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From the data in our possession derived from the literature, it has been shown that men have a high risk and appear to have a specific higher risk of suffering from thromboembolism than women, regardless of age group. Furthermore, at present, this difference between the two sexes has not yet been justified by scientific evidence. Taking this evidence into account, this review was designed to find information in the literature that could be potentially useful and that is crucial to knowledge about the differences between men and women in the genesis of thromboembolic disease. The role of the constitutional and physical factors underlying the difference between the two sexes, the different habitual lifestyles, the role of sex hormones, and what happens in situations such as venous thromboembolism in the course of a neoplastic disease or in the case of pregnancy. We have also focused our efforts on correlating the gender differences between men and women in thromboembolic disease with the dysregulation of the metabolism and the activation of the inflammatory response that often underlies this pathology.

Cancer is a chronic disease with long-term consequences for health and quality of life and is more prevalent among older people. Therefore, comorbidity among cancer patients is commonly observed. Several data indicate that 40% of cancer patients have at least one other chronic condition recorded, and of these, 15% have two or more medical conditions, including cardiovascular disease, obesity and metabolic disease, mental health problems, and muscle-skeletal conditions. There is no gold-standard approach for measuring comorbidity in the context of cancer, especially in recent years, when health systems have dealt with a pandemic emergency that has negatively impacted the management of cancer patients. The purpose of this narrative review is to clarify and provide the necessary insights to optimize the care of cancer patients. Ensuring the continuum of care for cancer patients is of vital importance and is considered a top priority. It is necessary to overcome the model that considers neoplastic pathology as a single morbid condition. Instead, the complexity of a cancer patient’s problems must be considered and related to complex medical conditions. Addressing the problem of comorbidity in cancer more decisively will be a central challenge if we are to avert a crisis in the models of diagnosis and treatment of cancer patients.

Introduction. Viral infections during pregnancy have always been considered to cause complications and adverse events and birth defects during pregnancy. In particular, we do not have any therapeutic or preventive tools aimed at protecting the mother and fetus during the gestational period during pandemics. Methods. The studies were identified by using the PubMed database published until 30 April 2021. The search was performed by using the following keywords: viral infection, SARS-CoV-2, COVID-19, vaccine, pregnancy, gestational period, pandemics, vaccination, complication, adverse events, drugs. Results. It has been reported that viral infections are considered to cause complications and adverse events during pregnancy. In this regard, pregnancy is associated with higher mortality rates and complications during viral infections. In fact, maternal immunization represents a unique approach to protect newborns from several infectious diseases. Conclusion. European Board and College of Obstetrics and Gynecology (EBCOG) and International public health institutions (WHO, CDC) report the recommendations about the use of vaccines during pregnancy.

Dysphagia refers either to the difficulty someone may have with the initial phases of a swallow (usually described as oropharyngeal dysphagia, “OD”) or to the sensation that foods and or liquids are somehow being obstructed in their passage from the mouth to the stomach (usually described as “esophageal dysphagia”). In patients with no indication of a somatic disease or abnormality, psychiatric conditions must be considered as a possible cause of OD. Moreover, diagnosis and treatment of dysphagia are not standardized. There is no universal standard tool for screening or clinical assessment of OD. Education of health professionals on early diagnosis and improvement of therapeutic strategies are mainstays to allow maximal recovery potential in this population. Future studies, clinical trials, clinical evidence and clear guidelines are needed to manage this condition.

Acute kidney injury (AKI) occurs in 3.2 - 9.6% of hospital admissions and in 2.1 - 22.1% of prevalent intensive care unit patients, worldwide. There is a sexual dimorphism in the AKI evolution with implications of sex hormones, endothelin etc. We provide a mini-review on the gender-related differences in the AKI evolution.

Cerebral sinus venous thrombosis (CSVT) is a relatively rare acute disorder of cerebral circulation, but it can potentially be associated with serious sequelae and a poor prognosis. The neurological manifestations associated with it are often not adequately taken into consideration given the extreme variability and nuances of its clinical presentation and given the need for radiological methods suitable for this type of diagnosis. CSVT is usually more common in women, but so far there are little data available in the literature on sex-specific characteristics regarding this pathology. CSVT is the result of multiple conditions and is therefore to be considered a multifactorial disease where at least one risk factor is present in over 80% of cases. From the literature, we learn that congenital or acquired prothrombotic states are to be considered extremely associated with the occurrence of an acute episode of CSVT and its recurrences. It is, therefore, necessary to fully know the origins and natural history of CSVT, in order to implement the diagnostic and therapeutic pathways of these neurological manifestations. In this report, we summarize the main causes of CSVT considering the possible influence of gender, bearing in mind that most of the causes listed above are pathological conditions closely linked to the female sex.

Background. On March 2020, WHO declares the world pandemic by COVID-19. In this report we report the COVID-19 infection, related to male gender, comorbidity and special population. Data resources. We describe the published studies by PubMed, Medscape and Scopus between December 2019 to May 2020. Keywords used: male/man gender, sex differences, COVID-19, comorbidity, diabetes, hypertension, elderly, pregnancy, children. Results. The elderly population and infants are a population at higher risk. The comorbidities are risk factors for the development of a more severe form of disease. There may be a sex predisposition to COVID-19 infection, with men more prone to be affected. 83.9% of COVID-19 patients with chronic kidney disease (CKD) and 57.3% of COVID-19 patients with liver diseases, have a severe disease. Conclusions. Older age, infants, male gender and comorbidity describe a crucial role for severity of COVID-19 disease. Future studies are need for the management of these patients.

