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Coronavirus disease 2019 (COVID-19) is characterized by a distinctive blood leucocyte pattern and B-lines on lung ultrasound (LUS) as marker of alveolar-interstitial syndrome. We aimed to evaluate the accuracy of blood leucocyte count alone or in combination with LUS for COVID-19 diagnosis. We retrospectively enrolled consecutive patients diagnosed with community acquired pneumonia (CAP) at hospital admission to derive and validate cutoff values for blood cell count that could be predictive of COVID-19 before confirmation by the nucleic acid amplification test (NAAT). Cutoff values, generated and confirmed in inception (41/115, positive/negative patients) and validation (100/180, positive/negative patients) cohorts, were ≤17 and ≤10 cells/mm3 for basophils and eosinophils, respectively. Basophils and/or eosinophils below cutoff were associated with sensitivity of 98% (95%CI, 94–100) and negative likelihood ratio of 0.04 (95%CI, 0.01–0.11). In a subgroup of 265 subjects, the sensitivity of B-line on LUS was 15% lower (p &lt, 0.001) than that of basophils and/or eosinophils below cutoff. The combination of B-lines with basophils and eosinophils below cutoff was associated with a moderate increase of the positive likelihood ratio: 5.0 (95%CI, 3.2–7.7). In conclusion, basophil and eosinophil counts above the generated cutoff virtually rule out COVID-19 in patients with CAP. Our findings can help optimize patient triage pending the NAAT results.

After successful endovascular aortic repair (EVAR), abdominal aortic aneurysms (AAA) sac will undergo negative remodeling (i.e., shrinkage) as a measure of successful exclusion. Determinants of shrinkage after EVAR are not fully known. In 84 post-EVAR patients, time course of AAA diameter after repair and occurrence of endoleaks (ELs) have been correlated with clinical history, medications, anthropometric data, vascular anatomy, and matrix metalloprotease (MMP) genetic variants (namely MMP-1 rs1799750, MMP-3 rs35068180, MMP-9 rs2234681, rs917576, rs917577, MMP-12 rs652438, and TIMP1 rs4898). During follow-up, 41 ELs were detected in 37 patients (44%, 10.4 events/100 pt./y), accounting for AAA dilation or reduced shrinkage (P < .001). High-flow ELs (type 1 and/or 3) occurrence was associated with warfarin use, MMP9 rs17577 polymorphism, and unfavorable anatomy, while low-flow type 2 ELs occurred more often in TIMP1 rs4898 non-T carriers. In EL-free patients, AAA diameter decreased for the first three years, (-4, -3 and - 2 mm/year respectively) and remained stable thereafter. Shrinkage between two measurements (n = 120) was associated with smaller AAA diameter at the baseline, peripheral arterial disease (PAD), patients’ older age at intervention, and G-/G- genotype in MMP1 rs1799750 (binary logistic regression, P = .0001). Aneurysmal sac shrinking occurs for few years after EVAR, only in patients without EL, and is related to older age, PAD, smaller aneurysm size and putative lower MMP1 expression while EL occurrence prevents such a remodeling and is mainly related to local-acting factors like unfavorable anatomy, anticoagulation, and MMP9 and TIMP1 genetic polymorphisms.

Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy for dyslipidemias and are considered the cornerstone of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention. Despite the statintherapy-mediated positive effects on cardiovascular events, patient compliance is often poor. Statinassociated muscle symptoms (SAMS) are the most common side effect associated with treatment discontinuation. SAMS, which range from mild-to-moderate muscle pain, weakness, or fatigue to potentially life-threatening rhabdomyolysis, are reported by 10% to 25% of patients receiving statin therapy. There are many risk factors associated with patient features and hypolipidemic agents that seem to increase the risk of developing SAMS. Due to the lack of a “gold standard”, the diagnostic test for SAMS is based on a clinical criteria score, which is independent of creatine kinase (CK) elevation. Mechanisms that underlie the pathogenesis of SAMS remain almost unclear, though a high number of risk factors may increase the probability of myotoxicity induced by statin therapy. Some of these, related to pharmacokinetic properties of statins and to concomitant therapies or patient characteristics, may affect statin bioavailability and increase vulnerability to high-dose statins. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Study objective: Early risk stratification of septic patients presenting to the emergency department (ED) is challenging. The aim of the study was to evaluate the prognostic role of plasmatic sodium level (PNa+) derangements at ED presentation in septic patients. Methods: According to PNa+ at ED presentation patients were divided in eunatremic (136–145 mEq/L), hypernatremic (>145 mEq/L) and hyponatremic (

