Efficacia della combinazione lapatinib-capecitabina in una paziente con metastasi plurime da carcinoma mammario HER2-positivo

HER2 overexpression occurs in about 15-20% of breast cancer cases and is associated with rapid tumor growth. The introduction in clinical practice of several drugs inhibiting the biological activity of HER2, such as trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1) and lapatinib, has clearly modified the prognosis for these patients. The combination of the two inhibitors of HER2, trastuzumab and pertuzumab, with a taxane (paclitaxel or docetaxel), is currently considered the first choice treatment for patients affected by HER2-positive metastatic breast cancer, whereas T-DM1 is considered the preferred treatment after the failure of first line therapy. We present the case of a 50-year-old woman affected by HER2-positive breast cancer with bone, hepatic, pulmonary and encephalic metastases, resistant both to trastuzumab-pertuzumab double-block treatment and to T-DM1, but sensitive to third line therapy to the combination lapatinib-capecitabine with a clinical response both for visceral and cerebral metastases (Oncology)

Position paper of the Italian Chapter, International Society Cardiovascular Ultrasound

SummaryBackground Over the last two decades the interest on patent foramen ovale (PFO) as a cause of cardioembolism in cryptogenic stroke has tremendously increased, thanks to the availability of better techniques to diagnose cardiac right-to-left shunt by ultrasounds and of percutaneous means of PFO treatment with interventional techniques. Many studies have been published that have attempted to define diagnostic methodology, prognosis, and optimal treatment (pharmacological or percutaneous closure) of PFO patients with cryptogenic stroke. Unfortunately, even today, definitive evidence is still lacking, and clinical management is not consistent among cardiologists. Aims This review aims to evaluate the role of PFO in cryptogenic stroke, the diagnostic accuracy of transcranial Doppler, contrast transthoracic and transesophageal echocardiography in the diagnosis of left–fright shunt and PFO; and discuss the indications to medical treatment and percutaneous closure of PFO. Methods All studies published in the literature on PFO and cryptogenic stroke are considered and discussed. Results We define an appropriate diagnostic and clinical management of PFO patients with cryptogenic stroke. Conclusion After many years of interest on PFO and many concluded studies, there are still no definitive data. However, we are on good track for an appropriate management of PFO patients and cryptogenic stroke

Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine

Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids and are broadly distributed in the plant kingdom. Many plants that contain RIPs are listed in the pharmacopoeias of folk medicine all over the world, mostly because of their toxicity. This review analyses the position occupied in traditional medicine by plants from which RIPs have been isolated. The overview starts from the antique age of the Mediterranean area with ancient Egypt, followed by the Greek and Roman classic period. Then, the ancient oriental civilizations of China and India are evaluated. More recently, Unani medicine and European folk medicine are examined. Finally, the African and American folk medicines are taken into consideration. In conclusion, a list of RIP-expressing plants, which have been used in folk medicine, is provided with the geographical distribution and the prescriptions that are recommended by traditional healers. Some final considerations are provided on the present utilization of such herbal treatments, both in developing and developed countries, often in the absence of scientific validation. The most promising prospect for the medicinal use of RIP-expressing plants is the conjugation of purified RIPs to antibodies that recognise tumour antigens for cancer therapy

Left ventricular diastolic dysfunction in normotensive postmenopausal women with type 2 diabetes mellitus

Background: The prevalence of heart failure among diabetic patients is high, also in those with normal blood pressure and without coronary artery disease, even when electrocardiogram (ECG) is normal. The goal of our study was to assess the prevalence of left ventricular diastolic dysfunction (LVDD) among diabetic women (DW) and its correlation with glycosylated hemoglobin (HbA1c) levels, obesity status, and ECG parameters. Methods: A group of 456 consecutive normotensive postmenopausal women affected by type 2 diabetes, diagnosed over 5 years, were enrolled. One hundred normotensive non-diabetic postmenopausal women were included as a control group (CG). Rest ECG and trans-thoracic echocardiogram and Doppler were performed. Results: LVDD was present in 103 (23.3%) out of 456 DW, and 8 out of 100 women in CG (8%), p < 0.001. There was no difference in mean age between the two groups: 56 ± 13 and 55 ± 3, respectively (p = 0.3). There were 191 (41.9%) DW with body mass index (BMI) > 30 kg/m2. Among those, there were 56 (12.3%) with significant prevalence of LVDD, while there were 49 (10.7%) with BMI < 30 kg/m2, p < 0.005. DW with HbA1c > 7.5% comprised a group of 243 (53.3%) patients. Among those, there were 45 (9.9%) with higher prevalence of LVDD, and 15 (3.3%) with HbA1c < 7.5%, p < 0.01. Out of a group of 147 (32.2%) DW with abnormal ECG , 21 had LVDD (4.6%), p = 0,1, and 84 (18.8%) had LVDD with normal ECG. Conclusions: Our data prove a high prevalence of LVDD in asymptomatic diabetic postmenopausal women. This finding is closely related with HbA1c levels and obesity status, not with abnormal ECG, which is a unique cardiologic test recommended by current guidelines in all diabetic patients. We conclude that early detection of high level of HbA1c and obesity (30 kg/m2) may identify women with major risk to develop LVDD. Furthermore, a simple ECG, when normal, is not enough to assess a normal LV diastolic function.

