Novel chimeric antigen receptor targets and constructs for acute lymphoblastic leukemia: Moving beyond CD19.

Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults with a poor prognosis with relapsed or refractory (R/R) B-cell lineage ALL (B-ALL). Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown excellent response rates in RR B-ALL, but most patients relapse due to poor persistence of CAR T-cell therapy or other tumor-associated escape mechanisms. In addition, anti-CD19 CAR T-cell therapy causes several serious side effects such as cytokine release syndrome and neurotoxicity. In this review, we will discuss novel CAR targets, CAR constructs, and various strategies to boost CARs for the treatment of RR B-ALL. In addition, we discuss a few novel strategies developed to reduce the side effects of CAR.

Serum Uric Acid to Creatinine Ratio with Estimated Glomerular Filtration Rate in Type 2 Diabetes Patients.

BACKGROUND: Diabetes mellitus is a metabolic disorder associated with cardiovascular and renal complications. The serum uric acid to creatinine ratio and estimated glomerular filtration rate are important markers used to assess kidney function in patients with type 2 diabetes. This study aimed to find the correlation between serum uric acid to creatinine ratio and estimated glomerular filtration rate to various parameters among the diabetes patients. METHODS: It is an observational hospital-based, cross-sectional study. Patients with a diagnosis of diabetes for three years or more duration were selected. This study designed to serum uric acid to creatinine ratio with estimated glomerular filtration rate and its relationship with other biochemical parameters. The Modification of Diet in Renal Disease formula was used to calculate estimated glomerular filtration rate (eGFR). eGFR (mL/min∙1.73 m2) = 186 × (Scr) -1.154 × (age) - 0.203 × (0.742 female). Low eGFR was defined as eGFR<60 mL/min∙1.73 m2. The data were analyzed by SPSS version 20. Mean values of different variables, standard deviations and p-values were calculated. RESULTS: Mean serum uric acid to creatinine ratio was 6.09±1.71 and elevated among 49.1%. Mean blood urea and serum creatinine levels were 28.0±10.72 and 1.01±0.18, respectively. There was a significant positive correlation between eGFR and serum uric acid : serum creatinine ( r = 0.246, p = 0.007) in this study. CONCLUSIONS: The serum uric acid to creatinine ratio can serve as an early marker for renal injury, showing a positive correlation with estimated glomerular filtration rate (eGFR). Monitoring serum uric acid to creatinine ratio levels alongside eGFR can assistance in the identification and management of kidney damage in its early stages.

Time from Admission to Right Heart Catheterization in Cardiogenic Shock Patients.

Cardiogenic shock (CS) presents with a complex spectrum of low output states, which can be provoked by Acute Coronary Syndrome (ACS) or Acute Decompensated Heart Failure (ADHF). Its management includes hemodynamic assessment via right heart catheterization (RHC). Herein, we describe the timing of RHC based on the etiology and severity of CS as defined by the Society of Cardiovascular Angiography & Interventions (SCAI) Shock Classification. We performed a single-center retrospective analysis of patients admitted with CS secondary to ACS or ADHF from January 7, 2018 to June 30, 2020 at the University of Iowa Hospitals and Clinics. Among the 647 patients admitted, 249 patients had RHC during their admission. Of those, 51 had underlying ACS and 198 had ADHF. The overall time from admission to invasive hemodynamic assessment was 2.73 days. The mean time for SCAI-A was 3.6 ± 2.8 days, SCAI-B 3.7 ± 3.7 days, SCAI-C 2.6 ± 3.0 days, SCAI-D 2.5 ± 4.1 days, and SCAI-E 1.3 ± 2.1 days. The linear regression model showed that RHC was performed earlier in patients with worse hemodynamics evaluated by Cardiac Power Output (CPO) (Coefficient 0.14, R- squared 0.01, P = 0.03). Hemodynamic parameters showed that high PAPi, RVSWi, and Cardiac Power Output during admission predicted low in-hospital mortality (P < 0.01). RHC was performed earlier in more critically ill patients. Patients with CS in the setting of ACS underwent RHC significantly earlier than those with ADHF.