The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose–response relationship is currently unknown. Nevertheless, low to medium-intensity high volume resistive exercise, easily implementable in home-settings, will have positive effects, particularly if combined with a 15–25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health. Highlights This paper describes the impact of sedentarism, caused by the COVID-19 home confinement on the neuromuscular, cardiovascular, metabolic and endocrine systems. Just few days of sedentary lifestyle are sufficient to induce muscle loss, neuromuscular junction damage and fibre denervation, insulin resistance, decreased aerobic capacity, fat deposition and low-grade systemic inflammation. Regular low/medium intensity high volume exercise, together with a 15-25% reduction in caloric intake are recommended for preserving neuromuscular, cardiovascular, metabolic and endocrine health.

Energy balance maintenance is crucial to preserve astronaut’s wellness and quality of life during long-duration spaceflight and nutritional intervention can effectively counteract the detrimental effect of microgravity on skeletal muscle mass and metabolism. NutrISS (Nutrition monitoring for the International Space Station) is an Italian Space Agency (ASI) biomedical experiment investigating the changes in body composition during long-term spaceflight. The goal of this proof-of-concept study is to monitor the body composition of astronauts and, if needed, to provide nutritional advice during the mission. It has been executed on the ISS, from July 2019 till January 2020 and sponsored by ESA. The payloads selected for the mission “BEYOND” result from a public-call funded and coordinated by ASI, in the frame of its national mission of promoting and fostering the culture of space across the Country and providing access to the ISS as a laboratory in space to the Italian research community. The utilization support services is ensured by Argotec/Telespazio (UTISS Team). An astronaut underwent to baseline data collections, i.e. body composition, anthropometric evaluation and energy and metabolic assessment carried out by the scientific team. Body composition, estimated through resistance/reactance to a low-intensity current has been assessed with a Bio-Impedance Analyser (BIA) device manufactured by Akern and modified by Kayser Italia. To maintain the participant in near-neutral energy balance, the science team monitored monthly the astronaut body mass during the entire space flight period. Advice on energy intake was given to the astronaut when needed

OBJECTIVE: The optimal protein intake for elderly individuals who exercise regularly has not yet been clearly defined. The aim of this study was to test the hypothesis that protein intake level is associated with muscle strength in elderly elite athletes. METHODS: We evaluated 50 elite senior athletes (38 men and 12 women) participating in the European Master Games 2011 in an observational cross-sectional study. Participants were divided into two groups-lower (LPI) or higher (HPI) protein intake-according to the median value of their ratio of urinary urea nitrogen to urinary creatinine (i.e., 8.8 g/L), as a marker of protein intake. A dietary interview confirmed differences in protein consumption between the LPI and HPI groups. We also evaluated body composition (bioimpedance), muscle strength, and hematochemical indices. RESULTS: LPI and HPI groups were homogeneous for age (72 [68-74] and 71 [68-74] y, respectively), fat-free mass index (18.4 [17-19.4] and 18.2 [17-19.1] kg/m2), body fat (18.3% [12.3-20.7%] and 16.6% [13.6-21.2%]), and glomerular filtration rate (57.7 [53.8-64.9] and 62.7 [56.1-69.3] mL/min/1.73 m2). The HPI group showed greater leg and trunk muscle strength (N) compared with the LPI group (left leg extension, 339 [238-369] versus 454 [273-561], respectively, P < 0.05; right leg extension, 319 [249-417] versus 432 [334-635], P ≤ 0.05; trunk extension, 435 [370-467] versus 464 [390-568], P ≤ 0.05). CONCLUSIONS: Higher protein intake in elite senior athletes is associated with a greater muscle strength.

Comment on Redox status alterations during the competitive season in élite soccer players: focus on peripheral leukocyte-derived ROS.

