Citations

OBJECTIVE Patients with ankylosing spinal disorders (ASDs), including ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), have been shown to experience significantly increased rates of postoperative complications. Despite this, very few risk stratification tools have been validated for this population. As such, the purpose of this study was to identify predictors of adverse events and mortality in ASD patients undergoing surgery for 3-column fractures. METHODS All adult patients with a documented history of AS or DISH who underwent surgery for a traumatic 3-column fracture between 2000 and 2020 were identified. Perioperative variables, including comorbidities, time to diagnosis, and number of fused segments, were collected. Three instruments, including the Charlson Comorbidity Index (CCI), modified frailty index (mFI), and Injury Severity Score (ISS), were computed for each patient. The primary outcomes of interest included 1-year mortality, as well as postoperative complications. RESULTS A total of 108 patients were included, with a mean ± SD age of 73 ± 11 years. Of these, 41 (38%) experienced at least 1 postoperative complication and 22 (20.4%) died within 12 months after surgery. When the authors controlled for potential known confounders, the CCI score was significantly associated with postoperative adverse events (OR 1.20, 95% CI 1.00–1.42, p = 0.045) and trended toward significance for mortality (OR 1.19, 95% CI 0.97–1.45, p = 0.098). In contrast, mFI score and ISS were not significantly predictive of either outcome. CONCLUSIONS Complications in spine trauma patients with ASD may be driven by comorbidity burden rather than operative or injury-related factors. The CCI may be a valuable tool for the evaluation of this unique population.

AbstractNew medical compression technologies that are simultaneously low‐profile, facile to don, and dynamic—applying medical compression only when needed—can expand the use of wearable compression, increase patient compliance, and lead to better medical outcomes. Dynamic and conformal wearable compression devices are presented that can be donned in a low‐stiffness state and transition into a high‐stiffness and, consequently, high‐compression state, on‐demand. These devices are enabled by active textiles developed from custom NiTi filaments that remain inactive at room temperature and accomplish actuation proximal to the human body surface. Further, these compression devices exploit NiTi material hysteresis to sustain a high‐compression state post‐heating and upon equilibrium with the body surface temperature for thermally‐comfortable, on‐body performance. Two case study examples—1) a consumer medical compression device and 2) a custom astronaut compression device—demonstrate the generalizability and flexibility of the engineering and design methods to develop a range of dynamic, tunable, and conformal compression devices with different goals and requirements. Further, this work demonstrates a roadmap for developing wearable systems that can accommodate a range of users without sacrificing system performance. This research opens doors for new NiTi‐based medical and consumer applications that interface with the body surface.

Introduction. This case report adds to current literature on management of a subdural hematoma following total knee arthroplasty and is particularly important as joint replacement moves into outpatient surgery centers where the orthopedic surgery team becomes the sole patient contact point. Case Presentation. A 66-year-old male presented to the emergency department five days after elective robotic-assisted left total knee arthroplasty performed with spinal epidural with the symptoms of a persistent nonpostural headache. CT of the head revealed a small bifrontal acute subdural hematoma. He was admitted for overnight monitoring as a precaution. No vascular abnormalities or underlying pathology was found on further advanced imaging. He was discharged the following morning after follow-up CT showed no focal changes. Magnetic resonance imaging (MRI) one month later confirmed resolution of the subdural hematoma. Conclusion. Orthopedic surgeons should be aware of the signs and symptoms, as well as the risk factors for subdural hematomas following lumbar puncture, as it is a rare, but potentially life-threatening complication of spinal epidural.

AbstractOraxol consists of an oral dosage form of the chemotherapeutic agent paclitaxel administered with a novel P‐glycoprotein inhibitor encequidar methanesulfonate monohydrate (formerly named HM30181A), which allows oral treatment of cancers that would otherwise be treated with intravenous paclitaxel. Here we describe the population pharmacokinetics (popPK) analyses for oral paclitaxel in patients with advanced/metastatic solid tumors to characterize pharmacokinetic (PK) profiles and quantify sources of PK variability. The best fit popPK model for oral paclitaxel, based on data from seven clinical studies (197 patients with advanced/metastatic solid tumors), involves a linear two‐compartment structural model containing first‐order absorption with a short lag time and first‐order elimination as well as a log additive error. In this popPK model, lower population estimates of central volume for Asian patients versus Caucasian patients did not translate into clinical meaningful differences in oral paclitaxel exposure. Age, sex, body weight or surface area, mild hepatic impairment, and mild to moderate renal impairment had no clinically meaningful effects on the systemic exposure of oral paclitaxel. Simulations were performed on clinical therapeutic dose (oral paclitaxel 205 mg/m2 once daily ×3 days per week) to predict exposure of oral paclitaxel and to support treatment benefits observed in a pivotal phase III trial.

