Analysis of prognostic factors in COVID-19 hospitalized patients: an Italian single-center case-control study.

OBJECTIVE: COVID-19 clinical presentation ranges from asymptomatic infection to an inflammatory cytokine storm with multi-organ failure and fatal outcomes. The identification of high-risk patients for severe disease is crucial to plan an early treatment and intensive follow-up. We aimed to investigate negative prognostic factors in a group of patients hospitalized for COVID-19. PATIENTS AND METHODS: 181 patients (90 men and 91 women, mean age 66.56 ± 13.53 years) were enrolled. Each patient received a work-up including medical history, clinical examination, arterial blood gas analysis, laboratory blood tests, feasible ventilatory support required during hospital stay, intensive care setting required, duration of illness and length of hospital stay (>or<25 days). For the assessment of the severity of COVID-19, three main indicators were considered: 1) the intensive care unit (ICU) admission 2) the hospitalization length >25 days; 3) the need of non-invasive ventilation (NIV). RESULTS: The independent risk factor associated with the ICU admission were lactic dehydrogenase elevation (p=0.046), C reactive protein elevation (p=0.014) at hospital admission and direct oral anticoagulant home therapy (p=0.048); for hospital length >25 days: early corticosteroid therapy (p=0.035); for NIV treatment: ferritin elevation at hospital admission (p=0.006). CONCLUSIONS: The presence of the above factors may be useful to identify patients at high risk of developing a severe COVID-19 that need an early treatment and intensive follow-up.

Relationship between plasma aldosterone levels and arterial stiffness parameters in hypertensive patients with subclinical vascular damage.

Purpose: Aldosterone plays important role in cardiovascular damage. Aim was to evaluate arterial subclinical damage through arterial stiffness parameters in patients with Essential Hypertension (EH) and Primary Aldosteronism (PA). Methods: From 2018 to 2019 we consecutively enrolled 82 subjects (37 males and 45 women), distinguished in two groups: 60 EH [systolic blood pressure (SBP) 143.4 ± 16.7 mmHg, diastolic blood pressure (DBP) 89.5 ± 12.1 mmHg] and 22 PA (SBP 149 ± 19.5 mmHg, DBP 92.7 ± 12.4 mmHg) [5 with aldosterone-secreting adrenal adenoma(APA), 17 with idiopathic aldosteronism(IHA)]; 40 matched normotensive subjects (NS) were enrolled (SBP 109.7 ± 6.2 mmHg, DBP 71.3 ± 9.7 mmHg). We used non-invasive applanation tonometer to acquire pressure waveform. Results: PA patients showed higher µ-Albuminuria (UAE) (65.7 ± 11.0mg/24 h) than EH and NS (21.5 ± 7.0 mg/24 h and 21.5 ± 7.0 mg/24 h, respectively); APA group showed increased levels of arterial stiffness index (11.7 ± 4.8 m/s; p < 0.02) compared to EH subjects (8.3 ± 3 m/s) and NS subjects (7.2 ± 1.7 m/s) as well as higher carotid intima-media thickness (c-IMT); APA patients showed significant reduction of subendocardial viability ratio (SEVR) and travel time of the reflected waves (TI) respect EH and NS. PA groups showed high percentage of augmented "worsening age" (60%), compared to EH (38%) and NS (37%). PAC was positively correlated with Arterial Stiffness Index. Performing multiple linear regression analysis (evaluating anthropometric and biochemical parameters), we found UAE as predictor of Augmentation Index, Arterial Stiffness Index and Travel Time of reflected waves in the enrolled population. Conclusion: PA patients showed higher cardiovascular subclinical damage respect to EH; UAE excretion had significant correlation with aldosterone, resulting best marker of subclinical vascular remodeling.

Work-related stress and cortisol levels: is there an association? Results of an observational study.

