Citations

Background: The purpose of this multicenter, randomized trial was to determine the optimal dosing regimen of tranexamic acid (TXA) to minimize perioperative blood loss in revision total hip arthroplasty. Methods: Six centers prospectively randomized 175 patients to 1 of 4 regimens: (1) 1-g intravenous (IV) TXA prior to incision (the single-dose IV group), (2) 1-g IV TXA prior to incision followed by 1-g IV TXA after arthrotomy wound closure (the double-dose IV group), (3) a combination of 1-g IV TXA prior to incision and 1-g intraoperative topical TXA (the combined IV and topical group), or (4) 3 doses totaling 1,950-mg oral TXA (the multidose oral group). Randomization was based on revision subgroups to ensure equivalent group distribution. An a priori power analysis (α = 0.05; β = 0.80) determined that 40 patients per group were required to identify a >1-g/dL difference in postoperative hemoglobin reduction between groups. Per-protocol analysis involved an analysis of variance, Fisher exact tests, and two 1-sided t tests for equivalence. Demographic and surgical variables were equivalent between groups. Results: No significant differences were found between TXA regimens when evaluating reduction in hemoglobin (3.4 g/dL for the single-dose IV group, 3.6 g/dL for the double-dose IV group, 3.5 g/dL for the combined IV and topical group, and 3.4 g/dL for the multidose oral group; p = 0.95), calculated blood loss (p = 0.90), or transfusion rates (14% for the single-dose IV group, 18% for the double-dose IV group, 17% for the combined group, and 17% for the multidose oral group; p = 0.96). Equivalence testing revealed that all possible pairings were statistically equivalent, assuming a >1-g/dL difference in hemoglobin reduction as clinically relevant. There was 1 venous thromboembolism, with no differences found between groups (p = 1.00). Conclusions: All 4 TXA groups tested had equivalent blood-sparing properties in the setting of revision total hip arthroplasty, with a single venous thromboembolism reported in this high-risk population. Based on the equivalence between groups, surgeons should utilize whichever of the 4 investigated regimens is best suited for their practice and hospital setting. Given the transfusion rate in revision total hip arthroplasty despite TXA utilization, further work is required in this area. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Amniotic band syndrome is a rare condition. There have been few cases reported of fetoscopic band dissection. The aim of this case series is to report 3 cases of fetoscopic treatment for amniotic band syndrome, including indication for surgery, technical aspects, complications and outcomes.Fetoscopic treatment was performed respectively at 23 5/7, 26 5/7 and 18 3/7 weeks' gestation. Two procedures were performed with a laser fiber through a single trocar whereas one surgery was performed with scissors.In conclusion, fetoscopic release of the amniotic bands in case of amniotic band syndrome is feasible with encouraging results in order to prevent amputation and dysfunction of the extremities.

