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Severe acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19). Therefore, this investigation aimed to provide an updated overview on the interplay between statins and COVID-19, with particular focus on their potentially protective role against progression toward severe or critical illness and death. A systematic electronic search was performed in Scopus and PubMed up to present time. Data on statins use and COVID-19 outcomes especially in studies performed in Europe and North America were extracted and pooled. A total of seven studies met our inclusion criteria, totaling 2,398 patients (1,075 taking statins, i.e., 44.8%). Overall, statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35–0.99). After excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified (odds ratio: 0.51; 95% confidence interval: 0.41–0.64). In conclusion, although randomized trials would be necessary to confirm these preliminary findings, current evidence would support a favorable effect of statins as adjuvant therapy in patients with COVID-19. Irrespective of these considerations, suspension of statin therapy seems highly unadvisable in COVID-19 patients.

Diabetes is one of the most prevalent diseases worldwide, whereby type 1 diabetes mellitus (T1DM) alone involves nearly 15 million patients. Although T1DM and type 2 diabetes mellitus (T2DM) are the most common types, there are other forms of diabetes which may remain often under-diagnosed, or that can be misdiagnosed as being T1DM or T2DM. After an initial diagnostic step, the differential diagnosis among T1DM, T2DM, Maturity-Onset Diabetes of the Young (MODY) and others forms has important implication for both therapeutic and behavioral decisions. Although the criteria used for diagnosing diabetes mellitus are well defined by the guidelines of the American Diabetes Association (ADA), no clear indications are provided on the optimal approach to be followed for classifying diabetes, especially in children. In this circumstance, both routine and genetic blood test may play a pivotal role. Therefore, the purpose of this article is to provide, through a narrative literature review, some elements that may aid accurate diagnosis and classification of diabetes in children and young people.

The worldwide spread of coronavirus disease 2019 (COVID-19) has generated a global health crisis and more than a million deaths so far. Epidemiological and clinical characteristics of COVID-19 are increasingly reported, along with its potential relationship with overweight and/or obesity. Therefore, we aim here to review the current scientific literature on the impact of overweight and/or obesity among hospitalized patients who have developed severe or critical forms of COVID-19. Following PRISMA guidelines, our literature search identified over 300 scientific articles using the keywords “obesity” and “COVID-19”, 22 of which were finally selected for reporting useful information on the association between overweight/obesity and disease severity. In particular, in 11 out of the 14 studies (79%) which evaluated the association between obesity and disease severity providing also a risk estimate (i.e., the odd ratio; OR), the OR value was constantly >2. Although the studies were found to be heterogeneous in terms of design, population, sample size and endpoints, in most cases a significant association was found between obesity and the risk of progressing to severe COVID-19 illness, intensive care unit admission and/or death. We can hence conclude that an increased body mass index shall be considered a negative prognostic factor in patients with COVID-19, and more aggressive prevention or treatment shall hence be reserved to overweight and/or obese patients.

Bile acids (BA) play a pivotal role in cholesterol metabolism. Their blood concentration has also been proposed as new prognostic and diagnostic indicator of hepatobiliary, intestinal, and cardiovascular disease. Liquid chromatography tandem mass spectrometry (LC&ndash, MS/MS) currently represents the gold standard for analysis of BA profile in biological samples. We report here development and validation of a LC&ndash, MS/MS technique for simultaneously quantifying 15 BA species in serum samples. We also established a reference range for adult healthy subjects (n = 130) and performed a preliminary evaluation of in vitro and in vivo interference. The method displayed good linearity, with high regression coefficients (&gt, 0.99) over a range of 5 ng/mL (lower limit of quantification, LLOQ) and 5000 ng/mL for all analytes tested. The accuracies were between 85&ndash, 115%. Both intra- and inter-assay imprecision was &lt, 10%. The recoveries ranged between 92&ndash, 110%. Each of the tested BA species (assessed on three concentrations) were stable for 15 days at room temperature, 4 &deg, C, and &minus, 20 &deg, C. The in vitro study did not reveal any interference from triglycerides, bilirubin, or cell-free hemoglobin. The in vivo interference study showed that pools obtained from hyper-cholesterolemic patients and hyper-bilirubinemic patients due to post-hepatic jaundice for benign cholestasis, cholangiocarcinoma and pancreatic head tumors had clearly distinct patterns of BA concentrations compared with a pool obtained from samples of healthy subjects. In conclusion, this study proposes a new suitable candidate method for identification and quantitation of BA in biological samples and provides new insight into a number of variables that should be taken into account when investigating pathophysiological changes of BA in human diseases.

