Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

American Radium Society Appropriate Use Criteria Postmastectomy Radiation Therapy: Executive Summary of Clinical Topics.

PURPOSE: To conduct an appropriate use criteria expert panel update on clinical topics relevant to current clinical practice regarding postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: An analysis of the medical literature from peer-reviewed journals was conducted from May 4, 2010 to May 4, 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to search the PubMed database to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures. RESULTS: Evidence for key questions in PMRT regarding benefit in special populations and technical considerations for delivery was examined and described. Risk factors for local-regional recurrence in patients with intermediate-risk disease that indicate benefit of PMRT include molecular subtype, age, clinical stage, and pathologic response to neoadjuvant chemotherapy. Use of hypofractionated radiation in PMRT has been examined in several recent randomized trials and is under investigation for patients with breast reconstruction. The use of bolus varies significantly by practice region and has limited evidence for routine use. Adverse effects occurred with both PMRT preimplant and postimplant exchange in 2-staged breast reconstruction. CONCLUSIONS: Most patients with even limited nodal involvement will likely benefit from PMRT with significant reduction in local-regional recurrence and potential survival. Patients with initial clinical stage III disease and/or any residual disease after neoadjuvant chemotherapy should be strongly considered for PMRT. Growing evidence supports the use of hypofractionated radiation for PMRT with equivalent efficacy and decreased acute side effects, but additional evidence is needed for special populations. There is limited evidence to support routine use of bolus in all patients. Timing of PMRT regarding completion of 2-staged breast reconstruction requires a discussion of increased risks with radiation postimplant exchange compared with increased risk of failure of reconstruction or surgical complications with radiation preimplant exchange.

Modifiable Post-Mastectomy Radiation Therapy Factors and Impact on Implant-Based Breast Reconstruction Outcomes.

INTRODUCTION: Intensity modulated radiation therapy (IMRT) and other modifiable radiation factors have been associated with decreased radiation toxicity. These factors could allow for improved reconstructive outcomes in patients requiring post-mastectomy radiation therapy (PMRT). However, they have not yet been well-studied in implant-based breast reconstruction (IBBR). METHODS: We performed a retrospective chart review of patients who underwent mastectomy with immediate tissue expander placement followed by PMRT. Radiation characteristics were collected, including radiation technique, bolus regimen, X-ray energy, fractionation, maximum radiation hot spot (DMax), and tissue volume receiving >105% (V105%) or >107% (V107%) of the prescription dose. Reconstructive complications occurring after initiation of PMRT were analyzed with respect to these radiation characteristics. RESULTS: 68 patients (70 breasts) were included in this study. The overall complication rate was 28.6%, with infection being the most common complication (24.3%), requiring removal of the tissue expander or implant in greater than half of infections (15.7%). DMax was greater in patients who required explant after PMRT, and this approached statistical significance (114.5+/-7.2% v. 111.4+/-4.4%, p=0.059). V105% and V107% were also greater in patients who required explant after PMRT (42.1+/-17.1% v. 33.0+/-20.9% and 16.4+/-14.5% v. 11.3+/-14.6%, respectively), however this was not statistically significant (p=0.176 and p=0.313, respectively). There were no significant differences in complication rates between patients with respect to radiation technique or other radiation characteristics studied. CONCLUSIONS: Minimizing the radiation hot spots and volumes of tissue receiving greater than the prescription dose of radiation may improve reconstructive outcomes in patients undergoing IBBR followed by PMRT.

The CDK4/6 Inhibitor Palbociclib Inhibits Estrogen-Positive and Triple Negative Breast Cancer Bone Metastasis In Vivo.

CDK 4/6 inhibitors have demonstrated significant improved survival for patients with estrogen receptor (ER) positive breast cancer (BC). However, the ability of these promising agents to inhibit bone metastasis from either ER+ve or triple negative BC (TNBC) remains to be established. We therefore investigated the effects of the CDK 4/6 inhibitor, palbociclib, using in vivo models of breast cancer bone metastasis. In an ER+ve T47D model of spontaneous breast cancer metastasis from the mammary fat pad to bone, primary tumour growth and the number of hind limb skeletal tumours were significantly lower in palbociclib treated animals compared to vehicle controls. In the TNBC MDA-MB-231 model of metastatic outgrowth in bone (intracardiac route), continuous palbociclib treatment significantly inhibited tumour growth in bone compared to vehicle. When a 7-day break was introduced after 28 days (mimicking the clinical schedule), tumour growth resumed and was not inhibited by a second cycle of palbociclib, either alone or when combined with the bone-targeted agent, zoledronic acid (Zol), or a CDK7 inhibitor. Downstream phosphoprotein analysis of the MAPK pathway identified a number of phosphoproteins, such as p38, that may contribute to drug-insensitive tumour growth. These data encourage further investigation of targeting alternative pathways in CDK 4/6-insensitive tumour growth.