Background: A substantial portion of stroke risk remains unexplained, and a contribution from genetic factors is supported by recent findings. In most cases, genetic risk factors contribute to stroke risk as part of a multifactorial predisposition. A major challenge in identifying the genetic determinants of stroke is fully understanding the complexity of the phenotype. Aims: Our narrative review is needed to improve our understanding of the biological pathways underlying the disease and, through this understanding, to accelerate the identification of new drug targets. Methods: We report, the research in the literature until February 2022 in this narrative review. The keywords are stroke, causes, etiopathogenesis, genetic, epigenetic, ischemic stroke. Results: While better risk prediction also remains a long-term goal, its implementation is still complex given the small effect-size of genetic risk variants. Some authors encourage the use of stroke genetic panels for stroke risk assessment and further stroke research. In addition, new biomarkers for the genetic causes of stroke and new targets for gene therapy are on the horizon. Conclusion: We summarize the latest evidence and perspectives of ischemic stroke genetics that may be of interest to the physician and useful for day-to-day clinical work in terms of both prevention and treatment of ischemic stroke.

Background and Aim The impact of hepatitis C virus (HCV) clearance by direct‐acting antiviral agents (DAAs) on HCV‐related extrahepatic manifestations is not well known. We evaluated the effect of viral clearance on metabolic and renal parameters. Methods In this prospective study, HCV patients who achieved a sustained virologic response (SVR) by DAAs were evaluated before, at the end, and 24 weeks after treatment for glycemic (serum glucose and insulin, HOMA‐IR, HOMA‐β, and HOMA‐S) and lipid (serum cholesterol, triglycerides, low‐density lipoprotein [LDL], high‐density lipoprotein) metabolism and renal function (serum creatinine, estimated glomerular filtration rate [eGFR]). Results A total of 343 consecutive HCV patients were evaluated. At 24 weeks of post‐follow‐up, an increase in body mass index (BMI) was observed (P, In a prospective study, 343 patients with hepatitis C virus (HCV) infection who achieved sustained virologic response by direct‐acting antiviral agent (DAA) treatments were followed up for 24 weeks to evaluate the impact of viral clearance on metabolic and renal parameters. HCV clearance was independently associated with a significant reduction in serum glucose, HOMA‐IR, and HOMA‐β and an increase in HOMA‐S. Furthermore, an increase in serum cholesterol and low‐density lipoprotein cholesterol levels was observed. Renal function was improved with a significant decrease in serum creatinine levels and an increase in estimated glomerular filtration rate. Data show that HCV clearance by DAA induces significant changes in metabolic and renal parameters.

Background and aims: HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events. Methods: In a prospective multicentre study, 2204 HCV patients (F0–F2:29.5%, F3–F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59–74) years and BMI 25.9 (23.1–28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels >200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24–39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral stroke (ICS), were recorded. An overall of 2204 patients were evaluated as control group and 1668 patients after HCV elimination were followed as a case group. Factors associated with CV events were evaluated by uni- and multi-variate analyses. Results: Incident CV rates per 100 patient years in pre-treatment and untreated controls and treated cases were 1.12, 1.14 and 0.44 (p = 0.0001 vs. controls), respectively, and a decreased of relative risk (RR = 0.379; p = 0.0002) was observed. CV risk was 2.0–3.5 times lower then in controls (HR 3.671; 95%C.I.:1.871–7.201; p < 0.001). The calculated number of patients to be treated to get a benefit in a patient was 55.26. The annual incidence reduction of CV events was 0.68%. HCV clearance was independently associated with CV events reduction (OR, 4.716; 95% C.I.:1.832–12.138; p = 0.001). Conclusions: HCV clearance by DAA reduces CV events (IHD and ICS) with both clinical and socio-economic benefits.

Atrial fibrillation (AF) is a very common in clinical practice. The prevalence of AF is high after the age of 65 years. Patients with AF have a worse quality of life than healthy controls. However, concomitant higher hemorrhagic risks, severe cognitive and functional impairment may at least partly explain under-prescription of oral anticoagulants in the elderly.

Coronavirus disease 2019 (Covid-19) is characterized by severe acute respiratory syndrome and is an emerging disease. Considering the changes in maternal physiological and immune function during pregnancy, pregnant women may be at increased risk of being infected with Covid-19 and developing more complicated clinical events. Vertical transmission of the Covid-19 virus is possible although to this day it is still considered a rare event. It is conceivable that most pregnant patients infected with the Covid-19 virus have mild or moderate flu symptoms. More serious symptoms, such as pneumonia, in fact, seem to be more common in the elderly population or in subjects suffering from chronic diseases. As a precaution, pregnant women are considered the most vulnerable and therefore isolation and limitation of contact are recommended. At the moment there are no data to indicate whether spontaneous delivery is preferable in case of coronavirus infection (suspected or confirmed) to a cesarean section. However, in case of breathing difficulties that require delivery as soon as possible, a cesarean section is recommended. There is no evidence that the virus can be transmitted through breast milk. Furthermore, breastfeeding is preferable and has numerous benefits for the newborn's immune system. Since pregnant people appear to have a high risk of becoming seriously ill if they have an infection, vaccination is particularly important. In addition, there is evidence that vaccinated people have a lower risk of baby problems, such as stillbirth.

