Liver and heart failure: an ultrasound relationship.

Liver and heart are anatomically and patho-physiologically related. In heart failure (HF) the increased right atrial pressure and volume overload cause histological changes in hepatocytes, leading to a condition known as "congestive hepatopathy" (CH), with consequent variations in liver functioning and ultrasound (US) findings. CH has specifical US findings especially regarding venous vessels aspect, easily detecting by gray-scale study, but many others can be distinguished by Doppler analysis. Usually, hepatic veins look enlarged and hypocollassing, together with signs of portal hypertension (hepatomegaly, ascites, splenomegaly, porto-systemic collaterals). Typically, in CH Doppler findings regard alterations in venous vessel flow and arterial resistance (venous system hyperpulsatility, reduced velocity flow, high resistance index in hepatic arterial Doppler spectrum). Sometimes CH and other primary hepatopathy can coexist, and therefore some of the expected variations may not manifest: it allows suspecting an unknown underlying liver disease. At last, US technologies of more recent applications, even if not routinely used, allow investigating additional aspects such as elastography that detects changes in liver elasticity or contrastographic US, able to show differences in hepatic venous opacification. However, most of these US signs are not pathognomonic, and therefore a multidisciplinary clinical reasoning must not be lacking. The aim of the present review is to easily provide US signs of liver alterations in HF, in particular right heart failure with volume overload, suggesting including liver US in instrumental diagnosis and therapeutic monitoring of HF.

Awareness of sex and gender dimensions among physicians: the European federation of internal medicine assessment of gender differences in Europe (EFIM-IMAGINE) survey.

Sociocultural gender is a complex construct encompassing different aspects of individuals' life, whereas sex refers to biological factors. These terms are often misused, although they impact differently on individuals' health. Recognizing the role of sex and gender on health status is fundamental in the pursuit of a personalized medicine. Aim of the current study was to investigate the awareness in approaching clinical and research questions on the impact of sex and gender on health among European internists. Clinicians affiliated with the European Federation of Internal Medicine from 33 countries participated to the study on a voluntary basis between January 1st, 2018 and July 31st, 2019. Internists' awareness and knowledge on sex and gender issues in clinical medicine were measured by an online anonymized 7-item survey. A total of 1323 European internists responded to the survey of which 57% were women, mostly young or middle-aged (78%), and practicing in public general medicine services (74.5%). The majority (79%) recognized that sex and gender are not interchangeable terms, though a wide discrepancy exists on what clinicians think sex and gender concepts incorporate. Biological sex and sociocultural gender were recognized as determinants of health mainly in cardiovascular and autoimmune/rheumatic diseases. Up to 80% of respondents acknowledged the low participation of female individuals in trials and more than 60% the lack of sex-specific clinical guidelines. Internists also express the willingness of getting more knowledge on the impact of sex and gender in cerebrovascular/cognitive and inflammatory bowel diseases. Biological sex and sociocultural gender are factors influencing health and disease. Although awareness and knowledge remain suboptimal across European internists, most acknowledge the underrepresentation of female subjects in trials, the lack of sex-specific guidelines and the need of being more informed on sex and gender-based differences in diseases.

Gender differences in vaccine therapy: where are we in COVID-19 pandemic?

Vaccination is one of the greatest achievements of public health. Vaccination programs have contributed to the decline in mortality and morbidity of various infectious diseases. This review aims to investigate the impact of sex/gender on the vaccine acceptance, responses, and outcomes. The studies were identified by using PubMed, until 30th June 2020. The search was performed by using the following keywords: SARS-CoV-2, COVID-19, gender, sex, vaccine, adverse reaction. Clinical trials, retrospective and prospective studies were included. Studies written in languages other than English were excluded. Studies were included if gender differences in response to vaccination trials were reported. All selected studies were qualitatively analyzed. Innate recognition and response to viruses, as well as, adaptive immune responses during viral infections, differ between females and males. Unfortunately, a majority of vaccine trials have focused on healthy people, with ages between 18 to 65 years, excluding the elderly, pregnant women, post-menopausal female and children. In conclusion, it is apparent that the design of vaccines and vaccine strategies should be sex-specific, to reduce adverse reactions in females and increase immunogenicity in males. It should be mandatory to examine sex-related variables in pre-clinical and clinical vaccine trials, such as their crucial role for successful prevention of pandemic COVID-19.

