Background and objectiveIn this different revision of our cohort of asymptomatic subjects with carotid atherosclerosis, particularly, we examined the behaviour of oxidative stress, some inflammation parameters, and blood viscosity in relation to the hemoglobin concentration.Patients and methodsOur study population includes 100 subjects (43 men and 57 women) with asymptomatic carotid atherosclerosis (SCA). Specifically, we evaluated the following variables: NOx (metabolites of NO, nitrate and nitrite), lipid peroxidation, high sensitivity C-reactive protein, neutrophil and lymphocyte counts, whole-blood viscosity and plasma viscosity, mean erythrocyte aggregation, hematocrit, fibrinogen, and Yield shear stress (YSS).ResultsFrom the obtained data, we observed an increase in diastolic pressure and uricemia in the subgroup above the median values oh hemoglobin level. In the same subgroup, we observed a reduction in NOx, not associated with an increase in lipid peroxidation, an increase in blood viscosity, at high and low shear rate, as well as an increase in plasma viscosity and erythrocyte aggregation and YSS.ConclusionsIn subjects with subclinical carotid atherosclerosis the subdivision according to the hemoglobin level underlines the role of this parameter in the pathogenesis and progression of the atherosclerosis.

BACKGROUND:Leukocyte count is a prognostic marker for cardiovascular diseases, with key role in atherosclerosis development. Specific number of neutrophils, lymphocytes and monocytes can predict cardiovascular risk, also in asymptomatic subjects. Among the lipoprotein fractions, HDL-C is a protective factor in the cardiovascular disorders. For the above reason, we have examined the peripheral count of leukocytes, neutrophils, lymphocytes and monocytes, and the ratios between neutrophils/HDL-cholesterol, lymphocytes/HDL-cholesterol, and monocytes/HDL-cholesterol, to evaluate the possible utility of the obtained values in progression of asymptomatic carotid atherosclerosis. METHODS:We performed our analysis in a cohort of 100 subjects with asymptomatic carotid atherosclerosis, of which 43 men and 57 women. The data were expressed as medians and IQR. To analyse the differences in leukocyte, neutrophil, lymphocyte, monocytes count and their ratio with HDL-cholesterol the Mann-Whitney test was employed. RESULTS:The peripheral count of leukocyte subtypes and the ratios, they change in relation to the number of cardiovascular risk factors and the degree of insulin resistance. CONCLUSIONS:In this cohort of subjects, the percentage of observed cardiovascular risk factors significantly affect some leukocyte parameters. These results, allow us to underline the importance of the leukocyte indices in the evaluation of subjects with asymptomatic vascular atherosclerosis.

BACKGROUND AND OBJECTIVE:Asymptomatic atherosclerosis is an important early marker of vascular damage and, among its risk factors, hemorheological alterations play an important role.PATIENTS AND METHODS:In a cohort of 85 non-diabetic subjects with asymptomatic carotid atherosclerosis (ACA), we have measured whole blood viscosity (cWBV) according to the haematocrit and plasma fibrinogen level. The cWBV distinguish the subgroup of ACA subjects with 3-5 cardiovascular risk factors (CRFs) from that with 1-2 CRFs and the same behavior is present for haematocrit and plasma fibrinogen level. Therefore, we divided the whole group of ACA subjects according to the medians of the four surrogate indexes with an insulin resistance degree of TG/HDL-C, TyG, VAI and LAP.RESULTS:The analysis of the correlation between cWBV and each index of insulin resistance has shown that no correlation is present in the whole group and in the group of ACA subjects with 1-2 CRFs, while in the subgroup with 3-5 CRFs there is a positive correlation between cWBV with TG/HDL-C and TyG at a low degree of statistical significance.CONCLUSIONS:The date underline that subjects with this clinical condition have an unaltered evaluation of the cWBV compared to the other indices.