The endothelium plays a fundamental role in the biological processes that ensure physiological vessel integrity, synthesizing numerous substances that are capable of modulating the tone of vessels, inflammation and the immune system, and platelet function. Endothelial dysfunction refers to an anomaly that develops at the level of the tunica that lines the internal surface of arterial and venous vessels, or, more precisely, an alteration to normal endothelial function, which involves the loss of some structural and/or functional characteristics. Studies on sex differences in endothelial function are conflicting, with some showing an earlier decline in endothelial function in men compared to women, while others show a similar age of onset between the sexes. Since increased cardiovascular risk coincides with menopause, female hormones, particularly estrogen, are generally believed to be cardioprotective. Furthermore, it is often proposed that androgens are harmful. In truth, these relationships are more complex than one might think and are not just dependent on fluctuations in circulating hormones. An increase in serum uric acid is widely regarded as a possible risk factor for cardiovascular disease; however, its role in the occurrence of endothelial dysfunction has not yet been elucidated. Several studies in the literature have evaluated sex-related differences in the association between elevated uric acid levels and cardiovascular events, with conflicting results. The association between uric acid and cardiovascular disease is still controversial, and it is not yet clear how gender differences affect the serum concentration of these substances. This review was primarily aimed at clarifying the effects of uric acid at the level of the vascular endothelium and describing how it could theoretically cause damage to endothelial integrity. The second aim was to determine if there are gender differences in uric acid metabolism and how these differences interact with the vascular endothelium.

Background: Tetanus infection remains a significant complication of wounds. Because most tetanus treatment guidelines rely on anamnestic data collected directly from patients, the congruence between anamnesis and laboratory evidence must be verified, especially in the elderly population. Aim: Assess, in both the geriatric population (>65) and the non-geriatric one, the reliability of anamnestic data for managing patients with tetanus-risk wounds, identified categories of populations most exposed to non-vaccination coverage, and assessed the agreement of the Tetanos Quick Stick (TQS) results with the therapy performed (administration of tetanus vaccine or immunoglobulin). Methods: In this retrospective single-center observational study, patients were asked their immunization status against tetanus vaccination. The decision to administer a vaccine or immunoglobulin was therefore clinical and based on anamnestic criteria. The TQS test was then given to patients who were unaware of their immunity status. Patients who thought they knew it but were not sure were given the TQS test to determine whether the anamnestic collection was supported by the test. The TQS test results were compared with the anamnestic data. Results: Most patients, geriatric and not geriatric, did not know their immune status. Among those who reported knowing their immune status, there was no agreement between the vaccine coverage declared by patients and the TQS test results (p < 0.001), mainly in geriatric patients but also in the control group. Elderly and women had significantly lower positive TQS test results (p < 0.001). There was a statistically significant discrepancy (p < 0.001) between the therapy based on anamnestic data and the TQS test results. Conclusion: The reliability of anamnestic data for the management of patients with tetanus-risk wounds is low and decreases with age, becoming minimal in geriatric patients. Elderly and women are less likely to have an effective vaccination status against tetanus.

In COVID-19 disease, are reported gender differences in relation to severity and death. The aim of this review is to highlight gender differences in the immune response to COVID-19. The included studies were identified using PubMed, until 30 October 2020. The search included the following keywords: SARS-CoV-2, COVID-19, gender, age, sex, and immune system. Literature described that females compared to males have greater inflammatory, antiviral, and humoral immune responses. In female, estrogen is a potential ally to alleviate SARS-COV-2 disease. In male, testosterone reduces vaccination response and depresses the cytokine response. In the older patients, and in particular, in female older patients, it has been reported a progressive functional decline in the immune systems. Differences by gender were reported in infection diseases, including SARS-CoV-2. These data should be confirmed by the other epidemiological studies.

In this study we analyzed the expression of circulating miRNAs, in the serum of diabetic retinopathy (DR) patients. Five miRNAs (hsa-miR-195-5p, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-27b-3p and hsa-miR-451a) were validated as biomarkers for stratification of DR stages, from the early non-proliferative (NPDR) to the late proliferative (PDR) phase. Furthermore, circulating levels of these miRNAs correlated with retinal hyper-reflective spots (HRS), assessed by optical coherence tomography (OCT). The number of HRS increased with worsening of DR stages. On the contrary, no significant vascular density differences between NPDR and PDR patients were detected by angio-OCT (OCTA). A post-hoc bioinformatics analysis associated these five miRNAs to target genes belonging to the “Tumor Necrosis Factor alfa signaling” pathway, and several molecules were predicted to modify miRNAs expression. In conclusion, correlation between specific circulating miRNAs and intraretinal hyper-reflective spots was demonstrated, confirming that these miRNAs were validated as prognostic biomarkers, and also as potential pharmacological targets, warranting further clinical evaluation to explore novel therapeutics for diabetic retinopathy.

