Variation in Fatty Acid Synthase, Ki67 and p53 Esophageal Mucosa Expressions in Barrett's Esophagus Patients Treated for One Year with Two Esomeprazole Different Regimens.

Barrett's esophagus (BE) is an acquired pre-malignant condition that results from chronic gastroesophageal reflux. The malignant transformation occurred in 0.5% of patients/year and was independent of medical and endoscopic conservative treatments. Fatty acid synthase (FAS) is a multifunctional enzyme that catalyzes the synthesis of long-chain fatty acids from acetyl-coenzyme A, malonyl-coenzyme A, a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), and adenosine triphosphate. Activation of FAS is closely linked to malignant transformation. The aim of the present study was to evaluate the variation of FAS, p53, and Ki67 expressions in two groups of 21 BE patients each, after one year of continuous (group A) or discontinuous (group B) treatment with esomeprazole 40 mg/day in comparison to the initial expression. In both the two groups of BE patients, biopsies were taken from pathologic sites of the mucosa for histological and immuno-histochemical detection of FAS, Ki67, and p53 at entry and after one year of Esomeprazole 40 mg treatment. FAS expression was positive when a strong granular cytoplasmic staining was observed in esophageal cells. Ki67 and p53 were defined as positive when nuclear staining was clearly detected at ×10 magnification. FAS expression was reduced in 43% of patients treated with Esomeprazole continuously in comparison to the 10% of patients treated with Esomeprazole on demand (p = 0.002). Ki67 expression was reduced in 28% of continuously treated patients in comparison to 5% of patients treated on demand (p = 0.001). The p53 expression decreased in 19% of continuously treated patients in comparison to an increase in 2 patients (9%) treated on demand (p = 0.05). Continuously Esomeprazole treatment could help in the diminution of metabolic and proliferative activities in the esophageal columnar epithelium and in part it can help prevent the oxidative damage against cellular DNA, resulting in a diminution in p53 expression.

Gender Differences in Insulin Resistance: New Knowledge and Perspectives.

Insulin resistance is the main mechanism in a whole series of pathological conditions, which are not only of metabolic interest but also of a systemic type. This phenomenon means that the body's cells become less sensitive to the hormone insulin, leading to higher levels of insulin in the blood. Insulin resistance is a phenomenon that can be found in both men and women and in particular, in the latter, it is found mainly after menopause. Premenopause, hormonal fluctuations during the menstrual cycle, and the presence of estrogen can affect insulin sensitivity. Androgens, such as testosterone, are typically higher in men and can contribute to insulin resistance. In both sexes, different human body types affect the distribution and location of body fat, also influencing the development of diabetes and cardiovascular disease. Insulin resistance is also associated with some neurological and neurogenerative disorders, polycystic ovary syndrome, atherosclerosis, and some of the main neoplastic pathologies. A healthy lifestyle, including regular physical activity, a balanced diet, and self-maintenance, can help to prevent the onset of insulin resistance, regardless of gender, although the different habits between men and women greatly affect the implementation of preventative guidelines that help in fighting the manifestations of this metabolic disorder. This review may help to shed light on gender differences in metabolic diseases by placing a necessary focus on personalized medical management and by inspiring differentiated therapeutic approaches.

Intra- and Extra-Hospitalization Monitoring of Vital Signs-Two Sides of the Same Coin: Perspectives from LIMS and Greenline-HT Study Operators.

BACKGROUND: In recent years, due to the epidemiological transition, the burden of very complex patients in hospital wards has increased. Telemedicine usage appears to be a potential high-impact factor in helping with patient management, allowing hospital personnel to assess conditions in out-of-hospital scenarios. METHODS: To investigate the management of chronic patients during both hospitalization for disease and discharge, randomized studies (LIMS and Greenline-HT) are ongoing in the Internal Medicine Unit at ASL Roma 6 Castelli Hospital. The study endpoints are clinical outcomes (from a patient's perspective). In this perspective paper, the main findings of these studies, from the operators' point of view, are reported. Operator opinions were collected from structured and unstructured surveys conducted among the staff involved, and their main themes are reported in a narrative manner. RESULTS: Telemonitoring appears to be linked to a reduction in side-events and side-effects, which represent some of most commons risk factors for re-hospitalization and for delayed discharge during hospitalization. The main perceived advantages are increased patient safety and the quick response in case of emergency. The main disadvantages are believed to be related to low patient compliance and an infrastructural lack of optimization. CONCLUSIONS: The evidence of wireless monitoring studies, combined with the analysis of activity data, suggests the need for a model of patient management that envisages an increase in the territory of structures capable of offering patients subacute care (the possibility of antibiotic treatments, blood transfusions, infusion support, and pain therapy) for the timely management of chronic patients in the terminal phase, for which treatment in acute wards must be guaranteed only for a limited time for the management of the acute phase of their diseases.

Microbiota and Glucidic Metabolism: A Link with Multiple Aspects and Perspectives.

The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.

Influence of Gender in Diabetes Mellitus and Its Complication.

