Citations

Abstract Objectives We describe the development and implementation of a system for monitoring patient-reported adverse events and quality of life using electronic Patient Reported Outcome (ePRO) instruments in the I-SPY2 Trial, a phase II clinical trial for locally advanced breast cancer. We describe the administration of technological, workflow, and behavior change interventions and their associated impact on questionnaire completion. Materials and Methods Using the OpenClinica electronic data capture system, we developed rules-based logic to build automated ePRO surveys, customized to the I-SPY2 treatment schedule. We piloted ePROs at the University of California, San Francisco (UCSF) to optimize workflow in the context of trial treatment scenarios and staggered rollout of the ePRO system to 26 sites to ensure effective implementation of the technology. Results Increasing ePRO completion requires workflow solutions and research staff engagement. Over two years, we increased baseline survey completion from 25% to 80%. The majority of patients completed between 30% and 75% of the questionnaires they received, with no statistically significant variation in survey completion by age, race or ethnicity. Patients who completed the screening timepoint questionnaire were significantly more likely to complete more of the surveys they received at later timepoints (mean completion of 74.1% vs 35.5%, P < .0001). Baseline PROMIS social functioning and grade 2 or more PRO-CTCAE interference of Abdominal Pain, Decreased Appetite, Dizziness and Shortness of Breath was associated with lower survey completion rates. Discussion and Conclusion By implementing ePROs, we have the potential to increase efficiency and accuracy of patient-reported clinical trial data collection, while improving quality of care, patient safety, and health outcomes. Our method is accessible across demographics and facilitates an ease of data collection and sharing across nationwide sites. We identify predictors of decreased completion that can optimize resource allocation by better targeting efforts such as in-person outreach, staff engagement, a robust technical workflow, and increased monitoring to improve overall completion rates. Trial Registration https://clinicaltrials.gov/study/NCT01042379.

Abstract Artificial intelligence (AI)–enabled interpretation of electrocardiogram (ECG) images (AI-ECGs) can identify patterns predictive of future adverse cardiac events. We hypothesized that such an approach would provide prognostic information for the risk of cardiac complications and mortality in patients undergoing hematopoietic cell transplantation (HCT). We retrospectively subjected ECGs obtained before HCT to an externally trained, deep-learning model designed to predict the risk of atrial fibrillation (AF). Included were 1377 patients (849 autologous [auto] HCT and 528 allogeneic [allo] HCT recipients). The median follow-up was 2.9 years. The 3-year cumulative incidence of AF was 9% (95% confidence interval [CI], 7-12) in patients who underwent auto HCT and 13% (10%-16%) in patients who underwent allo HCT. In the entire cohort, pre-HCT AI-ECG estimate of AF risk correlated highly with the development of clinical AF (hazard ratio [HR], 7.37; 95% CI, 3.53-15.4; P < .001), inferior survival (HR, 2.4; 95% CI, 1.3-4.5; P = .004), and greater risk of nonrelapse mortality (NRM; HR, 95% CI, 3.36; 1.39-8.13; P = .007), without increased risk of relapse. Association with mortality was only noted in allo HCT recipients, where the risk of NRM was greater. The use of cyclophosphamide after transplantation resulted in greater 90-day incidence of AF (13% vs 5%; P = .01) compared to calcineurin inhibitor–based graft-versus-host disease prophylaxis, corresponding to temporal changes in AI-ECG AF prediction after HCT. In summary, AI-ECG can inform risk of posttransplant cardiac outcomes and survival in HCT patients and represents a novel strategy for personalized risk assessment.

AbstractWith the proliferation of cancer research based on large databases, misalignment of research questions and data set capabilities is inevitable. Nationally maintained databases are appealing to cancer researchers because of the ease of access to large amounts of patient data available for analysis and risk estimation. Data sets that are commonly used in cancer research include the National Cancer Database, the SEER (Surveillance, Epidemiology, and End Results) program of the National Cancer Institute, the SEER–Medicare database, the American College of Surgeons National Surgical Quality Improvement Program, and the Healthcare Cost and Utilization Project databases, among others. Each data set has pros and cons with respect to variable availability and the ability to analyze cancer‐specific outcomes. It is critical for researchers to understand the strengths and limitations of each database. Changing variable definitions, the length of postoperative data collection, and the availability of patient‐reported outcomes or social determinants of health data are examples of factors that researchers must consider when selecting a data set for research purposes. For the current review, the authors summarized the advantages and disadvantages of various national data sets for cohort studies in cancer populations.

