Citations

BACKGROUND: Telehealth evaluations of musculoskeletal conditions have increased due to the stay-at-home policies enacted during the COVID-19 pandemic. Back pain is one of the most common complaints in primary care. While telehealth may never supplant in-person evaluation of back pain, it is imperative in a changing world to learn to perform this evaluation via telephone or video. Virtual visits rely on history-taking and patient self-reported descriptions of pain elicited from self-palpation or specific movements while on the telephone with the clinician. Video examinations provide a unique way of evaluating the lower back compared to telephone because of the ability to visualize the actions of the patient. OBJECTIVE: To create an evaluation pathway for examination of the lumbar spine via telehealth. METHODS: Our group has created a step-by-step evaluation pathway to help physicians direct their patients through typical lumbar examination elements, including inspection, palpation, range of motion, and strength, special, and functional testing. RESULTS: We have developed a table of questions and instructions and a glossary of images of each maneuver to facilitate lumbar spine examination via telemedicine. CONCLUSIONS: This paper provides a guide for extracting clinically relevant information while performing telemedicine examinations of the lumbar spine.

BackgroundMeasuring function with valid and responsive tools in patients with cancer is essential for driving clinical decision‐making and for the end points of clinical trials. Current patient‐reported outcome measurements of function fall short for many reasons. This study evaluates the responsiveness of the Patient‐Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile, a novel measure of function across multiple domains.MethodsTwo hundred nine participants across five geographically distinct tertiary care centers completed the assessment and pain rating at two outpatient cancer rehabilitation clinic visits. Patients and providers completed a global rating of change measure at the second visit to indicate whether the patient was improving or worsening in function. Multiple response indices and linear models measured whether the measure was responsive to self‐reported and clinician‐rated changes over time. Correlations between changes in function and changes in anchors (pain rating and performance status) were also calculated.ResultsFunction as measured by the PROMIS Cancer Function Brief 3D Profile changed appropriately as both patients and clinicians rated change. Small to moderate effect sizes supported the tool's responsiveness. Function was moderately correlated with pain and more strongly correlated with performance status, and changes in function corresponded with changes in anchor variables. No floor/ceiling effect was found.ConclusionsThe PROMIS Cancer Function Brief 3D Profile is sensitive to changes over time in patients with cancer. The measure may be useful in clinical practice and as an end point in clinical trials.Lay summary We gave patients a questionnaire by which they told their physicians how well they were functioning, including how fatigued they were. This study tested that questionnaire to see whether the scores would change if patients got better or worse.

7566 Background: Parenteral limited-duration BR chemoimmunotherapy and continuous orally administered Ibr, a Bruton tyrosine kinase inhibitor, dominate the treatment landscape of WM, a rare B cell lymphoma. No trials have assessed the comparative effectiveness of these 2 vastly different approaches. We conducted a multiinstitutional, international, collaborative study to compare BR and single-agent Ibr in patients (pts) with treatment naïve (TN) WM. Methods: Data from 347 pts with active TN WM, seen between 2011 and 2021 in the US and Europe, were analyzed. The pts on rituximab maintenance were excluded. The modified IWWM-6 criteria (based on IgM alone) were used for response assessment. All time-to-event analyses were performed from the frontline therapy initiation, using the Kaplan-Meier method. Results: The median age of the pts treated with BR (n=208) and Ibr (n=139) was 66 (range 40-86) years (y) and 69 (39-97) y, respectively, (p=0.005). With a median follow up of 4.2 y (95% CI 3.8-4.5), the 4-y progression free survival (PFS) was 73% in each group, p=0.6, and 4-y overall survival (OS) was 94% (95% CI 91-98) in the BR group versus ( v) 82% (95% CI 75-90) in the Ibr group, p=0.01. In a bivariate analysis adjusting for age and the treatment type, only age emerged as a predictor for OS (HR 7.2, p=0.0001). Therefore, a 1:1 age-matched analysis of 246 pts who received Ibr (n=123) or BR (n=123) was performed. Pts with a known MYD88WT status who had received Ibr and their age matched controls on BR were excluded. The international prognostic scoring system (IPSS) WM was comparable between the 2 groups (Table). A higher proportion of pts on BR attained very good partial or deeper response (≥VGPR) as the best response in comparison to the pts on Ibr (Table). The 4-y PFS for the BR and Ibr groups was similar [72% (95% CI 63-82) v 78% (95% CI 70-87), p=0.14] and 4-y OS was 95% (95% CI 91-99) with BR v 86% (95% CI 80-93) with Ibr (p=0.3). Premature discontinuation, during active treatment, due to adverse effects (AEs) or lack of response was noted in 13% and 33% of pts on BR and Ibr, respectively. A detailed assessment of the AEs will be presented at the meeting. Conclusions: Both BR and Ibr lead to comparable outcomes in pts with TN WM, although deeper responses are attained with BR. These findings require confirmation in prospective studies. For pts who harbor MYD 88L265P mutation, selection between the 2 approaches should be dictated by their potential toxicities, pt comorbidities, pt/clinician preference (parenteral fixed-duration v continuous oral) and access to therapies. [Table: see text]

Abstract We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine our latest data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting.