Left ventricular diastolic dysfunction in normotensive postmenopausal women with type 2 diabetes mellitus.

Background The prevalence of heart failure among diabetic patients is high, also in those with normal blood pressure and without coronary artery disease, even when electrocardiogram (ECG) is normal. The goal of our study was to assess the prevalence of left ventricular diastolic dysfunction (LVDD) among diabetic women (DW) and its correlation with glycosylated hemoglobin (HbA1c) levels, obesity status, and ECG parameters. Methods : A group of 456 consecutive normotensive postmenopausal women affected by type 2 diabetes, diagnosed over 5 years, were enrolled. One hundred normotensive non-diabetic postmenopausal women were included as a control group (CG). Rest ECG and trans-thoracic echocardiogram and Doppler were performed. Results : LVDD was present in 103 (23.3%) out of 456 DW, and 8 out of 100 women in CG (8%), p < 0.001. There was no difference in mean age between the two groups: 56 ± 13 and 55 ± 3, respectively (p = 0.3). There were 191 (41.9 %) DW with body mass index (BMI) > 30 kg/m2. Among those, there were 56 (12.3%) with significant prevalence of LVDD, while there were 49 (10.7%) with BMI < 30 kg/m2, p < 0.005. DW with HbA1c > 7.5% comprised a group of 243 (53.3%) patients. Among those, there were 45 (9.9%) with higher prevalence of LVDD, and 15 (3.3%) with HbA1c < 7.5%), p < 0.01. Out of a group of 147 (32.2%) DW with abnormal ECG , 21 had LVDD (4.6%), p = 0,1, and 84 (18.8%) had LVDD with normal ECG. Conclusions: Our data prove a high prevalence of LVDD in asymptomatic diabetic postmenopausal women. This finding is closely related with HbA1c levels and obesity status, not with abnormal ECG, which is a unique cardiologic test recommended by current guidelines in all diabetic patients. We conclude that early detection of high level of HbA1c and obesity (30 kg/m2) may identify women with major risk to develop LVDD. Furthermore, a simple ECG, when normal, is not enough to assess a normal LV diastolic function

Environmental DNA metabarcoding reveals the effects of seafloor litter and trawling on marine biodiversity

Environmental DNA (eDNA) techniques are emerging as promising tools for monitoring marine communities. However, they have not been applied to study the integrated effects of anthropogenic pressures on marine biodiversity. This study examined the relationships between demersal community species composition, key environmental features, and anthropogenic impacts such as fishing effort and seafloor litter using eDNA data in the central Tyrrhenian Sea. The results indicated that both fishing effort and seafloor litter influenced species composition and diversity. The adaptive traits of marine species played a critical role in their response to debris accumulation and fishing. Mobile species appeared to use relocation strategies, while sessile species showed flexibility in the face of disturbance. Epibiotic species relied on passive transport. The use of eDNA-based methods is a valuable resource for monitoring anthropogenic impacts during scientific surveys, enhancing our ability to monitor marine ecosystems and more effectively assess the effects of pollution

Dyskerin Downregulation Can Induce ER Stress and Promote Autophagy via AKT-mTOR Signaling Deregulation

: Dyskerin is an evolutionarily conserved nucleolar protein implicated in a wide range of fundamental biological roles, including telomere maintenance and ribosome biogenesis. Germline mutations of DKC1, the human gene encoding dyskerin, cause the hereditary disorders known as X-linked dyskeratosis congenita (X-DC). Moreover, dyskerin is upregulated in several cancers. Due to the pleiotropic functions of dyskerin, the X-DC clinical features overlap with those of both telomeropathies and ribosomopathies. In this paper, we evaluate the telomerase-independent effects of dyskerin depletion on cellular physiology by using inducible DCK1 knockdown. This system allows the downregulation of DKC1 expression within a short timeframe. We report that, in these cellular systems, dyskerin depletion induces the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum, which in turn induces the activation of the PERK branch of the unfolded protein response. We also demonstrate that the PERK-eIF2a-ATF4-CHOP signaling pathway, activated by dyskerin downregulation, triggers a functional autophagic flux through the inhibition of the PI3K/AKT/mTOR pathway. By revealing a novel unpredicted connection between the loss of dyskerin, autophagy and UPR, our results establish a firm link between the lowering of dyskerin levels and the activation of the ER stress response, that plays a key role in the pathogenesis of several diseases

