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BACKGROUND: Vitamin D (VitD) deficiency has been reported to be associated with respiratory tract infection. In this work we evaluated the concentration of VitD in COVID-19 patients experiencing acute respiratory infections of different levels of severity excluding those who underwent invasive respiratory support. METHODS: The levels of serum VitD and C-reactive protein (CRP) were analyzed in 118 consecutive hospitalized COVID-19 patients (74M, 44F), confirmed with rRT-PCR. Of these patients with ventilation support 52 (44.1%) received oxygen via nasal cannula, oxygen mask or an oxygen mask with a reservoir, 48 (40.7%) were on a continuous positive airway pressure device (CPAP) and 18 (15,3%) on non-invasive mechanical ventilation (NIMV). RESULTS: The median values (range) of VitD and of CRP were 15.1 ng/mL (1.3-73.3) and 14.2 mg/L (5.0-151.2), respectively. A negative correlation from VitD levels and those of CRP (correlation coefficient - 0.259: P=0.005) was observed. VitD levels in O2 support patients were significantly higher than in both CPAP and NIMV patients. No statistical differences were found for CRP levels (P=0.834) among the three type of oxygen support. Fewer patients with O2 support had VitD

In the brain, Oxidative Stress (OS) contribute to structural and functional changes associated with vascular aging, such as endothelial dysfunction, extracellular matrix degradation, resulting in age-related reduced vasodilatation in response to agonists. For this reason, OS is considered a key factor in Alzheimer’s Disease (AD) development and recent evidence correlated oxidative stress with vascular lesion in the pathogenesis of AD, but the mechanism still need to be fully clarified. The etiology of AD is still not completely understood and is influenced by several factors including Apolipoprotein E (ApoE) genotype. In particular, the Apo ε4 isoform is considered a risk factor for AD development. This study was aimed to evaluate the possible relationship between three plasmatic OS marker and Apo ε4 carrier status. Plasmatic soluble receptor for advanced glycation end products (sRAGE) levels, plasma antioxidant total defenses (by lag-time method) and plasmatic Reactive Oxygen species (ROS) levels were evaluated in 25 AD patients and in 30 matched controls. ROS were significantly higher while plasma antioxidant total defenses and sRAGE levels were significantly lower in AD patients compared to controls. In AD patients lag-time values show a significant positive linear correlation with sRAGE levels and a (even not significant) negative correlation with ROS levels. Lag-time is significantly lower in ε4 carrier (N = 13) than in ε4 non-carrier (N = 12). Our result confirms the substantial OS in AD. Lag-time levels showed a significant positive correlation with sRAGE levels and a significant association with ε4 carrier status suggesting that plasmatic lag-time evaluation can be considered as a potential useful OS risk marker in AD.

OBJECTIVES: Gastrointestinal manifestations of coronavirus disease 19 (COVID-19) have been well established, but pancreatic involvement is under debate. Our aims were to evaluate the presence of acute pancreatitis in COVID-19 patients and to assess the frequency of pancreatic hyperenzymemia. METHODS: From April 1, 2020, to April 30, 2020, 110 consecutive patients (69 males, 41 females; mean age, 63.0 years; range, 24-93 years) met these criteria and were enrolled in the study. The clinical data and serum activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits. RESULTS: None of the patients studied developed clinical signs or morphological alterations compatible with acute pancreatitis. However, it was found that 24.5% of the patients had amylase values above 53 IU/L and 16.4% had lipase values above 300 IU/L. Only 1 patient (0.9%) had both amylase and lipase values in excess of 3-fold the upper normal limit without clinical signs of pancreatitis. CONCLUSIONS: The presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results.

Background Breath-hold diving (BH-diving) is associated to extreme environmental conditions, prolonged physical activity, and complex adaptation mechanisms to supply enough O2 to vital organs. Consequently, one of the biggest effects could be an increased exercise-induced muscle fatigue, in both skeletal and cardiac muscles that can induce an increase of muscles injury markers including creatine kinase (CK), aspartate transferase (AST), and alanine transferase (ALT) when concerning the skeletal muscle, cardiac creatine kinase isoenzyme (CK-MBm) and cardiac troponin I (cTnI) when concerning the cardiac muscle, and lactate dehydrogenase (LDH) as index of muscle stress. The aim of this study is to investigate serum cardiac and skeletal muscle markers before and after a BH-diving training session. Results We found statistically significant increases of CK (T0: 136.1% p < 0.0001; T1: 138.5%, p < 0.0001), CK-MBm (T0: 145.1%, p < 0.0001; T1: 153.2%, p < 0.0001) LDH (T0: 110.4%, p < 0.0003; T1: 110.1%, p < 0.0013) in both T0 and T1 blood samples, as compared to basal value. AST showed a statistically significant increase only at T0 (106.8%, p < 0.0007) while ALT did not exhibit statistically significant changes. We did not find any changes in cTnI levels between pre-dive and post-dive samples. Conclusions Our data seem to indicate that during a BH-diving training session, skeletal and cardiac muscles react to physical effort releasing stress-related substances. Although the peculiar nature of BH-diving makes it difficult to understand if our results are related only to exercise induced muscle adaptation or whether acute hypoxia or a response to environmental changes (pressure) play a role to explain the observed changes, further studies are needed to better understand if these biomarker changes are linked to physical exercise or to acute hypoxia, or if both conditions play a role.

The severity of coronavirus disease 2019 (COVID‐19) is a crucial problem in patient treatment and outcome. The aim of this study is to evaluate circulating level of sphingosine‐1‐phosphate (S1P) along with severity markers, in COVID‐19 patients. One hundred eleven COVID‐19 patients and forty‐seven healthy subjects were included. The severity of COVID‐19 was found significantly associated with anemia, lymphocytopenia, and significant increase of neutrophil‐to‐lymphocyte ratio, ferritin, fibrinogen, aminotransferases, lactate dehydrogenase (LDH), C‐reactive protein (CRP), and D‐dimer. Serum S1P level was inversely associated with COVID‐19 severity, being significantly correlated with CRP, LDH, ferritin, and D‐dimer. The decrease in S1P was strongly associated with the number of erythrocytes, the major source of plasma S1P, and both apolipoprotein M and albumin, the major transporters of blood S1P. Not last, S1P was found to be a relevant predictor of admission to an intensive care unit, and patient’s outcome. Circulating S1P emerged as negative biomarker of severity/mortality of COVID‐19 patients. Restoring abnormal S1P levels to a normal range may have the potential to be a therapeutic target in patients with COVID‐19.