OBJECTIVE The goal of this study was to determine independent risk factors for vertebral compression fracture (VCF) following radiation for metastatic spine disease, including low bone mineral density as estimated by Hounsfield units (HU). METHODS A retrospective chart review identified patients with a single vertebral column metastasis treated with radiation therapy, a pretreatment CT scan, and a follow-up CT scan at least 6 weeks after treatment. Patients with primary spine tumors, preradiation vertebroplasty, preradiation spine surgery, prior radiation to the treatment field, and proton beam treatment modality were excluded. The HU were measured in the vertebral bodies at the level superior to the metastasis, within the tumor and medullary bone of the metastatic level, and at the level inferior to the metastasis. Variables collected included basic demographics, Spine Instability Neoplastic Score (SINS), presenting symptoms, bone density treatment, primary tumor pathology, Weinstein-Boriani-Biagini (WBB) classification, Enneking stage, radiation treatment details, chemotherapy regimen, and prophylactic vertebroplasty. RESULTS One hundred patients with an average age of 63 years and average follow-up of 18 months with radiation treatment dates ranging from 2017 to 2020 were included. Fifty-nine patients were treated with external-beam radiation therapy, with a median total dose of 20 Gy (range 8–40 Gy). Forty-one patients were treated with stereotactic body radiation therapy, with a median total dose of 24 Gy (range 18–39 Gy). The most common primary pathologies included lung (n = 22), prostate (n = 21), and breast (n = 14). Multivariable logistic regression analysis (area under the curve 0.89) demonstrated pretreatment HU (p < 0.01), SINS (p = 0.02), involvement of ≥ 3 WBB sectors (p < 0.01), primary pathology other than prostate (p = 0.04), and ongoing chemotherapy treatment (p = 0.04) to be independent predictors of postradiation VCF. Patients with pretreatment HU < 145 (n = 32), 145–220 (n = 31), and > 220 (n = 37) had a fracture rate of 59%, 39%, and 11%, respectively. An HU cutoff of 157 was found to maximize sensitivity (71%) and specificity (75%) in predicting postradiation VCF. CONCLUSIONS Low preradiation HU, higher SINS, involvement of ≥ 3 WBB sectors, ongoing chemotherapy, and nonprostate primary pathology were independent predictors of postradiation VCF in patients with metastatic spine disease. Low bone mineral density, as estimated by HU, is a novel and potentially modifiable risk factor for VCF.

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program ( n = 63,302) and UK Biobank ( n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions that enhance patient-physician communication by encouraging patients to ask questions during consultations. Aim: The aim of this study was to develop a preliminary achalasia-specific QPL created by esophageal experts. Methods: The QPL content was derived through a modified Delphi method consisting of 2 rounds. In round 1, experts provided 5 answers to the prompts “What general questions should patients ask when given a new diagnosis of achalasia” and “What questions do I not hear patients asking, but given my expertise, I believe they should be asking?” In round 2, experts rated questions on a 5-point Likert scale. Questions considered “essential” or “important” were accepted into the QPL. Feedback regarding the QPL was obtained in a pilot study wherein patients received the QPL before their consultation and completed surveys afterwards. Results: Nineteen esophageal experts participated in both rounds. Of 148 questions from round 1, 124 (83.8%) were accepted into the QPL. These were further reduced to 56 questions to minimize redundancy. Questions were categorized into 6 themes: “What is achalasia,” “Risks with achalasia,” “Symptom management in achalasia,” “Treatment of achalasia,” “Risk of reflux after treatment,” and “Follow-up after treatment.” Nineteen patients participated in the pilot, most of whom agreed that the QPL was helpful (84.2%) and recommended its wider use (84.2%). Conclusions: This is the first QPL developed specifically for adults with achalasia. Although well-received in a small pilot, follow-up studies will incorporate additional patient feedback to further refine the QPL content and assess its usability, acceptability, and feasibility.

596 Background: Genomic alterations (GA) that drive cancer development and predict therapeutic response remain elusive in patients (pts) with KRAS WT PDAC. We interrogated our institutional database to identify actionable GAs in pts with metastatic, KRAS WT PDAC and analyzed the therapeutic impact of matched TT. Methods: We reviewed electronic medical records of KRAS WT PDAC pts (n=24) who underwent comprehensive genomic profiling (CGP) utilizing Foundation One CDx (25.0%) or Tempus (75.0%) between 2015-2021. Duration of response (DOR) was calculated from date of treatment (Tx) initiation to Tx discontinuation. Overall survival (OS) was measured from the date of the diagnosis (Dx) of advanced disease (AD) to death or last follow-up. OS was estimated using the Kaplan-Meier method, with at-risk periods left-truncated at the time of CGP. The effect of covariates on survival was evaluated using Cox proportional hazards regression. Results: Of the 24 KRAS WT pts, 14 (58%) had AD: 8 (57%) pts had metastatic disease at or shortly after Dx, 6 (43%) pts developed metachronous recurrence. Median age at Dx for pts with AD was 65, and 57% were female. Seven of 14 pts with AD (50%) had highly actionable GA (HAGA), (Table). Pts with HAGA demonstrated durable responses to TT (Table) with manageable toxicities. Pts with HAGA had a median OS of 28 mo compared to 5.9 mo for those without (Hazard Ratio = 0.47, p = 0.33). Conclusions: The sustained therapeutic benefit noted with TT matched to HAGA in pts with KRAS WT PDAC underscores the need for systematic interrogation of the somatic genome in PDAC pts. Optimal sequencing of cytotoxic therapy with TT and its impact on modulating clonal selection pressure in pts with KRAS WT PDAC merits prospective evaluation.[Table: see text]