Satisfaction levels in relatives of suspected Covid-19 cases during hospital admission to an emergency department have not previously been reported. A prospective observational study was conducted using the Communication Attitude Test (CAT-T) questionnaire to describe educational level, age, and gender differences in 1201 relatives of suspected Covid-19 patients admitted to an emergency room between 21 February and 31 December 2020. Increased CAT-T scores, indicating low levels of satisfaction, were observed in older female relatives with low education levels (p < 0.01). These observations suggest that lack of accessible information during the Covid-19 pandemic can be a key aspect of anxiety not only in patients but for relatives, especially older women, and emphasizes the need for proactive communication. Keywords: COVID-19 pandemic, satisfaction of relatives, age, gender, education, communication

Resumen: Introducción: el cáncer de canal anal representa aproximadamente un 2% a 3% de todas las neoplasias digestivas. Nigro describió el tratamiento conservador del cáncer de canal anal utilizando radioterapia y quimioterapia con 5-fluorouracilo (5-FU) y mitomicina C (MMC), desde entonces este tratamiento es estándar. Objetivo: describir la técnica utilizada en nuestro servicio y los resultados en el control locorregional del cáncer de canal anal. Método: descriptivo, longitudinal, retrospectivo. Se analizaron historias de 72 pacientes consecutivos sin exclusiones, portadores de cáncer de canal anal, entre 1988 y 2016. El 67% recibió radioquimioterapia y el 33% de los pacientes radioterapia exclusiva por presentar contraindicaciones médicas específicas y fueron analizados en su conjunto. No se planificaron interrupciones en los tratamientos. Las interrupciones obligatorias fueron de 1 a 17 días con una media de 3 días. Las reacciones agudas fueron moderadas y no se comprobaron complicaciones tardías. Todos recibieron radioterapia locorregional. Resultados: el control local en N0 fue de 86% en T1 y T2 versus 42% en T3 y T4 a seis años, p=0,01 significativo. Conclusiones: la radioterapia con la técnica utilizada en nuestro servicio es efectiva en el tratamiento del cáncer de canal anal. La recidiva local ha sido la causa principal de persistencia lesional o recidiva. La curabilidad de la enfermedad está en relación directa con la extensión clínica/imagenológica de la lesión local. Abstract: Introduction: cancer of the anal canal accounts for approximately 2 to 3% of all digestive neoplasms. Nigro described the conservative treatment of cancer of the anal canal using radiation and chemotherapy of 5-fluorouracil (5-FU) and mitomycin-C (MMC). Since then, this is the standard therapy. Objective: to describe the technique used in our service and its results in the locoregional follow up of cancer of the anal canal. Method: descriptive, longitudinal, retrospective. The medical history of 72 consecutive patients with no exclusions, who were carriers of cancer of the anal canal were analysed between 1988 and 2016. 67% underwent radiation and chemotherapy and 33% only radiation therapy due to specific medical contraindications. All cases were comprehensively studied and no interruption of treatments were planned. Mandatory interruptions were from 1 to 17 days long and average length was 3 days. Severe reactions were moderate and no late complications were seen. All patients underwent locoregional radiation therapy. Results: local control in N0 was 86% in T1 and T2 versus 42% in T3 and T4 after 6 years p=0,01 meaningful. Conclusions: radiation therapy with the technique used in our service is effective to treat cancer of the anal canal. Local relapse has been the main cause of lesions or relapse. Curability of the disease is directly linked to the clinical/imaging extent of the local lesion. Resumo: Introdução: o câncer de canal anal representa aproximadamente 2 a 3% das neoplasias digestivas. Nigro descreveu o tratamento conservador do câncer de canal anal utilizando radioterapia e quimioterapia com 5-Fluorouracilo (5-FU) e Mitomicina C (MMC) que tem sido o tratamento padrão. Objetivo: descrever a técnica utilizada no nosso serviço e os resultados do controle locorregional do câncer de canal anal. Método: descritivo, longitudinal, retrospectivo. Foram analisados os prontuários de 72 pacientes consecutivos sem exclusões, portadores de câncer de canal anal, do período 1988-2016. 67% receberam radio quimioterapia e 33% radioterapia exclusivamente devido a contraindicações médicas específicas; os resultados foram analisados conjuntamente. Não se planejou interrupções nos tratamentos. As interrupções obrigatórias foram de 1 a 17 dias com uma média de 3 dias. As reações agudas foram moderadas e não se comprovaram complicações tardias. Todos receberam radioterapia locorregional. Resultados: o controle local em N0 foi de 86% em T1 e T2 versus 42% em T3 e T4 a 6 anos p=0,01 significativo. Conclusões: a radioterapia com a técnica utilizada no nosso Serviço é efetiva no tratamento do câncer de canal anal. A recidiva local foi a causa principal de persistência lesional ou recidiva. A curabilidade da enfermidade está diretamente relacionada com a extensão clínica e das imagens da lesão local.

