Development and external validation of a machine learning model for prediction of survival in extremity leiomyosarcoma.

PURPOSE: Machine learning (ML) models have been used to predict cancer survival in several sarcoma subtypes. However, none have investigated extremity leiomyosarcoma (LMS). ML is a powerful tool that has the potential to better prognosticate extremity LMS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of histologic extremity LMS (n = 634). Patient, tumor, and treatment characteristics were recorded, and ML models were developed to predict 1-, 3-, and 5-year survival. The best performing ML model was externally validated using an institutional cohort of extremity LMS patients (n = 46). RESULTS: All ML models performed best at the 1-year time point and worst at the 5-year time point. On internal validation within the SEER cohort, the best models had c-statistics of 0.75-0.76 at the 5-year time point. The Random Forest (RF) model was the best performing model and used for external validation. This model also performed best at 1-year and worst at 5-year on external validation with c-statistics of 0.90 and 0.87, respectively. The RF model was well calibrated on external validation. This model has been made publicly available at https://rachar.shinyapps.io/lms_app/ CONCLUSIONS: ML models had excellent performance for survival prediction of extremity LMS. Future studies incorporating a larger institutional cohort may be needed to further validate the ML model for LMS prognostication.

Association between neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and survival in undifferentiated pleomorphic sarcoma (NLR, PLR, and overall survival in UPS).

BACKGROUND AND OBJECTIVES: Cancer-related inflammation has been shown to be a driver of tumor growth and progression, and there has been a recent focus on identifying markers of the inflammatory tumor microenvironment. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are inflammatory indices that have been identified as prognostic biomarkers in various malignancies. However, there is limited and conflicting data regarding their prognostic value in soft tissue sarcoma (STS) and specifically in undifferentiated pleomorphic sarcoma (UPS). METHODS: This was a retrospective review of patients who underwent surgical treatment for primary UPS from 1993 to 2021. Cutoff values for NLR and PLR were determined by receiver operating curve analysis. Cox proportional hazards regression was used to determine prognostic factors on univariate and multivariate analysis. RESULTS: Eighty-six patients were included. The optimal cutoff value was 3.3 for NLR and 190 for PLR. Both high NLR (HR 2.44; 95% CI 1.29-4.63; p = 0.005) and high PLR (HR 1.99; 95% CI 1.08-3.67, p = 0.02) were associated with worse OS on univariate analysis. On multivariate analysis, metastasis at presentation and radiotherapy were independently predictive of OS, but high NLR (HR 1.30; 95% CI 0.64-2.98; p = 0.41) and high PLR (HR 1.63; 95% CI 0.82-3.25; p = 0.17) were not predictive of survival. CONCLUSIONS: High pre-treatment NLR and PLR were associated with decreased overall survival but were not independent predictors of survival in patients undergoing resection for UPS. Until additional prospective studies can be done, survival outcomes are best predicted using previously established patient- and tumor-specific factors.

Sustained Use of the Impella 5.0 Heart Pump Enables Bridge to Clinical Decisions in 34 Patients.

We studied whether sustained hemodynamic support (>7 d) with the Impella 5.0 heart pump can be used as a bridge to clinical decisions in patients who present with cardiogenic shock, and whether such support can improve their outcomes. We retrospectively reviewed cases of patients who had Impella 5.0 support at our hospital from August 2017 through May 2019. Thirty-four patients (23 with cardiogenic shock and 11 with severely decompensated heart failure) underwent sustained support for a mean duration of 11.7 ± 9.3 days (range, ≤48 d). Of 29 patients (85.3%) who survived to next therapy, 15 were weaned from the Impella, 8 underwent durable left ventricular assist device placement, 4 were escalated to venoarterial extracorporeal membrane oxygenation support, and 2 underwent heart transplantation. The 30-day survival rate was 76.5% (26 of 34 patients). Only 2 patients had a major adverse event: one each had an ischemic stroke and flail mitral leaflet. None of the devices malfunctioned. Sustained hemodynamic support with the Impella 5.0 not only improved outcomes in patients who presented with cardiogenic shock, but also provided time for multidisciplinary evaluation of potential cardiac recovery, or the need for durable left ventricular assist device implantation or heart transplantation. Our study shows the value of using the Impella 5.0 as a bridge to clinical decisions.