AbstractBackgroundTelemedicine plays a very important role in our society by allowing providers to treat patients who do not have easy access to a healthcare facility, especially in the setting of the COVID‐19 pandemic.ObjectiveWe aimed to create an extensive, yet concise guide for medical providers to virtually evaluate patients with foot concerns.MethodsThis article outlines how to conduct a well‐planned virtual consultation with specific questions, instructions, and examination manoeuvres to navigate musculoskeletal foot problems.ConclusionWith this narrative review, we have provided a guide with suggestions, questions and interpretations of answers to help physicians new to the practice of telemedicine have successful virtual encounters with patients suffering from foot musculoskeletal ailments.

Abstract Background. DCIS consists of a molecularly heterogeneous group of premalignant lesions, with variable risk of invasive progression. Understanding biomarkers for invasive progression could help individualize treatment recommendations based upon tumor biology. As part of the NCI Human Tumor Atlas Network (HTAN), we conducted comprehensive genomic analyses on two large DCIS case-control cohorts. Methods. We performed smart3-seq and low-pass whole genome sequencing on two independent, retrospective, longitudinally sampled DCIS case-control cohorts. TBCRC 038 was a multicenter cohort diagnosed with DCIS between 1998 and 2016 at one of the Translational Breast Cancer Research sites; the RAHBT (Resource of Archival Human Breast Tissue) cohort included women identified through the St. Louis Breast Tissue Repository, and the Women’s Health Repository diagnosed between 1997 and 2001. We studied the spectrum of molecular changes present and sought genomic predictors of subsequent ipsilateral breast events (iBEs: DCIS recurrence or invasive progression) in both DCIS epithelium and stroma in formalin fixed paraffin embedded tissue. We generated de novo tumor and stroma-centric subtypes for DCIS that represents fundamental transcriptomic organization. Copy number analysis was performed using low-pass DNA sequencing. Non-negative matrix factorization (NMF) was applied to the RNA expression of all coding genes to identify clusters. A negative-binomial regression model was used to identify differentially expressed genes. Results. We analyzed 677 DCIS samples from 481 patients with 7.1 years median follow-up. In TBCRC samples, we identified three clusters via NMF in TBCRC referred to as ER low, quiescent, and ER high. The ER-low cluster had significantly higher levels of ERBB2 and lower levels of ESR1 compared to quiescent and ER-high clusters. Quiescent cluster lesions were less proliferative and less metabolically active than ER high and ER low subtypes. These findings were replicated in the RAHBT cohort. Focusing on the stromal component of DCIS from laser capture microdissection in RAHBT samples, we identified four distinct DCIS-associated stromal clusters. A “normal-like” stromal cluster with ECM organization and PI3K-AKT signaling; a “collagen-rich” stromal cluster; a “desmoplastic” stromal cluster with high fibroblast and total myeloid abundance, mostly associated with macrophages and myeloid dendritic cells (mDC); and an “immune-dense” stromal cluster. Further, we compared differentially expressed genes in patients with or without subsequent iBEs within 5 years of diagnosis. Hypothesizing that the resulting 812 DE genes (DESeq2) represent multiple routes to subsequent iBEs, we leveraged NMF to identify paths to progression. In both TBCRC and RAHBT cohorts, poor outcome groups exhibited increased ER, MYC signaling, and oxidative phosphorylation, supporting that these pathways are important for DCIS recurrence and progression. Conclusion. Comprehensive genomic profiling in two independent DCIS cohorts with longitudinal outcomes shows distinct DCIS stromal expression patterns and immune cell composition. RNA expression profiles reveal underlying tumor biology that is associated with later iBEs in both cohorts. These studies provide new insight into DCIS biology and will guide the design of diagnostic strategies to prevent invasive progression. Citation Format: Siri H Strand, Belén Rivero-Gutiérrez, Kathleen E Houlahan, Jose A Seoane, Lorraine M King, Tyler Risom, Lunden Simpson, Sujay Vennam, Aziz Khan, Timothy Hardman, Bryan E Harmon, Fergus J Couch, Kristalyn Gallagher, Mark Kilgore, Shi Wei, Angela DeMichele, Tari King, Priscilla F McAuliffe, Julie Nangia, Joanna Lee, Jennifer Tseng, Anna Maria Storniolo, Alastair Thompson, Gaorav Gupta, Robyn Burns, Deborah J Veis, Katherine DeSchryver, Chunfang Zhu, Magdalena Matusiak, Jason Wang, Shirley X Zhu, Jen Tappenden, Daisy Yi Ding, Dadong Zhang, Jingqin Luo, Shu Jiang, Sushama Varma, Cody Straub, Sucheta Srivastava, Christina Curtis, Rob Tibshirani, Robert Michael Angelo, Allison Hall, Kouros Owzar, Kornelia Polyak, Carlo Maley, Jeffrey R Marks, Graham A Colditz, E Shelley Hwang, Robert B West. The Breast PreCancer Atlas DCIS genomic signatures define biology and correlate with clinical outcomes: An analysis of TBCRC 038 and RAHBT cohorts [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-07.

