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Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical research. Although a precise and unique cut-off value has not been yet found, its role as a flag of immune system homeostasis is well established. NLR has a well-known prognostic value and independently correlates with mortality in the general population and in several specific subsets of disease (sepsis, pneumonia, COVID-19, cancer, etc.). Moreover, NLR was recently considered as part of the decision-making processes concerning the admission/recovery of patients with COVID-19 pneumonia. This review aims to provide an overview of the main use of this biomarker, focusing on the pathophysiology and the molecular basis underlying its central role as a reliable mirror of inflammatory status and adaptive immunity.

Triple-negative breast cancer (TNBCs) account for 15–20% of all breast cancers and represent the most aggressive subtype of this malignancy. Early tumor relapse and progression are linked to the enrichment of a sub-fraction of cancer cells, termed breast tumor-initiating cells (BTICs), that undergo epithelial to mesenchymal transition (EMT) and typically exhibit a basal-like CD44 high /CD24 low and/or ALDH1 high phenotype with critical cancer stem-like features such as high self-renewal capacity and intrinsic (de novo) resistance to standard of care chemotherapy. One of the major mechanisms responsible for the intrinsic drug resistance of BTICs is their high ALDH1 activity leading to inhibition of chemotherapy-induced apoptosis. In this study, we demonstrated that aurora-A kinase (AURKA) is required to mediate TGF-β-induced expression of the SNAI1 gene, enrichment of ALDH1 high BTICs, self-renewal capacity, and chemoresistance in TNBC experimental models. Significantly, the combination of docetaxel (DTX) with dual TGF-β and AURKA pharmacologic targeting impaired tumor relapse and the emergence of distant metastasis. We also showed in unique chemoresistant TNBC cells isolated from patient-derived TNBC brain metastasis that dual TGF-β and AURKA pharmacologic targeting reversed cancer plasticity and enhanced the sensitivity of TNBC cells to DTX-based-chemotherapy. Taken together, these findings reveal for the first time the critical role of AURKA oncogenic signaling in mediating TGF-β-induced TNBC plasticity, chemoresistance, and tumor progression.

We investigated seasonal prevalence of hyponatremia in the emergency department (ED). A cross-sectional study using clinical chart review. University Hospital ED, with approximately 28 000 patient visits a year. We reviewed 15 049 patients, subdivided in 2 groups: the adult group consisting of 9822 patients aged between 18 and 64years old and the elderly group consisting of 5227 patients aged over 65years presenting to the ED between January 1st, 2014 and December 31st, 2015. Emergency patients were evaluated for the presence of hyponatremia by clinical chart review. Hyponatremia was defined as a serum sodium level<135mmol/l. Mean monthly prevalence of hyponatremia was of 3.74±0.5% in the adult group and it was significantly increased to 10.3±0.7% in the elderly group (p<0.05 vs adults). During the summer, hyponatremia prevalence was of 4.14±0.2% in adult and markedly increased to 12.52±0.7% (zenith) in elderly patients (p<0.01 vs adult group; p<0.05 vs other seasons in elderly group). In the elderly group, we reported a significant correlation between weather temperature and hyponatremia prevalence (r: 0.491; p<0.05). We observed a major influence of climate on the prevalence of hyponatremia in the elderly in the ED. Decline in renal function, salt loss, reduced salt intake and increased water ingestion could all contribute to developing hyponatremia in elderly patients during the summer. These data could be useful for emergency physicians to prevent hot weather-induced hyponatremia in the elderly.

