Context.—A strong independent association has been recently observed between elevated red blood cell distribution width (RDW) and increased incidence of cardiovascular events. Objective.—To assess whether RDW is associated with plasma markers of inflammation since the mechanism(s) underlying this association remain unknown. Design.—We retrospectively analyzed results of RDW, hemoglobin, mean corpuscular volume, ferritin, high-sensitivity C-reactive protein (hsCRP), and erythrocyte sedimentation rate (ESR) in a large cohort of unselected adult outpatients who were consecutively referred by general practitioners for routine medical check-up. Results.—Cumulative results of RDW and other factors were retrieved from the database of our laboratory information system for 3845 adult outpatients during a 3-year period. When participants were grouped according to RDW quartiles, there were strong, graded increases of ESR and hsCRP (P < .001), both parameters being up to 3-fold higher in the fourth versus the first quartile. Accordingly, the percentages of those with hsCRP greater than 3 mg/L (from 28% to 63%; P < .001) and ESR greater than 40 mm/h (from 8% to 40%; P < .001) increased steadily across RDW quartiles. In multivariable regression analysis, ESR and hsCRP predicted RDW independently of age, sex, mean corpuscular volume, hemoglobin, and ferritin. Conclusions.—To our knowledge, our study demonstrates for the first time a strong, graded association of RDW with hsCRP and ESR independent of numerous confounding factors. If confirmed in future follow-up studies, this association might provide a rationale to introduce the easy, inexpensive RDW in algorithms for cardiovascular risk prediction.

In patients who have never previously received bisphosphonate therapy, the intravenous administration of 4-amino-1-hydroxybuthilidene-1,1-bisphosphonate (AHButBP), 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), or 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) induced an acute-phase response (APR) irrespective of the underlying disease, manifested by a fall in circulating lymphocyte number and serum zinc concentration and in a rise in C-reactive protein (CRP); a febrile reaction occurred in 30% of the patients. The APR was maximally expressed within 28-36 hours of i.v. administration of the bisphosphonates and disappeared 2-3 days later despite continuous treatment. These effects were dose dependent and the lowest doses necessary for an APR were 10 mg of AHButBP and AHPrBP and 75 mg of AHHexBP. Doses up to 1,000 mg/day i.v. of dichloromethanebisphosphonate (Cl2MBP) were devoid of these side effects. In patients treated with either a single i.v. dose of amino-bisphosphonates which resulted in an APR or with a suboptimal dose, a subsequent challenge 12-160 days later of the high dose failed to cause a rise in CRP or a fall in the lymphocyte count. The desensitization to AHButBP or AHPrBP was also seen following pretreatment with Cl2MBP. These findings suggest that bisphosphonates interact with macrophage-like cells resident in the skeleton and stimulate interleukin-1 release which is responsible for the appearance of the APR. At the same time, however, the bisphosphonates render these cells insensitive to further stimulation for several months.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated the effect of 8 weeks of high intensity interval training (HIT) and isoinertial resistance training (IRT) on cardiovascular fitness, muscle mass-strength and risk factors of metabolic syndrome in 12 healthy older adults (68 yy ± 4). HIT consisted in 7 two-minute repetitions at 80%–90% of V˙O2max, 3 times/w. After 4 months of recovery, subjects were treated with IRT, which included 4 sets of 7 maximal, bilateral knee extensions/flexions 3 times/w on a leg-press flywheel ergometer. HIT elicited significant: i) modifications of selected anthropometrical features; ii) improvements of cardiovascular fitness and; iii) decrease of systolic pressure. HIT and IRT induced hypertrophy of the quadriceps muscle, which, however, was paralleled by significant increases in strength only after IRT. Neither HIT nor IRT induced relevant changes in blood lipid profile, with the exception of a decrease of LDL and CHO after IRT. Physiological parameters related with aerobic fitness and selected body composition values predicting cardiovascular risk remained stable during detraining and, after IRT, they were complemented by substantial increase of muscle strength, leading to further improvements of quality of life of the subjects.