BACKGROUND AND AIM Chronic hepatitis C virus (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. This study evaluated the impact of HCV clearance by all-oral direct-acting antiviral treatments on IR and glycemic control. METHODS Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty eight were treated with direct-acting antiviral and 65 were untreated. Liver fibrosis was assessed by transient elastography. Pre-treatment, end-treatment, and 3 months post-treatment withdrawal IR homeostasis was assessed by homeostatic model assessment (HOMA)-IR, HOMA-S, and HOMA-B. RESULTS At baseline, treated, and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90 ± 4.62 and 4.64 ± 5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and body mass index, and a reduction in HOMA-IR at 2.42 ± 1.85 was showed (P

The region of Lombardy was the epicenter of the COVID-19 outbreak in Italy. Emergency Hospital 19 (EH19) was built in the Milan metropolitan area during the pandemic’s second wave as a facility of Humanitas Clinical and Research Center (HCRC). The present study aimed to assess whether the implementation of EH19 was effective in improving the quality of care of COVID-19 patients during the second wave compared with the first one. The demographics, mortality rate, and in-hospital length of stay (LOS) of two groups of patients were compared: the study group involved patients admitted at HCRC and managed in EH19 during the second pandemic wave, while the control group included patients managed exclusively at HCRC throughout the first wave. The study and control group included 903 (56.7%) and 690 (43.3%) patients, respectively. The study group was six years older on average and had more pre-existing comorbidities. EH19 was associated with a decrease in the intensive care unit admission rate (16.9% vs. 8.75%, p &lt, 0.001), and an equal decrease in invasive oxygen therapy (3.8% vs. 0.23%, p &lt, 0.001). Crude mortality was similar but overlap propensity score weighting revealed a trend toward a potential small decrease. The adjusted difference in LOS was not significant. The implementation of an additional COVID-19 hospital facility was effective in improving the overall quality of care of COVID-19 patients during the first wave of the pandemic when compared with the second. Further studies are necessary to validate the suggested approach.

The Lean method entails a set of standardized processes intending to optimize resources, reduce waste, and improve results. Lean has been proposed as an operative model for the COVID-19 outbreak. Herein, we summarized data resulted from the Lean model adoption in an Emergency Department of the Lombardy region, the Italian epicenter of the pandemic, to critically appraise its effectiveness and feasibility. The Lean algorithm was applied in the Humanitas Clinical and Research Hospital, Milan, north of Italy. At admission, patients underwent outdoor pre-triage for fever, respiratory, and gastrointestinal symptoms, with a focus on SpO2. Based on these data, they were directed to the most appropriate area for the COVID-19 first-level screening. High-risk patients were assisted by trained staff for second-level screening and planning of treatment. Out of 7.778 patients, 21.9% were suspected of SARS-CoV-2 infection. Mortality was 21.9% and the infection rate in health workers was 4.8%. The lean model has proved to be effective in optimizing the overall management of COVID-19 patients in an emergency setting. It allowed for screening of a large volume of patients, while also limiting the health workers’ infection rate. Further studies are necessary to validate the suggested approach.

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were “cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome”. Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological.

Study objective We investigated the serum sodium correction rate on length of hospitalization and survival rate, in severe chronic hyponatremic patients at the Emergency Department (ED). Design An observational study using clinical chart review. Setting The ED of the University Hospital of Marcianise, Caserta, Italy with approximately 30,000 patients visits a year. Type of participants We reviewed sixty-seven patients with severe hyponatremia subdivided in 2 subgroups: group A consisting of 35 patients with serum sodium correction rate

Hepatitis C virus (HCV) infection is a systemic disease with hepatic and extrahepatic manifestations, including neuropsychiatric conditions. Depression is a frequent disorder, which has been reported in one-third of patients with HCV infection and has an estimated prevalence of 1.5 to 4.0 times higher than that observed in patients with chronic hepatitis B virus infection or the general population. HCV seems to play a direct and indirect role in the development of depression. Impaired quality of life and increasing health care costs have been reported for patients with HCV infection with depression. Treatment-induced HCV clearance has been associated with improvement of depression and quality of life.

Introduction: Early detection is crucial for prompt management of acute kidney injury (AKI) patients in emergency department (ED). This study aimed to investigate the usefulness of hyperchloremic metabolic acidosis (HCMA) levels in this regard.  Methods: In this retrospective observational study, > 18 years old critically ill patients presenting to ED of Marcianise Hospital, Italy, were divided into non-AKI and AKI group according to KDIGO guideline. The level of HCMA ((arterial pH x bicarbonate)/chloride) was compared between groups and correlation of HCMA with estimated glomerular filtration rate (e-GFR) in ARF patients was evaluated. Results: 134 patients with the mean age of 76.5 ± 3.1 years were enrolled (64 non-AKI and 70 AKI; 64% female). Two groups were similar regarding mean age (p = 0.251), sex (p = 0.091), APACHII score (p = 0.215), Charlson Comorbidity Index (p= 0.187), and body mass index (p = 0.129). The mean HCMA level was 1.98 ± 0.09 in the non-AKI group and 1.56 ± 0.07 in the AKI group (p=0.039). There was a positive correlation between HCMA and e-GFR levels in AKI group (r: 0.467, p=0.0092). Conclusions: If confirmed and validated in a future study, ABG derived formula for HCMA may be a useful tool for early detection of AKI patients in emergency department.