BACKGROUND AND OBJECTIVE: we have examined the concentration of serum uric acid and the serum uric acid/creatinine ratio as well as their correlations with the main determinants of the hemorheological profile in a group of subjects with subclinical carotid atherosclerosis. METHODS: we evaluated the concentration of serum uric acid and the serum uric acid/creatine ratio in 43 men and 57 women [median age 66.00 (25)] with subclinical carotid atherosclerosis, subsequently divided according to the number of traditional cardiovascular risk factors and to the insulin resistance degree. RESULTS: serum uric acid, but not the serum uric acid/creatinine ratio, results strongly influenced by the number of cardiovascular risk factors and by the insulin resistance degree. In the whole group and in the subgroups of subclinical carotid atherosclerosis subjects, serum uric acid and serum uric acid/creatinine ratio show significant correlation, besides with whole blood viscosity, with plasma viscosity and erythrocyte aggregation. The influence of the serum uric acid on the erythrocyte aggregability that is a part of the erythrocyte aggregation is to ascribe to the action carried out by serum uric acid on the erythrocyte zeta potential. CONCLUSIONS: it is reasonable to think that the treatment of the asymptomatic or symptomatic hyperuricemia with the urate-lowering therapy that reduces the serum uric acid concentration may reflect on the hemorheological profile which role on the atherosclerotic cardiovascular disease is well known.

In a cohort of subjects with asymptomatic carotid atherosclerosis (ACA), we have evaluated the neutrophil and lymphocyte count and their ratio (NLR), the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). At baseline, no difference was observed between ACA subjects and subject control group regarding neutrophil and lymphocyte count while was evident in ACA subjects a significant increase in MMP-2, MMP-9 and TIMP-2 associated to a significant decrease in TIMP-1. Dividing the ACA according to the number of cardiovascular risk factors (CRFs) we have observed an increase in lymphocyte count in the subgroup with 3-5 CRFs. Evaluating the leukocyte subtypes according to all the surrogate markers of insulin resistance has been noted, in the subgroups that exceed the medians of these markers, a significant increase in neutrophil and lymphocyte count without any variation of the NLR. Effecting the same evaluation for the MMP/TIMP pattern we observed, instead, that the same subgroups tend to show a decrease in MMP-2 and an increase in MMP-9. No difference instead for TIMP-1 and TIMP-2. The abnormality of the MMP/TIMP pattern, bearing in mind the cardiometabolic clustering present in this cohort of ACA subjects, would induce to use drugs able not only to cure the cardiometabolic risk factors but also to influence the MMP/TIMP profile.

Objective: In September-October 2020 our Poison Centre (PC) managed a cluster of 44 workmen who consumed food contaminated by botulinum neurotoxins (BoNT) at a workplace canteen in Sicily. Case series: Of the 100 workers using the canteen, 44 presented over a 7-day period to 6 Emergency Departments (ED) in Southern Italy complaining of neurological and gastrointestinal symptoms (Table 1). Our PC, consulted first by physicians in Cefalu, made the diagnostic suspicion of foodborne botulism. Heptavalent-botulism-antitoxin (HBAT) was mobilized from different National Stockpiles (Catania, Pavia, Rome, Trieste, Naples) after approval from the Ministry of Health (MoH). The early admitted patients (7/44, 17%, 2-days after meal) worsened rapidly and 5/7 required mechanical ventilation (MV) within 24 hours. Patients with minor symptoms were discharged and managed with telephone follow-up by PC toxicologists. Conclusion: Botulism diagnosis is based on clinical suspicion;laboratory testing has a crucial role in confirmation, but analyses do not always demonstrate BoNT (15/36 tested positive in our cluster). Therefore, the positivity of at least 1 patient of a cluster confirms the diagnosis. The antitoxin should be administered as soon as clinical suspicion is made. In our outbreak, HBAT was administered due to rapid worsening of neurological symptoms, in order to prevent MV. The rapid deterioration of the first 7 patients is attributable to the ingestion of higher titre of toxin. In Italy, HBAT in the National Stockpile can be mobilized only after MoH approval. The management of the outbreak was challenging because of difficulties in the capacity of the hospitals and the urgent need for antitoxin. An efficient collaboration between local physicians, clinical toxicologists, MoH and the National Stockpile system ensured optimal management with prompt HBAT mobilization in sufficient number. This was also possible because it occured before the second COVID-19 wave in which it would have been difficult to manage 44 patients potentially requiring ICU monitoring.

