Search

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.

Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor, and apart from supportive therapy, no other specific therapy exists. Furthermore, acute kidney injury increases the risk of developing chronic kidney disease (CKD) and end-stage renal disease. Acute tubular injury accounts for the most common intrinsic cause of AKI. The main site of injury is the proximal tubule due to its high workload and energy demand. Upon injury, an intratubular subpopulation of proximal epithelial cells proliferates and restores the tubular integrity. Nevertheless, despite its strong regenerative capacity, the kidney does not always achieve its former integrity and function and incomplete recovery leads to persistent and progressive CKD. Clinical and experimental data demonstrate sexual differences in renal anatomy, physiology, and susceptibility to renal diseases including but not limited to ischemia-reperfusion injury. Some data suggest the protective role of female sex hormones, whereas others highlight the detrimental effect of male hormones in renal ischemia-reperfusion injury. Although the important role of sex hormones is evident, the exact underlying mechanisms remain to be elucidated. This review focuses on collecting the current knowledge about sexual dimorphism in renal injury and opportunities for therapeutic manipulation, with a focus on resident renal progenitor stem cells as potential novel therapeutic strategies.

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.

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.

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. Three authors (TC, EB and IA) reviewed all study abstracts. 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.

(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.

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.

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

Atrial fibrillation (AF) is a frequent pathology in Internal Medicine departments. The aim of our study was to identify the risk factors associated with the development of new-onset AF during hospitalization and to evaluate its outcome as in-hospital mortality. We conducted a retrospective case–control study on a cohort of 14,179 patients admitted to an internal medicine department. We included in the study the patients who did not have an anamnestic history of AF, who presented a sinus rhythm at the time of admission and who developed a new-onset AF during hospitalization. For each of these cases, two controls were enrolled who were not affected by AF. The patients included in the study were 588, including 196 cases and 392 controls. Patients who developed AF during hospitalization had significantly more comorbidity than controls. The most frequent causes for hospitalization were sepsis, significantly higher in the case group. From the results of the multivariate analysis, the factors related independently to the development of AF were the presence of a number of comorbidities ≥ 3 (OR = 1.52; p = 0.017), sepsis as a reason of hospitalization (OR = 2, 16; p = 0.001) and glycemic value at the admission ≥ 130 mg/dL (OR = 1.44; p = 0.047). Both the length of hospital stay and in-hospital mortality were higher in the group of patients who developed AF, with a statistically significant difference compared to controls (p

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.

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

We investigated seasonal prevalence of hyponatremia in the emergency department (ED).A cross-sectional study using clinical chart review.University Hospital ED, with approximately 28 000 patient visits a year.We reviewed 15 049 patients, subdivided in 2 groups: the adult group consisting of 9822 patients aged between 18 and 64years old and the elderly group consisting of 5227 patients aged over 65years presenting to the ED between January 1st, 2014 and December 31st, 2015.Emergency patients were evaluated for the presence of hyponatremia by clinical chart review.Hyponatremia was defined as a serum sodium level135mmol/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 (p0.05 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 (p0.01 vs adult group; p0.05 vs other seasons in elderly group). In the elderly group, we reported a significant correlation between weather temperature and hyponatremia prevalence (r: 0.491; p0.05).We observed a major influence of climate on the prevalence of hyponatremia in the elderly in the ED. Decline in renal function, salt loss, reduced salt intake and increased water ingestion could all contribute to developing hyponatremia in elderly patients during the summer. These data could be useful for emergency physicians to prevent hot weather-induced hyponatremia in the elderly.

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.

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.

Late-life depression is one of the main health problems among elderly diabetic subjects. In addition, depression is a common psychopathological condition among renal failure patients and most of these patients follow a low protein diet regimen (LPD). However, the effects of LPD on depressive symptoms are unclear.In the present study, the effects of LPD regimen on depressive symptoms in elderly type 2 diabetic subjects with renal failure were investigated.Fifty-two young-old type 2 diabetic patients with renal failure were enrolled in the study. All participants after normal protein diet regimen providing 1.2g/kg per d were instructed to consume either a LPD providing 0.8 g/kg per d, 7 d a wk (LPD 7/7), or a LPD providing 0.8 g/kg per d 6 d a wk (LPD 6/7) randomly.Mean 15-item Geriatric Depression Scale (GDS-15) (2.0±0.6) and Beck Depression Inventory (BDI) (4.1±1.0), during normal protein diet regimen, significantly increased to (6.7±1.6) and (12.2±1.4), respectively, after LPD 7/7 (P0.05 versus normal protein diet). However, after LPD 6/7, mean GDS-15 and BDI significantly decreased to (4.4±1.5) and (6.7±1.6), respectively (P0.05 versus LPD 7/7).LPD 6/7 regimen significantly decreased depressive symptoms in young-old type 2 diabetic patients.