BACKGROUND & AIMS: Physical inactivity is associated with lean body mass wasting, oxidative stress and pro-inflammatory changes of cell membrane lipids. Alkalinization may potentially counteract these alterations. We evaluated the effects of potassium bicarbonate supplementation on protein kinetics, glutathione status and pro- and anti-inflammatory polyunsaturated fatty acids (PUFA) in erythrocyte membranes in humans, during experimental bed rest. METHODS: Healthy, young, male volunteers were investigated at the end of two 21-day bed rest periods, one with, and the other without, daily potassium bicarbonate supplementation (90 mmol × d-1), according to a cross-over design. Oxidative stress in erythrocytes was evaluated by determining the ratio between reduced (GSH) and oxidized glutathione (GSSG). Glutathione turnover and phenylalanine kinetics, a marker of whole body protein metabolism, were determined by stable isotope infusions. Erythrocyte membranes PUFA composition was analyzed by gas-chromatography. RESULTS: At the end of the two study periods, urinary pH was 10 ± 3% greater in subjects receiving potassium bicarbonate supplementation (7.23 ± 0.15 vs. 6.68 ± 0.11, p < 0.001). Alkalinization increased total glutathione concentrations by 5 ± 2% (p < 0.05) and decreased its rate of clearance by 38 ± 13% (p < 0.05), without significantly changing GSH-to-GSSG ratio. After alkalinization, net protein balance in the postabsorptive state improved significantly by 17 ± 5% (p < 0.05) as well as the sum of n-3 PUFA and the n-3-to-n-6 PUFA ratio in erythrocyte membranes (p < 0.05). CONCLUSIONS: Alkalinization during long-term inactivity is associated with improved glutathione status, anti-inflammatory lipid pattern in cell membranes and reduction in protein catabolism at whole body level. This study suggests that, in clinical conditions characterized by inactivity, oxidative stress and inflammation, alkalinization could be a useful adjuvant therapeutic strategy.

PURPOSE OF REVIEW: Cachexia is a disease-related multifactorial syndrome characterized by inflammation, massive muscle protein catabolism and carbohydrate and lipid metabolism disorder.Several studies tried to define the impact of either nutrition or physical exercise (single approach strategy) or their combination (multimodal approach strategy) on prevention and/or treatment of muscle wasting in cachectic patients. RECENT FINDINGS: Single approach strategies (i.e. nutrition or physical exercise) have the potential of preventing and improving features of the cachexia syndrome possibly with a differential impact according to the underlying disease. Limited information is available on the beneficial effect of multimodal approach strategies. SUMMARY: Multimodal approaches appear to be more effective than those based on single interventions in physiological condition and in cachectic patients with COPD or chronic kidney disease. Further studies, however, are required in cachexia induced by heart failure, cancer and critical illness.

Background: Acute myocardial infarction (AMI) survivors are at risk of major adverse cardiac events and their risk stratification is a prerequisite to tailored therapeutic approaches. Biomarkers could be of great utility in this setting. Methods: We sought to evaluate the utility of the combined assessment of Galectin 3 (Gal-3) and Galectin 3 binding protein (Gal-3bp) for post-AMI risk stratification in a large, consecutive population of AMI patients. The primary outcomes were: Recurrent angina/AMI and all-cause mortality at 12 months after the index event. Results: In total, 469 patients were included. The median Gal-3bp was 9.1 &mu, g/mL (IQR 5.8&ndash, 13.5 &mu, g/mL), while median Gal-3 was 9.8 ng/mL (IQR 7.8&ndash, 12.8 ng/mL). During the 12 month follow-up, 34 patients died and 41 had angina pectoris/reinfarction. Gal-3 was associated with all-cause mortality, while Gal-3bp correlated with the risk of angina/myocardial infarction even when corrected for other significant covariates. The final multivariable model for mortality prediction included patients&rsquo, age, left ventricular ejection fraction (LVEF), Gal-3, and renal function. The ROC curve estimated for this model has an area under the curve (AUC) of 0.84 (95%CI 0.78&ndash, 0.9), which was similar to the area under the ROC curve obtained using the GRACE score 1-year mortality. Conclusions: The integrated assessment of Gal-3 and Gal-3bp could be helpful in risk stratification after AMI.