We present a cohort of 100 subjects [43 men and 57 women; median age 66.00(25)] who were tested using carotid ultrasound to identify subclinical carotid atherosclerosis (SCA). We have evaluated the behaviour of whole blood viscosity (WBV) at high (450 s-1) and low (0.51 s-1) shear rates, plasma viscosity (450-1), hematocrit and mean erythrocyte aggregation. When compared to normal control subjects, using the Mann-Whitney test, we observed in SCA patients a significant increase in WBV only. The results were substantial after having divided the SCA subjects according to the cardiovascular risk factors (CRFs) and the degree of insulin resistance; the research was performed using two surrogate indexes such as TG/HDL-C and TyG. With the division carried out according to CRFs, employing the Kruskal-Wallis test, results show a significant increase in WBV (at high and low shear rates), in plasma viscosity, in erythrocyte aggregation and plasma fibrinogen level. Whereas by dividing them into the median of TG/HDL-C and TyG, we noticed a significant increase in WBV (at high and low shear rates) and in erythrocyte aggregation in the two groups with high TG/HDL-C ratio and with high TyG; having found an increased level of plasma fibrinogen in the latter. The data underlines the role of the main hemorheologic aspects in subclinical carotid atherosclerosis being closely correlated to the CRFs and different degrees of insulin resistance.

The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30-35 Kg/m2 and BMI> 35 Kg/m(2)); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI >30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1.

Abstract The association between obesity and cardiovascular diseases has a multifactorial pathogenesis, including the synthesis of inflammatory molecules, the increase in oxidative stress and the dysregulation of the matrix metalloprotease (MMP) concentration and activity. In a group of adults with obesity, divided in 2 subgroups according to the body mass index (BMI), we examined lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), protein oxidation, expressed as protein carbonyl groups (PCs), plasma gelatinases (MMP-2 and MMP-9), and their tissue inhibitors (TIMP-1 and TIMP-2). In the whole group, as well as in the 2 subgroups (with BMI 30–35 or BMI>35) of obese subjects, we observed an increase in TBARS, PCs, MMP-2, and MMP-9, and also TIMP-1 and TIMP-2 in comparison with the control group. A positive correlation between TBARS and PCs emerged in obese subjects and persisted after dividing obese subjects according to BMI. The correlation between MMP-2 and TIMP-2 was not statistically significant, while a significant correlation was present between MMP-9 and TIMP-1. The correlations between the markers of oxidative stress (TBARS and PCs) and those of the MMP/TIMP profile indicated a more marked influence of protein oxidation on MMPs and TIMPs in comparison with TBARS. The innovative aspect of our study was the simultaneous evaluation of oxidative stress markers and MMP/TIMP profile in adult obese subjects. We observed significant alterations and correlations that may negatively influence the clinical course of the disease.

Chronic obstructive pulmonary disease (COPD) is one of the world leading causes of death. It has been recently related to aging and inflammation, as well as sirtuins are actually recognized to be involved in both these phenomena. Sirtuins are a family of highly conserved protein deacetylases and they influence the factors that worsen physiological aging such as glucose metabolism, DNA stability and cancer, neurodegenerative processes, etc. Among the seven sirtuins, SIRT1 and SIRT6 have been deeply investigated in COPD. Actually researchers hypothesize that SIRT 1 activators could play a fundamental role in counteract COPD. Natural compounds as Resveratrol are actually retained SIRT1 activators and could be indicated as powerful weapons against this complex disease.

