A cohort study on the biochemical and haematological parameters of Italian blood donors as possible risk factors of COVID-19 infection and severe disease in the pre- and post-Omicron period

To investigate the association between biochemical and blood parameters collected before the pandemic in a large cohort of Italian blood donors with the risk of infection and severe disease. We also focused on the differences between the pre- and post-Omicron spread in Italy (i.e., pre- and post-January 01, 2022) on the observed associations. We conducted an observational cohort study on 13750 blood donors was conducted using data archived up to 5 years before the pandemic. A t-test or chi-squared test was used to compare differences between groups. Hazard ratios with 95% confidence intervals for SARS-CoV-2 infection and severe disease were estimated using Cox proportional hazards models. Subgroup analyses stratified by sex, age and epidemic phase of first infection (pre- and post-Omicron spread) were examined. We confirmed a protective effect of groups B and O, while groups A and AB had a higher likelihood of infection and severe disease. However, these associations were only significant in the pre-Omicron period. We found an opposite behavior after Omicron spread, with the O phenotype having a higher probability of infection. When stratified by variant, A antigen appeared to protect against Omicron infection, whereas it was associated with an increased risk of infection by earlier variants. We were able to stratify for the SARS CoV-2 dominant variant, which revealed a causal association between blood group and probability of infection, as evidenced by the strong effect modification observed between the pre- and post-Omicron spread. The mechanism by which group A acts on the probability of infection should consider this strong effect modification

Effect of Plasma Unit Weight and Donor Sex on Post-Donation Citrate Level: An Experimental Study on Plasmapheresis Donors

Introduction: Plasmapheresis donation is considered safe and well tolerated, although long-term effects need to be clarified. The volumes of anticoagulant (ACD-A) used are variable and depend primarily on hematocrit (HCT), total blood processed, amount of plasma collected, and donor characteristics. To elucidate the effect of the plasma unit weight setting on plasmapheresis efficiency and ACD-A distribution, we enrolled male donors undergoing a controlled apheresis process donating 700 g and 720 g in two different sessions. In parallel, we investigated a possible effect of sex, recruiting women donating 700 g of plasma. Methods: The study was conducted on men donating 720 g and (12 months later) 700 g of plasma, and on women donating 700 g of plasma. The main outcomes were pre-/post-donation delta (Delta) citrate concentration in donor plasma and ACD-A reinfused to the donor. Information concerning the annual check-up and the procedure was also collected. Intergroup comparisons (men donating 720 g vs. men donating 700 g and men vs. women both donating 700 g) and intragroup associations with donor and procedural characteristics were reported. Results: With the procedure set at 720 g, the machine processed around 44 mL more whole blood to collect 20 g more plasma, and 720 g donors received around 12 mL more anticoagulant than 700 g donors. Accordingly, Delta citrate concentration was 1.5 times higher (12 mu m), with a greater variability observed for 720 g donations. Citrate concentration in the plasma unit was lower in the 720 g group, although not significantly. Comparing outcomes between women and men donating 700 g, we observed higher (and highly variable) Delta citrate and reinfused ACD-A in women, accompanied by lower anticoagulant levels in the unit. Increased Delta citrate is inversely associated with HCT and age in men and with HCT and triglycerides in women. Reinfused ACD-A correlates with HCT in women but not in men. Conclusion: Unit weight setting and sex influence an ACD-A shift from the estimated values toward an increased reinfusion to donor. In parallel, we observed an impact of age and sex on post-donation citrate metabolism. Altogether, these elements should be taken into account for the development of tailored approaches aimed at maintaining similar safety profiles for all donors using different plasmapheresis settings

Are circulating Mg2+ levels associated with glucose tolerance profiles and incident type 2 diabetes?

Magnesium (Mg2+) is an enzyme co-factor that plays a key role in many biochemical reactions, as well as in glucose metabolism. Clinical evidences have demonstrated that depletion of serum Mg2+ increases exponentially with the duration of type 2 diabetes mellitus (T2DM). Diabetes is associated with low Mg2+, and hypomagnesemia is associated with insulin resistance, inflammation, and increased risk for cardiovascular disease. In subjects at high risk of inflammation and insulin resistance, supplementation of Mg2+ alone ameliorates both phenotypes, slowing the development and progression of hepatic steatosis. We analyze the relationship between serum Mg2+ levels and the onset of T2DM in a large cohort of well-characterized adult white individuals participating in the CATAMERI study, who were reexamined after a mean follow-up of 5.6 ± 0.9 years. In our analysis we acquired a significant negative correlation between Mg2+ levels, fasting glucose, and 2h-post load glucose in subjects who underwent an OGTT. Moreover, Mg2+ levels correlated negatively with fasting insulin levels, and positively with the lipid profile. As for the detrimental effect of lower circulating Mg2+ levels, our data revealed a significant reduction of T2DM risk of about 20% for each 1 mg/dL increase of circulating Mg2+. The present results are consistent with the theory that Mg2+ supplementation could ameliorate insulin sensitivity reducing the risk to develop T2DM

Vitamin D Deficiency and Risk Factors Related to Acute Psychiatric Relapses in Patients with Severe Mental Disorders: A Preliminary Study