OBJECTIVE: Chronic exposure to work-related stress (WRS) stimulates the hypothalamic-pituitary-adrenal (HPA) axis to increase glucocorticoid secretion, including cortisol, and these hormones can be measured both in serum and urine. The Health Safety Executive Toolkit (HSE) questionnaire is used to assess WRS risk objectively. The scope of our study is to investigate whether serum or urinary cortisol levels could be used as alternative objective indicators of WRS, specifically in those subjects who are chronically exposed to it. PATIENTS AND METHODS: 130 patients (75 males and 55 females, mean age 47.7 ± 11.3 years) were evaluated at a specialized Centre for Secondary Hypertension, where both their serum (8 AM) and 24-hours urinary cortisol were measured and they were asked to complete two questionnaires: one questionnaire to collect data about their socio-demographic and job characteristics, and the HSE questionnaire to evaluate WRS. RESULTS: Multiple linear regression analysis showed an association of urinary cortisol with several variables: tobacco smoke (ß = 69.6; p = 0.003); female gender (ß = -37.3; p = 0.041); exposure to physical risks (ß = 51.8; p = 0.032); control score (ß = -22.7; p = 0.039); role score (ß= 39.3; p = 0.020). Age was the only variable associated with serum cortisol levels (ß = -3.6; p = 0.042). CONCLUSIONS: Urinary cortisol levels, but not serum levels, are associated with variables linked to WRS (score control and role) and to socio-demographic variables, namely gender and tobacco smoke. Thus, urinary cortisol can be considered a useful and non-invasive biological indicator to quantify WRS.

Peri-implant diseases and metabolic syndrome components: a systematic review.

OBJECTIVE: Metabolic syndrome (MetS) is defined as a spectrum of conditions associated with an increased risk of developing CVD and type 2 diabetes. MetS include: hyperglycemia, hypertension, visceral obesity, dyslipidemia with elevated values of triglycerides (TG) and low levels of HDL. The aim of this review is to provide current knowledge of the relationship between MetS, its components and peri-implant diseases. MATERIALS AND METHODS: An electronic literature search was conducted in the English language in several databases. The Newcastle-Ottawa Scale was used for quality assessment of cohort and cross-sectional studies; while systematic reviews were evaluated through AMSTAR; results were reported according to the PRISMA Statement. RESULTS: A total of 272 records were identified through database searching, six studies were included for qualitative analysis. No study directly related to MetS was found, there was inconsistent and controversial evidence regarding association with cardiovascular disease. A higher risk of peri-implantitis was detected in people with hyperglycemia. CONCLUSIONS: Future research should be orientated in assessing the risk of peri-implant diseases, evaluating patient's therapeutic response, analyzing directionality of the relationship between MetS, its components and biologic implant complications.

Ambulatory blood pressure monitoring-derived short-term blood pressure variability in primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism is associated with a cluster of cardiovascular manifestations, including hypertension, leading to increased cardiovascular risk. PURPOSE: The aim of our study was to investigate the ambulatory blood pressure monitoring-derived short-term blood pressure variability in patients with primary hyperparathyroidism, in comparison with patients with essential hypertension and normotensive controls. METHODS: Twenty-five patients with primary hyperparathyroidism (7 normotensive,18 hypertensive) underwent ambulatory blood pressure monitoring at diagnosis, and fifteen out of them were re-evaluated after parathyroidectomy. Short-term-blood pressure variability was derived from ambulatory blood pressure monitoring and calculated as the following: 1) Standard Deviation of 24-h, day-time and night-time-BP; 2) the average of day-time and night-time-Standard Deviation, weighted for the duration of the day and night periods (24-h "weighted" Standard Deviation of BP); 3) average real variability, i.e., the average of the absolute differences between all consecutive BP measurements. RESULTS: Baseline data of normotensive and essential hypertension patients were matched for age, sex, BMI and 24-h ambulatory blood pressure monitoring values with normotensive and hypertensive-primary hyperparathyroidism patients, respectively. Normotensive-primary hyperparathyroidism patients showed a 24-h weighted Standard Deviation (P < 0.01) and average real variability (P < 0.05) of systolic blood pressure higher than that of 12 normotensive controls. 24-h average real variability of systolic BP, as well as serum calcium and parathyroid hormone levels, were reduced in operated patients (P < 0.001). A positive correlation of serum calcium and parathyroid hormone with 24-h-average real variability of systolic BP was observed in the entire primary hyperparathyroidism patients group (P = 0.04, P = 0.02; respectively). CONCLUSION: Systolic blood pressure variability is increased in normotensive patients with primary hyperparathyroidism and is reduced by parathyroidectomy, and may potentially represent an additional cardiovascular risk factor in this disease.

