High neutrophil-to-lymphocyte ratio as an early sign of cardiotoxicity in breast cancer patients treated with anthracycline.

BACKGROUND: Cardiotoxicity, defined mainly as left ventricle (LV) dysfunction, is a significant side effect of anthracyclines (ANT) therapy. The need for an early simple marker to identify patients at risk is crucial. A high neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in cancer patients; however, its role as a predictor for cardiotoxicity development is unknown. OBJECTIVE: Evaluating whether elevated NLR, during ANT exposure, plays a predictive role in the development of cardiotoxicity as defined by LV global longitudinal strain (LV GLS) relative reduction (≥10%). METHODS AND RESULTS: Data were prospectively collected as part of the Israel Cardio-Oncology Registry. A total of 74 female patients with breast cancer, scheduled for ANT therapy were included. NLR levels were assessed at baseline (T1) and during ANT therapy (T2). All patients underwent serial echocardiography at baseline (T1) and after the completion of ANT therapy (T3). NLR ≥ 2.58 at T2 was found to be the optimal predictive cutoff for LV GLS deterioration. A relative LV GLS reduction ≥10% was significantly more common among patients with high NLR (50% vs. 20%, p = .009). NLR ≥ 2.58 at T2 increases the risk for LV GLS reduction by fourfold (odds ratio [OR]: 4.63, 95% confidence interval [CI]: 1.29-16.5, p = .02), with each increase of 1-point NLR adding an additional 15% risk (OR: 1.15, 95% CI: 1.01-1.32, p = .046). CONCLUSIONS: Our study provides novel data that high NLR levels, during ANT exposure, have an independent association with the development of LV dysfunction. Routine surveillance of NLR may be an effective means of risk-stratifying

The impact of normal range estimated glomerular filtration rate on mortality in selected patients undergoing coronary angiography - A long-term follow-up

Background Estimated glomerular filtration rate (eGFR) predicts mortality and adverse cardiovascular events in people with chronic kidney disease. The significance of eGFR within the normal range and its long-term effect on clinical adverse events is unknown. We examined the effect of normal range or mildly reduced eGFR on long-term mortality in a large prospective registry. Methods The study included consecutive patients undergoing clinically-driven coronary angiography who had an eGFR ≥60 ml/min/1.73 m2. Baseline clinical characteristics were assessed, and patients were followed-up for the occurrence of all-cause mortality. Cox regression analysis was used to evaluate the impact of eGFR. Results A total of 4186 patients were recruited. Median follow-up time was 2883 days (7.9 years). Mean age was 62.0 ± 11.3 years with 77.4% males. Clinical presentation included acute coronary syndrome and stable angina. In a multivariable model adjusted for possible confounding factors, decreasing eGFR within the normal and mildly reduced range was inversely associated with long-term all-cause mortality with a hazard ratio (HR) of 1.32 for every decrease of 10 ml/min/1.732in eGFR. Compared to eGFR > 100 ml/min/1.732, there was a graded association between lower eGFR values and increased long term mortality with a HR of 1.16 (0.59-2.31) for eGFR 90-100 ml/min/1.732, HR 1.54 (0.81-2.91) for eGFR 80-90 ml/min/1.732, HR 2.62 (1.41-4.85) for eGFR 70-80 ml/min/1.732and HR 2.93 (1.58-5.41) for eGFR 60-70 ml/min/1.732. Conclusion eGFR within the normal and mildly reduced range is an independent predictor of long-term all-cause mortality in selected patients undergoing clinically driven coronary angiography

Pituitary MRI Features in Acromegaly Resulting From Ectopic GHRH Secretion From a Neuroendocrine Tumor: Analysis of 30 Cases.

CONTEXT: Ectopic acromegaly is a consequence of rare neuroendocrine tumors (NETs) that secrete GHRH. This abnormal GHRH secretion drives GH and IGF-1 excess, with a clinical presentation similar to classical pituitary acromegaly. Identifying the underlying cause for the GH hypersecretion in the setting of ectopic GHRH excess is, however, essential for proper management both of acromegaly and the NET. Owing to the rarity of NETs, the imaging characteristics of the pituitary in ectopic acromegaly have not been analyzed in depth in a large series. OBJECTIVE: Characterize pituitary magnetic resonance imaging (MRI) features at baseline and after NET treatment in patients with ectopic acromegaly. DESIGN: Multicenter, international, retrospective. SETTING: Tertiary referral pituitary centers. PATIENTS: Thirty ectopic acromegaly patients having GHRH hypersecretion. INTERVENTION: None. MAIN OUTCOME MEASURE: MRI characteristics of pituitary gland, particularly T2-weighted signal. RESULTS: In 30 patients with ectopic GHRH-induced acromegaly, we found that most patients had hyperplastic pituitaries. Hyperplasia was usually moderate but was occasionally subtle, with only small volume increases compared with normal ranges for age and sex. T2-weighted signal was hypointense in most patients, especially in those with hyperplastic pituitaries. After treatment of the NET, pituitary size diminished and T2-weighted signal tended to normalize. CONCLUSIONS: This comprehensive study of pituitary MRI characteristics in ectopic acromegaly underlines the utility of performing T2-weighted sequences in the MRI evaluation of patients with acromegaly as an additional tool that can help to establish the correct diagnosis

Viral infections in type 1 diabetes mellitus-why the beta cells?

Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection-particularly by enteroviruses (for example, coxsackievirus)-as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.SCOPUS: re.jinfo:eu-repo/semantics/publishe