Dosimetric characterization of single- and dual-port temporary tissue expanders for postmastectomy radiotherapy using Monte Carlo methods.

Purpose: The aim of this work was two-fold: a) to assess two treatment planning strategies for accounting CT artifacts introduced by temporary tissue-expanders (TTEs); b) to evaluate the dosimetric impact of two commercially available and one novel TTE. Methods: The CT artifacts were managed using two strategies. 1) Identifying the metal in the RayStation treatment planning software (TPS) using image window-level adjustments, delineate a contour enclosing the artifact, and setting the density of the surrounding voxels to unity (RS1). 2) Registering a geometry template with dimensions and materials from the TTEs (RS2). Both strategies were compared for DermaSpan, AlloX2, and AlloX2-Pro TTEs using Collapsed Cone Convolution (CCC) in RayStation TPS, Monte Carlo simulations (MC) using TOPAS, and film measurements. Wax slab phantoms with metallic ports and breast phantoms with TTEs balloons were made and irradiated with a 6 MV AP beam and partial arc, respectively. Dose values along the AP direction calculated with CCC (RS2) and TOPAS (RS1 and RS2) were compared with film measurements. The impact in dose distributions was evaluated with RS2 by comparing TOPAS simulations with and without the metal port. Results: For the wax slab phantoms, the dose differences between RS1 and RS2 were 0.5% for DermaSpan and AlloX2 but 3% for AlloX2-Pro. From TOPAS simulations of RS2, the impact in dose distributions caused by the magnet attenuation was (6.4 ± 0.4) %, (4.9 ± 0.7)%, and (2.0 ± 0.9)% for DermaSpan, AlloX2, and AlloX2-Pro, respectively. With breast phantoms, maximum differences in DVH parameters between RS1 and RS2 were as follows. For AlloX2 at the posterior region: (2.1 ± 1.0)%, (1.9 ± 1.0)% and (1.4 ± 1.0)% for D1, D10, and average dose, respectively. For AlloX2-Pro at the anterior region (-1.0 ± 1.0)%, (-0.6 ± 1.0)% and (-0.6 ± 1.0)% for D1, D10 and average dose, respectively. The impact in D10 caused by the magnet was at most (5.5 ± 1.0)% and (-0.8 ± 1.0)% for AlloX2 and AlloX2-Pro, respectively. Conclusion: Two strategies for accounting for CT artifacts from three breast TTEs were assessed using CCC, MC, and film measurements. This study showed that the highest differences with respect to measurements occurred with RS1 and can be mitigated if a template with the actual port geometry and materials is used.

Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia.

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Assessing Smoking Status and Risk of SARS-CoV-2 Infection: A Machine Learning Approach among Veterans.

The role of smoking in the risk of SARS-CoV-2 infection is unclear. We used a retrospective cohort design to study data from veterans' Electronic Medical Record to assess the impact of smoking on the risk of SARS-CoV-2 infection. Veterans tested for the SARS-CoV-2 virus from 02/01/2020 to 02/28/2021 were classified as: Never Smokers (NS), Former Smokers (FS), and Current Smokers (CS). We report the adjusted odds ratios (aOR) for potential confounders obtained from a cascade machine learning algorithm. We found a 19.6% positivity rate among 1,176,306 veterans tested for SARS-CoV-2 infection. The positivity proportion among NS (22.0%) was higher compared with FS (19.2%) and CS (11.5%). The adjusted odds of testing positive for CS (aOR:0.51; 95%CI: 0.50, 0.52) and FS (aOR:0.89; 95%CI:0.88, 0.90) were significantly lower compared with NS. Four pre-existing conditions, including dementia, lower respiratory infections, pneumonia, and septic shock, were associated with a higher risk of testing positive, whereas the use of the decongestant drug phenylephrine or having a history of cancer were associated with a lower risk. CS and FS compared with NS had lower risks of testing positive for SARS-CoV-2. These findings highlight our evolving understanding of the role of smoking status on the risk of SARS-CoV-2 infection.

