The fibrosis-4 score is associated with long-term mortality in different phenotypes of acute heart failure.

BACKGROUND: Fibrosis-4 score (FIB4) was a non-invasive surrogate to estimate the amount of liver scarring in chronic hepatitis. Considering the presence of increased central venous pressure and congestive hepatopathy in patients with decompensated heart failure, we therefore investigated the prognostic values of FIB4 in acute heart failure (AHF) patients. METHOD: Patients hospitalised primarily for HF were drawn from an intramural registry. FIB4 was calculated according to age, aspartate aminotransferase, alanine aminotransferase and platelet count. All-cause mortality up to 5 years after discharge was obtained by linking to the national death registry. RESULTS: Among a total of 1854 participants, 940 patients died during a mean follow-up of 28.3 ± 21.8 months. FIB4 score was related to mortality and the composite of cardiovascular death or HF rehospitalisation, independent of age, sex, left ventricular ejection fraction, left atrial dimension, sodium and haemoglobin levels, estimated glomerular filtration rate, comorbidities, and medications [hazard ratio and 95% confidence interval of mortality: 1.009 (1.002-1.015), and the composite of cardiovascular death or HF hospitalisation: 1.020 (1.010-1.031)]. The prognostic value of FIB4 was predominantly in the subjects with heart failure and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF), or coronary artery disease (CAD) than the counterparts [interaction p-value <0.001, and 0.004, respectively]. CONCLUSIONS: FIB4 was an independent predictor of survival in AHF patients, irrespective of the phenotypes of HF. The higher predictive value of mortality of FIB4 was observed in the subjects with HFpEF, HFmrEF or CAD.

Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats.

Neonatal lipopolysaccharide (LPS) exposure-induced brain inflammation resulted in motor dysfunction and brain dopaminergic neuronal injury, and increased the risks of neurodegenerative disorders in adult rats. Our previous studies showed that intranasal administration of insulin-like growth factor-1 (IGF-1) protects against LPS-induced white matter injury in the developing rat brain. To further examine whether IGF-1 protects against LPS-induced brain neuronal injury and neurobehavioral dysfunction, recombinant human IGF-1 (rhIGF-1) at a dose of 50 µg/pup was administered intranasally 1 h following intracerebral injection of LPS (1 mg/kg) in postnatal day 5 (P5) Sprague-Dawley rat pups. Neurobehavioral tests were carried out from P7 to P21, and brain neuronal injury was examined at P21. Our results showed that LPS exposure resulted in disturbances of motor behaviors in juvenile rats. Moreover, LPS exposure caused injury to central catecholaminergic neurons, as indicated by a reduction of tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN), ventral tegmental area (VTA) and olfactory bulb (OB), and brain noradrenergic neurons, as indicated by a reduction of TH immunoreactivity in the locus coeruleus (LC) of the P21 rat brain. The LPS-induced reduction of TH+ cells was observed at a greater degree in the SN and LC of the P21 rat brain. Intranasal rhIGF-1 treatment attenuated LPS-induced central catecholaminergic neuronal injury and motor behavioral disturbances, including locomotion, beam walking test and gait analysis. Intranasal rhIGF-1 administration also attenuated LPS-induced elevation of IL-1ß levels and numbers of activated microglia, and cyclooxygenase-2+ cells, which were double labeled with TH+ cells in the SN, VTA, OB and LC of the P21 rat brain. These results suggest that IGF-1 may provide protection against neonatal LPS exposure-induced central catecholaminergic neuronal injury and motor behavioral disturbances, and that the protective effects are associated with the inhibition of microglia activation and the reduction of neuronal oxidative stress by the suppression of the neuronal cyclooxygenase-2 expression.

Beyond prevalence: significance and differential impact of echocardiographic abnormalities in dialysis patients.

BACKGROUND: Echocardiography is commonly used to assess hydratation status and cardiac function in kidney failure patients, but the impact of structural or functional abnormalities on the prognosis of kidney failure patients was yet to be investigated. This study aimed to investigate the prevalence and clinical significance of echocardiographic abnormalities in kidney failure patients. METHODS: This study included 857 kidney failure patients who underwent echocardiography at dialysis initiation. Patients were followed up for a median of 4.2 years for the occurrence of major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Among the 857 patients studied, 77% exhibited at least one echocardiographic abnormality. The most common abnormalities were left ventricular hypertrophy and left atrial enlargement, but they were not significantly correlated with poor outcomes. Instead, the primary predictors of both major adverse cardiovascular events and mortality in kidney failure patients were left ventricular systolic function, right ventricular systolic function, left ventricular volume index, and valvular abnormalities. Although diastolic dysfunction was linked to major adverse cardiovascular events, it was not associated with mortality. Furthermore, the study revealed that increased left ventricular volume index and left ventricular systolic dysfunction had a more significant impact on peritoneal dialysis (PD) patients than on hemodialysis (HD) patients. CONCLUSION: This study provides insights into the echocardiographic abnormalities and their association with adverse outcomes in kidney failure patients, which can help clinicians optimize the management of patients and closely monitor possible high-risk populations.

Clinical characteristics of neutropenic patients under antithyroid drug: Twelve-year experience in a medical center.

BACKGROUND: Thionamide-induced agranulocytosis (TiA) is a rare adverse event with a reported incidence of approximately 0.1% to 1.75%. Prompt recognition of TiA is critical to reduce the mortality rate. However, the differential diagnosis between cases of TiA and non-TiA neutropenia can be challenging due to the potential simultaneous involvement of other causes of neutropenia, such as concomitant chemotherapy, liver dysfunction, or infection. The aim of the present study was to investigate the possible factors associated with the development of TiA. METHODS: This was a retrospective cohort study of patients treated with antithyroid drugs (ATDs) in Taipei Veterans General Hospital, Taipei, Taiwan, from 2006 to 2018. Patients who developed a neutropenic event during treatment with ATDs were identified from their medical records. The diagnosis of TiA was based on the following: (1) development of neutropenia during treatment or within 7 days after previous exposure to the same ATDs; (2) complete resolution of neutropenia within 1 month after discontinuation of the culprit drug with an absolute neutrophil count (ANC) >1500/µL; and (3) exclusion of other causes of neutropenia. The incidence and risk factors of TiA were analyzed and compared with those of non-TiA neutropenia. RESULTS: Among 6644 patients treated with ATDs, 66 (mean age: 53 ± 15 years; 16.2% men) developed a neutropenic event and 20 were diagnosed with TiA (incidence: 0.3%). In the univariate analysis, compared with non-TiA neutropenia, TiA was associated with a lower Charlson Comorbidity Index, shorter treatment duration, lower cumulative ATD dosage, higher ATD dosage, higher ANC, and higher levels of free T4 at the time of the neutropenic event. In the multivariate logistic regression analysis, after adjusting for age, gender and the time to neutropenia, the cumulative ATD dose to neutropenia and ATD dosage at the time of the neutropenic event, Charlson Comorbidity Index, free T4 levels (odds ratio [OR], 4.44; 95% CI, 1.48-13.25), and ANC (OR, 1.00; 95% CI, 1.00-1.01) remained independently associated with TiA. CONCLUSION: Patients with TiA were more likely to have higher levels of free T4 and ANC at the time of the neutropenic event vs those with non-TiA neutropenia.