Age-related male hypogonadism and cognitive impairment in the elderly: Focus on the effects of testosterone replacement therapy on cognition

Background. Epidemiological data report that male hypogonadism may play a role in cognitive impairment in elderly. However, the effect of testosterone replacement therapy (TRT) on cognitive abilities in this cluster of patients has not been well established. Methods. PubMed/MEDLINE, Google Scholar, Cochrane Library, and Web of Science were searched by using free text words and medical subject headings terms related with “male hypogonadism”, “late-onset hypogonadism”, elderly, cognition, “mild cognitive impairment”, memory, “testosterone replacement therapy” used in various combinations according to the specific clinical questions. Original articles, reviews, and randomized controlled trials written in English were selected. Results. A long-term TRT could improve specific cognitive functions, such as verbal and spatial memory, cognitive flexibility, and physical vitality. However, randomized controlled trials do not provide positive results, and in most of the cases TRT might not induce beneficial effects on cognitive function in elderly men. Discussion and conclusions. Since the lengthening of life expectancy, the prevalence rate of cognitive decline in elderly men is expected to increase remarkably over the next decade with considerable healthcare and economical concerns. Therefore, this remains a relevant clinical topic and further investigations are needed for clarifying the role of TRT especially in elderly men with hypogonadism

Hypothesized mechanisms explaining poor prognosis in type 2 diabetes patients with COVID-19: a review

Purpose: Epidemiological data suggest that comorbid patients, mostly those with type 2 diabetes (T2D), are predisposed to poor prognosis in Coronavirus disease 2019 (COVID-19), leading to serious healthcare concerns. The aim of the present manuscript is to review the main relevant mechanisms possibly contributing to worsen the clinical course of COVID-19 in T2D. Results: Poor glucose control, high glycaemic variability and diabetes-related comorbidities at baseline, particularly cardiovascular diseases and obesity, contribute in worsening the prognosis in the above-mentioned cluster of patients. Moreover, both a lower efficient innate immune system response and cytokine dysregulation predispose patients with T2D to impaired viral clearance and more serious pulmonary and systemic inflammation once the SARS-CoV-2 infection occurred. Inconclusive data are currently available for specifically indicate or contraindicate concurrent medications for managing T2D and its comorbidities in infected patients. Conclusions: T2D individuals should be considered as more vulnerable to COVID-19 than general population, and thus require adequate advices about hygienic tips to protect themselves during the pandemic. A careful management of glucose levels and diabetes-related comorbidities remains essential for avoiding further complications, and patient monitoring during the pandemic should be performed also at distance by means of telemedicine. Further studies are needed to clarify whether medications normally used for managing T2D and its associated comorbidities could have a protective or detrimental effect on COVID-19 clinical course

Experience treating electrical storm using an ultrasound guided stellate ganglion blockade

Introduction: Electrical storm is a life-threatening condition in an often medically complex patient population. Pharmacologic ultrasound-guided stellate ganglion blockade is a treatment option in combination with maximized systemic antiarrhythmic medications. There is an emerging body of case reports supporting stellate ganglion block efficacy and safety for this condition. Methods: Retrospective study on ultrasound-guided stellate ganglion blocks for electrical storm investigating patient clinical characteristics, immediate and long-term outcomes, and procedure related complications. Results: Four (75% men) critically ill patients maximized on standard antiarrhythmic therapy underwent six bedside ultrasound-guided stellate ganglion block procedures. All blocks were unilateral left-sided, two patients underwent repeat blocks for arrythmia reoccurrence. All patients experienced at least 12 hours free of ventricular arrhythmias with two thirds lasting beyond 24 hours. There were no observed complications. Conclusions: Ultrasound-guided stellate ganglion block is an effective and safe temporizing treatment option for electrical storm. Our institution-specific multidisciplinary guidelines were helpful in providing guidance for the use of stellate ganglion blocks in electrical storm

Signal transduction of mineralocorticoid and angiotensin ii receptors in the central control of sodium appetite: A narrative review

Sodium appetite is an innate behavior occurring in response to sodium depletion that induces homeostatic responses such as the secretion of the mineralocorticoid hormone aldosterone from the zona glomerulosa of the adrenal cortex and the stimulation of the peptide hormone angiotensin II (ANG II). The synergistic action of these hormones signals to the brain the sodium appetite that represents the increased palatability for salt intake. This narrative review summarizes the main data dealing with the role of mineralocorticoid and ANG II receptors in the central control of sodium appetite. Appropriate keywords and MeSH terms were identified and searched in PubMed. References to original articles and reviews were examined, selected, and discussed. Several brain areas control sodium appetite, including the nucleus of the solitary tract, which contains aldosterone‐sensitive HSD2 neurons, and the organum vasculosum lamina terminalis (OVLT) that contains ANG II‐sensitive neurons. Furthermore, sodium appetite is under the control of signaling proteins such as mitogen‐activated protein kinase (MAPK) and inositol 1,4,5‐thriphosphate (IP3). ANG II stimulates salt intake via MAPK, while combined ANG II and aldosterone action induce sodium intake via the IP3 signaling pathway. Finally, aldosterone and ANG II stimulate OVLT neurons and suppress oxytocin secretion inhibiting the neuronal activity of the paraventricular nucleus, thus disinhibiting the OVLT activity to aldosterone and ANG II stimulation