Left ventricular mass monitoring in the follow-up of dialysis patients: Prognostic value of left ventricular hypertrophy progression. Regression of left ventricular hypertrophy (LVH) in the setting of a well-planned intervention study has been associated with longer survival in hemodialysis patients. Whether changes in left ventricular mass (LVM) in clinical practice predict survival and cardiovascular events in these patients is still unknown. In a prospective study in 161 hemodialysis patients we tested the prognostic value of changes in LVM on survival and incident cardiovascular events. Echocardiography was performed twice, 18 ± 2 SD months apart. Changes in LVM occurring between the first and the second echocardiographic study were then used to predict mortality and cardiovascular events during the ensuing 29 ± 13months. The prognostic value of LVM changes was tested in a multivariate Cox's model with LVM index (LVMI) (expressed as LVM/height2.71), included as a covariate to control for regression to the mean. The rate of increase of LVMI was significantly (P = 0.029) higher in patients with incident cardiovascular events than in those without such events. Accordingly, cardiovascular event-free survival in patients with changes in LVMI below the 25th percentile was significantly (P = 0.004) higher than in those with changes above the 75th percentile. In a multiple Cox regression analysis, including age, diabetes, smoking, homocysteine, 1g/m2.7/month increase in LVMI was associated with a 62% increase in the incident risk of fatal and nonfatal cardiovascular events [hazard ratio 1.62 (95% CI 1.13–2.33), P = 0.009]. Changes in LVMI have an independent prognostic value for cardiovascular events and provide scientific support to the use of repeated echocardiographic studies for monitoring cardiovascular risk in dialysis patients.

Purpose To evaluate adherence to abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Methods In an observational prospective cohort study, we monitored patients with mCRPC for their adherence to abiraterone or enzalutamide in the pre- or post-chemotherapy setting. Results Fifty-eight patients with median age of 76 years (range 56–94), age-adjusted Charlson comorbidity score of 10 (range, 4–15), and geriatric G8 score of 14 (range, 6–17) were enrolled. Twenty-two (38%) patients were treated with abiraterone and 36 (62%) with enzalutamide, while forty-two (72%) were in the pre-chemotherapy setting. Forty-seven patients (81%) had a caregiver. Based on the pill counting, a non-adherence rate of 4.8% and 6.2% was observed for the whole period and the first 3 months, respectively, without a statistically significant difference between abiraterone and enzalutamide cohorts. A lower non-adherence rate (1.3%) was reported by patients during the whole period, mainly due to a misperception (77%) and forgetfulness (19%). Non-adherence rate to the fulfilling of the clinical diary was 38% for the whole period. Non-adherence in the whole period was related to the radiological response ( p  = 0.03) and geriatric G8 score ( p  = 0.005). By the receiver operating characteristic (ROC) curve based on the radiological response, non-adherence cut-off was 1.87% ( p  = 0.04). By this non-adherence cut-off, the G8 cut-off was 14.75 ( p  = 0.0003). Conclusion Non-adherence to abiraterone or enzalutamide for mCRPC may have an impact on disease response and be related to patients’ frailty, suggesting their geriatric assessment and clinical interventions to monitor and increase their adherence.

The presence of liver involvement in systemic sclerosis (SSc) is considered atypical, besides the possible coexistence of other autoimmune hepatic disorders. However, the occurrence of portal hypertension and, more specifically, of the syndromes called idiopathic portal hypertension (IPH) and regenerative nodular hyperplasia (RNH) have been anecdotally reported in the literature for SSc patients. We described a case of SSc woman complicated by IPH; moreover, we reviewed the literature on the topic. A 61-year-old female SSc patient was admitted to our hospital because of the onset of ascites. SSc, as a limited skin subset of disease with anticentromere antibodies, was diagnosed 11 years previously, with no significant visceral involvement. We excluded possible causes of portal hypertension, namely chronic infections, autoimmune hepatic diseases, neoplasia, thrombosis of portal vein, and Budd–Chiari syndrome. Finally, IPH was diagnosed. A review of the literature identified a number of case reports or case series that described IPH in the course of SSc. No specific SSc pattern linked to IPH emerged, even though reports from the literature often described the limited skin subset. Coexistence of prothrombotic states and overlap with other hepatic diseases could facilitate IPH onset. Besides being a rare condition, the onset of IPH in SSc patients is an occurrence that should be taken into account.

