Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis.

Rationale: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. Objective: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. Methods and Results: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors-matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. Conclusions: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.

Breakthroughs in the treatment of advanced squamous-cell NSCLC: not the neglected sibling anymore?

During the last years, translational research has contributed in many advances in the treatment of non-small cell lung cancer (NSCLC) discovering genetic alternations or recognizing the immuno-escape and neo-angiogenesis of lung cancer. Although the majority of these advances took place in the non-squamous histological subtype, therapeutic options for patients diagnosed with advanced squamous cell lung cancer (SqCLC) have been also enriched significantly with the addition of nab-paclitaxel in the conventional chemotherapy; the introduction of necitumumab, afatinib and erlotinib in the inhibition of epidermal growth factor receptor (EGFR) axis and of ramucirumab in the inhibition of VEGF-induced angiogenesis and last with the approvals of nivolumab, pembrolizumab atezolizumab and durvalumab soon in the promising field of immunotherapies. Agents targeted various other pathways including FGFR, IGF-1, PI3K, CDK4/6, MET and PARP inhibitors are under investigation in order to open new prospects in the treatment of SqCLC. In this review, we present all published data that led to recent approvals for the treatment of advanced SqCLC and all ongoing clinical trials that keep searching for new molecular targets following a more-personalized approach.

Acute and long-term hemodynamic effects of sesame oil consumption in hypertensive men.

The possible effects of sesame oil on hemodynamics are unknown. The aim of the study was to investigate the acute and long-term effects of sesame oil on hemodynamic responses in hypertensive men. The authors enrolled 30 hypertensive men in a two-phase study. In the first phase, patients consumed 35 g of either sesame oil or control oil. Central and peripheral blood pressure, pulse wave velocity, augmentation index (AI), C-reactive protein, tumor necrosis factor α, malonydealdehyde, and total antioxidant capacity (TAC) were assessed at fast and 2 hours postprandially. In the second phase, patients consumed 35 g of either sesame oil or control oil daily for 2 months. The above-mentioned parameters were assessed before and following 15, 30, and 60 days of oil consumption. Sesame oil decreased central and peripheral diastolic pressures 1 hour postprandially (P=.006). Fifteen days of sesame oil intake decreased peripheral systolic blood pressure (P=.016) and heart rate-corrected AI75 (P=.017) and increased TAC (P=.007). This is the first study to demonstrate a favorable acute and long-term effect of sesame oil on hemodynamics in hypertensive men. Further research is warranted to establish the potential protective role of sesame oil.

Arterial wave reflections during the menstrual cycle of healthy women: a reproducibility study.

Increased wave reflection is an independent factor associated with cardiovascular diseases, risk, and mortality. The influence of the menstrual cycle on wave reflections and particularly on the reproducibility of their measurement has never been examined. The aim of the present study was to examine the reproducibility and variability of wave reflection indices in premenopausal healthy women during their menstrual cycle. Thirty-two women were examined at 3 phases of their menstrual cycle: days 1 to 2 (menstrual phase), days 6 to 14 (late follicular), and days 4 to 7 after ovulation (early luteal phase). Applanation tonometry of the radial artery and aortic pulse wave analysis were performed for the calculation of augmentation pressure, augmentation index, and timing of reflected waves. Reproducibility of these measures was evaluated by intraclass correlation coefficient and Bland-Altman analysis, whereas ANOVA was performed to assess their variability during the menstrual cycle. The SD of augmentation index differences between repeated measurements within the menstrual cycle ranged from 7.6% to 9.9%. Bland-Altman analysis indicated no evidence of systemic bias and no trend for the reproducibility of measurements to vary with their underlying mean value. Intraclass correlation coefficient indicated a moderate reproducibility of augmentation index and augmentation pressure (>0.80) and a rather low reproducibility for timing of reflected waves (0.43). Mean augmentation pressure, augmentation index, and timing of reflected waves did not vary significantly during the menstrual cycle (ANOVA). Measurement of wave reflections at the same phase of the menstrual cycle or statistical adjustment could be suggested for optimal study design and data interpretation.