Primary Prevention Of Cardiovascular Risk In Octogenarians By Risk Factors Control

Primary prevention of cardiovascular events in older adults is a relevant problem, because of lack of evidence for safe and efficacious therapy, its costs and elderly quality of life, Italy's aging population is constantly increasing, so cardiovascular disease (CVD) primary prevention in the elderly is a prime objective. Life expectancy has dramatically increased over the last 2 decades,the proportion of individuals aged 80 years and older has grown rapidly in Europe and United States,but cost / effective ratio of CVD prevention through risk factors control is debated. It is therefore important to implement cardiovascular risk factors estimation in the elderly to maximize quality of life of patients and to lengthen their healthy life expectancy, choosing the better treatment for each patient sharing the choice with himself when it is possible, always remembering that elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of CVD prevention therapy. Anyway CVD are not an inevitable concomitant of aging. Sometimes autopsy in the elderly reveals atheroma-free coronary arteries,a normal-sized heart and unscarred valves. All primary prevention strategy decisions should consider estimated life expectancy and overall function not only cardiovascular event risks, magnitude and time to benefit or harm, potentially altered adverse effect profiles, and informed patient preferences.CVD primary prevention need to be more implemented in the elderly, this might contribute to improve health status and quality of life in this growing population if correctly performed

Prevalence and determinants of permanent atrial fibrillation in post-menopausal hypertensive women

Objective. We studied the prevalence and major predisposing factors of permanent atrial fibrillation (PAF) in a population of hypertensive post-menopausal (HPMW) women. Materials and Methods. We enrolled 125 consecutive HPMW with PAF, 125 HPMW in sinus rhythm were the control group (CG). Women with valvular heart disease, coronary artery disease, WPW syndrome, left ventricular (LV) ejection fraction <45% and thyroid disorders were excluded. The mean age was similar: 53±3 years for women on PAF and 51±6 for women with sinus rhythm (P<0.45). All women who underwent M-B mode echocardiography, LV mass, function, and left atrial (LA) volume were assessed according to American Society of Echocardiography guidelines. Diabetes was assessed according to American Diabetes Association guidelines. Results. In a population of 8945 consecutive women, 4497 were hypertensive (50.2%) and 125 were on PAF (0.3%). We observed a highly significant difference between the two groups in relation to obesity: 31 (24.8%) in the AF-group and 15 (12%) in CG, Chi-squared 10, P<0.0016, OR 2.8, 95%; to increased LA volume: 37 (29.6%) in AF-group and 13 (10.4%) in CG, Chi-squared 14.4, P<0.0001, OR 3.62, 95%. No difference in diabetes: 30 (24%) in AFgroup and 28 (22.4%) in CG, Chi-squared 0.09, P<0.76, OR 1.09, 95%, and LV diastolic dysfunction (LVDD): 24 (19.2%) in AF-group and 20 (16%) in CG, Chi-squared 0.44, P<0.5, OR 1.25, 95%. In contrast to what was expected LV hypertrophy had a lower incidence of 59 (47.2%) in AF-group than in CG 84 (67.2%), Chi-squared 10.21, P<0.0014, OR 0.44, 95%. Conclusions. The prevalence of PAF in HPMW is not elevated, obesity and increased LA volume are strong determinants of PAF, not depending on age. LVDD, LV hypertrophy, and diabetes status seem not to play a relevant role as PAF determinants

Nutraceuticals and dyslipidaemia: Beyond the common therapeutics

Dyslipidaemia accelerates the atherosclerotic process and its morbid consequences; statins represent the evidence-based treatment of choice for reducing low-density lipoprotein cholesterol levels and decreasing cardiovascular events. Unfortunately, statins are frequently not available for several reasons, including intolerance, side effects or, simply, patient preference. Nutraceuticals and functional food ingredients that are beneficial to vascular health may represent useful compounds that are able to reduce the overall cardiovascular risk induced by dyslipidaemia by acting parallel to statins or as adjuvants in case of failure or in situations where statins cannot be used. The mechanisms underlying such actions are not fully understood but may be related to reducing 7a-hydroxylase, increasing faecal excretion of cholesterol, decreasing 3-hydroxy-3-methylglutaryl-CoA reductase mRNA levels or reducing the secretion of very low-density lipoprotein. This contribution provides an overview of the mechanism of action of nutraceuticals and functional food ingredients on lipids and their role in the management of lipid disorders