Vitreous and plasma changes of endothelin-1, adrenomedullin and vascular endothelium growth factor in patients with proliferative diabetic retinopathy.

OBJECTIVE: To assess vitreous and plasma changes of vascular endothelial growth factor A (VEGF-A), adrenomedullin (ADM) and endothelin-1 (ET-1) in proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: 9 patients with PDR in type 2 diabetes (T2DM) and 11 age-matched non-diabetic patients were enrolled. The levels of VEGF-A, ADM and ET-1 were measured using an enzyme (ELISA) and a radioimmunoassay (RIA) both in vitreous and plasma samples. RESULTS: Vitreous ADM and VEGF-A levels were significantly higher in PDR patients (p=0.04 and p=0.02), whereas no differences were found in ET-1 levels (p=0.29). Plasma ADM levels were significantly higher in the PDR group (p<0.01), whereas no significant differences were found in the plasma ET-1 and VEGF-A levels (p=0.30 and p=0.37). The ADM vitreous/plasma ratio was significantly reduced in PDR group. CONCLUSIONS: The role of ET-1 in advanced PDR is still controversial; it has been supposed a role limited to induce hypoxic state and promote angiogenesis in the early phases. Once the neo-angiogenic process starts, other mediators are mainly involved as VEGF and ADM. Our findings suggest that ADM is an important marker of advanced PDR as well as VEGF. Conversely, ET-1 is not significantly involved in the advanced stage of PDR.

Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism.

Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients.

Epicardial Fat Thickness and Primary Aldosteronism.

Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings.

Hypokalemic rhabdomyolysis: a rare manifestation of primary aldosteronism.

Rhabdomyolysis is a rare presentation of hypokalemia, although muscle weakness is a well-known manifestation of hypokalemia. Primary aldosteronism is characterized by hypertension, suppressed plasma renin activity, increased aldosterone excretion and hypokalemia with metabolic alkalosis. Rhabdomyolysis is not common in primary aldosteronism. We present here a 40-year-old woman presenting with rhabdomyolysis accompanied by severe hypokalemia as heralding symptom of primary aldosteronism.

Primary aldosteronism with concurrent primary hyperparathyroidism: clinical case load in a single centre.

OBJECTIVE: Primary aldosteronism (PA) represents the main cause of endocrine secondary arterial hypertension in which aldosterone production is inappropriately elevated. Primary hyperparathyroidism (PHPT) is an endocrine disease characterized by hypercalcemia due to overproduction of parathyroid hormone (PTH). Although these two endocrine pathologies are secondary to hypertension in middle aged population, the occurrence of the PHPT in PA patients has rarely reported in the literature. The aim of the study was to describe some PA patients with concurrent PHPT, referred in a tertiary center of arterial hypertension. PATIENTS: We performed a retrospective study. In particular, the registry of 306 patients with PA seen in our center since 2004 was examined and revealed 8 patients (2.6%) with concurrent PHPT. CONCLUSIONS: There are several possible explanations for the association of these two endocrine disorders, including the combination was a random finding that PA inheres PHPT or vice versa.

Association between -308 G/A TNF-α polymorphism and appendicular skeletal muscle mass index as a marker of sarcopenia in normal weight obese syndrome.

BACKGROUND AND AIM: Normal weight obese (NWO) syndrome is characterized by normal body mass index (BMI), but high amount of fat mass and reduced lean mass. We evaluated allelic frequency of the G/A -308 TNF-α polymorphism and prevalence of sarcopenia in NWO. METHODS: We enrolled 120 Italian healthy women, distinguished into 3 groups: normal weight (NW); NWO, and preobese-obese (PreOB/OB) and evaluated anthropometric parameters, body composition by dual X-ray absorptiometry, blood tests, and genotyping of G/A -308 TNF-α polymorphism. RESULTS: We found a positive association between sarcopenic obesity and -308 TNF-α polymorphism. All obese women were sarcopenic and were no carrier of mutation (G/G). Among all G/G, NWO showed significant differences in lean mass and total body lean mass (TBLean) with respect to NW and PreOB/OB (P < 0.001). Regarding appendicular skeletal muscle mass index values, 4.21% of NW were sarcopenic (50% G/G and 50% G/A); the same percentage was observed in NWO subjects (100% G/G). Moreover, 2.10% of PreOB/OB were sarcopenic and all were G/G. CONCLUSION: Our study suggests that TNF-α polymorphism contributes to sarcopenic obesity susceptibility, in association with body composition. This is the first study that shows the importance of TNF-α polymorphism to determine TBLean variation in NWO syndrome.