Abstract Background: Obesity is a well established risk factor not only for increased prostate cancer incidence, but for poorer survival from prostate cancer. However, there is limited knowledge on the role of the circulating lipidome in prostate cancer. In order to target lipid metabolism optimally, it is critical to understand the spectrum of changes in circulating lipid profiles and the association with clinical outcome across the natural history of prostate cancer. Aim: To assess the relationship between the plasma lipidome and clinical outcome in localized and metastatic prostate cancer. Methods: Liquid chromatography-tandem mass spectrometry was used to quantitate over 500 lipid species in plasma samples from 3 cohorts (1) 389 men with localized prostate cancer, (2) 44 men with metastatic hormone-sensitive prostate cancer (mHSPC), and (3) 137 men with metastatic castration-resistant prostate cancer (CRPC). Associations between circulating lipids with metastatic relapse, androgen-deprivation therapy (ADT) failure or overall survival for each relevant disease stage were examined by latent class analysis and cox regression. Results: Circulating lipid profiles displaying elevated levels of ceramides were associated with metastatic relapse in localized prostate cancer (HR 5.8, 95% CI 3.0-11, P 1 × 10−6), early ADT failure in mHSPC (HR 2.4, 95% CI 1.1-5.3, P 0.03), and shorter overall survival in CRPC (HR 2.5, 95% CI 1.7-3.7, P 2 × 10−6). ADT failure in mHSPC and shorter overall survival in CRPC were also associated with elevated levels of other sphingolipids (sphingomyelins, hexosylceramides). The prognostic significance of the high risk lipid profiles in localized prostate cancer was independent of clinicopathological characteristics (lipid profile HR 4.7, 95%CI 2.4-9.3, P 7 × 10−6) when modeled with Gleason score (P<0.0001) and pathological stage (P<0.0001). Furthermore, the circulating lipid profiles were independent of metabolic factors (localized prostate cancer lipid profile HR 8.2, 95% CI 2.6-25, P 0.0003 when modeled with diabetes, statin, hypertension, body mass index [BMI]; CRPC lipid profile HR 2.6, 95% CI 1.7-3.8, P x10−6 when modeled with BMI). Conclusion: Elevated circulating ceramides are associated with poorer clinical outcomes across the natural history of prostate cancer (from localized to metastatic hormone-sensitive to metastatic castration resistant prostate cancer). This demonstrates that aberrant lipid metabolism in the patients occurs early in prostate cancer and could be therapeutically targeted in prospective clinical trials to improve prostate cancer outcomes. Citation Format: Lisa Glen Horvath, Hui-Ming Lin, Blossom Mak, Kate Mahon, Nicole Yeung, Maria Docanto, Peter Sutherland, andrew Shepherd, Winston Tan, Arun Azad, Manish Kohli, Peter Meikle, Lisa Butler. Lipidomic analysis of circulating lipids across the natural history of prostate cancer identifies aberrant ceramide metabolism [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4761.

Background: Functional bracing is often used as an adjunct to nonoperative treatment of anterior shoulder instability, but no study has evaluated the effectiveness of in-season bracing. The purpose of this study was to examine successful return to play in a nonoperative cohort of adolescent athletes with in-season shoulder instability and compare those athletes treated with bracing to those who were not. Hypothesis: The use of functional bracing will improve success rates in a cohort of athletes treated nonoperatively for in-season shoulder instability. Study Design: Cohort study. Level of Evidence: Level 3. Methods: A total of 97 athletes with anterior shoulder instability were followed for a minimum of 1 year. The mean age was 15.8 ± 1.4 years (range, 12.0-18.0 years). All athletes were treated with initial nonoperative management. Twenty athletes (21%) were also treated with bracing while 77 (79%) were not. The athlete completing the current season and 1 subsequent season without surgery or time lost from shoulder injury was defined as a successful outcome. Results: There was no statistical difference in nonoperative success rates between the braced and nonbraced athletes ( P = 0.33). Braced athletes (n = 20) returned to play 80% of the time, while nonbraced athletes (n = 77) returned at a rate of 88%. Of the braced athletes, 85% were football players (n = 17). A football-only comparison demonstrated no difference between braced failures (26%) and nonbraced failures (16%) ( P = 0.47). Conclusion: This is the first study to evaluate the utility of functional bracing in returning an athlete to sport and completing a full subsequent season without surgery or time loss due to injury of the shoulder. In adolescent athletes with shoulder instability treated nonoperatively, functional bracing did not result in increased success rates when compared with no bracing. Clinical Relevance: The data from this study indicate that functional bracing may not improve success rates for athletes with shoulder instability.

Abstract Aims To develop quality indicators (QIs) that may be used to evaluate the quality of care and outcomes for adults with atrial fibrillation (AF). Methods and results We followed the ESC methodology for QI development. This methodology involved (i) the identification of the domains of AF care for the diagnosis and management of AF (by a group of experts including members of the ESC Clinical Practice Guidelines Task Force for AF); (ii) the construction of candidate QIs (including a systematic review of the literature); and (iii) the selection of the final set of QIs (using a modified Delphi method). Six domains of care for the diagnosis and management of AF were identified: (i) Patient assessment (baseline and follow-up), (ii) Anticoagulation therapy, (iii) Rate control strategy, (iv) Rhythm control strategy, (v) Risk factor management, and (vi) Outcomes measures, including patient-reported outcome measures (PROMs). In total, 17 main and 17 secondary QIs, which covered all six domains of care for the diagnosis and management of AF, were selected. The outcome domain included measures on the consequences and treatment of AF, as well as PROMs. Conclusion This document defines six domains of AF care (patient assessment, anticoagulation, rate control, rhythm control, risk factor management, and outcomes), and provides 17 main and 17 secondary QIs for the diagnosis and management of AF. It is anticipated that implementation of these QIs will improve the quality of AF care.

