Audiogenic Seizures in the Streptozotocin-Induced Rat Alzheimer's Disease Model.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative and progressive disorder with no cure and constant failures in clinical trials. The main AD hallmarks are amyloid-ß (Aß) plaques, neurofibrillary tangles, and neurodegeneration. However, many other events have been implicated in AD pathogenesis. Epilepsy is a common comorbidity of AD and there is important evidence indicating a bidirectional link between these two disorders. Some studies suggest that disturbed insulin signaling might play an important role in this connection. OBJECTIVE: To understand the effects of neuronal insulin resistance in the AD-epilepsy link. METHODS: We submitted the streptozotocin (STZ) induced rat AD Model (icv-STZ AD) to an acute acoustic stimulus (AS), a known trigger of seizures. We also assessed animals' performance in the memory test, the Morris water maze and the neuronal activity (c-Fos protein) induced by a single audiogenic seizure in regions that express high levels of insulin receptors. RESULTS: We identified significant memory impairment and seizures in 71.43% of all icv-STZ/AS rats, in contrast to 22.22% of the vehicle group. After seizures, icv-STZ/AS rats presented higher number of c-Fos immunopositive cells in hippocampal, cortical, and hypothalamic regions. CONCLUSION: STZ may facilitate seizure generation and propagation by impairment of neuronal function, especially in regions that express high levels of insulin receptors. The data presented here indicate that the icv-STZ AD model might have implications not only for AD, but also for epilepsy. Finally, impaired insulin signaling might be one of the mechanisms by which AD presents a bidirectional connection to epilepsy.

C-reactive protein-to-albumin ratio and six-month mortality in incident hemodialysis patients.

BACKGROUND: The first few months of hemodialysis (HD) are associated with a higher risk of mortality. Protein-energy malnutrition is a demonstrated major risk factor for mortality in this population. The C-Reactive Protein to Albumin ratio (CAR) has also been associated with increased mortality risk. The aim of this study was to determine the predictive value of CAR for six-month mortality in incident HD patients. METHODS: Retrospective analysis of incident HD patients between January 2014 and December 2019. CAR was calculated at the start of HD. We analyzed six-month mortality. A Cox regression was performed to predict six-month mortality and the discriminatory ability of CAR was determined using the receiver operating characteristic (ROC) curve. RESULTS: A total of 787 patients were analyzed (mean age 68.34 ± 15.5 years and 60.6% male). The 6-month mortality was 13.8% (n = 109). Patients who died were significantly older (p < 0.001), had more cardiovascular disease (p = 0.010), had central venous catheter at the start of HD (p < 0.001), lower parathyroid hormone (PTH) level (p = 0.014) and higher CAR (p = 0.015). The AUC for mortality prediction was 0.706 (95% CI (0.65-0.76), p < 0.001). The optimal CAR cutoff was ≥0.5, HR 5.36 (95% CI 3.21-8.96, p < 0.001). CONCLUSION: We demonstrated that higher CAR was significantly associated with a higher mortality risk in the first six months of HD, highlighting the prognostic importance of malnutrition and inflammation in patients starting chronic HD.

One-Year Mortality after Hemodialysis Initiation: The Prognostic Role of the CHA2DS2-VASc Score.

BACKGROUND: CKD is a significant cause of morbidity, cardiovascular and all-cause mortality. CHA2DS2-VASc is a score used in patients with atrial fibrillation to predict thromboembolic risk; it also appears to be useful to predict mortality risk. The aim of the study was to evaluate CHA2DS2-VASc scores as a tool for predicting one-year mortality after hemodialysis is started and for identifying factors associated with higher mortality. METHODS: Retrospective analysis of patients who started hemodialysis between January 2014 and December 2019 in Centro Hospitalar Universitário Lisboa Norte. We evaluated mortality within one year of hemodialysis initiation. The CHA2DS2-VASc score was calculated at the start of hemodialysis. RESULTS: Of 856 patients analyzed, their mean age was 68.3 ± 15.5 years and the majority were male (61.1%) and Caucasian (84.5%). Mortality within one-year after starting hemodialysis was 17.8% (n = 152). The CHA2DS2-VASc score was significantly higher (4.4 ± 1.7 vs. 3.5 ± 1.8, p < 0.001) in patients who died and satisfactorily predicted the one-year risk of mortality (AUC 0.646, 95% CI 0.6-0.7, p < 0.001), with a sensitivity of 71.7%, a specificity of 49.1%, a positive predictive value of 23.9% and a negative predictive value of 89.2%. In the multivariate analysis, CHA2DS2-VASc ≥3.5 (adjusted HR 2.24 95% CI (1.48-3.37), p < 0.001) and central venous catheter at dialysis initiation (adjusted HR 3.06 95% CI (1.93-4.85)) were significant predictors of one-year mortality. CONCLUSION: A CHA2DS2-VASc score ≥3.5 and central venous catheter at hemodialysis initiation were predictors of one-year mortality, allowing for risk stratification in hemodialysis patients.

