The John N. Insall Knee Society Traveling Fellowship selects four international arthroplasty or sports fellowship-trained orthopaedic surgeons to spend 1 month traveling to various Knee Society ...members' joint replacement and knee surgery centers in North America. The fellowship aims to foster research and education and shares ideas among fellows and Knee Society members. The role of such traveling fellowships on surgeon preferences has yet to be investigated. A 59-question survey encompassing patient selection, preoperative planning, intraoperative techniques, and postoperative protocols was completed by the four 2018 Insall Traveling Fellows before and immediately after the completion of traveling fellowship to assess anticipated practice changes (e.g., initial excitement) related to their participation in a traveling fellowship. The same survey was completed 4 years after the completion of the traveling fellowship to assess the implementation of the anticipated practice changes. Survey questions were divided into two groups based on levels of evidence in the literature. Immediately after fellowship, there was a median of 6.5 (range: 3-12) anticipated changes in consensus topics and a median of 14.5 (range: 5-17) anticipated changes in controversial topics. There was no statistical difference in the excitement to change consensus or controversial topics (
= 0.921). Four years after completing a traveling fellowship, a median of 2.5 (range: 0-3) consensus topics and 4 (range: 2-6) controversial topics were implemented. There was no statistical difference in the implementation of consensus or controversial topics (
= 0.709). There was a statistically significant decline in the implementation of changes in consensus and controversial preferences compared with the initial level of excitement (
= 0.038 and 0.031, respectively). After the John N. Insall Knee Society Traveling Fellowship, there is excitement for practice change in consensus and controversial topics related to total knee arthroplasty. However, few practice changes that had initial excitement were implemented after 4-year follow-up. Ultimately, the effects of time, practice inertia, and institutional friction overcome most of the anticipated changes induced by a traveling fellowship.
There is growing clinical and policy emphasis on minimizing transfusion use in elective joint arthroplasty, but little is known about the degree to which transfusion rates vary across US hospitals. ...This study aimed to assess hospital-level variation in use of allogeneic blood transfusion in patients undergoing elective joint arthroplasty and to characterize the extent to which variability is attributable to differences in patient and hospital characteristics.
The study population included 228,316 patients undergoing total knee arthroplasty (TKA) at 922 hospitals and 88,081 patients undergoing total hip arthroplasty (THA) at 606 hospitals from January 1, 2009 to December 31, 2011 in the Nationwide Inpatient Sample database, a 20% stratified sample of US community hospitals.
The median hospital transfusion rates were 11.0% (interquartile range, 3.5%-18.5%) in TKA and 15.9% (interquartile range, 5.4%-26.2%) in THA. After fully adjusting for patient- and hospital-related factors using mixed-effects logistic regression models, the average predicted probability of blood transfusion use in TKA was 6.3%, with 95% of the hospitals having a predicted probability between 0.37% and 55%. For THA, the average predicted probability of blood transfusion use was 9.5%, with 95% of the hospitals having a predicted probability between 0.57% and 66%. Hospital transfusion rates were inversely associated with hospital procedure volume and directly associated with length of stay.
The use of blood transfusion in elective joint arthroplasty varied widely across US hospitals, largely independent of patient case-mix and hospital characteristics.
Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction.
The goal of this study was to ...derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction.
The T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe.
There were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% (297 of 1,121), 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination (AUC: 0.76; 95% CI: 0.73-0.79) for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient (AUC: 0.83; 95% CI: 0.77-0.88) and multicenter (AUC: 0.74; 95% CI: 0.64-0.83) cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts.
The T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome High-STEACS; NCT01852123)
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Context. As the ESA Rosetta mission approached, orbited, and sent a lander to comet 67P/Churyumov-Gerasimenko in 2014, a large campaign of ground-based observations also followed the comet. Aims. We ...constrain the total activity level of the comet by photometry and spectroscopy to place Rosetta results in context and to understand the large-scale structure of the comet’s coma pre-perihelion. Methods. We performed observations using a number of telescopes, but concentrate on results from the 8 m VLT and Gemini South telescopes in Chile. We use R-band imaging to measure the dust coma contribution to the comet’s brightness and UV-visible spectroscopy to search for gas emissions, primarily using VLT/FORS. In addition we imaged the comet in near-infrared wavelengths (JHK) in late 2014 with Gemini-S/Flamingos-2. Results. We find that the comet was already active in early 2014 at heliocentric distances beyond 4 au. The evolution of the total activity (measured by dust) followed previous predictions. No gas emissions were detected despite sensitive searches. Conclusions. The comet maintains a similar level of activity from orbit to orbit, and is in that sense predictable, meaning that Rosetta results correspond to typical behaviour for this comet. The gas production (for CN at least) is highly asymmetric with respect to perihelion, as our upper limits are below the measured production rates for similar distances post-perihelion in previous orbits.
