Increased CT-derived fat tissue radiodensity has been indicated as a poor prognostic factor in oncological settings, although the reasons are not clear. One hypothesis is that increased radiodensity may reflect the loss of fat droplets within adipocytes, being a proxy of recent weight loss. This study aims to test this hypothesis by evaluating the association between longitudinal variations in fat tissue radiodensity and area in a cohort of COVID-19 patients. Baseline and 2–3-month follow-up chest CT scans of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure subcutaneous, visceral, and intermuscular adipose tissue (SAT, VAT, and IMAT) areas and densities at the T7–T8 vertebrae, and longitudinal variations were computed for each variable. The associations between each compartment area and radiodensity variations (standardized values) were evaluated in univariate linear models and models adjusted by age and sex. A total of 196 COVID-19 survivors with suitable baseline and follow-up CT scans were included (mean age 65 ± 11 years, 62 (31.6%) females, 25% with diabetes and 2.6% with morbid obesity). Longitudinal variation in SAT area was inversely associated with longitudinal variation in SAT radiodensity in univariate models (coeff −0.91, 95%CI = −1.70/−0.12, p = 0.02) and after adjustment by age and sex (coeff −0.89, 95%CI = −1.7/−0.09, p = 0.03). The effect was similar and stronger for IMAT (coeff −2.1, 95%CI = −3.06/−1.19, p < 0.01 in adjusted models), and absent for VAT. Longitudinal variations in subcutaneous and intermuscular adipose tissue areas and densities are inversely associated. Higher adipose tissue radiodensity may be due to decrease in fat area (i.e., weight loss), explaining the poor prognostic effect found in cancer patients.

To examine real-life clinical data regarding hereditary factor XI (FXI) deficiency from a secondary care centre. Retrospective review of clinical records for every FXI:C 0.7 IU/ml or less reported from 2012 to 2020. Seventy-nine patients were included. Six (7.6%) had a severe deficiency (FXI:C <0.2 IU/ml). Only 55 (69.6%) patients were referred to the Haemostasis Centre. Among them, six (15%) were subsequently not identified at increased haemorrhagic risk before a surgical/obstetrical procedure. Thirty-three (41.8%) experienced at least one bleeding event, minor (25 patients) and/or major (16 patients). Minor bleedings were predominantly spontaneous and more frequent in women, major events were mainly provoked. No correlation was found between FXI:C and risk of bleeding ( P = 0.9153). Lower FXI:C, but not a positive bleeding history, was related with higher likelihood of being referred to the Haemostasis Centre ( P = 0.0333). Hereditary FXI deficiency prevalence is likely underestimated, real-life clinical practices outside reference centres could be suboptimal.

Cardiac troponins are key diagnostic and prognostic biomarkers in acute myocardial infarction and, more generally, for the detection of myocardial injury. Since the introduction of the first immunochemistry methods, there has been a remarkable evolution in analytical performance, especially concerning a progressive improvement in sensitivity. However, the measurement of circulating troponins remains rarely susceptible to analytical interferences. We report a case of persistently elevated troponin I concentrations in a patient with known ischemic heart disease, which almost led to unnecessary diagnostic–therapeutic interventions. A prompt laboratory consultation by the cardiologist ultimately led to the identification of an analytical interference due to troponin macrocomplexes (macrotroponin) causing elevated troponin values in the absence of a clinical presentation compatible with myocardial damage.

The aim of this study was to evaluate the association of adipose tissue characteristics with survival in rectal cancer patients. All consecutive patients, diagnosed with stage II–IV rectal cancer between 2010–2016 using baseline unenhanced Computed Tomography (CT), were included. Baseline total, subcutaneous and visceral adipose tissue areas (TAT, SAT, VAT) and densities (TATd, SATd, VATd) at third lumbar vertebra (L3) were retrospectively measured. The association of these tissues with cancer-specific and progression-free survival (CCS, PFS) was assessed by using competitive risk models adjusted by age, sex and stage. Among the 274 included patients (median age 70 years, 41.2% females), the protective effect of increasing adipose tissue area on survival could be due to random fluctuations (e.g., sub-distribution hazard ratio—SHR for one cm2 increase in SAT = 0.997; 95%confidence interval—CI = 0.994–1.000; p = 0.057, for CSS), while increasing density was associated with poorer survival (e.g., SHR for one Hounsfield Unit—HU increase in SATd = 1.03, 95% CI = 1.01–1.05, p = 0.002, for CSS). In models considering each adipose tissue area and respective density, the association with CSS tended to disappear for areas, while it did not change for TATd and SATd. No association was found with PFS. In conclusion, adipose tissue density influenced survival in rectal cancer patients, raising awareness on a routinely measurable variable that requires more research efforts.