Gender differences in treatment of Coronavirus Disease-2019.

Coronavirus Disease-2019 (COVID-19) is the worst worldwide pandemic with more than 12,000,000 cases and 560,000 deaths until 14th July 2020. Men were more infected by COVID-19 than women, and male subjects with underlying conditions, including diabetes, hypertension, and cardiovascular diseases developed a severe form of the affection, with increased mortality rate. Many factors can contribute to the disparity in disease outcomes, such as hormone-specific reaction and activity of X-linked genes, which modulate the innate and adaptive immune response to virus infection. Until now, only the Remdesivir was approved by FDA (Food Drug Administration) for COVID-19 treatment, although several clinical trials are ongoing worldwide also on other drugs. In this review, we analyzed published studies on several drugs (chloroquine or hydroxychloroquine, remdesivir, favipiravir, lopinavir-ritonavir in combination, tocilizumab, plasma, and immunoglobulins) with some efficacy to COVID-19 in humans, and evaluated if there were a gender analysis of the available data. In our opinion, it is essential to report data about COVID-19 disaggregated by sex, age, and race, because the knowledge of gender differences is fundamental to identify effective and customized treatments to reduce hospitalizations, admissions to intensive care units, and mortality.

Gender differences in patients with COVID-19: a narrative review.

In December 2019 a novel coronavirus emerged in Wuhan, China causing many cases of severe pneumonia. World Health Organization (WHO) named this disease Coronavirus Disease 2019 (COVID-19). The infection has rapidly spread across China to many other countries, and on March 12, 2020 the WHO declared pandemic outbreak of COVID-19. As of May 16, 2020, COVID-19 has been diagnosed in more than 4,490,000 patients, associated to 305,976 deaths worldwide; in Italy 224,760 COVID-19 cases have been reported with 31,763 deaths. The main routes of transmission are respiratory droplets and direct contact with infected people, so numerous prevention strategies are employed to mitigate the spread of disease, including social distancing and isolation. The aim of this narrative review is to underline gender differences in epidemiology, etiopathogenesis, risk factors, clinical presentation, diagnosis, prognosis and mortality of patients infected with SARS-CoV-2. Currently data on the sex indicators for admitted or deceased patients are only available, but there is no analysis about other gender indicators. The data considered in our study are the only currently available in the literature, but it is appropriate to implement a specific analysis with all gender indicators to identify appropriate strategies. Moreover, the evaluation of a health service efficiency is a key element to define gender outcomes. Knowing the gender differences in COVID-19 outbreak would be a fundamental tool to understand the effects of a health emergency on individuals and communities as well as to carry out effective and equitable policies, public health measures and targeted solutions.

Prospective validation of the International Warfarin Pharmacogenetics Consortium algorithm in high-risk elderly people (VIALE study).

We assessed the predictive accuracy of the Warfarin Pharmacogenetics Consortium (IWPC) algorithm in a prospective cohort of 376 high-risk elderly patients (≥65 years) who required new treatment with warfarin for either medical (non valvular atrial fibrillation) or surgical conditions (heart valve replacement), had ≥1 comorbid conditions, and regularly used ≥2 other drugs. Follow-up visits were performed according to clinical practice and lasted for a maximum of 1 year. Two hundred and eighty-three (75%) patients achieved a stable maintenance dose. Warfarin maintenance doses were low on average (median 20.3 mg/week, interquartile range, 14.1-27.7 mg/week) and were substantially overestimated by the IWPC algorithm. Overall the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable dose was equal to 37.5%, (95% CI 32.0-43.3%). IWPC algorithm explained only 31% of the actual warfarin dose variability. Modifications of the IWPC algorithm are needed in high-risk elderly people.