In medicine, there is growing evidence that gender differences are important and lead to variations in the pathophysiology and treatment of many diseases with traits that appear to be particularly relevant in influencing the outcomes of many morbid forms. Today, the inclusion of gender in biomedical research, to improve the scientific quality and scientific relevance of knowledge, of technology is an increasingly present element precisely due to the practical implications that derive from it. Gender differences describe the biological variability between women and men, which is, in turn, related to differences in the information contained in sex chromosomes, the specific gene expression of autosomes linked to sex, the different number and quality of sex hormones, and their different effects on systems and organs, without neglecting the fact that each of the sexes has different target organs on which these hormones act. Additionally, both genders undergo metabolic changes throughout their lives, and this is especially true for women who show more dramatic changes due to their role in reproduction. Gender differences are not only the result of our genetic makeup but are also mixed with socio-cultural habits, behaviors, and lifestyles, differences between women and men, exposure to specific environmental influences, different food and lifestyle styles or stress, or different attitude in compliance with treatments and disease prevention campaigns. Gender differences also affect behavior throughout life, and physical changes can have implications for lifestyle, social roles, and mental health. Therefore, determinism and therapeutic outcome in chronic diseases are influenced by a complex combination of biological and environmental factors, not forgetting that there are many interactions of social and biological factors in women and men. This review will address the role of gender differences in the management of various forms of diabetes and its complications considering the different biological functions of hormones, the difference in body composition, physiological differences in glucose and fat metabolism, also considering the role of the microbiota. intestinal, as well as the description of gestational diabetes linked to possible pathophysiological events typical of reproduction.

Gender in acute kidney disease: A narrative review.

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.

Cardiomyopathies: An Overview.

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.

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.

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.

Circulating MiRNA-195-5p and -451a in Diabetic Patients with Transient and Acute Ischemic Stroke in the Emergency Department.

(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.

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.

Serum sodium correction rate and the outcome in severe hyponatremia.

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<0.3mmol/h and group B consisting of 32 patients with serum sodium correction rate between <0.5 and ≥0.3mmol/h. INTERVENTION: Emergency patients were evaluated for serum sodium correction rate for hyponatremia by clinical chart review. MEASUREMENTS AND MAIN RESULTS: Severe hyponatremia was defined as a serum sodium level<120mmol/l. Mean serum sodium correction rate of hyponatremia was of 0.17±0.09% in group A and 0.41±0.05% in group B (p<0.001 vs group A). The length of hospital stay was 10.7±3.7days for group A, and it was significantly decreased to 3.8±0.4days for group B (p<0.005 vs group A). In addition we observed that correction rate of hyponatremia in group A was associated with a significantly lower survival rate (25%) in comparison to group B (60%) (p<0.001 vs group A). CONCLUSION: We observed that serum sodium correction rate ≥0.3 and <0.5mmol/h was associated with a shorter length of hospital stay and a major survival rate.

Seasonal variations of hyponatremia in the emergency department: Age-related changes.

STUDY OBJECTIVE: We investigated seasonal prevalence of hyponatremia in the emergency department (ED). DESIGN: A cross-sectional study using clinical chart review. SETTING: University Hospital ED, with approximately 28 000 patient visits a year. TYPE OF PARTICIPANTS: 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. INTERVENTION: Emergency patients were evaluated for the presence of hyponatremia by clinical chart review. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSION: 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.

Acute rhabdomiolisys in healthy woman.

Our patient is a 42-year-old woman with muscle paralysis, muscle weakness, and fever. On admission, a neurologic examination showed proximal and distal weakness in the leg. Serum creatine phosphokinase and serum myoglobin level were markedly increased (5600 UI/L and 5197 UI/L, respectively). There was no sign of renal failure. Nerve conduction study was negative. Serologic studies for virus titers showed the antibody immunoglobulin M cytomegalovirus. Muscle weakness and its paralysis, fever, and serum creatine kinase level gradually improved after the administration of methylprednisolone intravenous. Cytomegalovirus infection was thought to have played a central role in this case, leading to an acute but reversible peripheral muscle paralysis.

Diseases associated with electrolyte imbalance in the ED: age-related differences.

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.

Acute dysphagia in an octogenarian: an unusual case of tetanus.

Tetanus is a major worldwide health problem, and its global incidence has been estimated to be approximately 1 million cases per year. In particular, tetanus is more frequent in the elderly as compared with adults. We report a case of an octogenarian who presented with dysphagia and tremors as the only clinical symptoms. During hospitalization, the patient's clinical conditions worsened rapidly, and, although in absence of the classic clinical presentation (trisma, nuchal rigidity, and opisthotonus), a diagnosis of tetanus was suspected. Thus, the patient underwent a tetanus immunoglobulin immunization and antibiotic therapy with excellent clinical recovery.

Role of Helicobacter pylori Infection in Pathogenesis, Evolution, and Complication of Atherosclerotic Plaque.