Endocrine system dysfunction and chronic heart failure: a clinical perspective

Chronic heart failure (CHF) leads to an excess of urgent ambulatory visits, recurrent hospital admissions, morbidity, and mortality regardless of medical and non-medical management of the disease. This excess of risk may be attributable, at least in part, to comorbid conditions influencing the development and progression of CHF. In this perspective, the authors examined and described the most common endocrine disorders observed in patients with CHF, particularly in individuals with reduced ejection fraction, aiming to qualify the risks, quantify the epidemiological burden and discuss about the potential role of endocrine treatment. Thyroid dysfunction is commonly observed in patients with CHF, and sometimes it could be the consequence of certain medications (e.g., amiodarone). Male and female hypogonadism may also coexist in this clinical context, contributing to deteriorating the prognosis of these patients. Furthermore, growth hormone deficiency may affect the development of adult myocardium and predispose to CHF. Limited recommendation suggests to screen endocrine disorders in CHF patients, but it could be interesting to evaluate possible endocrine dysfunction in this setting, especially when a high suspicion coexists. Data referring to long-term safety and effectiveness of endocrine treatments in patients with CHF are limited, and their impact on several “hard” endpoints (such as hospital admission, all-cause, and cardiovascular mortality) are still poorly understood

COVID19 outbreak in Lombardy, Italy: An analysis on the short-term relationship between air pollution, climatic factors and the susceptibility to SARS-CoV-2 infection

Short-term exposure to air pollution, as well as to climate variables have been linked to a higher incidence of respiratory viral diseases. The study aims to assess the short-term influence of air pollution and climate on COVID19 incidence in Lombardy (Italy), during the early stage of the outbreak, before the implementation of the lockdown measures. The daily number of COVID19 cases in Lombardy from February 25th to March 10th, 2020, and the daily average concentrations up to 15 days before the study period of particulate matter (PM10, PM2.5), O3, SO2, and NO2 together with climate variables (temperature, relative humidity – RH%, wind speed, precipitation), were analyzed. A univariable mixed model with a logarithm transformation as link function was applied for each day, from 15 days (lag15) to one day (lag1) before the day of detected cases, to evaluate the effect of each variable. Additionally, change points (Break Points-BP) in the relationship between incident cases and air pollution or climatic factors were estimated. The results did not show a univocal relationship between air quality or climate factors and COVID19 incidence. PM10, PM2.5 and O3 concentrations in the last lags seem to be related to an increased COVID19 incidence, probably due to an increased susceptibility of the host. In addition, low temperature and low wind speed in some lags resulted associated with increased daily COVID19 incidence. The findings observed suggest that these factors, in particular conditions and lags, may increase individual susceptibility to the development of viral infections such as SARS-CoV-2

Sympatho-Excitatory Response to Pulmonary Chemosensitive Spinal Afferent Activation in Anesthetized, Vagotomized Rats

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli

Pinhole free thin film CdS deposited by chemical bath using a substrate reactive plasma treatment

Achieving a pinhole-free CdS layer is necessary to produce high performance thin film CdTe solar cells. Pinholes in the CdS layer can compromise the efficiency of a CdTe solar cell by causing shunts. We have investigated the use of a plasma treatment of a fluorine doped tin oxide coated glass substrate (NSG TEC15) and its effect on pinhole reduction in thin film CdS layers grown by Chemical Bath Deposition. CdS films, < 100 nm thickness, were deposited on both O2/Ar plasma cleaned and conventionally cleaned substrates. We show that the O2 /Ar plasma treatment of the TEC15 substrate reduced the water contact angle from ~55º to less than 12º indicating a substantial increase in the surface energy. The CdS deposited on the plasma treated TEC 15 was pinhole free, very smooth and homogenous in morphology and composition. Scanning electron microscopy images show that the O2/Ar plasma treatment is effective in increasing film density and grain size. Corresponding spectroscopic ellipsometry measurements show an increase in the refractive index from 2.18 to 2.43 at 550 nm wavelength

The role of male hypogonadism, aging, and chronic diseases in characterizing adult and elderly men with erectile dysfunction: a cross-sectional study

BackgroundErectile function depends on a complex interaction between demographic, metabolic, vascular, hormonal, and psychological factors that trigger erectile dysfunction (ED). In the present study we carried out a cross-sectional study assessing the impact of non-communicable chronic diseases (NCDs), male hypogonadism, and demographic factors in characterizing men with ED. Four hundred thirty-three consecutive outpatients with ED were extracted from the electronic database from January 2017 to December 2019. The International Index of Erectile Function (IIEF) 5 score was used to diagnose ED and stratify its severity, standardized values of serum testosterone (10.5 nM/L) and luteinizing hormone (LH 9.4 IU/L) to diagnose and classify male hypogonadism and the Charlson Comorbidity Index (CCI) to weigh the role of each NCD on ED. ResultsForty-six percent of participants were eugonadal (EuG), 13% had organic hypogonadism (OrH), and the remaining 41% had functional hypogonadism (FuH). Hypogonadal men had a significantly lower IIEF 5 score (p &lt; .0001) than EuG. FuH had a higher CCI than OrH and EuG (all p &lt; .0001). In a multivariable model, only free T (FT) and Sex Hormone Binding Globulin (SHBG) showed a direct correlation with the IIEF 5 score (all p &lt; .0001). Age and CCI had an inverse correlation with IIEF 5 score (all p &lt; .0001).ConclusionSerum FT, SHBG, and CCI are the leading determinants of ED severity. Besides overt hypogonadism, a relevant burden of severe NTCDs in middle-aged or older adults features the patient's characteristics who will suffer from severe ED. Appropriate clinical approaches and, when necessary, treatments are required in these clusters of patients