The Application of Digital Frailty Screening to Triage Nonhealing and Complex Wounds.

OBJECTIVE: We investigated the association between the complexity of diabetic foot ulcers (DFUs) and frailty. RESEARCH DESIGN AND METHODS: Individuals (n = 38) with Grade 2 Wagner DFU were classified into 3 groups based on the Society for Vascular Surgery risk-stratification for major limb amputation as Stage 1 at very low risk (n = 19), Stage 2 at low risk (n = 9), and Stage 3 to 4 at moderate-to-high risk (n = 10) of major limb amputation. Frailty status was objectively assessed using a validated digital frailty meter (FM). The FM works by quantifying weakness, slowness, rigidity, and exhaustion over a 20-second repetitive elbow flexion-extension exercise using a wrist-worn sensor. FM generates a frailty index (FI) ranging from 0 to 1; higher values indicate progressively greater severity of frailty. Skin perfusion pressure (SPP), albumin, and tissue oxygenation level (SatO2) were also measured. One-way analysis of variance (ANOVA) was used to identify group effect for wound complexity. Pearson's correlation coefficient was used to assess the associations with frailty and clinical endpoints. RESULTS: Frailty index was higher in Stage 3 and 4 as compared to Stage 1 (d = 1.4, P < .01) and Stage 2 (d = 1.2, P < .01). Among assessed frailty phenotypes, exhaustion was correlated with SPP (r = -0.63, P < .01) and albumin (r = -0.5, P < .01). CONCLUSION: Digital biomarkers of frailty may predict complexity of DFU and thus triage individuals who can be treated more simply in their primary clinic versus higher risk patients who require prompt referral to multidisciplinary, more complex care.

Association of mental health diagnosis with race and all-cause mortality after a cancer diagnosis: Large-scale analysis of electronic health record data.

BACKGROUND: Disparity in mental health care among cancer patients remains understudied. METHODS: A large, retrospective, single tertiary-care institution cohort study was conducted based on deidentified electronic health record data of 54,852 adult cancer patients without prior mental health diagnosis (MHD) diagnosed at the University of California, San Francisco between January 2012 and September 2019. The exposure of interest was early-onset MHD with or without psychotropic medication (PM) within 12 months of cancer diagnosis and primary outcome was all-cause mortality. RESULTS: There were 8.2% of patients who received a new MHD at a median of 197 days (interquartile range, 61-553) after incident cancer diagnosis; 31.0% received a PM prescription; and 3.7% a mental health-related visit (MHRV). There were 62.6% of patients who were non-Hispanic White (NHW), 10.8% were Asian, 9.8% were Hispanic, and 3.8% were Black. Compared with NHWs, minority cancer patients had reduced adjusted odds of MHDs, PM prescriptions, and MHRVs, particularly for generalized anxiety (Asian odds ratio [OR], 0.66, 95% CI, 0.55-0.78; Black OR, 0.60, 95% CI, 0.45-0.79; Hispanic OR, 0.72, 95% CI, 0.61-0.85) and selective serotonin-reuptake inhibitors (Asian OR, 0.43, 95% CI, 0.37-0.50; Black OR, 0.51, 95% CI, 0.40-0.61; Hispanic OR, 0.79, 95% CI, 0.70-0.89). New early MHD with PM was associated with elevated all-cause mortality (12-24 months: hazard ratio [HR], 1.43, 95% CI, 1.25-1.64) that waned by 24 to 36 months (HR, 1.18, 95% CI, 0.95-1.45). CONCLUSIONS: New mental health diagnosis with PM was a marker of early mortality among cancer patients. Minority cancer patients were less likely to receive documentation of MHDs or treatment, which may represent missed opportunities to identify and treat cancer-related mental health conditions.

A comparative evaluation of dietary exposure to glyphosate resulting from recommended U.S. diets.

