severe injuries with the highest operative rates were Lisfranc injuries, fifth metatarsal fractures, and midfoot fractures. The severe injuries associated with the highest season-ending IRs were Lisfranc injury, midfoot fracture, and general metatarsal fractures. Severe flexor/extensor injuries had the highest career-ending IRs, followed by turf toe. Severe injuries with the highest median time loss were sesamoidal fractures, calcaneal fractures, and plantar fascial injuries. CONCLUSION: Of all collegiate foot injuries sustained over a 10-year period, 18.7% were characterized as severe, and 24.3% of severe injuries required surgery. Basketball was the men's sport with the highest severe IR, and cross-country was the women's sport with the highest severe IR. Overall, female athletes experienced slightly higher severe foot IRs as compared with male athletes.

Adipokines and Subclinical Cardiovascular Disease in Post-Menopausal Women: Study of Women's Health Across the Nation.

Background The menopausal transition is characterized by increased cardiovascular risk, weight gain, and increased adiposity for many women. The adipose-derived secretory proteins adiponectin and leptin are associated with insulin resistance, metabolic syndrome, and cardiovascular disease but their role in subclinical atherosclerotic disease is unclear. This cross-sectional study evaluated the associations of adiponectin and leptin with carotid artery intima-media thickness, adventitial diameter, presence of carotid plaques, and brachial-ankle pulse wave velocity (baPWV) in women aged 54 to 65 years. Methods and Results Participants were 1399 women from SWAN (Study of Women's Health Across the Nation), a community-based study of women transitioning through menopause. Carotid ultrasound and baPWV measures were obtained at SWAN follow-up visits 12 or 13, when 97% of participants were post-menopausal. Adipokines were assayed from serum specimens obtained concurrently at these visits. Linear and logistic regression models were used to evaluate adiponectin or leptin, both log-transformed attributable to skewness, in relationship to carotid artery intima-media thickness, adventitial diameter, baPWV, and presence of carotid plaque. Covariates included age, race, study site, smoking, alcohol use, obesity, cardiovascular disease risk factors, and menopausal status. Lower levels of adiponectin were related to greater carotid artery intima-media thickness, wider adventitial diameter, and faster baPWV; associations were attenuated after adjusting for cardiovascular disease risk factors. Higher levels of leptin were associated with greater carotid artery intima-media thickness and wider adventitial diameter in minimally and fully adjusted models, and contrary to expectation, with slower baPWV, particularly among women with diabetes mellitus or obesity. Conclusions Adiponectin and leptin are 2 important inflammatory pathways that may contribute to adverse subclinical cardiovascular disease risk profiles in women at midlife.

An inflammatory cytokine signature predicts COVID-19 severity and survival.

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1ß in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.