Serum uric acid to eGFR ratio correlates with adverse outcomes in elderly hospitalized for acute heart failure.

BACKGROUND: Serum uric acid (SUA) is a known biomarker of severity in acute heart failure (AHF), reflecting the intricate interplay between cardiovascular and metabolic dysfunction. Since SUA can increase in response to worsening kidney function, and subjects with AHF often have cardiorenal syndrome or are on diuretic therapy, we tested whether the ratio of SUA to eGFR might provide prognostic value in elderly hospitalized for AHF. METHODS: The BOTERO-AHF Study (BOlogna study of Therapies, Epidemiology and Radiodiagnostic Outcomes in Acute Heart Failure patients) included 293 patients admitted for AHF who were consecutively enrolled from January 2020 onwards. We compared the baseline characteristics of participants who had a composite outcome (CO) (n = 203) of death or re-hospitalization for AHF within 12 months from discharge to those without CO (n = 90), and we assessed the prognostic impact of SUA/eGFR for 12-months CO. RESULTS: SUA/eGFR was significantly higher in participants who experienced a CO within 12 months from discharge for AHF, compared to those who did not experience any CO (17.8 (16.6) vs. 13.7 (12.1) mg/dl/ml/min*100, p = 0.008). SUA/eGFR, and not SUA alone, was associated with an increase in the rate of CO (unadjusted HR 1.011, CI 95% 1.004-1.019, p = 0.003). This association lost significance in participants under treatment with xanthine oxidase inhibitors but remained significant after adjustment for multiple confounders. CONCLUSION: The SUA/ eGFR ratio provides prognostic value in elderly patients hospitalized for AHF. Future studies may clarify if SUA/eGFR and XOI may represent novel diagnostic and therapeutic approaches for subgroups of patients with AHF.

Predicting Failure to Recover Swallowing in Patients with Severe Post-stroke Dysphagia: The DIsPHAGIc Score.

In post-stroke dysphagia, early identification of patients at highest risk of failing swallowing recovery (SR) would be useful to decide which of them should undergo percutaneous endoscopic gastrostomy. The studies on this subject were numerous but generally based on small statistical samples. In this retrospective study, 1232 patients with ischemic or hemorrhagic stroke (73.7 ± 13.0 years, 51% men) were assessed: 593 non-dysphagic, 351 partially dysphagic and 288 totally dysphagic. Among the latter, 45.1% could not recover oral intake. A score to assess the risk of failing SR was obtained from the group with total dysphagia, and further 210 patients with total post-stroke dysphagia were utilized for validation. A regular progression of stroke severity markers, complications and mortality was observed from non-dysphagic, to partially dysphagic, up to totally dysphagic patients. Among the latter, seven variables were independently associated with failure of SR, and formed the "DIsPHAGIc score": cerebral lesion Diameter ≥ 6 cm (+ 1), left frontal Ischemia (- 1), Partial anterior circulation syndrome (- 1), Hypoxia (+ 1), Antiplatelet drug (+ 1), GCS verbal reaction < 4 (+ 1), Internal capsule ischemia (- 1). The area under the ROC curve was 0.79 (95% CI 0.74-0.85). For total scores ≥ 2 there was a high risk of failing SR, with specificity 76.9%, sensitivity 72.1% and accuracy 74.7%. The application of the DIsPHAGIc score to the validation sample provided almost identical results. The evolution of post-stroke dysphagia towards irreversibility can be predicted by a simple, reproducible and robust scoring system based on 7 variables commonly available during hospitalization.

Prognostic significance of diabetes and stress hyperglycemia in acute stroke patients.

BACKGROUND: Hyperglycemic non-diabetic stroke patients have a worse prognosis than both normoglycemic and diabetic patients. Aim of this study was to assess whether hyperglycemia is an aggravating factor or just an epiphenomenon of most severe strokes. METHODS: In this retrospective study, 1219 ischemic or hemorrhagic stroke patients (73.7 ± 13.1 years) were divided into 4 groups: 0 = non-hyperglycemic non-diabetic, 1 = hyperglycemic non-diabetic, 2 = non-hyperglycemic diabetic and 3 = hyperglycemic diabetic. Hyperglycemia was defined as fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/l) measured the morning after admission, while the diagnosis of diabetes was based on a history of diabetes mellitus or on a glycated hemoglobin ≥ 6.5% (≥ 48 mmol/mol), independently of blood glucose levels. All diabetic patients, except 3, had Type 2 diabetes. The 4 groups were compared according to clinical history, stroke severity indicators, acute phase markers and main short term stroke outcomes (modified Rankin scale ≥ 3, death, cerebral edema, hemorrhagic transformation of ischemic lesions, fever, oxygen administration, pneumonia, sepsis, urinary infection and heart failure). RESULTS: Group 1 patients had more severe strokes, with larger cerebral lesions and higher inflammatory markers, compared to the other groups. They also had a high prevalence of atrial fibrillation, prediabetes, previous stroke and previous arterial revascularizations. In this group, the highest frequencies of cerebral edema, hemorrhagic transformation, pneumonia and oxygen administration were obtained. The prevalence of dependency at discharge and in-hospital mortality were equally high in Group 1 and Group 3. However, in multivariate analyses including stroke severity, cerebral lesion diameter, leukocytes and C-reactive protein, Group 1 was only independently associated with hemorrhagic transformation (OR 2.01, 95% CI 0.99-4.07), while Group 3 was independently associated with mortality (OR 2.19, 95% CI 1.32-3.64) and disability (OR 1.70, 95% CI 1.01-2.88). CONCLUSIONS: Hyperglycemic non-diabetic stroke patients had a worse prognosis than non-hyperglycemic or diabetic patients, but this group was not independently associated with mortality or disability when size, severity and inflammatory component of the stroke were accounted for.