AIMS/HYPOTHESIS: Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A low-protein diet has been recommended in patients with diabetic nephropathy, but its effects on albumin and fibrinogen synthesis are unknown. METHODS: We compared the effects of a normal (NPD; 1.38 +/- 0.08 g kg(-1) day(-1)) or low (LPD; 0.81 +/- 0.04 g kg(-1) day(-1)) -protein diet on endogenous leucine flux (ELF), albumin and fibrinogen synthesis (L-[5,5,5,-2H3]leucine infusion), and markers of inflammation in nine type 2 diabetic patients with macroalbuminuria. Six healthy participants on NPD served as control participants. RESULTS: In comparison with healthy participants, type 2 diabetic patients on an NPD had similar ELF, reduced serum albumin (38 +/- 1.1 vs 42 +/- 0.8 g/l; p < 0.05), similar fractional synthesis rates (FSR) and absolute synthesis rates (ASR) of albumin, and both increased plasma fibrinogen concentration [10.7 +/- 0.6 vs 7.2 +/- 0.5 micromol/l (3.64 +/- 0.22 vs 2.45 +/- 0.18 g/l); p < 0.05] and fibrinogen ASR [11.03 +/- 1.17 vs 6.0 +/- 1.8 micromol 1.73 m(-2) day(-1) (3.7 +/- 0.4 vs 1.9 +/- 0.3 g 1.73 m(-2) day(-1)); p < 0.01]. After LPD, type 2 diabetic patients had the following changes in comparison with NPD: reduced proteinuria (2.74 +/- 0.4 vs 4.51 +/- 0.8 g/day; p < 0.05), ELF (1.93 +/- 0.08 vs 2.11 +/- 0.08 micromol kg(-1) min(-1); p < 0.05) and total fibrinogen pool; increased serum albumin (42 +/- 1 vs 38 +/- 1 g/l; p < 0.01) and albumin ASR (14.1 +/- 1 vs 9.9 +/- 1 g 1.73 m(-2) day(-1); p < 0.05); and reduced plasma IL-6 levels, which were correlated with albumin ASR (r = -0.749; p < 0.05). CONCLUSIONS/INTERPRETATION: LPD in type 2 diabetic patients with diabetic nephropathy reduces low-grade inflammatory state, proteinuria, albuminuria, whole-body proteolysis and ASR of fibrinogen, while increasing albumin FSR, ASR and serum concentration.

Aims: We studied the relationship between the Beck Depression Inventory (BDI) and the 15-item Geriatric Depression Scale (GDS-15) in young–old hemodialysis and hospitalized patients in order to evaluate the possible usefulness of GDS-15 in hemodialysis patients. Methods: Thirty-one hospitalized and 31 young–old hemodialysis patients aged 65–74 (young–old) were enrolled in the study. Comprehensive geriatric assessment (Mini Mental State Examination (MMSE), BDI, GDS-15, Cumulative Illness Rating Scale (CIRS) and Activities of Daily Living (ADL)) was made for all patients. The internal consistency between BDI and GDS-15 was evaluated with Cronbach’s α coefficient. Sensitivity, specificity and receiver operating characteristic (ROC) curves for GDS-15 were determined using BDI as the standard. Results: In the hospitalized group, the prevalence of depressive symptoms, as evaluated by BDI (≧14) and GDS-15 (≧6), were 29 and 32%, respectively. In the hemodialysis group, the prevalence of depressive symptoms, as evaluated by BDI and GDS-15, were 61 and 58%, respectively. A significantly positive correlation between the BDI and GDS-15 was found in hospitalized (r = 0.808; p < 0.001), hemodialysis (r = 0.692; p < 0.001) and both patient groups together (r = 0.777; p < 0.001). The area under the ROC curve was 0.99 in the hospitalized and 0.95 in the hemodialysis groups. The ROC curves indicate a best effectiveness cutoff point (balancing sensitivity and specificity) of ≧6 for GDS-15 compared to BDI. Conclusions: The GDS-15 could be a useful instrument for evaluating depressive symptoms in young–old hemodialysis patients.

Objective: In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known ifkidney volume (KV) is associated with an increased urinary albumin and IgG excretion. Methods: The relationship between kidney volume, creatinine clearance (CrCI), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 ― 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. Results: In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). Conclusion: The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.