Chimeric Antigen Receptor (CAR) T Cell Therapy for Glioblastoma.

Genetic modification of T cells to express chimeric antigen receptors (CARs) has yielded remarkable clinical outcomes and initiated a novel era for cancer immunotherapy. The impressive clinical responses seen in hematologic malignancies have led to the investigation of CAR T cells in solid tumors but attaining similar results has been challenging to date. Glioblastoma (GBM) presents a particularly challenging malignancy for treatment and despite some progress in treatments over the past decade, prognosis remains poor for the vast majority of patients. However, recent data support the clinical efficacy and safety of CAR T cell therapy in GBM. In this review, common challenges associated with treating GBM will be discussed in addition to how CAR T cells can overcome such barriers. Additionally, emerging techniques of optimizing CAR T cell therapy for GBM will be emphasized, highlighting the prospective promise of cellular immunotherapy.

Tefillin use induces preconditioning associated changes in heart rate variability.

Short bouts of occlusion of blood flow can induce a preconditioning response that reduces subsequent damage from longer periods of ischemia. It has been shown that ischemic preconditioning (IPC) can be elicited remotely (RIPC) through limitation of blood flow and as recently described via only pain sensation. Non-obstructive banding (NOB) through the donning of tefillin (a box with sacred texts attached to a leather strap that is traditionally bound to the non-dominant arm of Jewish adults during morning prayers) has been shown to elicit an RIPC response at least partially through pain sensation. This study evaluated the effects of NOB on heart rate variability (HRV) dependent factors that are known to be affected by various RIPC stimuli. We recruited 30 healthy subjects and subjected them to NOB versus control and found various HRV markers associated with RIPC to be changed in the NOB group. This finding provides further evidence that tefillin, likely through NOB induced RIPC changes, may still be a viable clinical pathway to prevent and decrease the morbidity associated with ischemic events.

ParallelED-A novel screening and referral intervention using emergency department wait times to identify and address unmet social needs.

Background: People arriving at the emergency department (ED) often have unmet health-related social needs (HRSN). We implemented an intervention that used undergraduate student volunteers to screen patients in the ED waiting room (WR) for unmet social drivers of health and subsequently referred patients to community resources. Methods: This cross-sectional quality improvement study included patients who were approached to complete a HRSN screening questionnaire, subsequently referred to community resources, and followed up by phone from October 2021 to October 2022 in an ED WR of an academic medical center. Primary measures were the proportions of patients who had unmet HRSN and the proportions enrolled in a statewide database of social care resources-NCCARE360. Patient demographics and geospatial distribution were also assessed to better understand the population served. Results: Our intervention reached 3297 unique patients, with 398 patients (12%) agreeing to complete screening. Of those screened, 93% were positive for at least one social need and 95% of the aforementioned were interested in receiving assistance. A total of 60% of those who screened positive were enrolled into NCCARE360. Persons identifying as female or non-Hispanic Black were disproportionately represented at a higher rate among those who screened positive for at least one social need, with food and housing insecurity emerging as the most common referral categories. Conclusion: Our results demonstrate patients' willingness to be screened in the ED WR and a high identification of HRSN. Our findings show that idle time in the ED WR can be used to identify patients with unmet HRSN and refer them to resources.

Moderate Aortic Stenosis in Patients With Heart Failure.

BACKGROUND AND OBJECTIVES: Moderate aortic stenosis (AS) confers a surprisingly adverse prognosis, approaching that of severe AS. The objective of this study was to describe the clinical course of patients with moderate AS with evidence of concomitant heart failure manifesting as elevated brain natriuretic peptide (BNP) levels. METHODS: This is a single-center, retrospective cohort study of 332 patients with elevated BNP. 165 patients with moderate AS were compared with 167 controls with none-mild AS. The Median follow-up duration was 3.85 years. The primary outcome was a composite endpoint of all-cause hospitalizations and all-cause mortality. RESULTS: BNP levels were 530 and 515 pg/mL in the study and the control groups, respectively. Moderate AS had significantly higher rates of primary composite endpoint in both univariate analysis (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.14-1.97; p=0.004) and adjusted analysis (HR, 1.45; 95% CI, 1.05-2.01; p=0.02). Moderate AS had 1.41 (95% CI, 1.18-1.69; p<0.001) times more all-cause hospitalization per patient-year of follow-up compared to controls in the univariate model. After adjustment for significant covariates, moderate AS remained an independent predictor of all-cause hospitalizations (incidence rate ratio [IRR], 1.45; 95% CI, 1.18-1.79; p=0.005). Furthermore, moderate AS was significantly associated with higher all-cause hospitalization rates in both heart failure with reduced ejection fraction (IRR, 1.33; 95% CI, 1.02-1.75; p=0.038) and heart failure with preserved ejection fraction [IRR], 1.31; 95% CI, 1.03-1.67; p=0.026). CONCLUSIONS: Moderate AS in conjunction with elevated BNP portends a significantly worse prognosis than those without moderate AS and should be followed closely.

Single-Session Thrombolysis-Free Treatment of Deep Vein Thrombosis With a Novel Mechanical Thrombectomy Device.

Catheter-directed thrombolysis of iliofemoral deep vein thrombosis (DVT) carries an increased risk of major bleeding and may fail to rapidly remove thrombus or prevent post-thrombotic syndrome. We describe an alternative, thrombolysis-free, advanced DVT treatment strategy with rapid single-session percutaneous mechanical thrombectomy using the ClotTriever system. (Level of Difficulty: Intermediate.).