4010 Background: Prior studies suggested that older and younger pts with colon cancer receive similar benefit from IV fluoropyrimidine (FU) adjuvant (adj) therapy (rx). Combination and/or oral FU rx are increasingly given as adj rx. We sought to determine the impact of pts age <70 v ≥70 yrs on colon cancer recurrence and mortality from adj rx with these newer options. Methods: We used data from 10,499 pts <70 yrs and 2,170 pts ≥70 yrs in 6 phase III adj rx trials comparing IV FU to combinations with irinotecan, oxaliplatin or oral FU (capecitabine and UFT/LV) in stage II/III colon cancer from the ACCENT database. Endpoints were overall survival (OS; time to death), disease-free survival (DFS; time to recurrence or death), and time to recurrence (TTR; censoring at last follow-up). Cox models were stratified by age and adjusted for gender and stage; interaction testing was used to explore the differential benefit by age. Results: Approximately 75% of pts had stage III disease (74% age<70, 77% age≥70). OS, DFS, and TTR were statistically significantly improved for those in the experimental v control arms among pts <70 but not those >70 ( table ); the interaction between age and rx was statistically significant for all endpoints (p=0.01 for OS, DFS, and TTR). These results were consistent whether experimental rx was oxaliplatin-based, irinotecan-based or oral FU. Deaths in first 6 month of adj rx were not statistically significantly different between experimental and control arm. Conclusions: Our results show conclusively that pts >70 do not receive the same benefit from combination and/or oral FU as those <70. Any benefit, if present, compared to IV FU/LV would not be clinically meaningful. Outcomes of experimental (combination or oral FU) vs control (IV 5-FU) by treatment and age [Table: see text] [Table: see text]

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

AbstractNeuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases of neurodegenerative disease with intranuclear inclusions and applied in silico‐based screening using whole‐genome sequencing data from 20 536 participants in the 100 000 Genomes Project. We identified a single European case harbouring the pathogenic repeat expansion with a distinct haplotype structure. Thus, we propose new diagnostic criteria as European NIID represents a distinct disease entity from East Asian cases.

The first documented case of COVID-19 in the United States occurred on January 30th, 2020. Soon after, a global pandemic was declared in March 2020 with each state issuing stay at home orders based on population, risk for community transmission and current number of positive cases. A priority for each region was to develop efficient systems for testing large patient volumes in a safe manner to reduce the risk of community transmission. A community based United States health care system in the upper mid-west implemented a drive through testing site in an attempt to divert suspected cases of COVID-19 away from larger patient areas while protecting staff and patients. This commentary outlines the planning, work flow and challenges of implementing this drive through testing site in a rural community setting.

Hypertrophic cardiomyopathy (HCM) is a prevalent and untreatable cardiovascular disease with a highly complex clinical and genetic causation. HCM patients bearing similar sarcomeric mutations display variable clinical outcomes, implying the involvement of gene modifiers that regulate disease progression. As individuals exhibiting mutations in mitochondrial DNA (mtDNA) present cardiac phenotypes, the mitochondrial genome is a promising candidate to harbor gene modifiers of HCM. Herein, we sequenced the mtDNA of isogenic pluripotent stem cell-cardiomyocyte models of HCM focusing on two sarcomeric mutations. This approach was extended to unrelated patient families totaling 52 cell lines. By correlating cellular and clinical phenotypes with mtDNA sequencing, potentially HCM-protective or -aggravator mtDNA variants were identified. These novel mutations were mostly located in the non-coding control region of the mtDNA and did not overlap with those of other mitochondrial diseases. Analysis of unrelated patients highlighted family-specific mtDNA variants, while others were common in particular population haplogroups. Further validation of mtDNA variants as gene modifiers is warranted but limited by the technically challenging methods of editing the mitochondrial genome. Future molecular characterization of these mtDNA variants in the context of HCM may identify novel treatments and facilitate genetic screening in cardiomyopathy patients towards more efficient treatment options.