The therapeutic management of atherosclerosis focuses almost exclusively on the reduction of plasma cholesterol levels. An important role in the genesis and evolution of atherosclerosis is played by chronic inflammation in promoting thrombosis phenomena after atheroma rupture. This review aims to take stock of the knowledge so far accumulated on the role of endemic HP infection in atherosclerosis. The studies produced so far have demonstrated a causal relationship between Helicobacter pylori (HP) and CVD. In a previous study, we demonstrated in HP-positive patients that thrombin and plasma fragment 1 + 2 production was proportionally related to tumor necrosis factor-alpha levels and that eradication of the infection resulted in a reduction of inflammation. At the end of our review, we can state that HP slightly affects the risk of CVD, particularly if the infection is associated with cytotoxic damage, and HP screening could have a clinically significant role in patients with a high risk of CVD. Considering the high prevalence of HP infection, an infection screening could be of great clinical utility in patients at high risk of CVD.

Predictors for the prescription of pharmacological prophylaxis for venous thromboembolism during hospitalization in Internal Medicine: a sub-analysis of the FADOI-NoTEVole study.

Patients hospitalized in Internal Medicine Units (IMUs) may frequently experience both an increased risk for thrombosis and bleeding. The use of risk assessment models (RAMs) could aid their management. We present a post-hoc analysis of the FADOI-NoTEVole study, an observational, retrospective, multi-center study conducted in 38 Italian IMUs. The primary aim of the study was to evaluate the predictors associated with the prescription of thromboprophylaxis during hospitalization. The secondary objective was to evaluate RAMs adherence. Univariate analyses were conducted as preliminary evaluations of the variables associated with prescribing pharmacological thromboprophylaxis during hospital stay. The final multivariable logistic model was obtained by a stepwise selection method, using 0.05 as the significance level for entering an effect into the model. Thromboprophylaxis was then correlated with the RAMs and the number of predictors found in the multivariate analysis. Thromboprophylaxis was prescribed to 927 out of 1387 (66.8%) patients with a Padua Prediction score (PPS) ≥ 4. Remarkably, 397 in 1230 (32.3%) patients with both PPS ≥ 4 and an IMPROVE bleeding risk score (IBS) < 7 did not receive it. The prescription of thromboprophylaxis mostly correlated with reduced mobility (OR 2.31; 95% CI 1.90-2.81), ischemic stroke (OR 2.38; 95% CI 1.34-2.91), history of previous thrombosis (OR 2.46; 95% CI 1.49-4.07), and the presence of a central venous catheter (OR 3.00; 95% CI 1.99-4.54). The bleeding risk assessment using the IBS did not appear to impact physicians' decisions. Our analysis provides insight into how indications for thromboprophylaxis were determined, highlighting the difficulties faced by physicians with patients admitted to IMUs.

Utilization of Ocrelizumab within Different Treatment Strategies for Multiple Sclerosis: A 5-Year Population-Based Study.

BACKGROUND: We aim to provide up-to-date real-world evidence on the persistence, adherence, healthcare resource utilization, and costs of multiple sclerosis (MS) by comparing ocrelizumab to other disease-modifying treatments (DMTs) and within different DMT sequences. METHODS: We included 3371 people with MS who first received or switched DMT prescriptions from January 2018 to December 2022; they were identified through hospital discharge records, drug prescriptions, and exemption codes from the Campania Region (South Italy). We calculated persistence (time from the first prescription to discontinuation or switching to another DMT), adherence (proportion of days covered (PDC)), DMT costs, and MS hospital admissions and related costs. RESULTS: The most frequently prescribed DMT was dimethyl fumarate (n = 815; age 38.90 ± 11.91 years; 69.5% females), followed by ocrelizumab (n = 682; age 46.46 ± 11.29 years; 56.3%); 28.8% of the patients treated with ocrelizumab were naïve to DMTs. Using ocrelizumab as a statistical reference, the risk of discontinuation was higher for other highly active (HR = 6.32; 95%CI = 3.16, 12.63; p < 0.01) and low-/medium-efficacy DMTs (HR = 10.10; 95%CI = 5.10, 19.77; p < 0.01); adherence was lower for other highly active DMTs (Coeff = -0.07; 95%CI = -0.10, -0.04; p < 0.01) and low-/medium-efficacy DMTs (Coeff = -0.16; 95%CI = -0.19, -0.14; p < 0.01). monthly DMT costs were higher for other highly active DMTs (Coeff = 77.45; 95%CI = 29.36, 125.53; p < 0.01) but lower for low-/medium-efficacy DMTs (Coeff = -772.31; 95%CI = -816.95, -727.66; p < 0.01). The hospital admissions and related costs of MS were similar between ocrelizumab, other highly active DMTs, and other low-/medium-efficacy DMTs, and with ocrelizumab as the first-line DMT after other highly active DMTs and after low-/medium-efficacy DMTs, which was possibly due to the low number of observations. CONCLUSIONS: From 2018 to 2022, ocrelizumab was among the most frequently prescribed DMTs, with 28.8% prescriptions to incident MS patients, confirming its relevance in clinical practice. Ocrelizumab was associated with the highest persistence and adherence, pointing towards its favorable benefit-risk profile. The costs of ocrelizumab were lower than those of other highly active DMTs.