Background: Gastrointestinal manifestations of COVID-19 have been well established, but pancreatic involvement is under debate To evaluate the presence of acute pancreatitis in COVID-19 patient in a prospective, unicenter cohort study Methods: From April 1, 2020 to April 30, 2020, 110 consecutive patients (69 males, 41 females;mean age 63 0 years [range, 24-93 years]) met these criteria and were enrolled in the study The clinical data and serum activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits Results: The average time from the onset of respiratory symptoms to the blood samples was 22 2 days (range, 0-47) None of the patients studied developed clinical signs ormorphological alterations compatiblewith acute pancreatitis according to the Atlanta revised criteria It was found that 24 5% of the patients had amylase values above 53 IU/L and 16 4% had lipase values above 300 IU/L Only one patient (0 9%) had both amylase and lipase values in excess of three-fold the upper normal limit without clinical signs of pancreatitis There were no statistically significant difference in amylase and lipase serum activities in patients having nausea/vomiting (amylase: 32 1 ± 18 7 IU/L, P = 0 438;lipase: 80 7 ± 42 4 IU/L, P = 0 134) and in those who did not (amylase: 46 3 ± 35 7 IU/L;lipase: 200 3 ± 240 0 IU/L), or in patients having diarrhea (amylase: 65 4 ± 64 2 IU/L, P = 0 198;lipase: 303 0 ± 544 4 IU/L, P = 0 615) and in those who did not (amylase: 43 1 ± 28 5 IU/L;lipase: 181 5 ± 149 3 IU/L) Regarding the oxygen support, a statistical difference was found in amylase serum activities among the various types of oxygen support used (amylase P = 0 047) whereas this difference was not found for lipase (P = 0 065) Conclusions: The presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results

Background COVID-19 is an infectious disease caused by a novel coronavirus (SARS-CoV-2). The immunopathogenesis of the infection is currently unknown. Healthcare workers (HCWs) are at highest risk of infection and disease. Aim of the study was to assess the sero-prevalence of SARS-CoV-2 in an Italian cohort of HCWs exposed to COVID-19 patients. Methods A point-of-care lateral flow immunoassay (BioMedomics IgM-IgG Combined Antibody Rapid Test) was adopted to assess the prevalence of IgG and IgM against SARS-CoV-2. It was ethically approved (“Milano Area 1” Ethical Committee prot. n. 2020/ST/057). Results A total of 202 individuals (median age 45 years; 34.7% males) were retrospectively recruited in an Italian hospital (Milan, Italy). The percentage (95% CI) of recruited individuals with IgM and IgG were 14.4% (9.6–19.2%) and 7.4% (3.8–11.0%), respectively. IgM were more frequently found in males (24.3%), and in individuals aged 20–29 (25.9%) and 60–69 (30.4%) years. No relationship was found between exposure to COVID-19 patients and IgM and IgG positivity. Conclusions The present study did show a low prevalence of SARS-CoV-2 IgM in Italian HCWs. New studies are needed to assess the prevalence of SARS-CoV-2 antibodies in HCWs exposed to COVID-19 patients, as well the role of neutralizing antibodies.

Glyphosate is a non-selective systemic herbicide used in agriculture. For almost half a century, the International Agency for Research on Cancer has run a Monographs program, the conclusion in March 2015 that glyphosate is “probably carcinogenic to humans” in addition to being genotoxic and carcinogenic in animals, while the regulatory European Food Safety Authority have asserted that glyphosate poses no public risk. The scientific debate is still lively. We collected detailed socio-demographic, occupational exposures and health surveillance information for 26 winegrowers as aim to investigate exposure to glyphosate and other pesticide. Exposure was assessed through biological monitoring (24-hour urine collection), immune function (IL-4, IL-5, IL-8, IL-12, IL- 17, IL-33, IFN- γ), transcriptional and post transcriptional alterations (miRNA) and genotoxic effects (Comet assay). The exposure conditions in our winegrowers, as referred to the parameters so far analyzed, did not reveal a significant glyphosate absorption nor significant health concerns.

Background: Since December 2019, COVID-19 has widely spread throughout the world, causing thousands of deaths. Clinical characteristics of COVID-19 patients have been widely reported, but significative disease-associated biomarkers are needed. We aimed to evaluate the prognostic power of circulating sphingosine-1-phosphate (S1P) in COVID-19, to propose S1P as a novel prognostic and predictive biomarker. Methods: Clinical and blood parameters were investigated in 111 COVID-19 patients (COV) and 47 healthy subject (HLT), with a particular focus on patients who required intensive care unit (ICU) admission. We measured serum levels of S1P and its main transporter apolipoprotein M (apoM) by ELISA assay. Correlation with clinical and blood parameters were performed by Pearson correlations. Univariable and multivariable regression analysis were performed to assess the interaction between clinically significant factors and ICU admission. Further, Cox regression was used to evaluate the prognostic power of S1P for ICU admission and mortality. Findings: We reported statistically significant alterations of several blood parameters in COV, as an increase of white blood cells, neutrophil-to-lymphocyte ratio, ferritin, D-dimer and fibrinogen, and a decrease in hemoglobin, lymphocyte count and total proteins. Our major finding is the drop of serum S1P level in COV, strongly associated with the decrease of red blood cells, the major source of plasmatic S1P, and both apoM and albumin, the most important transporters of circulating S1P. The multivariable regression analysis revealed that S1P is the most important predictor for ICU admission (OR:39·45, [95%CI:1·51-1031·60]; p=0·027), and Cox proportional-hazards model demonstrated a high power of S1P in predicting patient’s outcome. Interpretation: COVID-19 patients showed a drastic decrease of serum S1P, suggesting that circulating S1P levels may be clinically used as negative biomarkers to predict severity/mortality of COVID-19. Taken together, our results suggest that restoring S1P at physiological level may represent a novel therapeutic strategy. Funding: Italian Ministry of Health. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement:This prospective, case-control study was approved by the Ethic Committee of Ospedale San Paolo in Milan, Lombardy, Italy (COST Action n.2020/ST/057).

The endocannabinoid system plays a substantial role in analgesia.To analyze N-arachidonoylethanolamine (AEA), N-oleoylethanolamine (OEA), linoleoyl ethanolamide (LEA), α-linoleoyl ethanolamine (α-LNEA), N-palmitoylethanolamine (PEA) and N-stearoyl ethanolamine (SEA) in two groups of patients having chronic pancreatic diseases.Twenty-six patients with chronic pancreatitis, 26 patients with pancreatic ductal adenocarcinoma and 36 healthy subjects were studied. The visual analogic scale (VAS) was used for assessing pain immediately before the venipuncture to obtain blood in all subjects. Six endocannabinoids were measured in serum of the patients enrolled.Only OEA, LEA and PEA serum levels were significantly higher in patients with pain as compared to those without. Using the cutoff values, the sensitivity and specificity of the various endocannabinoids in evaluating pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma were: 44.2% and 95.6% for AEA, 83.7% and 73.3% for LEA, 88.4% and 91.1% for LNEA, 81.4% and 82.2% for OEA, 81.4% and 88.9% for PEA, 86.0% and 88.9% for SEA, respectively.Endocannabinoids are not useful in assessing pain in patients with chronic pancreatic diseases and they cannot replace a simple method such as VAS for assessing the pain and its intensity.

