EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome.

BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy. OBJECTIVE: This study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy. STUDY DESIGN: EEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS. RESULTS: Twenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h. CONCLUSIONS: If confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment.

Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients.

PURPOSE: Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia. METHODS: We carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations. RESULTS: Between 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT ≥ 0.12 ng/mL was associated with higher 90 days mortality. CONCLUSION: Our study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19.

The Intricate Role of Non-Coding RNAs in Sepsis-Associated Disseminated Intravascular Coagulation.

Disseminated Intravascular Coagulation (DIC) is a type of tissue and organ dysregulation in sepsis, due mainly to the effect of the inflammation on the coagulation system. Unfortunately, the underlying molecular mechanisms that lead to this disorder are not fully understood. Moreover, current biomarkers for DIC, including biological and clinical parameters, generally provide a poor diagnosis and prognosis. In recent years, non-coding RNAs have been studied as promising and robust biomarkers for a variety of diseases. Thus, their potential in the diagnosis and prognosis of DIC should be further studied. Specifically, the relationship between the coagulation cascade and non-coding RNAs should be established. In this review, microRNAs, long non-coding RNAs, and circular RNAs are studied in relation to DIC. Specifically, the axis between these non-coding RNAs and the corresponding affected pathway has been identified, including inflammation, alteration of the coagulation cascade, and endothelial damage. The main affected pathway identified is PI3K/AKT/mTOR axis, where several ncRNAs participate in its regulation, including miR-122-5p which is sponged by circ_0005963, ciRS-122, and circPTN, and miR-19a-3p which is modulated by circ_0000096 and circ_0063425. Additionally, both miR-223 and miR-24 were found to affect the PI3K/AKT pathway and were regulated by lncGAS5 and lncKCNQ1OT1, respectively. Thus, this work provides a useful pipeline of inter-connected ncRNAs that future research on their impact on DIC can further explore.

Prognostic implications of stress hyperglycemia in acute ST elevation myocardial infarction. Prospective observational study.

INTRODUCTION AND OBJECTIVES: In patients with acute myocardial infarction, elevation of plasma glucose levels is associated with worse outcomes. The aim of this study was to evaluate the association between stress hyperglycemia and in-hospital mortality in patients with acute myocardial infarction with ST-segment elevation (STEMI). METHODS: We analyzed 834 consecutive patients admitted for STEMI to the Coronary Care Unit of our center. Association between admission glucose and mortality was assessed with Cox regression analysis. Discriminative accuracy of the multivariate model was assessed by Harrell's C statistic. RESULTS: Eighty-nine (10.7%) patients died during hospitalization. Optimal threshold glycemia level of 140mg/dl on admission to predict mortality was obtained by ROC curves. Those who presented glucose ≥140mg/dl showed higher rates of malignant ventricular tachyarrhythmias (28% vs. 18%, P=.001), complicative bundle branch block (5% vs. 2%, P=.005), new atrioventricular block (9% vs. 5%, P=.05) and in-hospital mortality (15% vs. 5%, P<.001). Multivariate analysis showed that those with glycemia ≥140mg/dl exhibited a 2-fold increase of in-hospital mortality risk (95% CI: 1.2-3.5, P=.008) irrespective of diabetes mellitus status (P-value for interaction=0.487 and 0.653, respectively). CONCLUSIONS: Stress hyperglycemia on admission is a predictor of mortality and arrhythmias in patients with STEMI and could be used in the stratification of risk in these patients.

N-acetylcysteine: short-term clinical benefits after coronary angiography in high-risk renal patients.