The diagnostic assessment of patients with Interstitial Lung Disease (ILD) can be challenging due to the large number of possible causes. Moreover, the diagnostic approach can be limited by the severity of the disease, which may not allow invasive exams. To overcome this issue, the referral centers for ILD organized Multidisciplinary Teams (MDTs), including physicians and experts in complementary discipline, to discuss the management of doubtful cases of ILD. MDT is currently considered the gold standard for ILD diagnosis, but it is not often simple to organize and, furthermore, rheumatologists are still not always included. In fact, even if rheumatologic conditions represent a common cause of ILD, they are sometimes difficult to recognize, considering the variegated clinical features and their association with all possible radiographic patterns of ILD. The first objective of this review is to describe the clinical, laboratory, and instrumental tests that can drive a diagnosis toward a possible rheumatic disease. The secondary objective is to propose a set of first-line tests to perform in all patients in order to recognize any possible rheumatic conditions underlying ILD.

(1) Background: Circulating micro-RNAs (miRNAs) modulate the expression of molecules in diabetes. We evaluated the expression of serum miRNA-195-5p and -451a in diabetic patients with ischemic stroke and correlated them with two markers of brain tissue integrity. (2) Methods: Seventy-eight subjects with acute ischemic stroke (AIS) or transient ischemic attack (TIA) (40 with diabetes) were enrolled. Serum miRNA levels, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF-A) were assessed at admission and 24 and 72 h after a post-ischemic stroke, and were compared to 20 controls. (3) Results: Both circulating miRNAs were two-fold up-regulated in diabetic AIS and TIA patients compared to non-diabetics. Their levels progressively decreased at 24 and 72 h in both AIS and TIA patients. Interestingly, in the non-diabetic TIA group, both circulating miRNAs, although higher than the controls, tended to achieve a complete decay after 72 h. Furthermore, miRNA-195-5p and miRNA-451a levels inversely correlated with both BDNF and VEGF-A serum levels. (4) Conclusions: These data show a different profile of both micro-RNAs in diabetic versus non-diabetic patients after acute ischemic stroke, suggesting their pivotal role in cerebrovascular ischemic attack.

Ventricular arrhythmias still represent an important cause of morbidity and mortality, especially in patients with heart failure and reduced left ventricular ejection fraction. Amiodarone is a Class III Vaughan-Williams anti-arrhythmic drug widely used in ventricular arrhythmias for its efficacy and low pro-arrhythmogenic effect. On the other hand, a significant limitation in its use is represented by toxicity. In this review, the pharmacology of the drug is discussed to provide the mechanistic basis for its clinical use. Moreover, all the latest evidence on its role in different clinical settings is provided, including the prevention of sudden cardiac death, implanted cardioverter defibrillators, ischemic and non-ischemic cardiomyopathies. A special focus is placed on everyday clinical practice learning points, such as dosage, indications, and contraindications from the latest guidelines.

Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction and fibroblasts activation. Microvascular disease may be easily observed by means of nailfold capillaroscopy. Recent evidences emphasized also the involvement of large-medium arteries in SSc, mainly in terms of increased stiffness of the vessel wall. The study aims to measure aortic root diameter in a cohort of SSc patients and to correlate echocardiographic findings with the capillaroscopic pictures. We analyzed the clinical records of 125 consecutive SSc patients (M/F 14/111, mean age 55 ± 12.7 years, median disease duration 11 years) referring in 3 second-level rheumatology centers. All subjects underwent to heart ultrasound evaluation and videocapillaroscopic evaluation. At capillaroscopy, the patients with early SSc pattern belonged to the subgroup 1, while those with the active/late patterns (characterized by the reduction of capillary density) belonged to the subgroup 2. We found aortic root dilation in 8 (6.4%) SSc patients, with a mean value of 37.8 ± 1.2 mm (range 37–40 mm). Aortic root dilation was observed in only one patient in the subgroup 1 (1/62, 1.6%) and in 7 cases of the subgroup 2 (7/63, 11.1%; p = 0.03). Our study found a significant association between aortic root dilation and impairment of capillary density at nailfold videocapillaroscopy in SSc patients. We hypothesize that SSc-related microangiopathy revealed by nailfold videocapillaroscopy could mimic that of aortic vasa vasorum, contributing to deteriorate the aortic wall structure and favoring aortic root dilation and stiffening.