Background Serum cancer antigen 19-9 (CA19-9) provides additional information about mucinous cystic pancreatic neoplasm (MPN). This study was undertaken to assess both CA19-9 and carcinoembryonic antigen (CEA) serum concentrations in consecutive patients affected by MPNs and other chronic benign and malignant pancreatic diseases. We also evaluated whether serum CA19-9 and CEA determinations provide additional information such as the presence of invasive carcinoma in MPN patients. Methods Serum CA19-9 and CEA from 91 patients with pancreatic diseases were tested by commercially available kits at the time of diagnosis. The upper reference limit of serum CA19-9 was 37 U/mL and that of serum CEA was 3 ng/mL. Results Thirty-five patients was diagnosed with chronic pancreatitis (CP), 32 with MPN, and 24 with pancreatic ductal adenocarcinoma (PDAC) confirmed histologically. Surgery was carried out in 5 CP patients, in 10 MPN patients (7 of them had severe dysplasia), and 9 PDAC patients. Serum CA19-9 activity was high in 12 (34.3%) CP patients, in 7 (21.9%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.089). High serum CEA concentrations were noted in 6 (17.1%) CP patients, in 6 (18.8%) MPN patients, and in 12 (50.0%) PDAC patients ( P =0.010). In the 7 MPN patients associated with histologically confirmed severe dysplasia, 3 (42.9%) patients had elevated serum activity of serum CA19-9, and 2 (28.6%) patients had high levels of CEA. Conclusion Serum determination of oncological markers is not useful in selecting MPN patients with malignant changes.

HIV-infected individuals with incomplete CD4⁺ T-cell recovery upon combination antiretroviral therapy (cART) display high levels of immune activation and microbial translocation. However, whether a link exists between gut damage and poor immunological reconstitution remains unknown.Cross-sectional study of the gastrointestinal tract in late cART-treated HIV-infected individuals: 15 immunological nonresponders (CD4⁺350 cells/μl and/or delta CD4⁺ change from baseline30%); 15 full responders (CD4⁺350 cells/μl and/or delta CD4⁺ change from baseline30%).We assessed gut structure (junctional complex proteins in ileum and colon) and function (small intestine permeability/damage and microbial translocation parameters). The composition of the fecal microbiome and the size of the HIV reservoir in the gut and peripheral blood were investigated as possible mechanisms underlying mucosal impairment.Markers of intestinal permeability, damage, systemic inflammation, and microbial translocation were comparable in all study individuals, yet the expression of junctional complex proteins in gut biopsies was significantly lower in HIV-infected patients with incomplete CD4⁺ restoration and negatively correlated with markers of CD4⁺ reconstitution. Electron microscopy revealed dilated intercellular spaces in individuals lacking immunological response to cART, yet not in patients displaying CD4⁺ T-cell recovery. Analysis of the fecal microbiome revealed an overall outgrowth of Bacteroides-Prevotella spp. with no differences according to CD4⁺ T-cell reconstitution. Interestingly, HIV reservoirs in peripheral CD4⁺ T cells and intestinal tissue negatively correlated with immune recovery.These observations establish gut damage and the size of the HIV reservoir as features of deficient immunological response to cART and provide new elements for interventional strategies in this setting.

Erectile dysfunction is a common disease characterized by endothelial dysfunction. The aetiology of ED is often multifactorial but evidence is being accumulated in favor of the proper function of the vascular endothelium that is essential to achieving and maintaining penile erection. Uric acid itself causes endothelial dysfunction via decreased nitric oxide production. This study aims to evaluate the serum uric acid (SUA) levels in 180 ED patients, diagnosed with the International Index of Erectile Function-5 (IIEF-5) and 30 non-ED control. Serum uric acid was analyzed with a commercially available kit using ModularEVO (Roche, Monza, Italy). Within-assay and between-assay variations were 3.0% and 6.0%, respectively. Out of the ED patients, 85 were classified as arteriogenic (A-ED) and 95 as non-arteriogenic (NA-ED) with penile-echo-color-Doppler. Uric acid levels (median and range in mg/dL) in A-ED patients (5.8, 4.3-7.5) were significantly higher (p .001) than in NA-ED patients (4.4, 2.6-5.9) and in control group (4.6, 3.1-7.2). There was a significant difference (p .001) between uric acid levels in patients with mild A-ED (IIEF-5 16-20) and severe/complete A-ED (IIEF-5 ≤ 10) that were 5.4 (range 4.3-6.5) mg/dL and 6.8 (range 6.4-7.2) mg/dL, respectively. There was no difference between the levels of uric acid in patients with different degree of NA-ED. Our findings reveal that SUA is a marker of ED but only of ED of arteriogenic aetiology.

Background: There are a limited number of studies investigating the type of serum proteins capable of differentiating intraductal papillary mucinous neoplasms from benign or malignant diseases of the pancreas. Aims: To select proteins able to differentiate intraductal papillary mucinous neoplasms from benign and malignant pancreatic disease using semiquantitative proteomics. Methods: Serum samples were obtained from 74 patients (19 with type II intraductal papillary mucinous neoplasms, 8 with type I/III intraductal papillary mucinous neoplasms, 24 with chronic pancreatitis, 23 with pancreatic ductal adenocarcinomas) and 21 healthy subjects. Small proteins and peptides were assayed by matrix-assisted laser desorption/ionization for the detection of differentially abundant species possibly related to tumor onset. Serum pancreatic amylase, lipase, carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9) were also assayed. Results: Twenty-six of 84 peaks detected were dysregulated (7 more abundant and 19 less abundant in the type II intraductal papillary mucinous neoplasms, p

Prosthetic joint infection (PJI) is the most common cause of failure of total joint arthroplasty, but a gold standard for PJI diagnosis is still lacking. Advanced glycation end products (AGEs) are proinflammatory molecules inducing intracellular oxidative stress (OS) after binding to their cell membrane receptors (RAGE). The aim of this study was to evaluate plasmatic soluble receptor for advanced glycation end products (sRAGE), as a new OS and infection marker correlating sRAGE to the level of OS and antioxidant defenses, in PJI, in order to explore the possible application of this new biomarker in the early diagnosis of PJI. Plasmatic sRAGE levels (by ELISA assay), plasma antioxidant total defenses (by lag time method), plasma reactive oxygen species (ROS), and thiobarbituric acid reactive substance (TBARS) levels (by colorimetric assay) were evaluated in 11 PJI patients and in 30 matched controls. ROS and TBARS were significantly higher (p<0.001) while plasma total antioxidant capacity and sRAGE were significantly lower (p<0.01) in patients with PJI compared to controls. Our results confirm the OS in PJI and show a strong negative correlation between the level of sRAGE and oxidative status, suggesting the plasmatic sRAGE as a potential marker for improving PJI early diagnosis.