• Local adaptation is an important process in plant evolution, which can be impacted by differential pathogen pressures along environmental gradients. However, the degree to which pathogen resistance ...loci vary in effect across space and time is incompletely described.
• To understand how the genetic architecture of resistance varies across time and geographic space, we quantified rust (Puccinia spp.) severity in switchgrass (Panicum virgatum) plantings at eight locations across the central USA for 3 yr and conducted quantitative trait locus (QTL) mapping for rust progression.
• We mapped several variable QTLs, but two large-effect QTLs which we have named Prr1 and Prr2 were consistently associated with rust severity in multiple sites and years, particularly in northern sites. By contrast, there were numerous small-effect QTLs at southern sites, indicating a genotype-by-environment interaction in rust resistance loci. Interestingly, Prr1 and Prr2 had a strong epistatic interaction, which also varied in the strength and direction of effect across space.
• Our results suggest that abiotic factors covarying with latitude interact with the genetic loci underlying plant resistance to control rust infection severity. Furthermore, our results indicate that segregating genetic variation in epistatically interacting loci may play a key role in determining response to infection across geographic space.
The dilated cardiomyopathy with ataxia syndrome (DCMA) is an autosomal recessive mitochondrial disease caused by mutations in the DnaJ heat shock protein family (Hsp40) member C19 (DNAJC19) gene. ...DCMA or 3‐methylglutaconic aciduria type V is globally rare, but the largest number of patients in the world is found in the Hutterite population of southern Alberta in Canada. We provide an update on phenotypic findings, natural history, pathological findings, and our clinical experience. We analyzed all available records for 43 patients diagnosed with DCMA between 2005 and 2015 at the Alberta Children's Hospital. All patients studied were Hutterite and homozygous for the causative DNAJC19 variant (c.130‐1G>C, IVS3‐1G>C) and had elevated levels of 3‐methyglutaconic acid. We calculated a birth prevalence of 1.54 cases per 1000 total births in the Hutterite community. Children were small for gestational age at birth and frequently required supplemental nutrition (63%) or surgical placement of a gastrostomy tube (35%). Early mortality in this cohort was high (40%) at a median age of 13 months (range 4‐294 months). Congenital anomalies were common as was dilated cardiomyopathy (50%), QT interval prolongation (83%), and developmental delay (95%). Tissue pathology was analyzed in a limited number of patients and demonstrated subendocardial fibrosis in the heart, macrovesicular steatosis and fibrosis in the liver, and structural abnormalities in mitochondria. This report provides clinical details for a cohort of children with DCMA and the first presentation of tissue pathology for this disorder. Despite sharing common genetic etiology and environment, the disease is highly heterogeneous for reasons that are not understood. DCMA is a clinically heterogeneous systemic mitochondrial disease with significant morbidity and mortality that is common in the Hutterite population of southern Alberta.
Mycosis fungoides is the most common subtype of cutaneous T-cell lymphoma. Skin-directed treatments often improve but do not cure mycosis fungoides skin lesions. The purpose of this study was to (i) ...assess whether remission was associated with malignant T-cell clone depletion at treated sites using either low-dose radiotherapy (LDRT, 8 Gy) or topical steroids and (ii) assess whether a clone-ablative therapy, like LDRT, is associated with overall survival in patients with high-risk early-stage CTCL.
Pre- and posttreatment biopsies from 20 lesional skin samples of 18 patients with mycosis fungoides who received either 8 Gy LDRT (
= 16) or topical steroids (
= 4) underwent high-throughput T-cell receptor sequencing of the TCRB gene to quantify the malignant T-cell clone. For the retrospective chart review, overall survival of 47 high-risk early-stage patients was compared between patients who did or did not receive radiation.
LDRT eradicated the clone in 5 of 16 lesions and reduced it >90% in 11 of 16; there were no recurrences in these lesions. Patients treated with topical steroids appeared to clinically improve, but the malignant clone persisted. We found that the number of residual malignant T cells predicted lesion recurrence. A retrospective review showed that early-stage high-risk patients who received radiation as part of their treatment regimen had prolonged overall survival compared with patients who did not.
These findings demonstrate that LDRT can eradicate malignant T cells in mycosis fungoides, provides robust disease control, and is associated with improved survival in high-risk early-stage patients.
Exosomes (EVs) have relevance in cell-to-cell communication carrying pro-tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery ...systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer.
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