We have evaluated circulating miRNAs (-195-5p and -451a) in subjects with acute ischemic stroke (AIS) and in patients with transient ischemic attack (TIA). In this study, 18 subjects with AIS and 18 patients with TIA were enrolled and examined at admission (T0) and at 24 h and 48 h after admission, and compared to 20 controls (C). At T0, circulating miRNA-195-5p and -451a were significantly upregulated in both AIS and TIA patients, compared to C. We also observed a progressive reduction of circulating miRNA levels at 24 h and 48 h in both AIS and TIA patients. Hypoxia inducible factor 1alpha (HIF-1α) serum level was significantly increased at T0, in both AIS and TIA patients, in comparison to C (both p < 0.01 vs. C) and it decreased in both AIS and TIA patients at 24 h and at 48 h, in comparison to T0 (both p < 0.01 vs. T0). Vascular endothelial growth factor (VEGF) serum level was significantly decreased at T0, in both AIS and TIA patients, if compared to C (both p < 0.01 vs. C) and increased, in both AIS and TIA patients, at 24 h and 48 h, if compared to T0 (both p < 0.01 vs. T0). The elevated expression of miRNA-195-5p and miRNA-451a significantly decreased over time at 24 h and 48 h, and it is associated with decreased HIF-α levels and increased VEGF serum levels. These data may suggest a role for this miRNAs as biomarker in the pathogenesis and prognosis of AIS patients and for the first time also in TIA patients.

Objective The objective of the study is to investigate the prevalence of electrolyte imbalance (EI) in the emergency department (ED) with systemic diseases in different decades of life. Methods We enrolled patients admitted to the ED. The population study included 7941 patients, subdivided in 3 groups: young group (Y), middle-aged group (MA), and elderly group (E). Results We observed EI in 13.7% of the whole population. Hyponatremia (hNa+) is the most frequent EI (44%) followed by hypokalemia (hK+) (39%), hyperkalemia (HK+) (13%), and hypernatremia (HNa+) (4.4%). In the Y group, the EI occurred in 7.1% of all patients (P< .05 vs MA and E), whereas in the MA group, they were shown in 11.5% of patients and in the E group in 22% of all patients group (P< .05 vs MA and Y). In the Y group, gastrointestinal diseases are the most frequently associated disease (24.6%; P< .05 vs MA and E). In the MA group, the most frequently associated disease was a current cardiovascular disease (29.7%; P< .05 vs Y and E). In the E group, the frequently associated diseases are cardiovascular (22.8%; P< .05 vs Y) and lung diseases (16.7%; P< .05 vs MA and Y). Conclusions In our study, 13.7% of all patients showed an EI, and only 2% of cases were alone without any associated systemic disease. Most EIs are associated to other systemic diseases. The present data also depict different age-related and disease-associated prevalence patterns of EI, thus highlighting a complex clinical scenario. © 2016

Purpose Endotoxin is a component of the outer membrane of gram-negative bacteria that live in the intestine. Endotoxinemia is reported in non-alcoholic fatty liver disease and in cirrhotic patients, causing various biological and clinical effects in the host. It is not known whether endotoxinemia occurs in chronic hepatitis C patients (CHC), therefore we evaluated the occurrence of endotoxinemia and its effect on inflammation, liver damage, insulin resistance (IR) and atherosclerosis. Methods Consecutive CHC patients assessed by liver biopsy were enrolled. Endotoxinemia was evaluated by LAL test. IR was estimated by HOMA-IR. Serum TNF-α, IL-8, adiponectin and MCP-1 were measured with ELISA tests. Oxidative stress was estimated by circulating IgG against malondialdehyde adducts with human serum albumin (MDA-HAS). Carotid atherosclerosis was assessed by ultrasonography. Results Endotoxinemia was found in 60% of the 126 patients enrolled. A serum level-dependent association between endotoxinemia, steatosis (p

Miguel Devronsky proposed in 1970’s a theory explaining mechanism of action of ingested pure protein; so-called protein-diet, as follows

The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF.We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p 0.001), WBC count (p 0.001), immobilization syndrome (p 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p 0.001) and anamnestic HF (p = 0.002).Our study shows that BNP600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP600 pg/ml and anamnestic HF.

Chronic hepatitis C virus (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. This study evaluated the impact of HCV clearance by all-oral direct-acting antiviral treatments on IR and glycemic control.Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty eight were treated with direct-acting antiviral and 65 were untreated. Liver fibrosis was assessed by transient elastography. Pre-treatment, end-treatment, and 3 months post-treatment withdrawal IR homeostasis was assessed by homeostatic model assessment (HOMA)-IR, HOMA-S, and HOMA-B.At baseline, treated, and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90 ± 4.62 and 4.64 ± 5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and body mass index, and a reduction in HOMA-IR at 2.42 ± 1.85 was showed (P 0.001); in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose, and insulin levels were observed. Data were confirmed 3 months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of sustained virologic response patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strictly associated with HCV clearance; however, patients with the highest levels of fibrosis remain associated with some degree of IR.The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.