Since its commercial introduction in 1974, national and international regulatory agencies have consistently reported no human health concerns associated with the herbicide glyphosate when used according to label directions. However, in 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen. Despite IARC being the sole outlier in its conclusion, dietary exposure to glyphosate remains a health concern to some members of the public. While glyphosate residues have been detected in foods, it is unclear whether a specific eating pattern substantially contributes to glyphosate exposure. Therefore, dietary glyphosate intake was determined for three eating patterns recommended in the U.S. The 95th percentile of glyphosate ingestion at 2,000 calories/day for adults for the U.S.-Style, Mediterranean-Style, and Vegetarian eating patterns ranged from 38 to 960, 39 to 1100, and 39 to 880 µg/day, respectively. No significant differences were observed in glyphosate intake between the dietary styles, and the 95th percentile glyphosate intakes were well below the current U.S. EPA chronic oral reference dose (RfD) of 0.1 mg/kg/day. Our data demonstrate that ingestion of certain high residue foods, particularly grains and legumes, is a driver of total dietary glyphosate body burden regardless of dietary style.

Interprofessional Education Curriculum for Medical Assistants in Radiation Oncology: A Single Institution Pilot Program.

PURPOSE: Medical assistants (MAs) occupy an increasingly prevalent role in the clinical setting. Subspecialized fields such as oncology require specific clinical knowledge; however, MAs have few requirements for continued education. Here we assess the role and effect of a pilot MA Radiation Oncology education curriculum. METHODS AND MATERIALS: A needs assessment survey was conducted and reviewed to develop a comprehensive introductory oncology curriculum. A resident physician-led program was implemented in an academic cancer care center consisting of monthly, 1-hour lectures. Pre- and postlecture surveys were administered to assess learning. Quarterly surveys were conducted over the 20-month curriculum timeframe. RESULTS: The needs assessment revealed that there were no pre-existing MA continuing education didactics, but all (100%) MAs surveyed were "very interested" in such a curriculum. Sessions were found to be clear, comprehensive, relevant, and associated with a significant increase in a sense of empowerment (P = .035). Topics in Head and Neck and Breast Cancer showed large improvements in understanding (change in median Likert score of 3-4 points each) whereas topics in Introduction to Oncology and New Patient Consultation showed the smallest change (change 0.5-1). For 20 months, there was a sustained improvement in clinical understanding within and outside the scope of the MA role and an improvement in perceived empathy for patients (from median Likert score 3.5-5). CONCLUSIONS: Dedicated education programs for MAs show the potential to improve clinical understanding and participation in patient care. Further studies may demonstrate how such programs translate to staff productivity or patient clinical outcomes. Interprofessional education may facilitate collaboration and enhanced clinical workflow.

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

Residents-as-Teachers Curriculum for Radiation Oncology: A Targeted Needs Assessment.

PURPOSE: Achieving competency as educators is increasingly recognized as a critical part of residents' training in graduate medical education across specialties. In addition to teaching medical students, radiation oncology residents often play a vital role in peer and interprofessional education. We conducted a survey to identify the needs of radiation oncology residents for developing skills in teaching. METHODS AND MATERIALS: An anonymous, web-based survey was developed and distributed to resident physicians at US radiation oncology programs. Analyses describe respondent demographics, experiences with teaching, and interest in various aspects of a formal "residents-as-teachers" curriculum. RESULTS: There were 171 completed survey responses (27.5% response rate). A total of 146 residents (85.4%) reported receiving no formal training in teaching before residency, and 121 (70.8%) reported no formal training during residency. Residents who had formal training in teaching were significantly more likely to be "quite" or "extremely" confident about teaching compared with residents who had no prior formal training (76.0% vs 51.4%; P = .022). Residents most commonly taught other residents and medical students (163 [95.3%] and 160 [93.6%] respondents, respectively). The most common settings for teaching were one-on-one teaching (164 respondents [95.9%]), small-group lectures (135 respondents [78.9%]), and intradepartmental lectures (136 respondents [79.5%]). In response to open-ended questions regarding desired teaching opportunities and domains for teaching development, many residents expressed a lack of confidence in teaching and were interested in improvement across many aspects of teaching. CONCLUSIONS: Radiation oncology residents are expected and desire to teach in a multitude of settings across a wide variety of audiences. However, a significant proportion of radiation oncology residents lack formal training and rarely receive feedback for their teaching skills. The results of this national survey support the development of a residents-as-teachers curriculum for radiation oncology residents that would address the needs for and significant interest in this area.

Matrix compliance permits NF-κB activation to drive therapy resistance in breast cancer.