An imbalance between degradation and reconstruction of the aortic wall is one of the leading causes of acute aortic dissection (AAD). Vitamin D seems an intriguing molecule to explore in the field of AAD since it improves endothelial function and protects smooth muscle cells from inflammation-induced remodeling, calcification, and loss of function, all events which are strongly related to the aging process. We quantified 25-hydroxy vitamin D, calcium, parathormone, bone alkaline phosphatase, and osteocalcin levels in 24 elderly AAD patients to identify a potential pathological implication of these molecules in AAD. Median 25-hydroxy vitamin D (10.75 ng/mL, 25th–75th percentiles: 6.86–19.23 ng/mL) and calcium levels (8.70 mg/dL, 25th–75th percentiles: 7.30–8.80 mg/dL) suggested hypovitaminosis D and a moderate hypocalcemia. Thirty-eight percent of AAD patients had severe (

Endothelial dysfunction has been demonstrated to play an important role in pathogenesis of erectile dysfunction (ED) and vitamin D deficiency is deemed to promote endothelial dysfunctions.To evaluate the status of serum vitamin D in a group of patients with ED.Diagnosis and severity of ED was based on the IIEF-5 and its aetiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile-echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum vitamin D and intact PTH concentrations were measured.Vitamin D levels of men with A-ED were compared with those of male with BL-ED and NA-ED.Fifty patients were classified as A-ED, 28 as ED-BL and 65 as NA-ED, for a total of 143 cases. Mean vitamin D level was 21.3 ng/mL; vitamin D deficiency (20 ng/mL) was present in 45.9% and only 20.2% had optimal vitamin D levels. Patients with severe/complete-ED had vitamin D level significantly lower (P = 0.02) than those with mild-ED. Vitamin level was negatively correlated with PTH and the correlation was more marked in subjects with vitamin D deficiency. Vitamin D deficiency in A-ED was significantly lower (P = 0.01) than in NA-ED patients. Penile-echo-color-Doppler revealed that A-ED (PSV ≤ 25 cm/second) was more frequent in those with vitamin D deficiency as compared with those with vitamin20 ng/dL (45% vs. 24%; P 0.05) and in the same population median PSV values were lower (26 vs. 38; P 0.001) in vitamin D subjects.Our study shows that a significant proportion of ED patients have a vitamin D deficiency and that this condition is more frequent in patients with the arteriogenic etiology. Low levels of vitamin D might increase the ED risk by promoting endothelial dysfunction. Men with ED should be analyzed for vitamin D levels and particularly to A-ED patients with a low level a vitamin D supplementation is suggested.

Summary Background & aims The optimal level and modality of glucose control in critically ill patients is still debated. A protocolized approach and the use of nearly-continuous technologies are recommended to manage hyperglycemia, hypoglycemia and glycemic variability. We recently proposed a pato-physiology-based glucose control protocol which takes into account patient glucose/carbohydrate intake and insulin resistance. Aim of the present investigation was to assess the performance of our protocol with an automated intermittent plasma glucose monitoring device (OptiScanner™ 5000). Methods OptiScanner™ was used in 6 septic patients, providing glucose measurement every 15′ from a side-port of an indwelling central venous catheter. Target level of glucose was 80–150 mg/dL. Insulin infusion and kcal with nutritional support were also recorded. Results 6 septic patients were studied for 319 h (1277 measurements); 58 [45–65] hours for each patient (measurements/patient: 231 [172–265]). Blood glucose was at target for 93 [90–98]% of study time. Mean plasma glucose was 126 ± 11 mg/dL. Only 3 hypoglycemic episodes (78, 78, 69 mg/dL) were recorded. Glucose variability was limited: plasma glucose coefficient of variation was 11.7 ± 4.0% and plasma glucose standard deviation was 14.3 ± 5.5 mg/dL. Conclusions The local glucose control protocol achieved satisfactory glucose control in septic patients along with a high degree of safeness. Automated intermittent plasma glucose monitoring seemed useful to assess the performance of the protocol.

This study aimed to assess the presence of pancreatic hyperenzymemia in patients with pancreatic cystic lesions as compared to other chronic diseases of the pancreas.Ninety-one patients were studied: 32 had mucinous cystic lesions, 35 had chronic pancreatitis (CP), and 24 had pancreatic ductal adenocarcinoma (PDAC). Surgery was carried out in 10 of the 32 patients with mucinous cystic lesion (7 of them had severe dysplasia), in 5 patients with CP, and in 9 patients with PDAC.Abnormally high serum pancreatic isoamylase activity was present in 11 (34.4%) patients with mucinous cystic lesions, in 14 (40.0%) patients with CP, and none in patients with PDAC (P = 0.002); whereas serum lipase activity was abnormally high in 8 (25.0%) patients with mucinous cystic lesion, in 17 (48.6%) patients with CP, and in 3 (12.5%) patients with PDAC (P = 0.009). In 7 patients with mucinous cystic lesions and histologically confirmed severe dysplasia, abnormally high levels of both serum pancreatic amylase and lipase were present in 3 (42.9%) patients.High serum concentrations of pancreatic amylase and lipase were found in no more than half of the patients with mucinous cystic lesions. High levels of pancreatic enzymes were not associated with a greater risk of malignancy.

Background Magnesium (Mg) and calcium (Ca) are the principal essential elements involved in endothelial cell homeostasis. Extracellular changes in the levels of either alter endothelial contraction and dilatation. Consequently Mg and Ca imbalance is associated with a high risk of endothelial dysfunction, the main process observed during acute aortic dissection (AAD); in this clinical condition, which mainly affects elderly men, smooth muscle cell alterations lead to intimal tears, creating a false new lumen in the media of the aorta. AAD patients have a high risk of mortality as a result of late diagnosis because often it is not distinguished from other cardiovascular diseases. We investigated Mg and Ca total circulating levels and the associated pro-inflammatory mediators in elderly AAD patients, to gain further information on the pathophysiology of this disorder, with a view to suggesting newer and earlier potential biomarkers of AAD. Results Total circulating Mg and Ca levels were both lower in AAD patients than controls (p 0.05) The levels of both ICAM-1 and EN-1 were lower in AAD than in a control group (p