A giant hemorragic adrenal pseudocyst: contrast-enhanced examination (CEUS) and computed tomography (CT) features.

INTRODUCTION: Adrenal pseudocysts are rare cystic masses that arise from the adrenal gland and which are usually non-functional and asymptomatic. We report a rare case of a giant hemorrhagic adrenal pseudocyst presenting with abdominal pain and we discussed the radiological features. PRESENTATION OF CASE: A 75 year old man was admitted with acute abdominal pain post mild-trauma. Computed tomography (CT) of abdomen revealed a hemorrhagic mass measuring 18 cm located in the right suprarenal region, displacing the right kidney and liver. He subsequently underwent to contrast enhancement ultrasound (CEUS), which showed features suggestive for hemorrhagic adrenal pseudocyst. A complete endocrine working didn't show any hormonal hypersecretion. The patient underwent laparotomy and right adrenal mass was excised. Histological examination revealed giant hemorrhagic adrenal pseudocyst. The abdominal pain resolved after surgery. CONCLUSIONS: to the best our knowledge, this is the first case studied with CEUS reported in the literature.

Adrenal ganglioneuroma incidentally discovered in a patient with dysuria: a case report.

A case of adrenal ganglioneuroma incidentally discovered during an abdominal ultrasound examination in a 26 year-old woman patient with recurrent episodes of dysuria. After a diagnostic work-up with laboratory and abdomen CT scan, the patient uderwent a laparotomic removal of the adrenal lesion. Histopathological examination of the adrenal mass confirmed the diagnosis.

Relation of adiponectin, visfatin and bone mineral density in patients with metabolic syndrome.

BACKGROUND: Adipose tissue has been suggested to influence bone density and metabolism through the effect of some adipokines. However, whether adiponectin and visfatin may correlate with bone metabolism is still unclear. AIM: The aim of this study was to investigate the relationship of adiponectin and visfatin with bone density in patients with metabolic syndrome (MS). SUBJECTS: We enroled 72 consecutive patients with MS (25 males, 47 females; mean age 58.14±11 yr) and 40 control subjects. METHODS: Plasma adiponectin and visfatin levels were measured. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) at the level of lumbar spine L2-L4 (BMD L2-L4) and femoral neck (BMD-Fn). RESULTS: MS patients had higher plasma visfatin and lower adiponectin levels than controls, (p<0.01 for both). Adiponectin was negatively correlated with BMD-Fn and BMD L2-L4 (r=-0.20, r=-0.24, respectively; p<0.05 for both) whereas plasma visfatin levels were positively correlated to BMD L2-L4 only in men (r=0.44; p<0.05). CONCLUSIONS: Our study shows that adiponectin and visfatin are oppositely associated with BMD. Although the mechanisms behind these correlations are unclear, a modulation of bone metabolism by these adipokines can be suggested.

Primary aldosteronism due to adrenocortical adenoma with concurrent ileum carcinoid tumor: case report.

Primary aldosteronism (PA) with synchronous carcinoid syndrome is extremely rare occurrence. In this article, we describe a case of PA due to adrenocortical adenoma ("aldosteronoma") and concurrent malignant carcinoid tumor of ileum. The patient was treated with synchronous right adrenalectomy and resection of the ileum. This case is an example of concomitant presence of two types of tumors, effectively managed surgically. We report a case of a nonclassical form of multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Renin-angiotensin-aldosterone system in patients with sleep apnoea: prevalence of primary aldosteronism.

Obstructive sleep apnoea (OSA) is a sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, representing an independent risk factor for cardiovascular disease, such as myocardial infarction, stroke, congestive heart failure and resistant hypertension. Several neurohormonal mechanisms have been suggested to account for blood pressure increases, such as sympathetic nervous system hyperactivity, oxidative stress, renin-angiotensin-aldosterone system (RAAS) activation, endothelin system activation, and endothelial dysfunction. The aim of this study was to evaluate the behaviour of RAAS and the presence of primary aldosteronism (PA) in these patients and possible correlations between RAAS and the severity of OSA. From October 2007 to November 2008 we studied 325 consecutive newly diagnosed hypertensive patients; 71 patients (21.8%) presented with clinical signs of sleep disorders, evaluated also through a specific questionnaire (Epworth Sleepiness Scale). In hypertensive patients with sleep disorders, 53 patients were affected by OSA; in this group 18 patients were affected by PA (five with aldosterone-producing adenoma (APA) and 13 with bilateral hyperplasia (IHA)); obesity was also demonstrated (BMI > 30 kg/m(2)). Overall, in patients with OSA PRA levels correlated positively with apnoea/hypopnoea index (AHI; r = 0.35; p<0.01), and in all groups the waist circumference and the neck circumference were correlated positively with AHI (r = 0.3 p<0.02 and r = 0.3 p<0.03, respectively). We revealed a high prevalence of PA in patients with OSA, and we can conclude that patients with hypertension and OSA, especially those who are newly diagnosed, must be evaluated for PA.

Parathyroidectomy erase increased myocardial electrical vulnerability in patients with primary hyperparathyroidism.

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) show an increased bioelectrical risk not related to cardiovascular complications, this risk seems to persist after surgery and this last finding is still controversial and probably related to follow-up length. METHODS: The aim of the study is to evaluate QT parameters in 11 patients with primary hyperparathyroidism (pHPT) 18 months after parathyroid surgery using computed standard 12-leads ECG compared to those of 29 healthy subjects (HS). RESULTS: In pHPT patients, 4 months after parathyroidectomy QT and QTc dispersion persist significantly higher than HS. 18 months after surgery, QT and QTc dispersion resulted comparable with HS. QT dispersion was found significantly higher in pHPT at 4 months respect 18 months after parathyroidectomy. CONCLUSIONS: ECG alteration after parathyroidectomy gradually return within normal limits and we can affirm that surgery erase bioelectrical risk in pHPT.

Endothelin-1 plasma concentrations in patients with retinitis pigmentosa.

PURPOSE: The aim of this study was to investigate the behaviour of plasma endothelin-1 (ET-1) levels in patients affected by retinitis pigmentosa (RP) and syndromic RP. METHODS: Blood samples were obtained from a group of 40 consecutive patients with RP matched with 35 healthy subjects (HS) as control. We carried out a complete ophthalmological examination. The study group included 26 patients with RP and 14 patients with syndromic RP. Plasma ET-1 levels were determined in duplicate with a specific radioimmunoassay method. RESULTS: In the HS plasma ET-1 levels were 7.48+/-2.58 pg/mL. The mean of plasma ET-1 concentrations in all patients with RP ( 16.2+/-5.6 pg/mL) was significantly (P<0.01) higher than that of HS. Moreover, in the syndromic RP patients, plasma ET-1 levels (18.9+/-6.8 pg/mL) were higher than those of HS and RP patients (P<0.01). CONCLUSION: The increase of plasma ET-1 levels in RP patients suggests that ET-1 may play a role in the pathophysiology of the diseases involving retinal pigment epithelial cells and the retinal vascular system such as RP.

Hyperhomocysteinemia: a biochemical link between bone and cardiovascular system diseases?

Homocysteine (HCY) is a sulfur-containing amino acid involved in two metabolic pathways, catalized by cystathionine-B-synthase and methionine synthase, depending on vitamin (vit) B6, B12, and folate levels and enzymatic activity of methylenetetrahydrofolate. High HCY levels (HHCY) are associated with cardiovascular (CV) and bone diseases, in particular osteoporosis (OP)/hip fracture. As regards the mechanisms involved in the link between HHCY, CV diseases (CVD), and OP, it has been proposed the role of lysyl-oxydase inhibition that might interfere with collagen crosslink formation. Some studies suggested the dysregulation of the osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK) ligand/RANK axis, others the involvement of oxidative stress. These mechanisms may act both on bone and CV system, but whether the common denominator is HCY itself or HCY is merely a marker, remains to be clearly established. Folate, vit B6, and B12 supplementation is associated with HCY reduction, but is unable to certainly reduce the incidence of OP/fracture and CVD, probably because, in the majority of patients, HCY is only moderately increased.