OBJECTIVES: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. DESIGN:Multicenter prospective study. SETTING: At emergency department admission in five University hospitals. PATIENTS:Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholipase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholipase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. CONCLUSIONS: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome

OBJECTIVE: The glutathione system plays an essential role in antioxidant defense after surgery. We assessed the effects of intensive insulin treatment (IIT) on glutathione synthesis rate and redox balance in cancer patients, who had developed stress hyperglycemia after major surgery. METHODS: We evaluated 10 non-diabetic cancer patients the day after radical abdominal surgery combined with intra-operative radiation therapy. In each patient, a 24-hr period of IIT, aimed at tight euglycemic control, was preceded, or followed, by a 24-hr period of conventional insulin treatment (CIT) (control regimen). Insulin was administered for 24 hours, during total parenteral nutrition, at a dosage to maintain a moderate hyperglycemia in CIT, and normoglycemic blood glucose levels in IIT (9.3±0.5 vs 6.5±0.3 mmol/L respectively, P

OBJECTIVE: The objective of this study was to assess whether functional genetic polymorphisms of matrix metalloproteinases (MMPs) 1, 3, 9, and 12 are associated with arterial enlargements or aneurysms of the thoracic aorta or popliteal arteries in patients with abdominal aortic aneurysm (AAA). METHODS: The associations between MMP1 (-1607 G in/del, rs1799750), MMP3 (-1171 A in/del rs35068180), MMP9 (13-26 CA repeats around -90, rs2234681, rs917576, rs917577), and MMP12 (G/T missense variation, rs652438) polymorphisms and enlargements or aneurysms of the thoracic aorta and popliteal arteries were tested in 169 consecutive AAA patients. RESULTS: Thoracic aorta enlargement or aneurysm (TE/A; maximum diameter, >35 mm) was detected in 34 patients (20.1% prevalence). MMP9 rs2234681 microsatellite was the only genetic determinant of TE/A in AAA patients (P = .003), followed by hypercholesterolemia and antiplatelet use. Carriers of both alleles with ≥22 CA repeats had a 5.9 (95% confidence interval, 1.9-18.6; P < .0001) increased odds of TE/A, and a score considering all three variables showed 98% negative predictive value and 30% positive predictive value for thoracic aortic aneurysm detection. Eighty-two popliteal artery enlargements or aneurysms (diameter >10 mm) occurred in 55 patients (33.1% prevalence). Carriers of MMP12 rs652438 C allele showed an 18% (P = .006) increased diameter in popliteal arteries and a 2.8 (95% confidence interval, 1.3-6; P = .008) increased odds of popliteal artery enlargement or aneurysm compared with TT genotype. CONCLUSIONS: Among patients with AAA, carriers of homozygous ≥22 CA repeats in MMP9 rs12234681 and of C allele in MMP12 rs652438 have a substantial risk of carrying thoracic and popliteal enlargements, respectively.

In chronic diseases, hypoxia and physical inactivity are associated with atherosclerosis progression. In contrast, a lower mortality from coronary artery disease and stroke is observed in healthy humans residing at high altitude in hypoxic environments. Eleven young, male volunteers completed the following 10-day campaigns in a randomized order: hypoxic ambulatory, hypoxic bed rest and normoxic bed rest. Before intervention, subjects were evaluated in normoxic ambulatory condition. Normobaric hypoxia was achieved in a hypoxic facility simulating 4000 m of altitude. Following hypoxia, either in bed rest or ambulatory condition, markers of cardiometabolic risk shifted toward a more atherogenic pattern consisting of: (a) lower levels of total HDL cholesterol and HDL2 sub-fraction and decreased hepatic lipase; (b) activation of systemic inflammation, as determined by C-reactive protein and serum amyloid A; (c) increased plasma homocysteine; (d) decreased delta-5 desaturase index in cell membrane fatty acids, a marker of insulin sensitivity. Bed rest and hypoxia additively decreased total HDL and delta-5 desaturase index. In parallel to the pro-atherogenic effects, hypoxia activated selected anti-atherogenic pathways, consisting of increased circulating TNF-related apoptosis-inducing ligand (TRAIL), a protective factor against atherosclerosis, membrane omega-3 index and erythrocyte glutathione availability. Hypoxia mediated changes in TRAIL concentrations and redox glutathione capacity (i.e., GSH/GSSG ratio) were greater in ambulatory conditions (+34 ± 6% and +87 ± 31%, respectively) than in bed rest (+17 ± 7% and +2 ± 27% respectively). Hypoxia-induced cardiometabolic risk is blunted by moderate level of physical activity as compared to bed rest. TRAIL and glutathione redox capacity may contribute to the positive interaction between physical activity and hypoxia. Highlights: - Hypoxia and bed rest activate metabolic and inflammatory markers of atherogenesis. - Hypoxia and physical activity activate selected anti-atherogenic pathways. - Hypoxia and physical activity positive interaction involves TRAIL and glutathione.

