CCL18, CHI3L1, ANG2, IL-6 systemic levels are associated with the extent of lung damage and radiomic features in SARS-CoV-2 infection.

OBJECTIVE AND DESIGN: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients. MATERIAL OR SUBJECTS: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled. METHODS: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann-Whitney U test, the Kruskal-Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses. RESULTS: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1. CONCLUSION: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes.

Hereditary coagulation factor XI deficiency: a rare or neglected disease? Results from a retrospective, single-centre cohort in northern Italy.

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.

"Troponinosis", the Cardiologist's Curse-When Clinic-Laboratory Interaction Unveils the Mystery: A Case Report.

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.

Four cases of acquired hemophilia A following immunization with mRNA BNT162b2 SARS-CoV-2 vaccine.

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.

The value of computed tomography in assessing the risk of death in COVID-19 patients presenting to the emergency room.

OBJECTIVE: 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. METHODS: 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). 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. 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. KEY POINTS: • 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.

Improvement of sperm morphology after surgical varicocele repair.

BACKGROUND: A causative relationship between varicocele and impairment of semen quality has been largely investigated in the context of male infertility, although its clinical benefit remains controversial. OBJECTIVE: To investigate the effect of varicocele correction on detailed morphologic microscopic semen parameters in a large homogeneous cohort of patients and to evaluate which factors could predict semen improvement after the surgical treatment. MATERIALS AND METHODS: An observational, retrospective cohort study was carried out including all patients undergoing surgical treatment for varicocele from September 2011 to March 2020 in the same clinical centre. Enrolled males performed at least one semen analysis before and one after surgical varicocele correction. Primary outcome was the detailed morphologic microscopic sperm evaluation. Secondary outcomes were conventional semen analyses. RESULTS: A total of 121 males (mean age 24.6 ± 6.1 years) were enrolled. Using detailed morphologic microscopic sperm evaluation, a significant morphological improvement was recorded, with a reduction in head and tail abnormalities. Moreover, a significant increase in sperm concentration (p = 0.015) and percentage of progressive and total motility (p = 0.022 and p = 0.039) were observed after surgery. The multivariate logistic analysis identified the ultrasonography varicocele degree before surgery as a main predictor of the sperm concentration improvement (p = 0.016), with the highest improvement for varicocele of I and II degree. DISCUSSION: For the first time, the detailed morphologic microscopic sperm evaluation highlights a relevant reduction in sperm abnormalities after varicocele surgery, showing its potential application in clinical practice.

The association between clinical laboratory data and chest CT findings explains disease severity in a large Italian cohort of COVID-19 patients.

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.

Accuracy of CT in a cohort of symptomatic patients with suspected COVID-19 pneumonia during the outbreak peak in Italy.

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.

Faecal haemoglobin concentration among subjects with negative FIT results is associated with the detection rate of neoplasia at subsequent rounds: a prospective study in the context of population based screening programmes in Italy.

OBJECTIVE: To estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer-CRC-or advanced adenoma). DESIGN: Prospective cohort of subjects aged 50-69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy. METHODS: All programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method. RESULTS: The cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels. CONCLUSION: The association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb.

Analytical Performance of 10 High-Volume Clinical Chemistry Assays on the Alinity c System.

BACKGROUND: Early access for routine testing with the Alinity c clinical chemistry system (Abbot Laboratories) presented the opportunity to characterize the analytical performance of multiple analytes across clinical laboratories in Europe. METHODS: A total of 8 laboratories from 7 European countries evaluated 10 high-volume chemistry assays on the Alinity c system for imprecision, linearity, and accuracy by method comparison to the routine ARCHITECT (Abbott Laboratories) method. RESULTS: Within-run precision was less than 4% coefficient of variation (CV), with total imprecision less than 5.6% CV for 5- and 20-day evaluations. Linearity met expectations, and method comparison showed strong correlation between the Alinity and ARCHITECT methods, with overall linear correlation coefficient between 0.980 to 1.000 and slopes of the regression line between 0.963 and 1.034. Mean percentage difference between the results of assays run on the ARCHITECT and the Alinity ranged between -1.7% and 2.15%. CONCLUSIONS: Our results demonstrated acceptable key analytical performance across all assays tested at each participating laboratory.