Objectives: The long term effects of a low protein diet (LPD) on depressive symptoms and the quality of life in elderly Type 2 diabetic are unclear. Methods: 38 elderly Type 2 diabetic patients with CRD (Stage 3 - 4) were enrolled in the study. After 4 weeks on a normal protein diet regimen (NPD) providing 1.0 g/kg per day, all participants were assigned for 30 months, randomly, to a LPD (0.7 g/kg per day), either 7 days a week (LPD 7/7) or 6 days a week (LPD 6/7). Mini mental state examination (MMSE), activities daily living (ADL), cumulative illness severity (CIRS-IS), geriatric depression scale (GDS-15) and short-form healthy survey (SF-36) were evaluated every 3 months. Results: Before the LPD regimen creatinine clearance (CrCl), MMSE, ADL, CIRS-IS, GDS-15 and SF-36 were similar in both LPD 7/7 and LPD 6/7 groups. After 30 months, the mean GDS-15 increased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). Both mean SF-36 MCS and SF-36 PCS were decreased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). After 30 months, the decline in CrCl observed was similar in LPD 7/7 and LPD 6/7 groups (2.77 +/- 0.3 and 2.84 +/- 0.3 ml/min/year, respectively). Conclusion: In elderly Type 2 diabetic patients, long term effects of LPD 6/7 regimen in comparison to LPD 7/7 are associated with a similar decline in CrCl, but with decreased depressive symptoms and a better quality of life.

Background: Auto-algometry has been previously proposed as a toll to evaluate hypertension-associated hypoalgesia. The aim of the present work was to confirm the robustness of this method and to evaluate other possible variables associated with hypertension and hypoalgesia. Methods: All routinary ambulatory data were collected from 111 hypertensive subjects along with the evaluation of pain threshold assessed with the auto-algometer. Results: The results confirmed the sensibility of the auto-algometer in revealing the hypertension-associated hypoalgesia and revealed unexpected higher pain thresholds in patients consuming angiotensin receptor 1 antagonists compared to patients consuming other medications. Conclusion: The results encourage the use of the auto-algometer to study unexplored mechanisms involved in hypertension and in hypoalgesia.

One hundred and ninety-five aged (mean age: 67+/-4.8 years), non-insulin dependent diabetic patients underwent a randomised single-blind study for investigating the effect of statin administration on insulin resistance and respiratory quotient. After 4 weeks run-in period, all patients were randomised in three groups: placebo (n=67), simvastatin (10 mg/day) (n=61) and atorvastatin (5 mg/day) (n=67). Each treatment period lasted 8 weeks. At the beginning, after the run-in and at the end of the study, insulin resistance was assessed by homeostasis model assessment (HOMA) index, while respiratory quotient (Rq) was evaluated by indirect calorimetry. Statins versus placebo significantly lowered plasma total, LDL-, HDL-cholesterol and triglyceride concentrations and improved insulin resistance and Rq and metabolic control. Atorvastatin had a greater effect than simvastatin on plasma triglyceride concentration (-26.3+/-3.1 vs. -19.7+/-2.8%, P

In poorly controlled diabetics, the whole-body protein flux is increased by 20–30% in comparison to well-controlled type I diabetes (IDDM) and normal subjects. Intensive insulin administration completely reverses these abnormalities. In poorly controlled IDDM, the primary effect of insulin administration is to reduce the increased protein catabolic rate by suppressing the accelerated rate of protein breakdown. Studies in humans have demonstrated that the increased rate of protein synthesis observed in these patients is the consequence of elevated plasma amino acid levels. When IDDM subjects develop renal complications, a protein-restricted diet may be recommended to preserve the remnant kidney function. However, it has been demonstrated that in IDDM patients, metabolic adaptation to protein restriction is incomplete because suppression of endogenous proteolysis is impaired. Since this component of protein metabolism is very sensitive to insulin action, maintaining strict metabolic control during the protein restriction regimen has been suggested. The major studies on the effects of amino acid and insulin on protein metabolism in patients with diabetes mellitus are reviewed.

To establish relationship, if any, between renal morphology and renal haemodynamic response to amino acids.We investigated the correlation between renal haemodynamic regulation and morphology in a group of 15 patients with primary IgA nephropathy (IgAN) (age 26 +/- 2 years, BMI 24.4 +/- 1, GFR 64 +/- 5 ml/min, RPF 377 +/- 34 ml/min, FF 0.17 +/- 0.02). Twelve normal subjects (age 30 +/- 3 years, BMI 24 +/- 1, GFR 82 +/- 6 ml/min, RPF 421 +/- 42 ml/min, FF 0.19 +/- 0.02) were studied as controls. IgA patients were divided into two groups according to the histological staging of glomerular lesions: group I (n = 7) stage II, and group II (n = 8) stage III-IV.In the basal state GFR was similar in the two groups and averaged 64 +/- 9 and 64 +/- 6 ml/min respectively. In contrast, FF was significantly lower in group II (0.14 +/- 0.01) (P0.05) in comparison to group I (0.21 +/- 0.03) and controls (0.19 +/- 0.02). In order to evaluate the renal functional reserve, all study groups underwent to an intravenous amino-acid infusion designed to increase plasma amino acid levels twofold (total from 2096 +/- 145 to 4301 +/- 221 mumol/l in IgA nephropathy patients and from 2272 +/- 83 to 3844 +/- 238 mumol/l in controls). In response to amino-acid infusion, GFR rose significantly in group I (GFR 20 +/- 2% and RPF 37 +/- 4% versus basal) and controls (GFR 20 +/- 2% and RPF 20 +/- 3% versus basal) (both P0.01 vs basal). In contrast, in patients with more severe glomerular lesions (group II) neither GFR nor RPF rose significantly (GFR -1 +/- 4% and RPF -8 +/- 6% versus basal) (P NS versus basal, P0.01 versus group I and controls).The data show that in IgA nephropathy: severe forms of glomerular lesions are associated with a complex alteration of glomerular haemodynamic regulation, characterized by lower basal FF and loss of haemodynamic response to hyperaminoacidaemia.