Because of its high biocompatibility, bio-degradability, low-cost and easy availability, cellulose finds application in disparate areas of research. Here we focus our attention on the most recent and attractive potential applications of cellulose in the biomedical field. We first describe the chemical/structural composition of cellulose fibers, the cellulose sources/features and cellulose chemical modifications employed to improve its properties. We then move to the description of cellulose potential applications in biomedicine. In this field, cellulose is most considered in recent research in the form of nano-sized particle, i.e., nanofiber cellulose (NFC) or cellulose nanocrystal (CNC). NFC is obtained from cellulose via chemical and mechanical methods. CNC can be obtained from macroscopic or microscopic forms of cellulose following strong acid hydrolysis. NFC and CNC are used for several reasons including the mechanical properties, the extended surface area and the low toxicity. Here we present some potential applications of nano-sized cellulose in the fields of wound healing, bone-cartilage regeneration, dental application and different human diseases including cancer. To witness the close proximity of nano-sized cellulose to the practical biomedical use, examples of recent clinical trials are also reported. Altogether, the described examples strongly support the enormous application potential of nano-sized cellulose in the biomedical field.

Purpose of review In clinical management of acutely ill adults and children, continuous enteral feeding (CEF), being considered the most tolerable approach, in comparison to other temporal patterns of nutrient administration (i.e. intermittent, cyclic and bolus), is the most frequently applied method. However, uncertainties remain about the most efficient approach to counteract protein catabolism. Recent findings In critically ill adults, protein loss is mainly driven by increased protein breakdown whereas, in pediatric patients, acute illness is mainly characterized by blunted regulation of protein synthesis and stunted growth. Kinetic studies in fed adult volunteers indicate that protein synthesis can be stimulated for a limited period only. However, continuous feeding persistently improves protein balance through a sustained suppression of protein breakdown. This leads to the hypothesis that CEF could be more anticatabolic than intermittent enteral feeding (IEF) in these patients. Differently from adults, experimental models of acute disease in growing animals have consistently indicated that IEF can improve protein anabolism more efficiently than CEF, mainly through protein synthesis stimulation. The scarce number of clinical studies in acutely ill adults or pediatric patients, mostly performed with inadequate methodology, could not define the best approach to maintain protein balance. Summary There is a need for pragmatic studies to directly compare the protein anabolic action of CEF and IEF using accurate methodologies, such as stable isotopes of amino acids, in both adult and pediatric patients with acute illness.

Summary Background & aims Arachidonic (AA) and eicosapentaenoic (EPA) polyunsaturated fatty acids can play respectively a pro- and an anti-inflammatory role. We hypothesized that, at the end of 5-week experimental bed rest, baseline AA/EPA in red blood cells (RBC) membranes, considered the result of dietary fat intake over the previous month, could influence lean body mass wasting in twenty-six healthy volunteers (age: 23.5 ± 0.5 years; body mass index: 22.9 ± 0.5 kg/m2). Methods We measured AA and EPA content in RBC membranes at baseline ambulatory conditions and at the end of the study protocol, to verify the PUFA concentrations stability. We assessed changes, between beginning and end of bed, in lean body mass (bioimpedance), insulin resistance (homeostasis model assessment), systemic inflammation (C-reactive protein) and oxidative stress (thiobarbituric acid reactive substances). Volunteers were divided in two groups according to the AA/EPA ratio median value (i.e. AA/EPA = 44): High AA/EPA group (60 ± 3; n = 13) and Low AA/EPA group (37 ± 1; n = 13). Results At baseline, all analyzed anthropometrical and biochemical indices were similar in the two groups. Bed rest induced a major decrease in lean body mass in High AA/EPA group (−5.2 ± 0.5%), when compared to Low AA/EPA group (−3.7 ± 0.5%; p = 0.03; ANOVA). Bed rest mediated-changes of insulin resistance, fat mass, systemic inflammation and oxidative stress, failed to show significant interaction with baseline AA/EPA (ANOVA). In pooled data, baseline AA/EPA ratio and percent lean body mass delta changes showed a significant inverse correlation (n = 26; R = −0.50; p < 0.01). Conclusions Results suggest that baseline AA/EPA, in RBC membranes, can independently predict lean body mass wasting in immobilized subjects during long term disuse.