Hypoalbuminaemia and One-Year Mortality in Haemodialysis Patients with Heart Failure: A Cohort Analysis.

INTRODUCTION: The prevalence of chronic kidney disease (CKD) and heart failure (HF) has been rising over the past decade, with a prevalence close to 40%. Cardiovascular disease and malnutrition are common comorbidities and known risk factors for mortality in haemodialysis (HD) patients. We aimed to evaluate the one-year mortality rate after dialysis induction, and the impact of serum albumin levels on survival outcomes, in patients with CKD and HF. METHODS: This was a retrospective analysis of patients with CKD and HF who underwent chronic HD between January 2016 and December 2019 in a tertiary-care Portuguese hospital. Variables were submitted to univariate and multivariate analysis to determine factors predictive of one-mortality after HD start. RESULTS: In total, 204 patients were analysed (mean age 75.1 ± 10.3 years). Within the first year of HD start, 28.7% of patients died. These patients were significantly older [79.8 ± 7.2 versus 72.9 ± 10.9 years, p < 0.001; OR 1.08 (1.04-1.13), p < 0.001] and had a higher mean Charlson Index [9.0 ± 1.8 versus 8.3 ± 2.0, p = 0.015; OR 1.22 (1.04-1.44), p = 0.017], lower serum creatinine [5.1 ± 1.6 mg/dL versus 5.8 ± 2.0 mg/dL; p = 0.021; OR 0.80 (0.65-0.97), p = 0.022], lower albumin levels [3.1 ± 0.6 g/dL versus 3.4 ± 0.6 g/dL, p < 0.001; OR 0.38 (0.22-0.66), p = 0.001] and started haemodialysis with a central venous catheter more frequently [80.4% versus 66.2%, p = 0.050]. Multivariate analysis identified older age [aOR 1.07 (1.03-1.12), p = 0.002], lower serum creatinine [aOR 0.80 (0.64-0.99), p = 0.049] and lower serum albumin [aOR 0.41 (0.22-0.75), p = 0.004] as predictors of one-year mortality. CONCLUSION: In our cohort, older age, lower serum creatinine and lower serum albumin were independent risk factors for one-year mortality, highlighting the prognostic importance of malnutrition in patients starting chronic HD.

Challenges in the use of NG2 antigen as a marker to predict MLL rearrangements in multi-center studies.

Rearrangements in MLL (MLL-r) are common within very young children with leukemia and affect the prognosis and treatment. Previous studies have suggested the use of the NG2 molecule as a marker for MLL-r but these studies were performed using a small number of infants. We analyzed 148 patients (all less than 24 months, 86 less than 12 months) from various centers in Brazil to determine the predictive power of NG2 within that cohort. We show that NG2 can be used for MLL-r prediction; however, proper staff training and standardized sampling procedures are essential when receiving samples from multiple centers as the accuracy of the prediction varies greatly on a per center basis.

SIL-TAL1 fusion gene negative impact in T-cell acute lymphoblastic leukemia outcome.

SIL-TAL1 fusion gene and the ectopic expression of HOX11L2 are common molecular abnormalities in T-cell acute lymphoblastic leukemia (T-ALL). To verify their influence on outcome, we analyzed a Brazilian pediatric T-ALL series of cases. One hundred and ninety two children, age ranged 0-21 years old, were consecutively diagnosed and treated. Reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to identify the molecular alterations. Kaplan-Meyer method was applied to estimate overall survival. The most frequent maturation stage was T-IV (40.1%), and 30.7% of cases were CD10(+). SIL-TAL1(+) and HOX11L2(+) accounted for 26.7% and 10.3% of the cases, respectively. The overall survival (OS) was 74% in 80-month follow-up. HOX11L2(+) was not predictive factor for outcome. Considering patients younger than nine years-old, those with SIL-TAL1(+) presented a poorer outcome (p = 0.02). The results of this study suggest that in the Brazilian population only the presence of SIL-TAL1 can predict outcome in a restricted group of patients.