Surgical aortic valve replacement for low-gradient aortic stenosis.

AIMS: Low-gradient aortic stenosis is a challenging entity that needs accurate preoperative evaluation. For this high-risk patient population, ad hoc predictive scores are not available and profile risk is currently revealed by the EuroSCOREs. Aims of this study are to verify the suitability of the ES II as predictor of mortality in low-gradient aortic stenosis and to analyse the role of surgery as a treatment. METHODS: From June 2013 to August 2019, 414 patients underwent surgical aortic valve replacement for low-gradient aortic stenosis. Mean age was 75.78 ±â€Š6.77 years and 190 were women. The prognostic value of Logistic EuroSCORE and EuroSCORE II were compared by receiver-operating characteristics (ROC) curve analysis. RESULTS: In-hospital, 30-day and 1-year mortality rates were respectively 3.4, 2.9 and 4.8% (14, 12 and 20 patients over 414). In-hospital mortality risk calculated by the Additive EuroSCORE was 7.2 ±â€Š2.7%, by the Logistic EuroSCORE was 9 ±â€Š5.2% and by the ES II was 4.13 ±â€Š2.56%. The prognostic values of the EuroSCORE II and of the EuroSCORE were analysed in a ROC curve analysis for the prediction of in-hospital mortality [area under the curve (AUC): 0.62 vs. 0.58], 30-day mortality (AUC: 0.63 vs. 0.64) and 1-year mortality (AUC: 0.79 vs. 0.65). Both scores did not show significant differences with the only exception of 1-year mortality, for which EuroSCORE II had a better predictive ability than the Logistic EuroSCORE (P < 0.05). CONCLUSION: In low-gradient aortic stenosis undergoing surgery, the EuroSCORE II is a strong predictor of 1-year mortality.

What do spinal cord injury patients think of their improvement? A study of the minimal clinically important difference of the Spinal Cord Independence Measure III.

BACKGROUND: The Spinal Cord Independence Measure (SCIM III) is a scale of independence in the activities of daily life, specifically designed for spinal cord injury subjects. AIM: The aim of this study was to calculate the minimal clinically important difference (MCID) of the SCIM III according to distribution and anchor based approach. DESIGN: Prospective study. SETTING: Four Spinal Cord Units in Italy. POPULATION: Patients with acute/subacute spinal cord injury/lesion. METHODS: The scores of the total SCIM and of the four subscale was recorded at admission and discharge. Clinical significance was calculated according to anchor based methodology using a global rating of change questionnaire. The accuracy of MCID values in predicting a judgment of small improvement by the patients has been assessed by means of the area under the receiving operating curves (aROC). RESULTS: Total SCIM MCID values varied from 12 for patients with complete tetraplegia to 45.3 for those with incomplete thoracic lesions. The MCID of self-care varied from 3.3 to 8.5 and from 10 to 18 for respiration and sphincter management, depending on the level and severity of the lesion. With regard to mobility (room and toilet), the MCID varied from 1 to 3 and from 2.5 to 7.26 for mobility (indoors and outdoors). The aROC was between good and excellent for all these values. CONCLUSIONS: The results provide benchmarks for clinicians and researchers to interpret whether patients' change score on the SCIM III can be interpreted as true or clinically meaningful and to make clinical judgments about the patients' progress. CLINICAL REHABILITATION IMPACT: Our data could be useful for both clinicians and researchers. At the beginning of rehabilitation clinicians may have an idea of the minimal improvement of the patient (based on his neurological status) that could have an impact on patient's life. At the end of rehabilitation process, it is possible to control if the patient achieved an improvement that is true and significant. Researchers could also use these criteria to evaluate the clinical significance of an intervention by calculating the number of subjects in the treatment and control groups (or in two different treatment groups) who achieved a change calculated as the natural recovery plus the MCID.