Nitric oxide is a physiologic signal essential to penile erection. l-citrulline (l-Cit) is converted into l-arginine (l-Arg), the precursor from which nitric oxide is generated. The level of l-Arg and l-Cit in the field of male sexual function remains relatively underexplored. The aim of the study was to evaluate the level of serum l-Arg and of l-Cit in a group of patients with erectile dysfunction. Diagnosis and severity of erectile dysfunction was based on the IIEF-5 and its etiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum l-Arg and l-Cit concentrations were measured by a cation-exchange chromatography system. l-Arg and l-Cit levels of men with A-ED were compared with those of male with BL-ED and NA-ED. Median level of l-Arg and l-Cit in 122 erectile dysfunction patients (41 A-ED, 23 ED-BL, 58 NA-ED) was 82.7 and 35.4 μmol/L, respectively. l-Arg and l-Cit levels in control patients were not significantly different (p = 0.233 and p = 0.561, respectively) than in total erectile dysfunction patients. l-Arg and l-Cit levels in control patients were significantly higher (p 0.001 and p 0.018, respectively) than in A-ED patients, but no difference (p 0.50) was observed in controls and in both BL-ED and NA-ED patients. Patients with severe/complete-erectile dysfunction (IIEF-5 10) had l-Arg or l-Cit level significantly lower (-17%, p 0.03; -13%, p 0.04) and were more frequent (p 0.01 and p 0.04) under the respective median level (82.7 and 35.4 μmol/L) than those with mild-erectile dysfunction (IIEF-5 = 16-20). l-Arg and l-Cit levels in A-ED were significantly lower (p 0.007 and p 0.001, respectively) than in NA-ED patients. Penile echo-color-Doppler revealed that A-ED (peak systolic velocity ≤ 25 cm/sec) was more frequent in men with l-Arg under 82.7 μmol/L or l-Cit under 35.4 μmol/L and in the same population, the median peak systolic velocity values were lower in l-Arg deficient (29 vs. 35; p 0.04) and also in l-Cit deficient (31 vs. 33, p 0.3) but without reaching the statistical significance. Our study shows that a significant proportion of erectile dysfunction patients have low l-Arg or l-Cit level and that this condition is more frequent in patients with arteriogenic etiology. Low levels of these nitric oxide synthase substrates might increase the erectile dysfunction risk by reducing the concentration of nitric oxide.

The measurement of circulating free light chains (FLC) is of utmost importance in immunoglobulin light chain (AL) amyloidosis, being a fundamental part of the diagnostic workup, prognostic stratification and assessment of response to therapy. Renal failure is a common feature of AL amyloidosis and can considerably affect the concentration of FLC.We assessed the impact of renal failure on the clinical performance of the Freelite assay in 982 consecutive, newly diagnosed patients with AL amyloidosis, 822 with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 mThe diagnostic sensitivity of the κ/λ FLC ratio was lower for λ amyloidogenic FLC in patients with renal failure (81% vs. 60%, pRenal failure is a relevant interference factor when using the Freelite assay for the identification of the amyloidogenic light chain and for prognostic assessment in patients with AL amyloidosis and renal failure.

Summary Background: Biochemical predictors of infants' growth changes are not available. Objectives: We tested whether retinol-binding protein (RBP), docosahexaenoic acid and insulin (I) meas-ured within 72 h from birth are associated with growth changes in infants born to mothers with gestationaldiabetes mellitus (GDM). Methods: Fifty-six children, 32 born to diabetic mothers treated with insulin (GDM-I) and 24 born todiabetic mothers treated with diet (GDM-D), were evaluated at 0, 1, 3, 6 and 12 months of life. Results: At multivariable regression performed using generalized estimating equations, early RBP levelsand maternal body mass index were associated to average weight changes and early RBP and insulin levelsto average length changes, respectively. There was no difference between GDM-I and GDM-D infants. Conclusions: This exploratory study suggests that early RBP levels may be a predictor of growthchanges.Keywords: Docosahexaenoic acid, gestational diabetes, growth, retinol-binding protein.Metabolic and nutritional adaptations to the intrau-terine and early post-natal environment may causemetabolic derangements leading to obesity, type 2diabetes mellitus and cardiovascular disease (1).Metabolic programming is the phenomenon wherebya nutritional stress applied during critical periods ofearly development permanently alters host metabo-lism, with consequences to be observed later in life.In particular, accelerated growth rates in the earlystages of life may increase the risk of adult over-weight (2). Gestational diabetes mellitus (GDM) isassociated with a higher risk of later metabolicdisease for the offspring. Infants born to diabeticmothers have also a higher risk of early weight gain(3). Differently from anthropometric indicators, nodata are available on the ability of biochemicalmarkers to identify infants at risk of growth accelera-tion. We performed an exploratory study to testwhether selected anabolic markers, i.e. retinol-binding protein (RBP), docosahexaenoic acid (DHA)and insulin (I), are associated with growth changes ininfants born to diabetic mothers. RBP is a marker ofshort-term nitrogen incorporation into proteins (4)while DHA is a polyunsaturated fatty acid with apermissive role on anabolism and insulin action (5).Fifty-six infants were consecutively enrolled intothe study. GDM was diagnosed using an oralglucose tolerance test following current guide-lines. Gestational age

Background Subclinical inflammation and atrial stretch have been recognized as important contributors to atrial fibrillation (AF) onset and perpetuation. The aim of the study was to compare the predictive role of serum inflammatory markers (serum amyloid A [SAA], and C-reactive protein [CRP]) and N-terminal pro brain natriuretic peptide (NT-proBNP) an indice of atrial strain in relation to subacute arrhythmic recurrence rate in patients with persistent AF and normal left ventricular ejection fraction (LVEF). Methods We studied 57 patients with a mean LVEF of 58.7 ± 6%. NT-proBNP, SAA and CRP levels were determined few hours before electrical cardioversion and 3 weeks after cardioversion. Results Subacute AF recurrences were documented in 19 (33 %) patients. Whereas NT-proBNP levels did not predict arrhythmic outcome, higher SAA (> 6.16-6.19 mg/L) and CRP levels (> 2.99-3.10 mg/L) were significantly associated with AF recurrences (odds ratio [OR], 5.39; 95% confidence interval [CI], 1.59-18.26; P = 0.007 and OR, 14.93; 95% CI, 3.90-57.19; P P = 0.009) and high sensitivity CRP (OR, 42.03; 95% CI, 4.83-365.45; P = 0.001) through the multivariate logistic regression analysis show an independent role in predicting the AF recurrence with a sensitivity of 100% (38/38) and a specificity of 52.6% (10/19). Conclusions The present study demonstrates that in patients with persistent AF and preserved LVEF, SAA and CRP levels are independent predictors of AF subacute recurrence rate, whereas NT-proBNP, not associated with arrhythmic outcome, reflects the hemodynamic alterations secondary to arrhythmia presence. The simultaneous determination of SAA and high sensitivity CRP has a very high sensitivity (100%) in predicting the AF recurrence.

The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between ADMA, symmetric dimethylarginine (SDMA) and L-arginine concentrations and erectile dysfunction. We compared plasma levels of ADMA, SDMA and L-arginine in 61 men in good health with erectile dysfunction of arteriogenic and non-arteriogenic origin. Diagnosis of erectile dysfunction was based on the International Index of Erectile Function Score and its aetiology was classified with penile echo-colour-Doppler in basal condition and after intracavernous injection of prostaglandin E1. The ADMA and SDMA concentrations were significantly higher in men with arteriogenic erectile dysfunction compared with those with erectile dysfunction of non-arteriogenic origin (p 0.05) nor between each of the two erectile dysfunction subgroups and controls (p > 0.05). The L-arginine/ADMA and the L-arginine/SDMA ratios in arteriogenic erectile dysfunction subgroups were significantly lower than both in controls (p 0.05). We conclude that ADMA and SDMA concentrations are significantly higher and L-arginine/ADMA ratio lower in patients who have arteriogenic erectile dysfunction compared with both patients with non-arteriogenic erectile dysfunction and controls. The negative correlation between ADMA and severity of erectile dysfunction is present only in patients with arteriogenic erectile dysfunction. This study supports the importance to always distinguish arteriogenic from non-arteriogenic erectile dysfunction patients to study the complicate erectogenic mechanisms that lead to erectile dysfunction and also to provide potential therapeutic agents for patients with arteriogenic erectile dysfunction.