Dyslipidemia among Patients with Ischemic Stroke in the Department of Medicine of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Stroke is a leading cause of morbidity and disability in Asian population. Dyslipidemia is considered a major risk factor for various cardiovascular diseases. The study aimed to find the prevalence of dyslipidemia among patients with ischemic stroke in the Department of Medicine of a tertiary care centre. Methods: This is a descriptive cross-sectional study conducted among 150 diagnosed cases of ischemic stroke admitted in the Department of Medicine from 1st October, 2020 to 1st October, 2021. The ethical clearance was taken from the Institutional Review Committee (Reference number: 358/2077/78). Fasting blood samples were collected from the patients, serum lipids were measured and atherogenic indices of plasma were calculated. Demographic, anthropometric and cardiovascular risk factors related data were collected. Data were entered in Microsoft Excel 2010 and analysis was using the Statistical Package for the Social Sciences version 22.0. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data, and mean and standard deviation for continuous data. Results: The prevalence of dyslipidemia among the ischemic stroke patients was 120 (80.00%) (73.60-86.40 at 95% Confidence Interval). High total cholesterol was found in 64 (53.33%) patients, high triglycerides in 70 (58.33%), high low-density lipoprotein cholesterol in 54 (45.00%) and low high-density lipoprotein cholesterol in 51 (42.50%) patients. Conclusions: The prevalence of dyslipidemia among ischemic stroke patients was higher than the studies done in similar settings. Keywords: dyslipidemia; ischemic stroke; lipid; prevalence.

Impact of Pre-Operative Right Ventricular Response to Hemodynamic Optimization on Outcomes in Patients with LVADs.

Background: Right ventricular failure (RVF) continues to affect patients supported with durable left ventricular assist devices (LVAD) and results in increased morbidity and mortality. Information regarding the impact of right ventricular response to pre-operative optimization on outcomes is scarce. Methods: Single-center retrospective analysis of consecutive patients who underwent first continuous flow LVAD implantation between 2006 and 2020. Patients with bi-ventricular support before LVAD or without hemodynamic data were excluded. Invasive hemodynamics at baseline and after pre-operative medical and/or temporary circulatory support were recorded. Patients were grouped in the following categories: A: No Hemodynamic RV dysfunction (RVD) at baseline; B: RVD with achievement of RV hemodynamic optimization goals; C: RVD without achievement of RV optimization goals. The main outcomes were right ventricular failure defined as inotropes >14 days after implantation, or postoperative right ventricular mechanical support, and all-cause mortality. Results: Overall, 128 patients were included in the study. The mean age was 58 ±12.5 years, 74.2% were males and, 68.7% had non-ischemic cardiomyopathy. Hemodynamic RVD was present in 70 (54.7%) of the patients at baseline. RV hemodynamic goals were achieved in 46 (79.31%) patients with RVD and in all the patients without RVD at baseline. Failure to achieve hemodynamic optimization goals was associated with a significantly higher risk of RVF after LVAD implantation (adjusted OR 4.37, 95% CI 1.14−16.76, p = 0.031) compared with no RVD at baseline and increased 1-year mortality compared with no RVD (adjusted HR 4.1, 95% CI 1.24−13.2, p = 0.02) and optimized RVD (adjusted HR 6.4, 95% CI 1.6−25.2, p = 0.008).Conclusion: Among patients with RVD, the inability to achieve hemodynamic optimization goals was associated with higher rates of RV failure and increased 1-year all-cause mortality post LVAD implantation.

Prognostic Implications of Ambulatory N-Terminal Pro-B-Type Natriuretic Peptide Changes in Patients with Continuous-Flow Left Ventricular Assist Devices.

Data regarding the role of N-terminal Pro-B-type natriuretic peptide (NT-pro BNP) in patients with a continuous-flow left ventricular assist device (CFLVAD) is scarce. To evaluate the prognostic implications of measuring both absolute values and changes in NT-pro BNP concentrations in ambulatory patients with a CFLVAD, we performed a retrospective study of 168 consecutive patients who had an LVAD implantation at our institution and survived beyond their index hospitalization. Of these, 127 patients (56.2 ± 12.5 years, 21.2% female) had NT-pro BNP measured at 1 and 3 months postdischarge in ambulatory settings. Compared to the NT-pro BNP concentration at 1 month, 94 patients (74%) had a decline, and 33 patients (26%) had an increase in concentrations, from their 1 month baseline. After a median follow-up of 17 months, a total of 53 (41.7%) adverse events occurred. Of these, 37 (69.8%) were heart failure (HF) hospitalizations, and 16 (30.2%) were deaths. For each 1,000 unit increase in NT-pro BNP concentration at 3 months, there was a 17% increase in the risk of HF hospitalization or death (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.04-1.32, p = 0.007). Conversely, each 1000 unit decline during the same time, was associated with an 11% decrease in the risk of HF hospitalization or death (HR = 0.89, 95% CI = 0.77-0.98, p = 0.04). In conclusion, in patients with a CFLAD, an increase in NT-pro BNP concentration from 1 to 3 months is associated with an increased risk of HF hospitalization and death. In contrast, a decline is associated with a reduction in the risk of HF hospitalization and death.