Background: This study monitored total anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RBD (receptor-binding domain) antibodies levels in a large population of healthcare workers undergoing mRNA COVID-19 vaccination. Methods. The study population consisted of employees of Pederzoli Hospital of Peschiera del Garda (Verona, Italy), who underwent voluntary vaccination with two doses of COVID-19 mRNA BNT162b2 (Comirnaty; Pfizer Inc). Venous blood was drawn immediately before the first vaccine dose, as well as 21 days (immediately before second vaccine dose) and 50 days afterwards. Humoral response was assessed with Roche Elecsys Anti-SARS-CoV-2 S total antibodies, on Roche Cobas 6000 (Roche Diagnostics). Results: The final study population consisted of 925 subjects (mean age, 44 ± 13 years; 457 women), 206 (22.3%) anti-SARS-CoV-2 baseline seropositive. The increase of total anti-SARS-CoV-2 RBD antibodies levels 21 days after the first vaccine dose was ~3 orders of magnitude higher in seropositive than in seronegative individuals (11782 vs. 42 U/mL; p < 0.001). Total anti-SARS-CoV-2 RBD antibodies levels further increased by over 30-fold after the second vaccine dose in baseline seronegative subjects, while such increase was only ~1.3-fold in baseline seropositive subjects. In multivariate analysis, total anti-SARS-CoV-2 RBD antibodies level was inversely associated with age after both vaccine doses and male sex after the second vaccine dose in baseline seronegative subjects, while baseline antibodies value significantly predicted immune response after both vaccine doses in baseline seropositive recipients. Conclusion: Significant difference exists in post-mRNA COVID-19 vaccine immune response in baseline seronegative and seropositive subjects, which seems dependent on age and sex in seronegative subjects, as well as on baseline anti-SARS-CoV-2 antibodies level in seropositive patients.

Introduction:The activities involving phlebotomy, a critical task for obtaining diagnostic blood samples, are poorly studied as regards the major sources of errors and the procedures related to laboratory quality control. The aim of this study was to verify the compliance with CLSI documents of clinical laboratories from South America and to assess whether teaching phlebotomists to follow the exact procedure for blood collection by venipuncture from CLSI/NCCLS H03-A6 - Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture might improve the quality of the process.Materials and methods:A survey was sent by mail to 3674 laboratories from South America to verify the use of CLSI documents. Thirty skilled phlebotomists were trained with the CLSI H03-A6 document to perform venipuncture procedures for a period of 20 consecutive working days. The overall performances of the phlebotomists were further compared before and after the training program.Results:2622 from 2781 laboratories that did answer our survey used CLSI documents to standardize their procedures and process. The phlebotomists’ training for 20 days before our evaluation completely eliminated non-conformity procedures for: i) incorrect friction of the forearm, during the cleaning of the venipuncture site to ease vein location; ii) incorrect sequence of vacuum tubes collection; and iii) inadequate mixing of the blood in primary vacuum tubes containing anticoagulants or clot activators. Unfortunately the CLSI H03-A6 document does not caution against both unsuitable tourniquet application time (i.e., for more than one minute) and inappropriate request to clench the fist repeatedly. These inadequate procedures were observed for all phlebotomists.Conclusion:We showed that strict observance of the CLSI H03-A6 document can remarkably improve quality, although the various steps for collecting diagnostic blood specimens are not a gold standard, since they may still permit errors. Tourniquet application time and forearm clench should be verified by all quality laboratory managers in the services. Moreover, the procedure for collecting blood specimens should be revised to eliminate this source of laboratory variability and safeguard the quality.

The diagnostic approach to acute coronary syndromes (ACS) remains one of the most difficult and controversial challenges facing emergency physicians. In recent years, cardiac troponins have emerged as the biochemical "gold standard" for diagnosis of patients with acute chest pain, enhancing our ability to recognize ACS. Early diagnosis and treatment of myocardial ischemia improve patient outcomes, but conventional markers are often nondiagnostic at the time of arrival at the emergency department. Promising new biomarkers, which appear earlier after the onset of ischemia, are being studied and integrated into clinical practice. Some are markers of myocyte necrosis, but others, including ischemia-modified albumin and natriuretic peptides, detect myocardial ischemia and myocardial dysfunction. The aim of the present article is to review the diagnostic approach to ACS, focusing on recent literature describing novel biochemical markers. If ongoing and future studies confirm their role in probability-based models risk assessment, a new era in the diagnostic approach to ACS may be dawning. RÉSUMÉLa démarche diagnostique face aux syndromes coronariens aigus (SCA) demeure l'un des défis les plus complexes et controversés auxquels sont confrontés les médecins d'urgence. Au cours des dernières années, les troponines cardiaques sont devenues la «méthode de référence» biochimique pour le diagnostic de la douleur thoracique aiguë, améliorant notre capacité d'identifier le SCA. Le diagnostic précoce et le traitement de l'ischémie myocardique améliorent le pronostic pour le patient, mais les marqueurs conventionnels sont souvent non diagnostiques au moment de l'arrivée du patient au département d'urgence. De nouveaux biomarqueurs prometteurs, qui se manifestent plus tôt après le début de l'ischémie, sont présentement à l'étude et intégrés à la pratique clinique. Certains sont des marqueurs de la nécrose myocytaire, mais d'autres, incluant l'albumine modifée par l'ischémie et les peptides niatrurétiques, détectent l'ischémie myocardique et le dysfonctionnement myocardique. Le présent article a pour but de revoir la dé-marche diagnostique face au SCA, en se concentrant sur la littérature récente décrivant les nouveaux marqueurs biochimiques. Si les études en cours et futures confirment le rôle de ces derniers quant à l'évaluation des risques à partir de modèles fondés sur la probabilité, une nouvelle ère dans la démarche diagnostique face au SCA pourrait être sur le point de voir le jour.