INTRODUCTION AND OBJECTIVES: Previous studies on the role of N-acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography and on the drug's long-term effects have produced contradictory findings. The aim of this study was to clarify the benefits of N-acetylcysteine. METHODS: A prospective, randomized, double-blind study was carried out in patients with chronic renal failure (plasma creatinine= >or=1.4 mg/dL) who underwent coronary angiography. This study concerns the second arm of the main study. Findings on the arm involving patients with normal renal function have been published previously. As before, patients were randomly assigned to receive either N-acetylcysteine, 600 mg every 12 h intravenously, or placebo. The primary end-point was the development of contrast-induced nephropathy. RESULTS: The study included 81 patients (39 on N-acetylcysteine, 42 on placebo) with comparable baseline clinical characteristics. The overall incidence of contrast-induced nephropathy was 14.8% (12 patients): 5.1% (2 patients) in the N-acetylcysteine group and 23.8% (10 patients) in the placebo group (odds ratio [OR]=0.17; 95% confidence interval [CI], 0.03-0.84; P=.027). One patient (1.2%) in the latter group required dialysis while in the coronary unit. Multivariate analysis showed that N-acetylcysteine was an independent protective factor against the composite end-point of contrast-induced nephropathy, need for dialysis and mortality during the coronary unit stay (OR=0.20; 95% CI, 0.04-0.97; P=.04). Nevertheless, no significant difference was observed between the N-acetylcysteine and placebo groups in the rates of in-hospital (10.3% vs. 16.7%, respectively) or 1-year mortality (15.4% vs. 21.4%, respectively). CONCLUSIONS: Prophylactic administration of N-acetylcysteine provided significant short-term clinical benefits in high-risk renal patients who underwent coronary angiography.

Intravenous N-acetylcysteine for preventing contrast-induced nephropathy: a randomised trial.

BACKGROUND: Studies evaluating the role of N-acetylcysteine in patients undergoing coronary angiography have yielded inconsistent data. Less is known about patients with normal renal function at baseline. METHODS: Prospective, double-blind, placebo-controlled trial to determine the benefits of intravenous N-acetylcysteine as an adjunct to hydration in this kind of population. Patients were randomly assigned to receive either N-acetylcysteine (600 mg twice daily) or placebo, in addition to 0.45% intravenous saline. The primary end point was development of contrast-induced nephropathy, defined as an acute increase in the serum creatinine concentration > or = 0.5 mg/dl and/or > 25% increase above baseline level at 48 h after contrast dosing. RESULTS: A total of 216 patients were studied: N-acetylcysteine = 107 and placebo = 109. Treatment groups were similar with respect to baseline clinical characteristics. Overall incidence of contrast-induced nephropathy was 10.2%, 10.3% in the N-acetylcysteine group and 10.1% in the placebo group. Furthermore, no significant differences were observed when considering the non-diabetic population, although there was a trend towards a protective effect of N-acetylcysteine in the subgroup of 47 patients with both hypertension and diabetes. There were no significant changes in serum urea nitrogen concentrations. The incidence of in-hospital adverse clinical events was low: no patient with contrast-induced nephropathy required dialysis, the median Coronary Unit stay was 4.5 vs. 4 days, and the mortality rate was 2.8% vs. 4.6% in the N-acetylcysteine and placebo groups, respectively (p=NS). CONCLUSIONS: The prophylactic administration of intravenous N-acetylcysteine provides no additional benefit to saline hydration in high-risk coronary patients with normal renal function.

Preoperative use of sotalol versus atenolol for atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation is one of the most common complications of cardiac surgery. Beta blockers have been demonstrated to decrease the incidence of postoperative atrial fibrillation. Preliminary investigations reporting sotalol and atenolol to be effective in preventing postoperative atrial fibrillation are encouraging, but no studies have been conducted comparing both drugs. METHODS: A total of 253 consecutive eligible patients (66 +/- 8 years; mean +/- standard deviation) scheduled to undergo cardiac surgery were enrolled in this study. Patients were randomized in a prospective open manner 1.5:1 to atenolol group (50 mg/daily; 153 patients) or sotalol group (80 mg twice daily; 100 patients). RESULTS: Atrial fibrillation occurred in 44/253 patients (17.45%). A significant difference was found in the occurrence of atrial fibrillation in the atenolol group (34 patients, 22%) compared with those receiving sotalol (10 patients, 10%; p = 0.013). Therapeutic efficiency and efficacy was 12% and 54%, respectively. Stepwise logistic regression analysis revealed that age more than 68 years old (odds ratio = 2.72; 95% confidence interval [CI] = 1.37-5.41; p = 0.004), the use of beta-adrenergic agents (odds ratio = 2.74; 95% CI = 1.5-5; p = 0.001), and sotalol (odds ratio = 0.46; 95% CI = 0.23-0.95; p = 0.035) were independently associated with development of atrial fibrillation. CONCLUSIONS: Oral low-dose sotalol provides a considerable reduction in the occurrence of atrial fibrillation. A selective approach based on clinical risk prediction should decrease the occurrence of atrial fibrillation after cardiac surgery.