Previous studies have indicated that vitamin (Vit) D deficiency is frequent in psychiatric patients, regardless of diagnostic category. We aimed to assess whether acute psychiatric relapses in inpatients was associated with Vit D deficiency compared to stabilized outpatients. The cohort (152 total patients, 75 males and 77 females) had a mean age of 47.3 ± 14.4 years at admission and was grouped according to psychiatric diagnosis. Psychopathological symptom severity was assessed by the Brief Psychiatric Rating Scale (BPRS), a multidimensional symptom inventory. Total calcium serum levels were measured using standard laboratory methods, while plasma levels of 25-OH-Vit D and parathyroid hormone (PTH) were measured by automated chemiluminescence immunoassays. The psychiatric inpatient subgroup showed a significant difference in serum levels of 25-OH-Vit D and PTH (p < 0.001). Correlation analysis between serum levels of 25-OH-Vit D and BPRS total and subitem scores indicated a significantly negative relationship. In addition, linear regression analysis evidenced that the inpatient condition might predict low PTH and 25-OH-Vit D serum levels. Hospitalized psychiatric patients are at increased risk for Vit D deficiency regardless of their diagnostic categories. The mechanism underlying the association between acute psychiatric relapses and Vit D deficiency remains unclear. Therefore, screening for Vit D deficiency should pertain to the health assessment of patients with major psychiatric disorders

One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography

Aim: To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE).Methods: We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis.Results: Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (beta = 0.274, P = 0.008) and fasting insulin levels (beta = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (beta = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG >= 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS.Conclusion: Our data confirm that 1-hour PG >= 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy

Serum miRNAs Expression and SNAP-25 Genotype in Alzheimer’s Disease

MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by binding their 3′ untranslated region (3′UTR) region; these molecules play a fundamental role in several pathologies, including Alzheimer’s disease (AD). Synaptosomal-associated protein of 25 kDa (SNAP-25) is a vesicular protein of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) involved in neural plasticity and in the exocytosis of neurotransmitters, processes that are altered in AD. Recent results showed that a reduction of SNAP-25 is associated with dementia, and that the rs363050 SNAP-25 polymorphism correlates with cognitive decline and brain atrophy, as well as with the outcome of multistructured rehabilitation in AD patients. We verified the presence of possible correlations between the serum concentration of miRNAs that bind the SNAP-25 3′UTR region and AD. Six different microRNAs (miR-181a-5p, miR-361-3p, miR-23a-3p, miR-15b-3p, 130a-3p and miR-27b-3p) that bind the SNAP-25 3′UTR region were measured by qPCR in serum of AD patients (n = 22), mild cognitive impairment (MCI) subjects (n = 22) and age- and sex-matched controls (n = 22); analysis of results was done stratified for the rs363050 SNAP-25 genotype. Results showed that miR-27b-3p, miR-23a-3p and miR181a-5p serum concentration was significantly reduced in rs363050 SNAP-25 GG homozygous AD patients. Notably, concentration of these miRNAs was comparable in rs363050 AA homozygous AD patients, MCI and healthy controls (HCs). Data herein suggest that miRNAs that bind the SNAP-25 3′UTR region interact with SNAP-25 polymorphisms to influence the neural plasticity typical of AD brains, possibly as a consequence of modulatory activity on SNAP-25 mRNA and/or protein

Glucagon kinetics assessed by mathematical modelling during oral glucose administration in people spanning from normal glucose tolerance to type 2 diabetes

Background/ObjectivesGlucagon is important in the maintenance of glucose homeostasis, with also effects on lipids. In this study, we aimed to apply a recently developed model of glucagon kinetics to determine the sensitivity of glucagon variations (especially, glucagon inhibition) to insulin levels (“alpha-cell insulin sensitivity”), during oral glucose administration.Subjects/MethodsWe studied 50 participants (spanning from normal glucose tolerance to type 2 diabetes) undergoing frequently sampled 5-hr oral glucose tolerance test (OGTT). The alpha-cell insulin sensitivity and the glucagon kinetics were assessed by a mathematical model that we developed previously.ResultsThe alpha-cell insulin sensitivity parameter (named SGLUCA; “GLUCA”: “glucagon”) was remarkably variable among participants (CV=221%). SGLUCA was found inversely correlated with the mean glycemic values, as well as with 2-hr glycemia of the OGTT. When stratifying participants into two groups (normal glucose tolerance, NGT, N=28, and impaired glucose regulation/type 2 diabetes, IGR_T2D, N=22), we found that SGLUCA was lower in the latter (1.50 ± 0.50·10-2vs. 0.26 ± 0.14·10-2 ng·L-1GLUCA/pmol·L-1INS, in NGT and IGR_T2D, respectively, p=0.009; “INS”: “insulin”).ConclusionsThe alpha-cell insulin sensitivity is highly variable among subjects, and it is different in groups at different glucose tolerance. This may be relevant for defining personalized treatment schemes, in terms of dietary prescriptions but also for treatments with glucagon-related agents

The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases

IntroductionMinimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilution, several flow cytometry (FC) strategies for hemodilution evaluation have been compared. MethodsFor each BM sample, cells populations with a well-known distribution in BM and peripheral blood - e.g., mast cells (MC), immature (IG) and mature granulocytes (N) - have been studied by FC and quantified alongside the BM differential count. ResultsThe frequencies of cells' populations were correlated to the IG/N ratio, highlighting a mild correlation with MCs and erythroblasts (R=0.25 and R=0.38 respectively, with p-value=0.0006 and 0.0000052), whereas no significant correlation was found with B or T-cells. The mild correlation between IG/N, erythroblasts and MCs supported the combined use of these parameters to evaluate BM hemodilution, hence the optimization of the ALLgorithMM. Once validated, the ALLgorithMM was employed to evaluate the dilution status of BM samples in the context of MRD assessment. Overall, we found that 32% of FC and 52% of Next Generation Sequencing (NGS) analyses were MRD negative in samples resulted hemodiluted (HD) or at least mildly hemodiluted (mHD). ConclusionsThe high frequency of MRD-negative results in both HD and mHD samples implies the presence of possible false negative MRD measurements, impairing the correct assessment of patients' response to therapy and highlighs the importance to evaluate BM hemodilution

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening