Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper.

Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient's values and target the best outcome possible given the patient's desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes.

Trauma Center model application in the University Hospital of Pisa: a single-center comparative study.

The Trauma Center, Hub, is a highly specialized hospital indicated for complex major trauma management after stabilization at a 1st level hospital, Spoke. Although in the United States this organization demonstrated its effectiveness in mortality, in the Italian context, data available are limited. On 30 September 2018, the University Hospital of Pisa formalized the introduction of the Trauma Center, optimizing Emergency Department (ED) organization to guarantee the highest standard of care. The aim of this study was to demonstrate that the new model led better outcomes. We conducted a comparative retrospective study on 1154 major traumas over 24 months: the first 12 months (576 patients) correspond to the period before Trauma Center introduction, and the following 12 (457 patients) to the subsequent period. Results showed increase in greater dynamics and primary centralization by helicopter (p < 0.001, p 0.006). A systematic assessment with ABCDE algorithm was performed in a higher number of patients in the most recent period, from 38.4% to 80.3% (p < 0.001). Focused Assessment with Sonography for Trauma (FAST) performed by the emergency doctor increased after Trauma Center introduction, p value < 0.001. The data show an increase of ATLS certification among staff from 51.9 to 71.4% and a reduction in early and late mortality after the Trauma Center introduction (p value 0.05 and < 0.01). Fewer patients required intensive and surgical treatments, with a shorter hospital stay. The results demonstrate the advantage in terms of outcomes in the organization of the Trauma Center in the Italian context.

Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Antiangiogenic Drugs in NASH: Evidence of a Possible New Therapeutic Approach.

Non-alcoholic fatty liver disease is the most common liver disorder worldwide, and its progressive form non-alcoholic steatohepatitis (NASH) is a growing cause of liver cirrhosis and hepatocellular carcinoma (HCC). Lifestyle changes, which are capable of improving the prognosis, are hard to achieve, whereas a pharmacologic therapy able to combine efficacy and safety is still lacking. Looking at the pathophysiology of various liver diseases, such as NASH, fibrosis, cirrhosis, and HCC, the process of angiogenesis is a key mechanism influencing the disease progression. The relationship between the worsening of chronic liver disease and angiogenesis may suggest a possible use of drugs with antiangiogenic activity as a tool to stop or slow the progression of the disorder. In this review, we highlight the available preclinical data supporting a role of known antiangiogenic drugs (e.g., sorafenib), or phytotherapeutic compounds with multiple mechanism of actions, including also antiangiogenic activities (e.g., berberine), in the treatment of NASH.

Procalcitonin, white blood cell count and C-reactive protein as predictors of S. aureus infection and mortality in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell - WBC - count, C-reactive protein - CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. METHODS: Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. RESULTS: Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers < cut-offs. AUC values for in-hospital death were 0.702, 0.725 and 0.727 for the WBC, CRP, and procalcitonin, respectively. Among inflammatory biomarkers, WBC and procalcitonin independently predicted in-hospital death. Procalcitonin refined risk stratification when added to WBC, and to the combination of WBC and CRP. Patients with WBC ≥ 10,535/mm3, CRP ≥ 85 mg/dL, and procalcitonin ≥ 0.4 ng/mL had a 27-fold higher risk of in-hospital death than patients with all biomarkers < cut-offs. CONCLUSIONS: Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

Vascular Function Is Improved After an Environmental Enrichment Program: The Train the Brain-Mind the Vessel Study.

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65-89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid-femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P=0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10-3; P=0.009); only the latter remained significant after adjustment for confounders (P=0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P=0.006; P=0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34+ cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa-1; P=0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34+ cells, and preserved carotid distensibility. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01725178.

Polyphenols, Antioxidants and the Sympathetic Nervous System.

BACKGROUND: A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. METHODS: This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. RESULTS: The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. CONCLUSIONS: While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic strategy to reduce the deleterious effects of increased adrenergic tone, particularly in essential hypertension.

Cardiovascular risk and hypertension control in Italy. Data from the 2015 World Hypertension Day.

BACKGROUND: Cardiovascular diseases (CVD) are the first cause of death and disability in western countries. Despite therapeutic advances, their prevalence is constantly increasing. Detailed assessment of modifiable CV risk factors could improve CVD prevention and management. METHODS: to assess CV risk and hypertension control in a sample of the Italian population, individuals participating to the 2015 "World Hypertension Day" were interviewed in 62sites all over Italy. Blood pressure was measured with a validated auscultatory or oscillometric device and information on demography and prevalence of CVD risk factors was collected by an anonymous questionnaire. An ad-hoc modified version of the Systematic COronary Risk Evaluation (SCORE) system was then applied. RESULTS: 8657 recruited individuals (43%women, aged 56.68±16years) were subdivided into 3 age groups (40-49y, 50-59y, 60-69y) for analysis. CV risk was low in 62.4%, 18.0% and 0%; moderate in 26.0%, 66.0% and 62.5%; high/very high in 11.6%, 16% and 37.4%, respectively. Smoking was mainly responsible for increased CV risk among those aged 40-49y (26%smokers), while hypertension was the main factor in the whole sample and in subjects over 50y (36% and 42% respectively). Overall, BP control was unsatisfactory in 36% of individuals (28%, 48% and 31% of those who declared to be normotensive, hypertensive on treatment or unaware of their BP condition, respectively). CONCLUSIONS: In this sample of the Italian population, CV risk was alarmingly high, irrespectively of age, mostly due to presence of modifiable risk factors, including hypertension, which should thus be better addressed, especially in the youngsters.

Olfactory evaluation in Mild Cognitive Impairment: correlation with neurocognitive performance and endothelial function.

Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able to predict MCI with a good sensitivity and specificity (70.3 and 77.4% respectively). In MCI, olfactory identification score is correlated with a number of neurocognitive abilities, including overall cognitive status, dementia rating, immediate and delayed memory, visuospatial ability and verbal fluency. FMD was reduced in MCI (2.90 ± 2.15 vs. 3.66 ± 1.96%, P = 0.016) and was positively associated with olfactory identification score (ρs =0.219, P = 0.025). The association remained significant after controlling for age, gender, and smoking. In conclusion, olfactory evaluation is able to discriminate between MCI and healthy individuals. Systemic vascular dysfunction might be involved, at least indirectly, in olfactory dysfunction in MCI.

Adolescents with Classical Polycystic Ovary Syndrome Have Alterations in the Surrogate Markers of Cardiovascular Disease but Not in the Endothelial Function. The Possible Benefits of Metformin.

STUDY OBJECTIVE: To study whether adolescents with the classical form of polycystic ovary syndrome (PCOS) have alterations in metabolic and vascular structure and function. The effect of metformin was evaluated. DESIGN: Controlled study. SETTING: University outpatient clinic. PARTICIPANTS: Eighteen nonobese adolescents with PCOS were enrolled. Seventeen healthy age-matched adolescents were recruited as control subjects. INTERVENTIONS: The metabolic profile and the endothelial structure and function were evaluated. MAIN OUTCOME MEASURES: Hormonal and lipid profile, blood pressure (BP) measurement, fasting glucose and insulin levels, C-reactive protein (CRP), homocysteine, tissue-type plasminogen activator, plasminogen activator inhibitor-1 (PAI-1), and plasmin-antiplasmin complexes (PAP) were measured. Flow mediated dilation (FMD), central pulse wave velocity (PWV), radial artery pulse wave, and common carotid intima-media thickness (IMT) were also assessed. Girls with PCOS were also studied 6 months after treatment with metformin (850 mg twice per day). RESULTS: Adolescents with PCOS were insulin resistant and/or hyperinsulinemic and they had higher BP values and levels of CRP and PAI-1 than the control subjects. The levels of tissue-type plasminogen activator and PAP were similar in both groups. FMD, PWV, and IMT were also similar. Metformin significantly (P < .05) reduced insulin, BP, CRP, and PAI-1 levels. The PAP levels significantly (P < .05) increased. Radial artery pulse wave was significantly reduced after metformin treatment. No modifications in FMD, PWV, and IMT were observed. CONCLUSION: Adolescents with classical PCOS have alterations in some surrogate markers of cardiovascular risk and they are ameliorated by metformin. No deterioration of vascular structure and function has been detected, probably because of the short duration of exposure to the disease.

Clinical management of drug-induced hypertension: 2013 Practical Recommendations of the Italian Society of Hypertension (SIIA).

Results from recent observational studies conducted in our country and including approximately 160,000 patients with hypertension, reported that only 37 % of patients achieve effective blood pressure control under treatment. These data confirm that blood pressure control amongst the hypertensive population is still largely unsatisfactory in Italy. For this reason, the Italian Society of Hypertension aims to generate a number of interventions to improve blood pressure control in Italy, including integrated actions with General Practitioners, the implementation of hypertension awareness in the general population, a larger use of home blood pressure measurements, and a survey aimed at identifying all clinical and excellence centers for hypertension diagnosis and treatment throughout the whole national territory. Many therapeutic agents or chemical substances can induce a persistent or transient increase in blood pressure or interfere with the effect of antihypertensive drugs, causing sodium retention and expansion of the extra-cellular volume, activating the sympathetic nervous system and inducing vasoconstriction. This aspect represents one of the most common cause of secondary forms of hypertension, which often is under-evaluated by the physicians. In this review article, the potential causes of secondary forms of hypertension caused by use/abuse of drugs or substances are summarized.

Predictive role of renal resistive index for clinical outcome after revascularization in hypertensive patients with atherosclerotic renal artery stenosis: a monocentric observational study.

BACKGROUND: The present study evaluated the predictive value of renal resistive index (RI) for renal function and blood pressure (BP) outcome in hypertensive patients with unilateral atherosclerotic renal artery stenosis submitted to successful revascularization. METHODS: In 158 hypertensive patients with atherosclerotic renal artery stenosis RI was acquired. Twelve months after revascularization, they were classified on the basis of renal function and BP outcome as benefit (BP < 140/90 mmHg or diastolic BP reduction > 15 mmHg with the same of reduced drugs; decrease in glomerular filtration rate > 20%), or failure. RESULTS: Regarding renal function outcome, RI in the stenotic and in the contralateral kidney were significantly higher in patients with failure (n = 20) than in those with benefit (0.72 ± 0.11 vs 0.61 ± 0.11 and 0.76 ± 0.08 vs 0.66 ± 0.09, p < 0.05). Among different cutpoints generated, RI in the contralateral kidney >0.73 provided the largest area under the curve (0.77), and the highest sensitivity (80%) and specificity (72%). In the multivariate logistic regression analysis, RI in the contralateral kidney >0.73 was an independent predictor of a failure in renal function outcome.Regarding BP outcome, patients with no benefit from revascularization (n = 60) had similar RI in the stenotic and contralateral kidney (p = ns), but presented higher pulse pressure, albuminuria and hypertension duration in comparison to patients with improved BP control. CONCLUSIONS: RI in the contralateral kidney is an independent predictor of renal function outcome after successful revascularization in hypertensive patients with unilateral atherosclerotic renal artery stenosis, whereas it is not able to predict blood pressure outcome.

Task force on: 'Early markers of atherosclerosis: influence of age and sex'.

Atherosclerosis and its complications are the most important causes of death all over the world, especially in Western countries. Diet habits, modern stress life, smoking, sedentary way of life and an involvement of genetic pattern of individuals lead to a sure degeneration of quality of life increasing the risk of atherosclerosis development. For this reason, the main purpose of actual medicine is to identify all the markers that could allow the physicians to evaluate the first moments of the development of this dangerous pathological process. The aim is to reduce the speed of its evolution, trying to delay indefinitely the risk coming from the morphological alterations of the vessels. 'Endothelium function' could allow physicians to detect the first moment of the natural history of atherosclerosis process. Its impairment is the first step in the degeneration of vascular structures. Many methods [flow-mediated vasodilatation (FMD); antero-posterior abdominal aorta diameter (APAO); intima-media thickness of the common carotid artery (CCA-IMT); arterial stiffness; and so on] try to evaluate its function, but many limitations come from general population characteristics. A standardization of the methods should take into account individuals' peculiarities. Two elements, not modifiable, should be taken into account for vascular evaluation: age and sex. The aim of this review is to outline the linkage among age, sex and instrumental evaluation of patients considered for a noninvasive assessment of their cardiovascular risk profile.

Functional and structural alterations of large arteries: methodological issues.

Ultrasound assessment of vascular biomarkers has been implemented for screening, prevention and improvement of cardiovascular risk stratification beyond classical risk factors including smoking, diabetes, hypercholesterolemia and hypertension. Thus, the presence of vascular damage at the sub-clinical, asymptomatic stages can identify a "vulnerable" patient, and aid in implementing cardiovascular prevention strategies. Increased intima-media thickness of the common carotid artery is a well-known marker of early atherosclerosis, which significantly correlates with the development of coronary or cerebro-vascular disease. More recently, guidelines for cardiovascular prevention in hypertension also introduced other vascular parameters evaluating both mechanical and functional arterial properties of peripheral arteries. Increased arterial stiffness, which can be detected by ultrasound at the common carotid, has been shown to predict future cardiovascular events and it is already considered a subclinical target organ of hypertensive patients. Even earlier vascular abnormalities such as endothelial dysfunction in the peripheral arteries, detected as reduced flow-mediated dilation of the brachial artery by ultrasound, have also been mentioned for their possible clinical use in the future. This manuscript reviews clinical evidence supporting the use of these different vascular markers for cardiovascular risk stratification, focusing on the need for an accurate, robust and reliable methodology for the assessment of vascular markers, which could improve their predictive value and increase their use in routine clinical practice.

Adipocytokine levels mark endothelial function in normotensive individuals.

BACKGROUND: Endothelial dysfunction is an independent risk factor for cardiovascular events. Inflammatory mediators released by the adipose tissue can lead to local insulin resistance and endothelial dysfunction. This study addressed the relationship of adipocytokines with endothelial function and blood pressure. METHODS: In 92 newly diagnosed, drug-naïve essential hypertensive patients (HT, mean age 49 yrs) without organ damage and 66 normotensive subjects (NT, mean age 47 yrs), by an automated system, we measured endothelium-dependent and -independent vasodilation as brachial artery flow-mediated dilation before and after administration of glyceryl-trinitrate. Retinol binding protein-4 (RBP4) and resistin levels were determined by ELISA and RIA, respectively. Oxidative stress was evaluated by measuring serum malondyaldehyde (MDA). RESULTS: Flow-mediated dilation was significantly (p = 0.03) lower in HT (5.3 ± 2.6%) than NT (6.1 ± 3.1%), while response to glyceryl-trinitrate (7.5 ± 3.7% vs 7.9 ± 3.4%) was similar. RBP4 (60.6 ± 25.1 vs 61.3 ± 25.9 µg/ml), resistin (18.8 ± 5.3 vs 19.9 ± 6.1 ng/ml) and MDA levels (2.39 ± 1.26 vs 2.08 ± 1.17 nmol/ml) were not different in HT and NT.RBP4 (r = -0.25; p = 0.04) and resistin levels (r = -0.29; p = 0.03) were related to flow-mediated dilation in NT, but not in HT (r = -0.03 and r = -0.10, respectively). In NT, multivariate analysis including RBP4 and confounders showed that only BMI or waist circumference remained related to flow- mediated dilation. In the multivariate model including resistin and confounders, BMI, age and resistin were significantly related to flow-mediated dilation, while only age significant correlated with this parameter when BMI was replaced by waist circumference. CONCLUSIONS: Adipocytokine levels may be independent predictors of endothelial dysfunction in the peripheral circulation of healthy subjects, providing a pathophysiological link between inflammation from adipose tissue and early vascular alterations.

Soluble CD40 ligand is predictive of combined cardiovascular morbidity and mortality in patients on haemodialysis at a relatively short-term follow-up.

BACKGROUND: We tested the hypothesis that soluble CD40 ligand (sCD40L), a biomarker of proatherogenic inflammation, may be predictive of cardiovascular (CV) events in a subgroup of patients from the RISCAVID study, an observational and prospective study in patients on haemodialysis (HD). METHODS: Plasma sCD40L levels were assessed at the time of the enrollment in 300 HD patients (mean age: 65 ± 15 years), recruited in five different centres. During a follow-up of 24 months, overall mortality, CV mortality and CV major nonfatal events (acute myocardial infarction, congestive heart failure and stroke) were registered. Cox proportional hazards regression assessed adjusted differences in CV morbidity and mortality risk. RESULTS: Stratifying patients according to plasma sCD40L levels in those with levels lower or equal to (sCD40L-) and greater than (sCD40L+) the median value of 7.6 ng/mL, no significant difference was observed at baseline between the two groups in age, gender, blood pressure values and previous CV events. At 24-month follow-up, a significant (P < 0.01) lower incidence of the combined end point of CV morbidity and mortality was observed in the sCD40L- group (29%) as compared to the sCD40L+ group (36%). In the multivariate Cox proportional hazards regression model, the presence of sCD40L above the median value is associated with a significant increase in the risk of CV morbidity and mortality (hazard ratio: 1.61, 95% confidence interval 1.03-3.11). CONCLUSIONS: These observational results support the prognostic value of sCD40L in end-stage renal disease, thus providing a useful tool to better stratify CV prognosis in these patients.

[Resistant hypertension: a case report]. / Un caso di ipertensione arteriosa resistente.

A 72-years-old man, having 230-210/110-90 mmHg with a 5-drugs antihypertensive regimen, was diagnosed with an aldosterone-producing adenoma. Blood pressure values remained elevated in spite of spironolactone therapy and surrenectomy, possibly because of renal insufficiency and vascular damage subsequent to long-term uncontrolled hypertension.

Human endothelial dysfunction: EDCFs.

Human studies, conducted in the presence of clinical conditions characterized by endothelial dysfunction, evidenced that endothelial cells, in response to different agonists and physical stimuli, become a source of endothelium-derived contracting factors (EDCFs), mainly cyclooxygenase (COX)-derived prostanoids. Their production has been documented in several human diseases, mostly in essential hypertension and aging. The EDCF production was at first identified as responsible for impaired endothelium-dependent vasodilation in the forearm microcirculation of patients with essential hypertension. Subsequent studies demonstrated that COX-dependent EDCF products are also a characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. Of note, in aging and hypertension, both indomethacin, a COX inhibitor, and vitamin C, an antioxidant, totally reverse the blunted vasodilation to acetylcholine by restoring NO availability, thus suggesting that EDCFs could be one of the major sources of oxygen free radicals. The presence of EDCFs was documented also in other clinical setting, such as coronary artery disease and estrogen deprivation. In conclusion, many human pathological conditions characterized by a decline in endothelial function are associated with a progressive decrease in NO bioavailability and increase in the production of EDCFs. The mechanisms that regulate the balance between NO and EDCFs and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators, remain to be determined.