Introduction: We measured serum creatinine concentrations in 17 male athletes of the Italian national rugby team. Methods: Blood was obtained before the start of training and during the competitive season. Serum creatinine level was measured by Jaffé reaction at 4 time points during the season, with a formal measure of creatinine clearance in midseason. Results: The values of estimated glomerular filtration rate (eGFR) calculated with the Cockcroft-Gault (CG) equation were higher than those calculated with the Modification of Diet in Renal Disease (MDRD) Study formula (p

Background. There is increasing evidence regarding the involvement of inflammation processes in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Aim. To evaluate the circulating concentrations of MMP-3 and TIMP-2 in patients with IPMNs and in those with ductal adenocarcinomas. Patients. Sixty patients (32 males, 28 females, mean age 69.3±11.3 years) were enrolled: 31 (51.7%) had IPMNs and 29 (48.3%) had histologically confirmed pancreatic adenocarcinomas. Thirty blood donors were also studied as controls. Methods. The serum concentrations of MMP-3 and TIMP-2 were determined in all study subjects using commercially available kits. Results. Serum concentrations of MMP-3 were significantly higher both in patients with pancreatic ductal adenocarcinomas and in those with IPMNs as compared to the healthy subjects whereas serum levels of TIMP-2 were significantly lower both in IPMN patients and in patients with pancreatic adenocarcinomas than in those of the healthy subjects. No significant differences in the serum levels of both MMP-3 and TIMP-2 were found between patients with IPMNs and those with pancreatic adenocarcinomas, and, in the patients with IPMN, they were not related to the type of tumor. Conclusions. IPMNs have a pattern of extracellular matrix factors and their inhibitors are similar to those of ductal adenocarcinoma; MMP-3 and TIMP-2 cannot be utilized to routinely differentiate IPMNs from ductal adenocarcinomas.

Background: The aim of the study was to evaluate the circulating concentrations of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial growth factor-D (VEGF-D) and endostatin in patients with intraductal papillary mucinous neoplasm (IPMN), and in those with ductal adenocarcinomas. Methods: Sixty patients (32 males, 28 females, mean age 69.3±11.3 years) were enrolled: 31 (51.7%) had IPMNs and 29 (48.3%) had histologically confirmed pancreatic adenocarcinomas. Thirty blood donors were also studied as controls. In all study subjects, the concentrations of VEGF, VEGF-D, VEGFR-2, and endostatin were determined using enzyme-linked immunosorbent assays. Results: Serum concentrations of VEGF, VEGF-D, and VEGFR-2 were significantly higher in patients with pancreatic ductal adenocarcinoma and those with IPMNs compared with healthy subjects, while endostatin was significantly higher only in patients with pancreatic ductal adenocarcinoma compared with healthy subjects. Within the group of patients, VEGFR-2 was significantly higher in patients with ductal adenocarcinoma compared to those with IPMNs. The sensitivity and the specificity of VEGFR-2 in differentiating patients with ductal adenocarcinomas from those with IPMN at a cut-off range of 4003–4034 pg/mL was 86.2% and 54.8%, respectively. Conclusions: IPMNs have serum VEGFR-2 concentra-tions different from those in patients with ductal adenocarcinomas. However, serum VEGFR-2 cannot be routinely utilized to differentiate IPMNs from pancreatic ductal adenocarcinomas.

In light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction. N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) are used to assess the severity of cardiac damage. We evaluated the prognostic relevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 months after treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but the best multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77 ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff). After treatment, response and progression of NT-proBNP and a more than 75% increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis, hs-cTnT is the best baseline prognostic marker. Therapy should be aimed at preventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit.

The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.

IntroductionThe recent sophisticated diagnostic procedures aimed at identifying the exact cause of erectile dysfunction (ED) are often complicated in clinical application, invasive, or highly expensive. Microalbuminuria, a test easy to perform and of low cost, is a marker of extensive endothelial dysfunction, and it has been suggested to be linked to ED.AimThe aim of this study was to investigate the eventual role of microalbuminuria in differentiating patients with arteriogenic and non arteriogenic ED.MethodsThe diagnosis of ED was based on the International Index of Erectile Function 5-questionnaire, and patients were classified as arteriogenic (N=29) and non-arteriogenic (N=49) in relation to the results of echo-color-doppler examination of cavernosal arteries in basal conditions and after intracavernous injection of 10 µg prostaglandin E1.Main Outcome MeasuresThe microalbuminuria of 78 males without the most common atheriosclerotic risks and with ED was measured.ResultsMicroalbuminuria, defined as urinary albumin/creatinine ratio, was not significantly (P > 0.05) different between patients of the two groups.ConclusionsOur data show that in ED patients the cavernosal arteries damage, as assessed by dynamic echo-color-doppler, may be independent on or precede extensive endothelial dysfunction, and that microalbuminuria cannot be predictive of penile arteriogenic etiology.

OBJECTIVE: Serum leptin and adiponectin determinations have been proposed as markers for distinguishing pancreatic cancer and chronic pancreatitis from autoimmune pancreatitis; however, no studies exist in patients with autoimmune pancreatitis and in those with intraductal papillary mucinous tumors of the pancreas. The aim of this paper was to evaluate the circulating concentrations of receptor for advanced glycation end products (RAGE), leptin and adiponectin in patients with chronic pancreatic diseases. MATERIAL AND METHODS: Seventy-five consecutive patients with chronic pancreatic diseases (47 males, 28 females; mean age 67.0 +/- 13.2 years; range 37-97 years) were studied: six (8.0%) had autoimmune pancreatitis, 23 (30.7%) had chronic pancreatitis, 34 (45.3%) had pancreatic cancer and the remaining 12 (16.0%) had intraductal papillary mutinous tumors of the pancreas. Leptin, adiponectin and RAGE were determined in serum using commercially available kits. The leptin concentrations were normalized to the lower and upper reference limits because of the different gender reference ranges. RESULTS: Normalized leptin concentrations were significantly lower in chronic pancreatitis patients (0.53 +/- 1.28; p = 0.008) and in those with pancreatic cancer (0.12 +/- 0.33; p < 0.001) compared to the overall population (0.58 +/- 1.23), whereas autoimmune pancreatitis patients had significantly higher concentrations of this protein (2.18 +/- 2.56; p = 0.004) compared to the overall population. RAGE and adiponectin concentrations were similar among the four groups of patients studied. Among the clinical variables considered, only pain was significantly related to leptin concentrations (patients with pain 0.18 +/- 0.54, patients without pain 1.07 +/- 1.64; p = 0.001). CONCLUSION: Serum leptin seems to be a good serum marker for differentiating autoimmune pancreatitis patients from those with chronic pancreatitis and pancreatic cancer.