Background. The Philadelphia (Ph) chromosome (chr.) is the hallmark of chronic myeloid leukemia (CML) and typically results from the reciprocal translocation t(9;22)(q34;11.2). Complex variant translocations (CVT) involving one or more additional chr. are identified in less than 5% of newly diagnosed CML. There are conflicting reports about the prognostic impact of CVT in the achievement of optimal response to tyrosine kinase inhibitor (TKI), and very few studies addressed the role of frontline treatment with imatinib or second generation (2G)-TKI in patients with CVT. Aims. To assess the response to imatinib or 2G-TKI in a large cohort of newly diagnosed CML with CVT, and to explore the impact of the different chr. translocations on outcome. Methods. This observational retrospective study was conducted in 19 hematologic centers in the framework of Campus CML, a network of Italian physicians involved in the management of CML patients. All newly diagnosed CML from 2000 to 2019 were evaluated and patients with CVT were selected for the present analysis. Karyotypes were defined according to the 2016 International System for Human Cytogenetic Nomenclature. Responses to frontline treatment were retrospectively categorized according to the 2013 ELN recommendations, as they include cytogenetic milestones. Deep molecular response (DMR, i.e. MR4or better) was defined as BCR-ABLIS ratio ≤0.01% or undetectable disease with ≥10,000 ABL copies. Patients with DMR lasting ≥2 years and at least a Q-PCR test every 6 months were defined as stable DMR responders. Failure-free survival (FFS) was calculated from the start of frontline TKI treatment to progression to advanced phase, death, or switch to other treatments for resistance. For FFS calculation, patients were censored at TKI stop for treatment-free remission (TFR) or in case of switch for intolerance only. Differences between subgroups according to the partner chr. were presented for descriptive purposes. Results. CVT were identified in 109 (3.2%) patients from a whole population of 3,361 subjects with newly diagnosed CML. Ninety-five out of 109 patients (87%) exhibited three-way translocations, with chr. 1, 4, 6, 10, 11, 12, 14, 15 and 17 representing the most common additional partners (figure). Four- and five-way translocations were identified in 13 and 1 patients, respectively. Additional chr. abnormalities (ACA) in the Ph+ cells were observed in 15/109 (13.8%) patients and were more common in older individuals (p=0.018). Overall, median age at diagnosis was 50.6 years (range 20-90). Risk distribution according to the ELTS score was 54%, 28% and 8% for L, I and H risk, respectively (10% missing). Cytogenetic result was available before the choice of frontline treatment in 45% of cases and represented a decisive factor in 28% of them (i.e. clinicians selected a 2G-TKI or high-dose imatinib, according to the available options). Frontline TKI treatment was imatinib in 80 cases (73%) and 2G-TKI (nilotinib n=22, dasatinib n=6, bosutinib n=1) in the remaining cases. The frequency of optimal response at 3, 6 and 12 months was 48%, 45% and 53%, respectively, for imatinib-treated patients, and 76%, 83% and 76%, respectively, for the 2G-TKI cohort (p The subtype of CVT had an impact on response and long-term outcome. Patients with CVT involving chr. 1, 4, 6, 11 or 12 had a higher frequency of MMR at 12 months than patients with CVT involving chr. 10, 14, 15 or 17 (75.8% vs 30.4%, respectively, p=0.001), higher frequency of stable DMR (48.7% vs 22.2%, respectively; p=0.04) and tended to have better median FFS (p=0.07), regardless of the type of frontline TKI and of the ELTS score. Conclusions. Due to its retrospective nature, this study does not allow to define which is the optimal therapy for CML harboring CVT at diagnosis. However, our data reinforce the usefulness of bone marrow karyotyping in CML. The observed differences between partner chr. may also depend on the breaking points, which are variable. Further dissection of CVT will help to identify which are associated to a poor response to TKIs. Figure Disclosures D'Adda: Incyte: Other: Advisory board; Novartis: Other: Advisory board; Pfizer: Other: Advisory board. Galimberti:Novartis: Speakers Bureau; Incyte: Honoraria. Crugnola:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria. Bocchia:Incyte: Honoraria; CELGENE: Honoraria. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Breccia:Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Saglio:Novartis: Research Funding; Ariad: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding; Incyte: Research Funding; Roche: Research Funding.

Background Xq duplication is a rare condition with a very variable phenotype, which could mimic other genetic syndromes involving the long arm of chromosome X. Sometimes short stature and diminished ovarian reserve (DOR) may be present. Treatments with rGH (Recombinant growth Hormon) or with fertility preservation strategies have not been previously described. Case presentation We present the case of a female with a novel de novo Xq partial duplication (karyotype: 46,Xder(X)(qter→q21.31::pter→qter) confirmed by array-CGH analysis. She presented with short stature, Nonverbal Learning Disability, developmental delay during childhood, severe scoliosis, spontaneous onset of menarche and irregular menstrual cycles. AMH (Anti-Müllerian Hormone) allowed detection of a preserved but severely diminished ovarian reserve with a POI (Premature Ovarian insufficiency) onset risk. She was effectively subjected to fertility preservation strategies and rGH therapy. We also reviewed other published cases with Xq duplication, reporting the main clinics characteristics and any adopted treatment. Conclusions rGH treatment and cryopreservation in a multidisciplinary approach are good therapeutic strategies for Xq duplication syndrome with short stature and premature ovarian failure.

Vitamin D deficiency (VDD) is a global health care issue, with billion carrying deficiency or insufficiency around the world. This hormone plays a kaleidoscope of important roles throughout pregnancy, so that maintenance of an adequate vitamin D status is essential in this setting. Several studies, which have investigated vitamin D status in different populations of pregnant women, have convincingly reported high prevalence of vitamin D insufficiency, consistently higher than 50%. Although VDD developing during pregnancy has been associated with some adverse maternal and pregnancy outcomes, especially gestational diabetes mellitus (GDM) and preeclampsia (PE), the risk estimated are considerably heterogeneous, which makes it challenging to define operative recommendations. The mean differences in serum 25-hydroxy- cholecalciferol [25(OH)D] between GDM and non-GDM pregnant women varies between −4.93 and −7.36 nmol/L, whilst that between pre-eclamptic and non-pre-eclamptic pregnant women is even wider, being comprised between −3.86 and −14.53 nmol/L. It is hence still unclear whether assessment of vitamin D during pregnancy shall be recommended, as well as which dose of vitamin D shall be administered in pregnant women with VDD. Further studies shall be planned, which will need to be based on reliable quantification techniques [preferably liquid chromatography tandem mass spectrometry (LC-MS/MS)-based methods], but will also need to reduce the impact of many confounding factors such as ethnicity, sunlight exposure and sampling time.

This study was designed to evaluate the analytical performance of the recently commercialized Beckman Coulter Access procalcitonin (PCT) chemiluminescent test on the Access immunoassay system. The analytical assessment encompassed the estimation of limit of blank (LoB), limit of detection (LoD), functional sensitivity (i.e., PCT value with ≤10% imprecision), linearity, imprecision and comparability of values with BRAHMS PCT-sensitive Kryptor. LoB, LoD and functional sensitivity were 0.002 μg/L, 0.003 μg/L and 0.003 μg/L, respectively. Intra-assay, inter-assay and total imprecision for plasma pools with low, medium and high PCT values were 1.8%−2.1%, 2.4%−3.7% and 3.1%−4.3%, respectively. The assay exhibited excellent linearity between 0.02 and 84.0 μg/L. Excellent correlation (r = 0.999; p < 0.001) and negligible bias (3.2%) were found by comparing values obtained in paired plasma samples with BRAHMS PCT-sensitive Kryptor. Diagnostic agreement at 0.5, 2.0 and 10 μg/L PCT values ranged between 98%-100%. The results of this study confirm that Access PCT displays excellent analytical performance and high comparability with BRAHMS PCT-sensitive Kryptor.

Background This two-center study was designed to verify comparability of procalcitonin (PCT) values among 10 different commercial immunoassays. Methods A total number of 176 routine lithium-heparin plasma samples were divided in identical aliquots and simultaneously analyzed with 10 different PCT immunoassays, including Kryptor BRAHMS PCT sensitive, Abbott Architect BRAHMS PCT, Beckman Coulter Access PCT (on Access and DXI), BioMérieux Vidas BRAHMS PCT, Diasorin Liaison BRAHMS PCT, Fujirebio Lumipulse G BRAHMS PCT, Roche BRAHMS PCT (on Cobas E801), Diazyme PCT (on Roche Cobas C702) and SNIBE Maglumi PCT. Results Highly significant correlation was always found across multiple comparisons, with correlation coefficients comprised between 0.918 and 0.997 (all p 80% (all p Conclusions Although we found acceptable correlation among 10 commercial PCT immunoassays, the limited agreement at clinical decision thresholds remains a major issue, especially at lower end of PCT concentration, thus potentially contributing to jeopardize the clinical value of this biomarker.

Background: The diagnosis of kidney disease strongly relies on accurate and reproducible measurements of creatinine, even when performed with point of care testing (POCT) devices. Therefore, this study aimed at performing a comprehensive evaluation of the analytical performance of a creatinine enzymatic assay on the Radiometer ABL90 FLEX PLUS. Methods: This analytical evaluation encompassed the assessment of intra-assay, inter-assay and total imprecision, along with linearity on routine lithium-heparin plasma samples. Method comparison was also carried out using results generated with Radiometer ABL90 FLEX PLUS in heparinized whole blood and those obtained in paired heparinized plasma with a reference enzymatic creatinine assay and a Jaffe method, both assayed on Roche Cobas c702. Results: The intra-assay imprecision of Radiometer ABL90 FLEX PLUS creatinine enzymatic assay was between 0.33–1.26%, the inter-assay imprecision between 0.64–1.78%, thus yielding a total imprecision of 0.79–1.99%. The linearity of the assay was excellent (r=1.000; P Conclusions: The results of this analytical evaluation confirm that Radiometer ABL90 FLEX PLUS creatinine enzymatic assay is at least as suitable as a conventional clinical chemistry enzymatic technique for routine and urgent diagnosis of kidney diseases.

Background The use of alternative sample matrices may be an advantageous perspective when the laboratory falls short of serum or lithium-heparin plasma for performing clinical chemistry and/or immunochemistry testing. This study was aimed at exploring whether some tests may be performed in citrate plasma as an alternative to lithium-heparin plasma. Methods Paired lithium-heparin and citrate plasma samples collected from 55 inpatients were analyzed on Roche Cobas 8000 for 28 different clinical chemistry and immunochemistry parameters. Data obtained in citrate plasma were adjusted for either the dilution factor or using an equation corresponding to the linear regression calculated by comparing unadjusted lithium-heparin and citrate plasma values. Results Except for magnesium (+17%) and sodium (+11%), unadjusted values of all remaining analytes were significantly lower in citrate than in lithium-heparin plasma, with bias ranging between −6.4% and −25.9%. The correlation between lithium-heparin and citrate plasma values was generally excellent (i.e. >0.90). The adjustment of citrate plasma values for the dilution factor (i.e. 1.1) was only effective in harmonizing the results of albumin and lipase, whilst the concentration of all other analytes remained significantly different between the two sample matrices. The adjustment of plasma citrate values using corrective formulas was instead effective in harmonizing all parameters, with no results remaining statistically different between the two sample matrices. Conclusions Citrate plasma may be used in exceptional circumstances for clinical chemistry and immunochemistry testing as a replacement for lithium-heparin plasma, provided that citrate plasma values are adjusted by using validated corrective equations.

Background: Hemolysis is the most frequent and potentially one of the most harmful causes of poor sample quality. Many strategies have been attempted for minimizing the risk of generating spurious hemolysis during blood collection, such as using the HOLDEX ® single-use holder, which features a chamber that decelerates blood flow pressure before entering evacuated blood tubes. We have hence designed a study to establish whether the new VACUETTE ® SAFELINK, which shares different structure but similar strategy affecting blood flow pressure, may ensure a comparable sample quality as using HOLDEX ® single-use holder. Methods: A total number of 24 clinical chemistry, hematologic and hemostasis parameters were measured in paired blood samples collected from 30 healthy volunteers using either HOLDEX ® single-use holder or VACUETTE ® SAFELINK. Test results were compared with paired Student’s t-test, Pearson’s correlation and Bland-Altman plots. Results: All test results were non-significantly different in blood samples collected with HOLDEX ® single-use holder or VACUETTE ® SAFELINK except potassium, whose values were marginally higher in plasma collected with VACUETTE ® SAFELINK. All Pearson’s correlation coefficients were excellent except potassium, chloride and H-index. In this latter case, the correlation did not reach statistical significance. The percent bias of different parameters in samples collected with HOLDEX ® single-use holder or VACUETTE ® SAFELINK was minimal, comprised between −4.5% and +1.6%. In all cases the percent bias was comprised within the quality specifications tests. The rate of plasma samples with H-index >3 was eventually lower when blood was collected using SAFELINK than with HOLDEX ® single use holder (odds ratio, 0.52; 95% confidence interval, 0.17–1.60). Conclusions: The results of this comparative study suggest that sample quality is thoughtfully comparable using HOLDEX ® single-use holder and VACUETTE ® SAFELINK, thus translating into the concept that VACUETTE ® SAFELINK may also be an effective means for reducing spurious hemolysis, especially when drawing blood from catheters.