Gender Differences and Quality of Life in Parkinson's Disease.

Parkinson's disease has been found to significantly affect health-related quality of life. The gender differences of the health-related quality of life of subjects with Parkinson's disease have been observed in a number of studies. These differences have been reported in terms of the age at onset, clinical manifestations, and response to therapy. In general, women with Parkinson's disease showed more positive disease outcomes with regard to emotion processing, non-motor symptoms, and cognitive functions, although women report more Parkinson's disease-related clinical manifestations. Female gender predicted poor physical functioning and socioemotional health-related quality of life, while male gender predicted the cognitive domain of health-related quality of life. Some studies reported gender differences in the association between health-related quality of life and non-motor symptoms. Depression and fatigue were the main causes of poorer health-related quality of life in women, even in the early stages of Parkinson's disease. The aim of this review was to collect the best available evidence on gender differences in the development of Parkinson's disease symptoms and health-related quality of life.

Prulifloxacin vs Levofloxacin for Exacerbation of COPD after Failure of Other Antibiotics.

The chronic course and evolution of chronic obstructive pulmonary disease (COPD) is often characterized by periods of exacerbation of symptoms, which have a negative impact on the quality of life of patients, as well as on the evolution of COPD, and represent a significant cause of medical intervention and hospitalization. Very few data are available on the efficacy of rescue antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to previous treatment. The aim of this study was to evaluate the efficacy of two fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR study is a randomized, single-blind, non-inferiority comparison between levofloxacin and prulifloxacin. Primary end-point was "therapeutic success" at Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at least three points of a global score of symptomatology (maximum score = 15). 258 patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A very high proportion of patients in the two groups had therapeutic success at Day-10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat; 94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7 days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in 17.8% of patients treated with levofloxacin and 14.2% of those receiving prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in the treatment of AECOPD resistant to other antibiotics.

Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease.

OBJECTIVES: The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear. METHODS: Seventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b-G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo. RESULTS: During T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD). CONCLUSION: In older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass.

[Management of patients with cerebral stroke in Molise (Italy): MO.STRO (MOlise STROke).]. / MO.STRO (Molise Stroke): la gestione dei pazienti affetti da Ictus cerebrale.

Acute stroke patients in the Molise region (Italy) are generally admitted to an Internal Medicine or Geriatrics hospital ward. In this study all 446 acute stroke admissions which occurred in Molise in 2004 were evaluated by analysing the following data: time from symptom onset to admission, diagnosis, acute care treatment, comorbidities, disease severity, complications, disability level, mortality, discharge modality and adherence to current guidelines. Mortality was very low in the study population (approximately 8% vs. 15-17% for the rest of Italy) and was found to be related to age above 80 years, disease severity, presence of dysphagia and to being admitted to the hospital of Campobasso (a sub-analysis of this population showed an equal degree of risk in the Geriatrics and Internal Medicine Units). Forty-two percent of survivors had a moderately severe to severe level of disability (Rankin score 4-5) and went home immediately after discharge (with a major part of the burden of care resting on families). At all study hospitals, computed tomography scan was performed within 48 hours of symptom onset, as per current guidelines for the management of acute stroke. On the other hand, adherence to current guidelines regarding other components of management such as evaluation for dysphagia, placement of a urinary catheter, aspirin therapy, rehabilitation, and performance of diagnostic procedures (e.g. doppler, echocardiogram) was not uniform in all study hospitals. Several aspects of stroke management should certainly be improved, in accordance with current international guidelines, in order to provide optimal acute stroke care in the Molise region. These include: time to hospital admission (e.g. by improving the emergency service "118"), standard treatment and diagnostic procedures, physical rehabilitation services and involvement of family physicians.