Revascularization Strategies in Patients with Chronic Kidney Disease and Acute Coronary Syndromes.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is a highly prevalent condition that increases the incidence and complexity of acute coronary syndrome (ACS). The purpose of this review is to summarize current evidence, uncertainties, and opportunities in the management of patients with CKD and ACS, with a focus on revascularization. RECENT FINDINGS: Patients with CKD have been systematically under-represented or excluded from clinical trials in ACS. Available data, however, demonstrates that although patients with CKD and ACS benefit from revascularization, they are also less likely to receive recommended medical and revascularization therapies when compared to patients with normal kidney function. Despite the increased short-term risk of major morbidity and mortality, patients with CKD and ACS should be considered for an early invasive strategy while also trying to mitigate the risks of procedural related complications. Until evidence emerges from randomized clinical trials, the decision about revascularization strategy should involve multi-disciplinary collaboration, heart team consensus, and patient shared decision-making.

Probenecid: An Oral Inotrope for End-Stage Heart Failure in a Case With Myotonic Dystrophy.

A 56-year-old man with multiple cardiac manifestations of type 1 myotonic dystrophy, including severe, nonischemic cardiomyopathy, presented in refractory cardiogenic shock requiring inotropic therapy. Given his wishes to die without having any intravenous medications, he was started on oral probenecid therapy, which allowed for successful elimination of his intravenous therapies. (Level of Difficulty: Intermediate.).

Increased Excitability Induced in the Primary Motor Cortex by Transcranial Ultrasound Stimulation.

Background: Transcranial Ultrasound Stimulation (tUS) is an emerging technique that uses ultrasonic waves to noninvasively modulate brain activity. As with other forms of non-invasive brain stimulation (NIBS), tUS may be useful for altering cortical excitability and neuroplasticity for a variety of research and clinical applications. The effects of tUS on cortical excitability are still unclear, and further complications arise from the wide parameter space offered by various types of devices, transducer arrangements, and stimulation protocols. Diagnostic ultrasound imaging devices are safe, commonly available systems that may be useful for tUS. However, the feasibility of modifying brain activity with diagnostic tUS is currently unknown. Objective: We aimed to examine the effects of a commercial diagnostic tUS device using an imaging protocol on cortical excitability. We hypothesized that imaging tUS applied to motor cortex could induce changes in cortical excitability as measured using a transcranial magnetic stimulation (TMS) motor evoked potential (MEP) paradigm. Methods: Forty-three subjects were assigned to receive either verum (n = 21) or sham (n = 22) diagnostic tUS in a single-blind design. Baseline motor cortex excitability was measured using MEPs elicited by TMS. Diagnostic tUS was subsequently administered to the same cortical area for 2 min, immediately followed by repeated post-stimulation MEPs recorded up to 16 min post-stimulation. Results: Verum tUS increased excitability in the motor cortex (from baseline) by 33.7% immediately following tUS (p = 0.009), and 32.4% (p = 0.047) 6 min later, with excitability no longer significantly different from baseline by 11 min post-stimulation. By contrast, subjects receiving sham tUS showed no significant changes in MEP amplitude. Conclusion: These findings demonstrate that tUS delivered via a commercially available diagnostic imaging ultrasound system transiently increases excitability in the motor cortex as measured by MEPs. Diagnostic tUS devices are currently used for internal imaging in many health care settings, and the present results suggest that these same devices may also offer a promising tool for noninvasively modulating activity in the central nervous system. Further studies exploring the use of diagnostic imaging devices for neuromodulation are warranted.