OBJECTIVE Suprasellar meningioma resection via either the transcranial approach (TCA) or the endoscopic endonasal approach (EEA) is an area of controversy and active evaluation. Skull base surgeons increasingly consider patient-reported outcomes (PROs) when choosing an approach. No PRO measure currently exists to assess quality of life for suprasellar meningiomas. METHODS Adult patients undergoing suprasellar meningioma resection between 2013 and 2019 via EEA (n = 14) or TCA (n = 14) underwent semistructured interviews. Transcripts were coded using a grounded theory approach to identify themes as the basis for a PRO measure that includes all uniquely reported symptoms. To assess content validity, 32 patients and 15 surgeons used a Likert scale to rate the relevance of items on the resulting questionnaire and the general Patient-Reported Outcomes Measurement Information System–29 (PROMIS29). The mean scores were calculated for all items and compared for TCA versus EEA patient cohorts by using unpaired t-tests. Items on either questionnaire with mean scores ≥ 2.0 from patients were considered meaningful and were aggregated to form the novel Suprasellar Meningioma Patient-Reported Outcome Survey (SMPRO) instrument. RESULTS Qualitative analyses resulted in 55 candidate items. Relative to patients who underwent the EEA, those who underwent the TCA reported significantly worse future outlook before surgery (p = 0.01), tiredness from medications 2 weeks after surgery (p = 0.001), and word-finding and memory difficulties 3 months after surgery (p = 0.05 and < 0.001, respectively). The items that patients who received a TCA were most concerned about included medication-induced lethargy after surgery (2.9 ± 1.3), blurry vision before surgery (2.7 ± 1.5), and difficulty reading due to blurry vision before surgery (2.7 ± 2.7). Items that patients who received an EEA were most concerned about included blurry vision before surgery (3.5 ± 1.3), difficulty reading due to blurry vision before surgery (2.4 ± 1.3), and problems with smell postsurgery (2.9 ± 1.3). Although surgeons overall overestimated how concerned patients were about questionnaire items (p < 0.0005), the greatest discrepancies between patient and surgeon relevance scores were for blurry vision pre- and postoperatively (p < 0.001 and < 0.001, respectively) and problems with taste postoperatively (p < 0.001). Seventeen meningioma-specific items were considered meaningful, supplementing 8 significant PROMIS29 items to create the novel 25-item SMPRO. CONCLUSIONS The authors developed a disease- and approach-specific measure for suprasellar meningiomas to compare quality of life by operative approach. If demonstrated to be reliable and valid in future studies, this instrument may assist patients and providers in choosing a personalized surgical approach.

ABSTRACT Fibrodysplasia ossificans progressiva (FOP) is a progressive, debilitating genetic disease in which skeletal muscle and connective tissue is episodically replaced by heterotopic bone. Discovery of surrogate biomarkers of disease (genotype)-related and flare-up-associated activity of FOP in a readily accessible matrix, such as plasma, would facilitate an understanding of the complex pathophysiology of FOP, aid patient care, and provide a valuable tool for the development and monitoring of potential therapeutics. In a case–control study, using a carefully collected and curated set of plasma samples from 40 FOP patients with the classic ACVR1R206H mutation and 40 age- and sex-matched controls, we report the identification of disease-related and flare-up-associated biomarkers of FOP using a multiplex analysis of 113 plasma-soluble analytes. Adiponectin (implicated in hypoxia, inflammation, and heterotopic ossification) as well as tenascin-C (an endogenous activator of innate immune signaling through the TLR4 pathway and a substrate for kallikrein-7) were highly correlated with FOP genotype, while kallikrein-7 was highly correlated with acute flare-up status. Plasma-soluble biomarkers for FOP support a flare-up-related acute inflammatory phase of disease activity superimposed on a genotypic background of chronic inflammation. © 2021 American Society for Bone and Mineral Research (ASBMR).