Introduction Telestroke enables timely and remote evaluation of patients with acute stroke syndromes. However, stroke mimics represent more than 30% of this population. Given the resources required for the management of suspected acute ischemic stroke, several scales have been developed to help identify stroke mimics. Our objective was to externally validate four mimic scales (Khan Score (KS), TeleStroke Mimic Score (TS), simplified FABS (sFABS), and FABS) in a large, academic telestroke network. Methods This is a retrospective, Institutional Review Board-exempt study of all patients who presented with suspected acute stroke syndromes and underwent video evaluation between 2019 and 2020 at a large academic telestroke network. Detailed chart review was conducted to extract both the variables needed to apply the mimic scales, the final diagnosis confirmed by final imaging, and discharge diagnosis (cerebral ischemic vs stroke mimic). Overall score performance was assessed by calculating the area under curve (AUC). Youden cutpoint was established for each scale and used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. Results A total of 1043 patients were included in the final analysis. Final diagnosis of cerebral ischemia was made in 63.5% of all patients, and stroke mimic was diagnosed in 381 patients (36.5%). To predict stroke mimic, TS had the highest AUC (68.3), sensitivity (99.2%), and NPV (77.3%); KS had the highest accuracy (67.5%); FABS had the highest specificity (55.1%), and PPV (72.5%). Conclusions While each scale offers unique strengths, none was able to identify stroke mimics effectively enough to confidently apply in clinical practice. There remains a need for significant clinical judgment to determine the likelihood of stroke mimic at presentation.

Previous studies have highlighted differences in the risk of periprosthetic fracture between tapered slip (TS) and composite beam (CB) stems. This biomechanical study explored periprosthetic fractures around these stems and the effect of adding a 16-gauge calcar or diaphyseal wire to TS stems on their resistance to torque.A power analysis determined a sample size of 7 specimens per group, assuming a standard deviation of 14.8 Nm in peak torque, to provide 90% power to detect a difference of at least 30 Nm between groups. Twenty-one TS stems (eight alone, six with calcar wiring, seven with diaphyseal wiring placed 2 cm distal to the lesser trochanter) and seven CB stems were cemented into standard Sawbones. A servo-hydraulic test machine applied a 1000 N load with a 1-degree rotation per second until failure. The peak torque at failure was measured, and the fracture location recorded. Comparisons were performed using two-sample t-tests.CB stems exhibited a significantly higher peak torque at failure (205.3 Nm) than TS stems (159.5 Nm, p=0.020). Calcar-wire-TS (148.2 Nm, p=0.036) and diaphyseal-wire-TS (164.9 Nm, p=0.036) were both weaker than CB stems. Wired-TS stems showed no significant difference from non-wired-TS stems. Additionally, the study could not conclude that calcar wiring is stronger than diaphyseal wiring. All TS fractures occurred at the mid-stem, simulating a B-type fracture, while the addition of the diaphyseal wire shifted the fracture location more distally in four of seven stems (p=0.0699).This biomechanical study supports the clinical evidence that CB stems have stronger resistance to torque than TS stems and may explain lower risk of periprosthetic fracture. The addition of calcar or diaphyseal wires to TS stems resulted in no significant changes in peak torque to fracture. In patients at high risk of periprosthetic fracture, CB cemented stems should be considered.