Lactate represents the main product of pyruvate reduction catalyzed by the lactic dehydrogenase family of enzymes. Cancer cells utilize great quantities of glucose, shifting toward a glycolytic metabolism. With the contribution of tumor stromal cells and under hypoxic conditions, this leads toward the acidification of the extracellular matrix. The ability to shift between different metabolic pathways is a characteristic of breast cancer cells and is associated with an aggressive phenotype. Furthermore, the preliminary scientific evidence concerning the levels of circulating lactate in breast cancer points toward a correlation between hyperlactacidemia and poor prognosis, even though no clear linkage has been demonstrated. Overall, lactate may represent a promising metabolic target that needs to be investigated in breast cancer.

Introduction:The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Materials and methods:Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer's cut-offs. Sample turnaround time (TAT) was examined. Results:Imprecision repeatability CVs were 1.1-4.7% and within-lab imprecision were 1.8-7.6% (10.0-25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer's values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Conclusions:Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2–3 and 6–7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase = 1.79; 95% confidence interval [CI] = 1.23–2.62) at 2–3 months and CRP integral (OR for one SD increase = 2.24; 95%CI = 1.53–3.28) at 6–7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.

Background and aimsFamilial hypercholesterolemia (FH) is a common inherited disorder of low-density lipoprotein (LDL) catabolism that causes elevated LDL-cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Despite the availability of effective treatments, FH remains underdiagnosed and undertreated. The aims of the study were to identify putative FH subjects using data from laboratory and cardiology databases, genetically characterize suspected FH patients referred to the Lipid Clinic and monitor attainment of treatment goals in identified patients.Methods and resultsWe retrieved the electronic health records of 221,644 individuals referred to laboratory for routine assessment and of 583 ASCVD patients (age ≤65) who underwent percutaneous transluminal coronary angioplasty (PTCA). We monitored the lipid profiles of subjects with LDL-C ≥ 250 mg/dl identified by laboratory survey (LS-P), PTCA patients and patients from the Lipid Clinic (LC-P). The laboratory survey identified 1.46% of subjects with LDL-C ≥ 190 mg/dl and 0.08% with LDL-C ≥ 250 mg/dl. Probable/definite FH was suspected in 3% of PTCA patients. Molecularly-confirmed FH was found in 44% of LC-P subjects. Five new LDLR mutations were identified. The 50% LDL-C reduction target was achieved by 70.6% of LC-P patients. Only 18.5% of PTCA patients reached the LDL-C < 55 mg/dl target.ConclusionBy using a combined approach based on laboratory lipid profiles, documented ASCVD and Lipid Clinic data, we were able to identify subjects with a high probability of being FH. Attainment of LDL-C goals was largely suboptimal. Efforts are needed to improve FH detection and achievement of lipid targets.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by neutralizing autoantibodies against coagulation Factor VIII. Immunomodulatory effects of SARS-CoV-2 vaccination are still poorly understood, with reports of immune-mediated conditions developing after immunization. In the province of Reggio Emilia, Northern Italy, we observed four cases of AHA following SARS-CoV-2 immunization with mRNA BNT162b2 vaccine (produced by Pfizer-BioNTech) during the first eight months from the beginning of SARS-CoV-2 vaccination campaign. During this time frame, 235,597 people received at least one dose of BNT162b2 vaccine. The total population of Reggio Emilia province is 526,349. The unusual observation of four cases of AHA in our province could be of interest and could sensitize healthcare personnel toward a possible complication of SARS-Cov-2 immunization. Nonetheless, vaccination benefits exceed potential side effects and play a central role in individual and public health to effectively protect people from COVID-19 and to stop the pandemic.