Risk Factors for Lacunar Strokes with Visible Cerebral Lesions on Computed Tomography Scan.

BACKGROUND: The aim of this study was the detection of risk factors for lacunar strokes with visible lesions on computed tomography (CT) scan, considering in particular clinical characteristics, echocardiographic parameters, and carotid-femoral pulse wave velocity (PWV, a marker of large-artery stiffness). Lacunar strokes with very small or nonvisible lesions may have different risk factors. METHODS: We examined 106 patients (mean age 66.9 ± 12.3 years, 60 men), including 55 patients with clinically lacunar stroke associated with deep ischemic lesions of .3-1.5 cm on brain CT scan, and 51 control patients with cortical ischemic stroke, with lesions of 2.5-10.0 cm. RESULTS: In multiple logistic regression, with respect to cortical strokes, the following variables were independently associated with lacunar strokes: tricuspid regurgitation velocity (inverse relationship, odds ratio [OR] .13, 95% confidence interval [CI] .04-.43, P = .0007, cutoff at 228 cm/s), mean systolic blood pressure (SBP) (OR 3.98, 95% CI 2.78-7.79, P = .008, cutoff at 145 mmHg), ever-smoker status (OR 2.68, 95% CI 1.06-6.80, P = .04), and atrial fibrillation (inverse relationship, OR .11, 95% CI .01-1.00, P = .0496). In univariate analysis, the patients with lacunar stroke also had a lower prevalence of mitral regurgitation. There were no differences between the 2 groups in relation to diabetes, cholesterol, left ventricular mass and dimensions, and PWV. CONCLUSIONS: The patients with lacunar strokes with visible cerebral lesions on CT scan, compared with the patients with cortical infarct, had a lower tricuspid regurgitation velocity, a higher mean SBP, a greater prevalence of ever-smokers, and a lower prevalence of atrial fibrillation.

PPARß/δ and γ in a rat model of Parkinson's disease: possible involvement in PD symptoms.

Parkinson's disease is one of the most common neurologic disorder, affecting about 1-4% of persons older than 60 years. Among the proposed mechanisms of PD generation, free radical damage is believed to play a pivotal role in the development and/or progression of the disease. Recently, PPARs, a class of transcription factors involved in several pathways both in physiological and pathological conditions, have been linked by us and others to neurodegeneration. Particularly, PPARγ and its ligands have been indicated as potential therapeutic targets for the treatment of several pathological conditions associated with neuroinflammation within the CNS. The anti-inflammatory function of PPARγ has attracted attention since agonists exert a broad spectrum of protective effects in several animal models of neurological diseases, including psychiatric diseases. On the other hand a detrimental role for PPARß/δ has been proposed in Alzheimer, being closely related to the decrease of BDNF and Trkfl. On these bases, in this work we used a 6-OHDA hemi-lesioned rat model, inducing loss of dopaminergic neurons, to study the effects of the lesion at three time points from the lesion (1, 2, and 3 weeks), in relevant areas of PD motor symptoms, such as substantia nigra and globus pallidus and in the area of reward and mood control, the nucleus accumbens. In particular, it was studied: (i) the expression of BDNF and its downstream signals; (ii) the modulation of PPARs levels. The results obtained indicate the possible use of a dual PPARß/δ antagonist/PPARγ agonist to counteract primary and secondary signs of PD neurodegeneration.

Involvement of peroxisome proliferator-activated receptor ß/δ (PPAR ß/δ) in BDNF signaling during aging and in Alzheimer disease: possible role of 4-hydroxynonenal (4-HNE).

Aging and many neurological disorders, such as AD, are linked to oxidative stress, which is considered the common effector of the cascade of degenerative events. In this phenomenon, reactive oxygen species play a fundamental role in the oxidative decomposition of polyunsaturated fatty acids, resulting in the formation of a complex mixture of aldehydic end products, such as malondialdehyde, 4-hydroxynonenal, and other alkenals. Interestingly, 4-HNE has been indicated as an intracellular agonist of peroxisome proliferator-activated receptor ß/δ. In this study, we examined, at early and advanced AD stages (3, 9, and 18 months), the pattern of 4-HNE and its catabolic enzyme glutathione S-transferase P1 in relation to the expression of PPARß/δ, BDNF signaling, as mRNA and protein, as well as on their pathological forms (i.e., precursors or truncated forms). The data obtained indicate a novel detrimental age-dependent role of PPAR ß/δ in AD by increasing pro-BDNF and decreasing BDNF/TrkB survival pathways, thus pointing toward the possibility that a specific PPARß/δ antagonist may be used to counteract the disease progression.