Pain is the hallmark of acute pancreatitis and it is localized in the epigastrium in more than 60% of patients having mild or severe disease. Acute pancreatitis may mimic other diseases such as acute coronary syndrome. In addition, the acute illness of the pancreas is associated with a number of metabolic abnormalities, such as hypocalcemia and hypophosphatemia, which may cause hemodynamic changes and variations in the concentration of ionized calcium. In turn, these have been directly correlated to changes in myocardial contractility. The aim of this paper is to review the current literature on the involvement of heart during the course of acute pancreatitis and also to evaluate experimental and clinical data on this topic.

Background.Evidence is accumulating in favour of a link between erectile dysfunction (ED) and coronary artery diseases. We investigated the presence of cardiac injury in patients who have had arteriogenic and nonarteriogenic ED using the hs-Tn levels.Methods.The diagnosis of ED was based on the International Index of Erectile Function 5-questionnaire (IIF-5) and patients were classified as arteriogenic (A-ED,n=40), nonarteriogenic (NA-ED,n=48), and borderline (BL-ED,n=32) patients in relation to the results of echo-color-Doppler examination of cavernous arteries. The level of hs-TnT and hs-TnI was measured in 120 men with a history of ED of less than one year with no clinical evidence of cardiac ischemic disease.Results.The levels of both hs-TnT and hs-TnI were within the reference range and there was no significant (P>0.05) difference between patients of the three groups. The hs-CRP values were higher in A-ED men compared with NA-ED (P=0.048) but not compared with BL-ED (P=0.136) and negatively correlated with IIF-5 (r=-0.480;P=0.031).Conclusions.In ED patients of the three groups the measurement of hs-Tn allows us to exclude the presence of cardiac involvement at least when the history of ED is less than one year and the men are without atherosclerotic risk factors.

Evidence suggests that endurance and even recreational cycling may stimulate bone resorption; however, little is known about cartilage response to endurance cycling exercise. We investigated effort-dependent changes in bone turnover and cartilage biomarkers in blood and urine samples from elite cyclists during a 3-week stage race. Whole blood and urine samples were collected the day before the start of the race, at mid and end-race for serum and urinary CTx-I, NTx-I, PINP, COMP (only in serum), and CTx-II analysis by enzyme-linked immunosorbent assay. The values were corrected for plasma volume or creatinine excretion, respectively, and correlated with power output (corrected for body weight) and net energy expenditure. Bone marker concentrations in both serum and urine were slightly but significantly decreased. Among the cartilage degradation markers, only CTx-II was decreased, while COMP remained unchanged. The changes in bone and cartilage turnover indexes were correlated with the indexes of physical effort and energy consumption. Strenuous physical effort, in the absence of mechanical loading, slows bone metabolism and only minimally affects cartilage turnover. Since changes in plasma and urine volume, which normally occur in exercising athletes, can mask these effects, biomarker concentrations need to be corrected for shifts in plasma volume and urinary creatinine for correct interpretation of the data.

Background Mid-infrared spectral technology has shown a high degree of promise in detecting glucose in plasma. OptiScan Biomedical has developed a glucose monitor based on mid-infrared spectroscopy that withdraws blood samples and measures plasma glucose. The objective of this study was to evaluate the accuracy and performance of the OptiScanner™ 5000 system on different pools of blood. Methods This study was performed to validate the blood glucose measurements obtained with the OptiScanner™ 5000 by comparing them to Central Laboratory glucose measurements (VITROS® 5600 Integrated System) as a comparative method across a broad range of glucose values over a three day period to obtain 80–90 paired measurements. Results A total of 81 paired measurements, distributed between 33 and 320 mg/100 mL of glucose, were performed. The aggregate data points were within International Organization for Standardization standards, with 100% of the glucose values within ± 15%. Conclusions The current study suggests that a mid-IR fixed-wavelength system (OptiScanner) can measure glucose accurately across a wide range of glucose values in plasma of ICU patients.

Introduction Erectile dysfunction (ED) is often associated with metabolic disorders. Leptin and adiponectin are adipose tissue‐derived hormones involved in the regulation of metabolic homeostasis and considered important players in the relationship among obesity and cardiovascular diseases. Aim Leptin, adiponectin, leptin to adiponectin ratio (L/A), and their correlation with hormonal and metabolic parameters were examined in male with arteriogenic‐ (A‐ED) and nonarteriogenic‐ED (NA‐ED). Main Outcome Measures Biochemical, metabolic, and hormonal parameters of men with A‐ED were compared with those of male with NA‐ED. Methods Diagnosis of ED was based on the International Index of Erectile Function Score. Its etiology was classified with penile echo‐color Doppler at baseline and after intracavernous injection of prostaglandin E1. Leptin and adiponectin were measured by enzyme‐linked immunosorbent assay. Results In A‐ED subjects, increased levels of insulin, glycated hemoglobin, homeostasis model assessment of insulin resistance (HOMA‐IR) index, body mass index (BMI), leptin, and L/A and decreased levels of total, free, and bioavailable testosterone were observed compared with NA‐ED subjects. A trend toward lower estradiol level was also present in A‐ED patients, even if not statistically significant. Reduced levels of adiponectin have been observed in both groups compared with patients without ED. Leptin and L/A correlated similarly with several parameters (negatively with testosterone/estradiol ratio and positively with BMI, insulin, HOMA‐IR, and 17‐beta estradiol). L/A resulted further correlated negatively with high‐density lipoprotein and positively with triglycerides. Conclusions Not all ED cases are similar. In fact, A‐ED patients display a more complicated metabolic status characterized by overweight and obesity and associated to sexual hormone alteration. Whether changes in body composition and modulation of adipokine levels can improve local endothelial function need further investigation. Dozio E, Barassi A, Dogliotti G, Malavazos AE, Colpi GM, D'Eril GVM, and Corsi MM. Adipokines, hormonal parameters, and cardiovascular risk factors: Similarities and differences between patients with erectile dysfunction of arteriogenic and nonarteriogenic origin. J Sex Med 2012;9:2370–2377.

OBJECTIVE: We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART). DESIGN: We studied 163 patients receiving virologically suppressive cART. METHODS: We measured IMT (carotid ultrasound); CD4+/CD8+ T-cell activation (CD38, CD45R0), differentiation (CD127), apoptosis (CD95), and senescence (CD28, CD57) (flow cytometry); plasma sCD14, IL-6, TNF- α, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA); LPS (LAL). The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression. RESULTS: Of 163 patients, 112 demonstrated normal IMT (nIMT), whereas 51 (31.3%) had pathological IMT (pIMT: ≥1 mm). Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT), and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p = .95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p = .038) and apoptotic CD4+CD95+ (p = .01) and CD8+CD95+ cells (p = .003). In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57- memory CD4+ (p = .048) and CD28-CD57-CD8+ cells (p = .006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p = .046). No differences in anti-CMV IgG was shown. Although circulating levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors. CONCLUSIONS: Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further.