We aimed to describe body composition changes up to 6–7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2–3 months (T1), and 6–7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) −1.11 (−1.72; −0.51) cm2] and in body fat areas were observed [−3.13 (−10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [−3.55 (−4.94; −2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6–7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.

Heart-type fatty acid binding protein (H-FABP), a low molecular weight protein found primarily in myocardial tissue, has been identified as a potential biomarker in the detection of acute coronary syndrome and acute kidney injury. To further investigate clinical utility, we sought to establish an upper reference limit (URL) of H-FABP within a healthy U.S. population.Serum samples of healthy donors were acquired from the AACC Universal Sample Bank. We analyzed 355 samples for H-FABP concentration using the Randox Laboratories immunoturbidimetric assay on the Roche Cobas 8000 series analyzer.The final sample population consisted of individuals aged 18–74 y, with 170 males and 185 females. The distribution of the population exhibited a strong positive skew, affecting outlier analysis and URL determination. The 97.5th-percentile URL was found to be 7.4 ng/ml (95% CI: 6.3–9.2), while the 99th-percentile URL was 12.1 ng/ml (8.6–14.9).As the URL for H-FABP is highly affected by population distribution and outlier removal, final determination for an assay cutoff should be made in the context of clinical utility, either as a standalone assay or in conjunction with other biomarkers, and the desired clinical sensitivity and specificity.

Background Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. Methods This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. Results Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. Conclusions Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.

The aims of this study were to develop a multiparametric prognostic model for death in COVID-19 patients and to assess the incremental value of CT disease extension over clinical parameters. Consecutive patients who presented to all five of the emergency rooms of the Reggio Emilia province between February 27 and March 23, 2020, for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20–39%, 40–59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (cvAUC). Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level. CT disease extension was also independently associated with death (HR = 7.56, 95% CI = 3.49; 16.38 for ≥ 60% extension). cvAUCs were 0.927 (bootstrap bias-corrected 95% CI = 0.899–0.947) for the clinical model and 0.936 (bootstrap bias-corrected 95% CI = 0.912–0.953) when adding CT extension. A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy. • Early identification of COVID-19 patients at higher risk of disease progression and death is crucial; the role of CT scan in defining prognosis is unclear. • A clinical model based on age, sex, comorbidities, days from symptom onset, and laboratory results was highly accurate in predicting death in COVID-19 patients presenting to the emergency room. • Disease extension assessed with CT was independently associated with death when added to the model but did not produce a valuable increase in accuracy.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Aim: During pregnancy, thyroid homeostasis is physiologically modified, leading to altered levels of thyrotropin (TSH): hence, the adoption of pregnancy-related, population- and method-specific reference ranges is recommended. This monocentric and retrospective study was conducted to establish local pregnancy-related reference intervals for serum TSH in singleton pregnant women using real-life clinical data. Methods: We included women who measured serum TSH during pregnancy at our Laboratory over six years, excluding pregnant women with current or past history of thyroid disease, pituitary or autoimmune diseases, use of medications known to influence thyroid function, multiple and/or pathological pregnancies, BMI >30 Kg/m(2). Results: We retrieved a total of 3744 TSH results. Reference limits (90% confidence intervals) for TSH (in mIU/L) are: first trimester 0.09 (0.06-0.12) - 3.16 (3.05-3.29); second trimester 0.25 (0.11-0.30) - 3.55 (3.34-3.73); third trimester 0.42 (0.15-0.48) - 3.93 (3.80-4.08). Conclusion: In conclusion, real-life clinical data could be used to establish or verify local reference intervals for TSH in pregnant women: this may reduce the risk of misclassification of pregnant women undergoing thyroid function testing.

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.