In tro duc tion: Tour niquet due ve nous sta sis can al ter bo th con cen tra tion and/or ac ti vi ty of se ve ral blood ana lytes, but is ra re ly re gar ded as an is sue of la bo ra to ry va ria bi li ty. To over co me the prob lem tran sil lu mi na tion de vi ces (TD) ha ve been pro po sed for a sta si s-free phle bo to my. In this pa per the use of a TD in pla ce of tour niquet du ri ng blood col lec tion has been eva lua ted. Ma te ria ls and met ho ds: Blood was col lec ted from 250 vo lun tee rs di vi ded in fi ve ho mo ge nous grou ps of tour niquet ti mes (G1: 30 sec, G2: 60 sec, G3: 90 sec, G4: 120 sec, G5: 180 sec) and com pa red to blood ob tai ned usi ng TD. All sam ples we re ana lyzed for glu co se (GLU), total pro tein (TP), albumin (ALB), trig lyce ri des (TRIG), potas sium (K), sodium (NA), phos pha te (PHOS), cal cium (CA), alka li ne phos pha ta se (ALKP) and mag ne sium (MG). Re sul ts: In res pe ct of TD, G1 did not show sta tis ti cal ly sig ni fi ca nt in crea ses in all cli ni cal che mis try tes ts; G2 showed in crea ses for GLU, TP, ALB, TRIG, K, CA, MG and ALKP. G3 and G4, showed no sig ni fi ca nt in crea se on ly for PHOS. G5 showed sig ni fi ca nt in crea ses in all the tes ts eva lua ted. Mo reo ver, cli ni cal ly sig ni fi ca nt va ria tio ns we re ob ser ved for TP, ALB, K and CA in G2 to G5; for NA in G3 to G5; for MG in G4 and G5; for GLU, TRIG, ALKP on ly in G5. Con clu sio ns:The se re sul ts sup po rt the ap pli ca tion of TD in blood col lec tion for rou ti ne cli ni cal che mis try la bo ra to ry tes ts, sug ges ti ng its use shou ld be mo re diff u sed. Key wor ds: phle bo to my and blood col lec tion; pre ana lyti cal pha se; qua li ty ma na ge me nt system in cli ni cal la bo ra to ry; tran sil lu mi na tion; ve nous sta sis.

BackgroundThis study was aimed to investigate the acute effect of medium-distance running on bile acids concentration and composition, in order to verify whether the positive impact of physical exercise on cancer risk may also be mediated by variation of bile acids concentration and composition in serum.MethodsThe concentration and composition of serum bile acids was analyzed in 30 middle-aged and healthy recreational athletes with a reference liquid chromatography-mass spectrometry technique, immediately before and shortly after the end of the running trial. The concentration of bile acids after the run was adjusted for plasma volume change.ResultsAll athletes successfully completed the trial. After correction of values for the individual plasma volume change calculated after the run, the serum concentration of total bile acids was found to be significantly reduced by approximately 46%. A statistically significant decrease was observed for cholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, glycoursodeoxycholic and hyodeoxycholic acids, whereas the concentration of the remaining compounds remained unvaried after the run. A considerable variation of bile acids profile was also observed. No significant association was found between running performance and variation of bile acids concentrations.ConclusionThese results show that middle distance running acutely decreases the concentration of total bile acids in serum, especially that of the more mutagenic and carcinogenic compounds, so providing an intriguing support to the favorable effects of physical exercise for lowering the risk of many gastrointestinal cancers.