The RNA interference (RNAi) is a biological process by which a double stranded RNA (dsRNA also called small interfering RNA - siRNA) triggers the sequence-dependent degradation of a target RNA within the cellular environment. Thus siRNAs can be used to combat the expression of deleterious gene(s) causing disease or to destroy invading pathogen RNAs. Despite their enormous therapeutic potential, the use of siRNA as drugs presents two major problems: the difficulties to identify optimal delivery systems and the possible induction of different unwanted side effects. In this review, after presenting an overview about the mechanisms ruling the process of RNAi, we focus the attention on the description of the strategies developed to optimise systemic siRNA delivery; in this sense, considerations about the attempts to improve siRNA stability in the biological environment, the development of synthetic vectors for siRNA delivery, the siRNA bio-distribution and pharmacokinetics together with the selection of siRNA targeted delivery systems, are discussed. Since in the optimisation of the siRNA delivery systems the minimization of siRNA side effects should not be neglected, in the last part of the review we consider the problems related to the possible induction of siRNA mediated side effects focusing on the so called microRNA like off-targeting.

The prevalence of atrial fibrillation (AF) is related to age and is projected to rise exponentially as the populationages and the prevalence of cardiovascular risk factors increases. The risk of ischemic stroke is significantly increasedin AF patients, and there is evidence of a graded increased risk of stroke associated with advancingage. Oral anticoagulation (OAC) is far more effective than antiplatelet agents at reducing stroke risk in patientswith AF. Therefore, increasing numbers of elderly patients are candidates for, and could benefit from, the use ofanticoagulants. However, elderly people with AF are less likely to receive OAC therapy. This is mainly due to concernsabout a higher risk of OAC-associated hemorrhage in the elderly population. Until recently, older patientswere under-represented in randomized controlled trials of OAC versus placebo or antiplatelet therapy, and thereforethe evidence base for the value of OAC in the elderly population was not known. However, analyses of theavailable trial data indicate that the expected net clinical benefit of warfarin therapy is highest among patientswith the highest untreated risk for stroke, which includes the oldest age category. An important caveat with warfarintreatment is maintenance of a therapeutic international normalized ratio, regardless of the age of the patient,where time in therapeutic range should be 65%. Therefore, age alone should not prevent prescription ofOAC in elderly patients, given an appropriate stroke and bleeding risk stratification. (J Am Coll Cardiol 2010;56:827–37) © 2010 by the American College of Cardiology Foundation

Genetic variants of matrix metalloproteases (MMPs)-1, -3, and 9, together with clinical variables, might predict the growth rate (GR) of abdominal aortic aneurysm (AAA). Genotyping of MMP-1 (-1,607 G+/G-), MMP-3 (- 1,171 6A/5A), and MMP-9 microsatellite (13-26 cytosine-adenosine repeats around -90) from peripheral blood was performed in 137 AAA patients with two AAA diameter measurements (at least 3 months to 1 year apart). When the same technique (either ultrasound or computed tomography) was used for the two measurements, yearly GR was estimated and compared with MMP genotype and clinical features by linear and binary logistic regression. Collectively, 36 patients provided 94 observations, with a median GR of 3 mm/year (interquartile range, 0-5.8); GRs in carriers of MMP-1 polymorphism G-/G-, G-/G+, and G+/G+ genotype were 0.3, 3.5, and 4.7mm/year, respectively (p = 0.008). In linear logistic regression, the main determinant of GR was growth arrest (GA, i.e., GR = 0, occurring in 32 observations, 34%). In turn, GA occurred mainly in G-/G- MMP-1 genotype (odds ratio, 3.9; 95% confidence interval, 1.6-9.7; p = 0.002), while variables accounting for GR > 0 were MMP-1 G + /G+ genotype, intake of any antihypertensive drug, and MMP-3 6A/6A genotype. Carriers of none, one, or two/three of these conditions accounted for a GR of 3, 4, and 9 mm/year, respectively (p = 0.001). MMP-1 (-1,607 G+/-) variant is associated to differential GR in AAA: homozygous G deletion variant shows higher GA prevalence and lower GR, while carriers of G + /G+ MMP-1 genotype, together with intake of antihypertensive drugs, and 6A/6A in MMP-3 present cumulative GR increase.