Considering the role of hemorheology in coronary circulation, we studied blood viscosity in patients with juvenile myocardial infarction. We examined whole blood viscosity at high shear rate using the cone-on-plate viscosimeter Wells-Brookfield ½ LVT and at low shear rate employing a viscometer Contraves LS30 in 120 patients (aged <46 years) with myocardial infarction, at the initial stage and subsequently 3 and 12 months after. At the initial stage, patients had an increased whole blood viscosity in comparison to normal controls. This hemorheological profile was not influenced by the cardiovascular risk factors, nor by the extent of coronary lesions, even if some differences were evident between patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). The blood viscosity pattern at the initial stage did not influence recurring ischemic events or the onset of heart failure during an 18 months’ follow-up. The neutrophil to lymphocyte ratio did not affect the blood viscosity pattern. We reevaluated 83 patients 3 months after and 70 patients 12 months after the acute coronary syndrome, and we found that the hemorheological parameters were still altered in comparison to normal controls at both times. We observed an impairment of the hemorheological pattern in young patients with myocardial infarction, partially influenced by the infarction type (STEMI and NSTEMI) and persisting in the long term.

Spurious electrolyte disorders refer to artifactually elevated or decreased serum electrolyte values that do not correspond to their actual levels. These disorders are not infrequently observed in clinical practice during multiple myeloma. Monoclonal immunoglobulins (MG), also called paraproteins, can occur in serum in high concentrations, and they may cause significant interference in clinical chemistry assays. Examples of gammopathy interference for the analytes glucose, bilirubin,gamma-glutamyltransferase (GGT), urea, high-density lipoprotein cholesterol (HDL), creatine kinase, and ferritin have often been reported. Electrolyte abnormalities include inorganic phosphorus, sodium, and the anion gap. MG can interfere with a wide range of automated nephelometric, turbidimetric, and immunological assays through a variety of mechanisms, including precipitate formation, MG binding to an assay reagent, and incomplete antibody binding. The recognition that an electrolyte disturbance or other analyte abnormality may be an artifact may prevent inappropriate therapeutic interventions that could potentially have unfavorable outcomes.

Despite huge progress in acidbase knowledge, several confusing, irrational and controversial issues still remain. Acid-base disturbances have been usually evaluated with the traditional Henderson-Hasselbach method and with BE evaluation that seem inadequate since they define the magnitude of metabolic acidosis rather than its cause. Some studies have shown that the traditional approach is often not able to highlight the complicated acid-base disorders in critically ill patients; in these subjects, the possibility to identify tissue acids could offer a greater prognostic value than the evaluation of traditional parameters. An alternative approach is the Stewarts physiochemical method that defines the aetiology of a metabolic acidosis by quantifying the tissue acids. But the clinical utility of this method is limited due to its mathematical complexity. Therefore, some parameters of simplification were proposed in order to allow greater clinical applicability of this system. Specifically, it was observed that in the presence of metabolic acidosis, the chloride/sodium ratio (Cl-/Na+ ratio) or the sodium-chloride difference (DiffNa-Cl) would be useful indicators of the presence of unmeasured anions (UMA) and/or lactate.

In this brief review, we have examined some clinical disorders which are associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be, in fact, observed in patients with primary plasma hyperviscosity such as multiple myeloma, Waldenstrom macroglobulinemia, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia and connective tissue diseases. It must be underlined that the altered hemorheological pattern is not the only responsible for this skin complication but, as it worsens the microcirculatory flow, it contributes to determine the occurrence of the skin ulcers.

In this brief review, we have examined some clinical conditions that result to be associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). In addition, it may be present in patients with secondary hyperviscosity conditions such as diabetes mellitus, arterial hypertension, critical limb ischemia and chronic venous insufficiency.