Objective: The added value of CT in prognostic models for coronavirus disease 2019 (COVID-19) patients is unclear. The aim of this study was to develop a prognostic model for death in COVID-19 patients using clinical and CT variables. Methods: Consecutive patients who presented to the emergency room between February 27 and March 23, 2020 for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20-39%, 40-59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (CvAUC). Results: Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level (SO2). CT disease extension was also independently associated with death (HR=7.56, 95% CI=3.49; 16.38 for ≥ 60% extension). CvAUCs were 0.927 (bootstrap bias corrected-95%CI=0.899-0.947) for the clinical model and 0.936 (bootstrap bias corrected-95%CI=0.912-0.953) when adding CT extension. Conclusions: A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy.

Background Early prognostication in trauma patients is challenging, but particularly important. We wanted to explore the ability of copeptin, the C-terminal fragment of arginine vasopressin, to identify major trauma, defined as Injury Severity Score (ISS) > 15, in a heterogeneous cohort of trauma patients and to compare its performances with lactate. We also evaluated copeptin performance in predicting other clinical outcomes: mortality, hospital admission, blood transfusion, emergency surgery, and Intensive Care Unit (ICU) admission. Methods This single center, pragmatic, prospective observational study was conducted at Arcispedale Santa Maria Nuova, a level II trauma center in Reggio Emilia, Italy. Copeptin determination was obtained on Emergency Department (ED) arrival, together with venous lactate. Different outcomes were measured including ISS, Revised Trauma Score (RTS), hospital and ICU admission, blood transfusion, emergency surgery, and mortality. Results One hundred and twenty five adult trauma patients admitted to the ED between June 2017 and March 2018. Copeptin showed a good ability to identify patients with ISS > 15 (AUC 0.819). Similar good performances were recorded also in predicting other outcomes. Copeptin was significantly superior to lactate in identifying patients with ISS > 15 ( P 0.0015), and in predicting hospital admission ( P 0.0002) and blood transfusion ( P 0.016). Comparable results were observed in a subgroup of patients with RTS 7.84. Conclusions In a heterogeneous group of trauma patients, a single copeptin determination at the time of ED admission proved to be an accurate biomarker, statistically superior to lactate for the identification of major trauma, hospital admission, and blood transfusion, while no statistical difference was observed for ICU admission and emergency surgery. These results, if confirmed, may support a role for copeptin during early management of trauma patients.

Objective To assess sensitivity/specificity of CT vs RT-PCR for the diagnosis of COVID-19 pneumonia in a prospective Italian cohort of symptomatic patients during the outbreak peak. Methods In this cross-sectional study, we included all consecutive patients who presented to the ER between March 13 and 23 for suspected COVID-19 and underwent CT and RT-PCR within 3 days. Using a structured report, radiologists prospectively classified CTs in highly suggestive, suggestive, and non-suggestive of COVID-19 pneumonia. Ground-glass, consolidation, and visual extension of parenchymal changes were collected. Three different RT-PCR-based reference standard definitions were used. Oxygen saturation level, CRP, LDH, and blood cell counts were collected and compared between CT/RT-PCR classes. Results The study included 696 patients (41.4% women; age 59 ± 15.8 years): 423/454 (93%) patients with highly suggestive CT, 97/127 (76%) with suggestive CT, and 31/115 (27%) with non-suggestive CT had positive RT-PCR. CT sensitivity ranged from 73 to 77% and from 90 to 94% for high and low positivity threshold, respectively. Specificity ranged from 79 to 84% for high positivity threshold and was about 58% for low positivity threshold. PPV remained ≥ 90% in all cases. Ground-glass was more frequent in patients with positive RT-PCR in all CT classes. Blood tests were significantly associated with RT-PCR and CT classes. Leukocytes, lymphocytes, neutrophils, and platelets decreased, CRP and LDH increased from non-suggestive to suggestive CT classes. Conclusions During the outbreak peak (in a high-prevalence setting), CT presented high PPV and may be considered a good reference to recognize COVID-19 patients while waiting for RT-PCR confirmation. Key Points • During the epidemic peak, CT showed high positive predictive value and sensitivity for COVID-19 pneumonia when compared with RT-PCR. • Blood tests were significantly associated with RT-PCR and CT classes.