INTRODUCTION: A growing body of evidence points out that a large amount of patients with sepsis are admitted and treated in medical ward (MW). With most of the sepsis studies conducted in intensive care unit (ICU), these patients, older and with more comorbidities have received poor attention. Provided the differences between the two groups of patients, results of diagnostic and therapeutic trials from ICU should not be routinely transferred to MW, where sepsis seems to be at least as common as in ICU. METHODS: We analyzed clinical trials on novel tools for an early diagnosis of sepsis published in the last two year adopting strict research criteria. Moreover we conducted a target review of the literature on non-invasive monitoring of severe sepsis and septic shock. RESULTS AND CONCLUSIONS: The combination of innovative and non-invasive tools for sepsis rule in/out, as quick alternatives to blood cultures (gold standard) with bedside integrated ultrasonography could impact triage, diagnosis and prognosis of septic patients managed in MW, preventing ICU admissions, poor outcomes and costly complications, especially in elderly that are usually highly vulnerable to invasive procedures.

Purpose: To assess if a polymorphism (PM) of the microsatellite (CA13–27) in the promoter region of Matrix Metalloproteinase 9 (MMP-9) was associated with the exudative form of age-related macular degeneration (AMD) and to its risk factors. Methods: In 107 patients with AMD (AMD Group) and 223 age- and gender-matched controls (Control Group) with cataract, demographic, clinical data, and MMP-9 PM have been compared. Results: The comparison of allelic frequencies showed a different pattern of CA repeats between AMD and Control Group (P < 0.00005), in particular the prevalence of longer microsatellites (≥ 22 CA repeats) was higher in AMD than in Control Group (O.R. 2.49, 95% CI 1.71 - 3.37, P < 0.001). Analyses of genetic frequencies gave similar results. Logistic regression confirmed that 22 or more CA repeats are associated to AMD. The only association between MMP-9 PM and other risk factors for AMD was with BMI (Spearman’s R = 0.298, P < 0.00005): all patients with both microsatellites ≥ 22 CA repeats were overweight or obese (χ2 test P < 0.0005, compared to other genotypes). Conclusions: Longer microsatellites in the promoter of MMP-9 are associated to the exudative form of AMD and to body mass index, a well-known risk factor for the disease.

Background: SIRS/sepsis accounts for vast majority of deaths in ICU a medical ward department. More than 650,000 cases of sepsis are diagnosed in the United States annually, with 30-50% mortality and individually cost more than 22,000 dollars. Biomarkers could be useful tools for early risk stratification in these patients. Angiopioietin-2 (Ang-2) is a proinflamma- tory mediator of endothelial injury, which has received considerable attention over the past decade but little is known about its correlation with organ failure and mortality in SIRS/sepsis admitted to a medical ward. Methods: Ang-2 plasma levels, Charlson index, SOFA and routine laboratory test were carried out in 80 SIRS patients admitted to medical ward within 4 hours from diagnosis. Survival and organ dysfunction in the following week were recorded. Investigators were blinded from Ang-2 results. Results: Ang-2 plasma levels were higher in patients suffering from renal, pulmonary and hemostatic dysfunction (16, 6, 4% respectively) and patients who died within 1 week (11%). Ang-2 plasma levels higher than 15 ∝/mL account for 13 fold increased risk of death with 94% negative predictive value. Conclusions: Ang-2 plasma level at admission is predictive of early mortality and kidney, lung and hemostasis dysfunc- tion in SIRS/sepsis patients newly admitted in a medical ward.

A polymorphism (PM) in the microsatellite of the promoter region of matrix metalloproteinase 9 (MMP-9), modulating its expression, could play a role in susceptibility to multiple sclerosis (MS). MMP-9 PM was determined in 95 patients with MS (MS Group) and 95 ageand sex-matched controls (Control Group). Comparison of allelic frequencies showed that a higher number of CA repeats characterized the MS group ( P < 0.0001) and prevalence of carriers of z22 CA repeats was higher in the MS than in the Control Group (OR 3.4, 95% CI: 1.7–6.8, P < 0.0001). An earlier age at disease onset was a characteristic of patients with >22 CA repeats (33F10 vs. 28F10, P= 0.027). No differences were found in the main MRI parameters.