We previously reported the five to ten-year results of the Birmingham Hip Resurfacing (BHR) implant. The purpose of this study was to evaluate the survivorship, radiographic results, and clinical outcomes of the BHR at long-term follow-up.We retrospectively reviewed 250 patients from the original cohort of 324 BHRs performed from 2006 to 2013 who met contemporary BHR indications. Of these, 4 patients died and 4 withdrew. From the 242 patients, 224 patients (93%) were available for analysis. Modified Harris hip score (mHHS) and University of California, Los Angeles (UCLA) scores were collected and compared to a matched total hip arthroplasty (THA) cohort. Mean follow-up was 14 years.Survivorship free of aseptic revision was 97.4% and survivorship free of any revision was 96.0% at 15 years. Revisions included 3 periprosthetic joint infections, 2 for elevated metal ions and symptomatic pseudotumor, 2 for aseptic femoral loosening, and 1 for unexplained pain. The mean mHHS was 93 in BHR patients at final follow-up, similar to the THA cohort (p=0.44). The UCLA score was significantly higher for BHR patients (p=0.02), however there were equal proportions of patients who remained highly active (UCLA 9 or 10) in both groups, 60.5% and 52.2% (p=0.45) for BHR and THA respectively. Metal ion levels at long term follow-up were low (mean serum cobalt 1.8±1.5 ppb and mean serum chromium 2.2±2.0 ppb).BHR demonstrated excellent survivorship in males less than 60 years of age at time of surgery. Clinical outcomes and activity levels were similar to THA patients. Failures related to the metal-on-metal bearing were rare and metal levels were low at long-term follow-up.Level of evidence: IIIKeywords: survivorship; hip arthroplasty; activity; metal-on-metalSurface Replacement Arthroplasty demonstrates low revision rates and similar activity level compared to total hip arthroplasty at long-term follow-up.

Angular proximal femoral deformities increase the technical complexity of primary total hip arthroplasties (THAs). The goals were to determine the long-term implant survivorship, risk factors, complications, and clinical outcomes of contemporary primary THAs in this difficult cohort.Our institutional total joint registry was used to identify 119 primary THAs performed in 109 patients with an angular proximal femoral deformity between 1997 and 2017. The deformity was related to previous femoral osteotomy in 85%, and developmental or metabolic disorders in 15%. 53% had a predominantly varus angular deformity. The mean age was 44 years, mean BMI was 29 kg/m2, and 59% were female. An uncemented metaphyseal fixation stem was used in 30%, an uncemented diaphyseal fixation stem in 28%, an uncemented modular body stem with metaphyseal fixation sleeve in 24%, and a cemented stem in 18%. Simultaneous corrective femoral osteotomy was performed in 18%. Kaplan-Meier survivorships and Harris hip scores were reported. Mean follow-up was 8 years.The 10-year survivorships free of femoral loosening, aseptic femoral revision, any revision, and any reoperation were 95%, 93%, 90% and 88%, respectively. Revisions occurred in 13 hips for: aseptic femoral component loosening (3), stem fracture (2), dislocation (2), aseptic acetabular loosening (2), polyethylene liner exchange (2), and infection (2). Preoperative varus angular deformities were associated with a higher risk of any revision (HR 10, p=0.03), and simultaneous osteotomies with a higher risk of any reoperation (HR 3.6, p=0.02). Mean Harris hip scores improved from 52 preoperatively to 82 at 10 years (p<0.001).In the largest series to date of primary THAs in patients with angular proximal femoral deformities, we found a good 10-year survivorship free from any revision. Varus angular deformities, particularly those treated with a simultaneous osteotomy due to the magnitude or location of the deformity, had a higher reoperation rate.Keywords: Proximal femoral deformity; dysplasia; femoral osteotomy; survivorship; revisionLevel of evidence: Level III, comparative retrospective cohort

ABSTRACT His domain protein tyrosine phosphatase (HD-PTP; also known as PTPN23) facilitates function of the endosomal sorting complexes required for transport (ESCRTs) during multivesicular body (MVB) formation. To uncover its role in physiological homeostasis, embryonic lethality caused by a complete lack of HD-PTP was bypassed through generation of hypomorphic mice expressing reduced protein, resulting in animals that are viable into adulthood. These mice exhibited marked lipodystrophy and decreased receptor-mediated signaling within white adipose tissue (WAT), involving multiple prominent pathways including RAS/MAPK, phosphoinositide 3-kinase (PI3K)/AKT and receptor tyrosine kinases (RTKs), such as EGFR. EGFR signaling was dissected in vitro to assess the nature of defective signaling, revealing decreased trans-autophosphorylation and downstream effector activation, despite normal EGF binding. This corresponds to decreased plasma membrane cholesterol and increased lysosomal cholesterol, likely resulting from defective endosomal maturation necessary for cholesterol trafficking and homeostasis. The ESCRT components Vps4 and Hrs have previously been implicated in cholesterol homeostasis; thus, these findings expand knowledge on which ESCRT subunits are involved in cholesterol homeostasis and highlight a non-canonical role for HD-PTP in signal regulation and adipose tissue homeostasis.