It has been hypothesized that both the cyclosporine (CsA) treatment and the reduction of renal mass may affect the renal hemodynamic regulation in kidney transplant recipients. To address this question, we evaluated the renal hemodynamic response to hyperaminoacidemia (i.v. mixed amino acid infusion 3.3 mg/kg/minute for 150 minutes) in four study groups: (1) 16 renal transplant recipients (Tx), (2) 6 uninephrectomized (Nx) subjects, (3) 7 subjects treated with CsA for chronic uveitis (CsA), and (4) 9 normal controls (NC). In response to amino acid administration (AA), glomerular filtration rate (GFR) rose significantly in NC subjects (80 +/- 6 vs. 91 +/- 6 ml/minute; P

In the present study we investigated the effect of a selective alpha 1-adrenergic blocker (doxazosin), an angiotensin-converting enzyme (ACE) inhibitor (captopril), and a calcium channel antagonist (nifedipine) on renal function in hypertensive non-insulin-dependent diabetic patients. 30 NIDD hypertensive patients (age = 50 +/- 3 years; BMI = 30 +/- 1 kg/m2) (mean +/- SEM) were studied before and after a 12-week period of antihypertensive treatment. Ten patients were treated with doxazosin (Cardura) (2-8 mg once daily or 8 mg b.i.d.), 9 with captopril (Capoten) (25-50 mg b.i.d.), and 11 with nifedipine (Procardia-XL) (30-60 mg once daily). Blood pressure, creatinine clearance, 24-hour urinary protein excretion, fasting plasma glucose concentration and glycosylated hemoglobin were measured before and after drug treatment. Fasting plasma glucose and glycosylated hemoglobin (HbA1c) were similar in all three groups prior to the start of antihypertensive therapy and did not change significantly from baseline in any treatment groups. In the doxazosin group creatinine clearance rose from 99 +/- 8 to 122 +/- 8 ml/1.73 m2.min (p0.01), while 24-hour urinary protein excretion declined from 2.66 +/- 0.05 to 1.76 +/- 0.02 mg/day/ml/1.73 m2.min (p0.01). In diabetics treated with captopril creatinine clearance rose from 93 +/- 6 to 109 +/- 9 ml/1.73 m2.min (p0.05), while the 24-hour urinary protein excretion fell from 2.70 +/- 0.05 to 2.03 +/- 0.04 mg/day/ml/1.73 m2.min (p0.05). In patients treated with nifedipine creatinine clearance did not change (97 +/- 6 vs. 94 +/- 7 ml/1.73 m2.min), while 24-hour urinary protein excretion decreased from 2.84 +/- 0.04 to 1.95 +/- 0.03 mg/day/ml/1.73 m2.min. Systolic and diastolic blood pressure were similar in doxazosin (150 +/- 3/95 +/- 2 mm Hg), captopril (153 +/- 3/93 +/- 1), and nifedipine (155 +/- 4/93 +/- 1) groups prior to the start of antihypertensive therapy and declined to 143 +/- 3/84 +/- 3 (doxazosin), 139 +/- 3/82 +/- 3 (captopril), and 141 +/- 3/84 +/- 1 (nifedipine) mm Hg (all p0.01 vs. pretreatment). In summary, both doxazosin and captopril treatment were associated with significant rises in GFR, while all three antihypertensive agents caused a significant decline in proteinuria. These results indicate that alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists can safely and effectively be used in the clinical management of non-insulin-dependent diabetic patients with hypertension.

Approximately 45% of the elderly population suffers from chronic kidney disease (CKD). The onset and the course of CKD can be ameliorated to a significant degree by several interventions, such as lowering blood pressure and serum lipid levels and achieving optimal glucose control in diabetes. In elderly patients with more advanced CKD, additional treatment may be needed. In these patients, a low-protein diet (LPD) regimen may delay the need for dialysis therapy. However, in the elderly, feasibility and compliance to LPD could be difficult and its effects are uncertain. In this contribution, we discuss the usefulness and the barriers of LPD regimen in the elderly.

The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.

We examined the acute effects of insulin-like growth factor I (IGF-I) on renal function in 8 normal subjects who received a 3-hour intravenous infusion of IGF-I at a rate of 0.4 micrograms/kg.min. After starting the IGF-I infusion, the plasma IGF-I concentration rose quickly and achieved a plateau after 90 min that was threefold above the basal value. During IGF-I infusion, progressive rises in glomerular filtration rate (from 93 +/- 4 to 121 +/- 6 ml/173 m2.min; p < 0.01) and renal plasma flow (from 529 +/- 31 to 703 +/- 55 ml/1.73 m2.min; p < 0.01) were observed, with no change in filtration fraction. The plasma levels of potassium and phosphate decreased significantly during the last 90 min of the study, while the plasma sodium concentration remained unchanged. A significant decrease in the fractional excretion of sodium, potassium, and phosphate was observed during the last 90 min of the IGF-I infusion period. The heart rate rose modestly with no change in mean arterial pressure. These findings show that, when administered acutely, IGF-I is a potent renal vasodilator, but is antinatriuretic. IGF-I also enhances potassium and phosphate uptake by extrarenal tissues and reduces renal potassium and phosphate excretion.