Triple-negative breast cancers (TNBCs) are associated with poor survival mediated by treatment resistance. TNBCs are fibrotic, yet little is known regarding how the extracellular matrix (ECM) evolves following therapy and whether it impacts treatment response. Analysis revealed that while primary untreated TNBCs are surrounded by a rigid stromal microenvironment, chemotherapy-resistant residual tumors inhabit a softer niche. TNBC organoid cultures and xenograft studies showed that organoids interacting with soft ECM exhibit striking resistance to chemotherapy, ionizing radiation, and death receptor ligand TRAIL. A stiff ECM enhanced proapoptotic JNK activity to sensitize cells to treatment, whereas a soft ECM promoted treatment resistance by elevating NF-κB activity and compromising JNK activity. Treatment-resistant residual TNBCs residing within soft stroma had elevated activated NF-κB levels, and disengaging NF-κB activity sensitized tumors in a soft matrix to therapy. Thus, the biophysical properties of the ECM modify treatment response, and agents that modulate stiffness-dependent NF-κB or JNK activity could enhance therapeutic efficacy in patients with TNBC.

An artificial intelligence framework integrating longitudinal electronic health records with real-world data enables continuous pan-cancer prognostication.

Despite widespread adoption of electronic health records (EHRs), most hospitals are not ready to implement data science research in the clinical pipelines. Here, we develop MEDomics, a continuously learning infrastructure through which multimodal health data are systematically organized and data quality is assessed with the goal of applying artificial intelligence for individual prognosis. Using this framework, currently composed of thousands of individuals with cancer and millions of data points over a decade of data recording, we demonstrate prognostic utility of this framework in oncology. As proof of concept, we report an analysis using this infrastructure, which identified the Framingham risk score to be robustly associated with mortality among individuals with early-stage and advanced-stage cancer, a potentially actionable finding from a real-world cohort of individuals with cancer. Finally, we show how natural language processing (NLP) of medical notes could be used to continuously update estimates of prognosis as a given individual's disease course unfolds.

Association Between Wearable Device-Based Measures of Physical Frailty and Major Adverse Events Following Lower Extremity Revascularization.

Importance: Physical frailty is a key risk factor associated with higher rates of major adverse events (MAEs) after surgery. Assessing physical frailty is often challenging among patients with chronic limb-threatening ischemia (CLTI) who are often unable to perform gait-based assessments because of the presence of plantar wounds. Objective: To test a frailty meter (FM) that does not rely on gait to determine the risk of occurrence of MAEs after revascularization for patients with CLTI. Design, Setting, and Participants: This cohort study included 184 consecutively recruited patients with CLTI at 2 tertiary care centers. After 32 individuals were excluded, 152 participants were included in the study. Data collection was conducted between May 2018 and June 2019. Exposures: Physical frailty measurement within 1 week before limb revascularization and incidence of MAEs for as long as 1 month after surgery. Main Outcomes and Measures: The FM works by quantifying weakness, slowness, rigidity, and exhaustion during a 20-second repetitive elbow flexion-extension exercise using a wrist-worn sensor. The FM generates a frailty index (FI) ranging from 0 to 1; higher values indicate progressively greater severity of physical frailty. Results: Of 152 eligible participants (mean [SD] age, 67.0 [11.8] years; 59 [38.8%] women), 119 (78.2%) were unable to perform the gait test, while all could perform the FM test. Overall, 53 (34.9%), 58 (38.1%), and 41 (27.0%) were classified as robust (FI <0.20), prefrail (FI ≥0.20 to <0.35), or frail (FI ≥0.35), respectively. Within 30 days after surgery, 24 (15.7%) developed MAEs, either major adverse cardiovascular events (MACE; 8 [5.2%]) or major adverse limb events (MALE; 16 [10.5%]). Baseline demographic characteristics were not significantly different between frailty groups. In contrast, the FI was approximately 30% higher in the group that developed MAEs (mean [SD] score, 0.36 [0.14]) than those who were MAE free (mean [SD] score, 0.26 [0.13]; P = .001), with observed MAE rates of 4 patients (7.5%), 7 patients (12.1%), and 13 patients (31.7%) in the robust, prefrail and frail groups, respectively (P = .004). The FI distinguished individuals who developed MACE and MALE from those who were MAE free (MACE: mean [SD] FI score, 0.38 [0.16]; P = .03; MALE: mean [SD] FI score, 0.35 [0.13]; P = .004) after adjusting by body mass index. Conclusions and Relevance: In this cohort study, measuring physical frailty using a wrist-worn sensor during a short upper extremity test was a practical method for stratifying the risk of MAEs following revascularization for CLTI when the administration of gait-based tests is often challenging.