Aim: The aim of the study is to evaluate the chloride/sodium ratio ([Cl-]/[Na+] ratio) and the sodium-chloride difference (Diff(Na-Cl)) in a group of patients with renal failure and metabolic acidosis receiving hemodialysis treatment. Materials and methods: Arterial blood samples were drawn from 62 patients, before and after 169 hemodialysis sessions; 114 of these samples came from clinically unstable (group A) and 55 from clinically stable (group B) patients. We measured these parameters: [Cl-]/[Na+] ratio, Diff(Na-Cl), [K+], partial pressure of carbon dioxide (PaCO2), [H+], standard bicarbonate concentration (SBC), base excess (BE), and anion gap (AG). Results: In group A the [Cl-]/[Na+] ratio was negatively correlated with AG only, while in group B it was positively correlated to [H+] and negatively to SBC, BE, and AG. After hemodialysis, both group A and group B showed a decrease in [Cl-]/[Na+] ratio, in K+, in [H+], and in AG, and an increase in Diff(Na-Cl), in PaCO2, in SBC, and in BE. After hemodialysis, as compared to baseline, the values of D% were different between the two groups with regard to Diff(Na-Cl), SBC, and BE, the variations of which were higher in group B. Conclusion: In this study, the [Cl-]/[Na+] ratio and the Diff(Na-Cl) seem to be correlated with the conventional parameters of the acid-base pattern. In the unstable group of patients, the [Cl-]/[Na+] ratio is negatively correlated with AG, while there is no correlation with lactate. This parameter might be useful to identify AG acidosis with normal lactate levels.

Fasting from dawn to sunset during Ramadan is one of the five pillars of Islam.A significant number of diabetic patients insist on fasting during Ramadan against the recommendations of their physicians.Fasting in diabetic subjects may be associated with increased risk of hypoglycemia and hyperglycemia, diabetic ketoacidosis, dehydration and thrombosis.Patients with uncontrolled diabetes mellitus are predisposed to major metabolic risks.Another problem is the reluctance of diabetic patients in taking their medications during the fast; therefore the timing and the dosage of anti-diabetic drugs must be adapted for each patient.It is important for diabetic patients who wish to fast during Ramadan to effect the necessary preparation to approach the fasting as safely as possible.Up to now, the management of these patients is a challenge for healthcare professionals.The aim of this minireview is that to offer a simple guide for management of Muslim diabetic patient during Ramadan.

About 50% of deaths from heart failure (HF) are sudden, presumably referable to arrhythmias. Electrolyte and acid-base abnormalities are a frequent and potentially dangerous complication in HF patients. Their incidence is almost always correlated with the severity of cardiac dysfunction; furthermore leading to arrhythmias, these imbalances are associated with a poor prognosis. The frequency of ventricular ectopic beats and sudden cardiac death correlate with both plasma and whole body levels of potassium, especially in alkalemia. The early recognition of these alterations and the knowledge of the pathophysiological mechanisms are useful for the management of these HF patients.

Obstructive sleep apnea syndrome (OSAS) is commonly associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders. On the basis of this observation, our aim was to examine the oxidative status and the matrix metalloproteases (MMP) profile in a group of subjects with OSAS. We enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, who were subsequently subdivided in two subgroups according to the severity of OSAS (low grade=L-OSAS; high grade=H-OSAS). We measured the parameters of oxidative stress, such as lipid peroxidation, protein oxidation, total antioxidant status (TAS), nitric oxide metabolites (NOx), and the plasma concentrations of the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). We found a significant impairment of oxidative status in H-OSAS compared to L-OSAS and higher plasma levels of MMP-9 and TIMP-1 in H-OSAS compared to L-OSAS. In this study we observed a positive correlation between TBARS and MMP-9, a positive correlation between PC and MMP-9, and a negative correlation between NOx and MMP-9, especially in the whole group of OSAS subjects. These data underline how strong interrelationships among some parameters of the oxidative stress, in particular those reflecting lipid peroxidation, protein oxidation and NOx, and MMP-9 are evident in OSAS subjects. All these information may be useful in the clinical practice keeping in mind the cardiovascular complications generally accompanying the obstructive sleep apnea syndrome.