Background: Increased plasma levels of acute phase reactants are correlated with acute coronary syndromes and increased risk of in-hospital events. Interleukin-1 receptor antagonist (IL-1Ra) modulates the activity of IL-1, a cytokine associated with inflammatory response; we have prospectively investigated whether detection of increased levels of IL-1Ra in patients may be useful in the characterization of coronary syndromes. Methods: Plasma levels of IL-1Ra were measured in 118 consecutive patients undergoing coronary angiography with a clinical diagnosis of recent unstable angina (N = 57), chronic stable angina (N = 49) or atypical chest pain (N = 12). Results: Angiography showed significant coronary disease in the first two groups and was normal in the latter group. Patients with unstable angina had significantly higher levels of IL-1Ra than stable patients [158 (110–224) vs 108 (95–154) pg/ml, P = 0.002] and individuals with chest pain and normal coronary angiogram [110 (97–123) pg/ml, P: = 0.038]. In contrast, while C-reactive protein levels were significantly higher in patients with stable and unstable angina vs those without coronary disease (0.29 vs 0.06 mg/dl, P: = 0.022), they did not discriminate between stable and unstable angina patients (0.22 vs 0.32 mg/dl, P: = 0.66). Conclusions: These results indicate that IL-1Ra may be a sensitive marker of clinical instability in patients with coronary artery disease.

A relevant amount of patients with clinical suspect of sepsis is admitted and treated in medical wards (MW). These patients have a better prognosis but are older and with more comorbidities compared to those admitted to intensive care units (ICU). Procalcitonin (PCT) is extensively used in emergency departments for the diagnosis of sepsis, but its accuracy in the setting of a MW has not been thoroughly investigated. Predicted low PCT levels also call for the comparison of immunomagnetic-chemiluminescent (L-PCT) and time-resolved amplified cryptate emission (TRACE, K-PCT) technologies, in PCT determination.In 80 patients with systemic inflammatory response syndrome (SIRS) diagnostic criteria and suspect of sepsis newly admitted to a MW, PCT was determined with L- and K-PCT method.Sixty patients were diagnosed as sepsis (20 microbiologically and 40 clinically proven) and 20 with non-infective SIRS. The sepsis group had significantly higher levels of both PCTs, with no differences between the clinically and microbiologically proven subgroups. The areas under ROC curves for L- and K-PCT were 0.72 and 0.78 (pIn MW patients, customized PCT cut-off levels provide better accuracy than customary levels adopted from ICU, and TRACE technology seems to offer a wider analysis range.

The objective of the study was to determine the accuracy of phospholipase A2 group II (PLA2-II), interferon-gamma-inducible protein 10 (IP-10), angiopoietin-2 (Ang-2), and procalcitonin (PCT) plasma levels in early ruling in/out of sepsis among systemic inflammatory response syndrome (SIRS) patients. Biomarker levels were determined in 80 SIRS patients during the first 4 h of admission to the medical ward. The final diagnosis of sepsis or non-infective SIRS was issued according to good clinical practice. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for sepsis diagnosis were assessed. The optimal biomarker combinations with clinical variables were investigated by logistic regression and decision tree (CART). PLA2-II, IP-10 and PCT, but not Ang-2, were significantly higher in septic (n = 60) than in non-infective SIRS (n = 20) patients (P ≤ 0.001, 0.027, and 0.002, respectively). PLA2-II PPV and NPV were 88 and 86 %, respectively. The corresponding figures were 100 and 31 % for IP-10, and 93 and 35 % for PCT. Binary logistic regression model had 100 % PPV and NPV, while manual and software-generated CART reached an overall accuracy of 95 and 98 %, respectively, both with 100 % NPV. PLA2-II and IP-10 associated with clinical variables in regression or decision tree heterogeneous models may be valuable biomarkers for sepsis diagnosis in SIRS patients admitted to medical ward (MW). Further studies are needed to introduce them into clinical practice.