Introduction: The study of cardiac response to strenuous and continuous exercise is crucial to un-derstanding the physiology of endurance. N-terminal proB-type natriuretic peptide (NT-proBNP) is a potential marker for monitoring myocardial wall stress, and troponins (TnT and TnI) are widely used in the diagnosis of cardiac ischemia and infarction. Strenuous exercise may generate transitory ische-mia, myocardial stress, and diastolic left ventricular dysfunction, inducing the increased production of both these biomarkers. We measured changes in NT-proBNP and TnT in elite cyclists during a 3-week stage race, a model of strenuous exercise. Materials and methods: The study population was 9 professional cyclists participating in the 2011 Giro d’Italia. Pre-analytical and analytical phases scrupulously followed official recommendations. Anthropometric data, net energy expenditure and cardiac indexes (rate, diastolic and systolic blood pressure) were recorded. Blood samples were drawn pre-race (day -1) and at days 12 and 22; NT-proBNP and highly sensitive-troponin (Hs-TnT) concentrations were assayed and corrected for plas-ma volume changes. Results: Body-mass index decreased and energy expenditure increased by 52% during the race. NT-proBNP concentrations increased [day -1: 23.52 ng/L (9.67-34.33); day 12: 63.46 ng/L (22.15-93.31); P = 0.039; day 22: 89.26 ng/L (34.66-129.78) vs. day -1; P < 0.001] and correlated with heart rate (r = -0.51; P = 0.006), systolic pressure (r = 0.39; P = 0.046) and energy expenditure (r = 0.70; P < 0.001). TnT concentrations did not vary, but a widened TnT amplitude distribution was observed. Conclusions: Increases in NT-proBNP correlated with higher energy expenditure over a 3-week cy-cling stage race, possibly indicating myocardial stress.

Cardiac biomarkers play a major role in the identification of patients at risk of early death in AL amyloidosis, and a staging system based on amino-terminal pro-natriuretic peptide type-B (NT-proBNP) and troponins (cTn) is used for prognostic stratification. Adrenomedullin is produced by several tissues including the heart, and portends a poor prognosis in heart diseases. We investigated the ability of midregional proadrenomedullin (MR-proADM) to predict early death in AL amyloidosis.One-hundred and thirty consecutive patients with newly-diagnosed AL amyloidosis were prospectively enrolled. The impact on survival of NT-proBNP, cTnI and MR-proADM was evaluated.The concentration of MR-proADM correlated with systolic and diastolic function, but did not reflect the amount of amyloid deposited in the heart. Moreover, MR-proADM was associated with non-cardiac markers of advanced disease. The staging system based on NT-proBNP and cTnI identified high-risk subjects, but could not discriminate good-risk and intermediate-risk patients. Conversely, a staging system based on MR-proADM and cTnI identified 3 groups with significantly different survivals.Midregional-proADM is a powerful prognostic marker in AL amyloidosis, which may not only reflect cardiac dysfunction but also widespread systemic disease, and can be combined with cTn for detecting patients at risk of early death.

Adequate plasma trough concentrations (Ctrough) of protease inhibitors are required to maintain antiviral activity throughout the dosing interval. Therapeutic drug monitoring is used in clinical practice to optimize dosage and avoid toxic or subtherapeutic drug exposure. The pharmacokinetic variability of Atazanavir (ATV) can be relatively large, as a result of several factors. One of the affecting factors may be hepatic impairment due to hepatitis C virus (HCV) coinfection.We collected trough plasma samples from human immunodeficiency virus (HIV)-1-infected outpatients, with and without HCV coinfection and/or cirrhosis, receiving stable highly active antiretroviral therapy containing ATV. In the total population, we mainly compared the 2 regimens: 300ATV + 100RTV OD [ritonavir (RTV), once daily (OD)] versus 400ATV OD. We used a threshold value of 0.15 μg/mL, based on the proposed therapeutic range (0.15-0.85 μg/mL). Plasma concentrations of ATV were determined by a validated assay using high-performance liquid chromatography with ultraviolet detection. A total of 214 HIV-infected outpatients were included. For each regimen, we compared 3 groups of subjects: HIV+/HCV-, HIV+/HCV+, and HIV+/HCV+ with cirrhosis.In the whole study population, we observed a large variability and found suboptimal Ctrough levels (0.15 μg/mL) in 23 subjects (2 belonging to the 300/100 OD group and 21 to the 400 OD group). For the standard dosage regimen of 300ATV + 100RTV OD, we did not find a statistical difference between HIV-infected patients without HCV coinfection versus HIV-infected patients with HCV coinfection: median 0.85 (interquartile range 0.53-1.34) and 0.95 (0.70-1.36) μg/mL, respectively. In HIV+/HCV+-infected patients with cirrhosis, we found a median Ctrough of 0.70 (0.43-1.0) μg/mL, with no statistical difference when compared with HIV+/HCV- infected patients. For the 400ATV OD (n=90) dosage regimen, the total median ATV Ctrough was 0.40 (0.23-1.0) μg/mL. In this group, we found a statistically significant difference between HIV+/HCV- and HIV+/HCV+-infected patients: median Ctrough was 0.23 (0.11-0.42) and 0.52 (0.20-1.0) μg/mL, respectively. In HIV+/HCV+ subjects with cirrhosis, the Ctrough median value was 0.42 (0.13-0.75) μg/mL, and there was a significant difference when compared with HIV patients without coinfection.Therapeutic drug monitoring of ATV in patients receiving unboosted regimen may be useful to identify those HIV-infected subjects, with or without HCV coinfection, who may benefit from adding low RTV doses, or the subset of patients in whom removal of RTV could be attempted without the risk of suboptimal plasma ATV exposure.

Equations to estimate the glomerular filtration rate (GFR) have recently been advocated over serum creatinine values as a means to more accurately assess kidney function. The Cockcroft-Gault (CG) equation requires a body weight parameter, whereas the Modification of Diet in Renal Disease (MDRD) Study and Mayo Clinic Quadratic Equation (MCQE) formulae do not. We measured the serum creatinine and cystatin C concentrations in male athletes belonging to the Italian National Rugby team. Blood was obtained before the start of training and during competitive season. The serum creatinine level was measured by Jaffe and enzymatic reactions, cystatin C by nefelometry. The same parameters were measured in a control group of male, sedentary and overweight subjects. The concentrations of cystatin C were always into the reference ranges. The concentrations of creatinine were often higher than reference interval. The use of enzymatic method did not improve the specificity. The equations based on cystatin C and creatinine were not correlated. The two equations based on cystatin C were correlated. Two equations based on creatinine values were correlated (MDRD and MCQE); they were not correlated with CG. 29 level athletes, characterized from a high release of creatinine. The use of equations should be accurately evaluated: the CG equation can overestimate the eGFR, the MDRD and MCQE formulae systematically underestimates it. The use of equations to estimate GFR in the general population needs examination of their behaviour in subjects having atypical anthropomorphic characteristics.