Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients.

BACKGROUND: Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. METHODS: Blood and spot urine were collected in "severe" (n = 26), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. RESULTS: U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. CONCLUSIONS: U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Adding protein to a carbohydrate pre-exercise beverage does not influence running performance and metabolism.

BACKGROUND: To analyze whether pre-exercise CHO+PRO vs. CHO intake distinctly influences running performance and metabolic biomarkers along a various of exercise intensities. METHODS: In a randomized, double blind, counterbalanced, crossover and placebo control design, 10 middle distance runners were tested in 3 occasions. After 10 h of fasting, participants ingested isovolumic beverages (0.75+0.25g·BW-1 of CHO+PRO, 1.0g·BW-1 of CHO and placebo control) 30 min before a treadmill running incremental protocol of 4 min steps until exhaustion. Venous blood was collected at fasting, 30 min after beverage ingestion and after the 3rd and 7th running steps. Oxygen uptake-related variables, including respiratory exchange ratio, heart rate, plasma glucose, insulin, glucagon, free fatty acids, blood lactate concentrations, gastrointestinal discomfort and rate of perceived exertion were measured. RESULTS: The addition of PRO to CHO had no influence on the measured variables, which did not differ between conditions along all incremental protocol intensities. The intake of CHO+PRO (compared to CHO) tended to decrease glycemia (106.5±21.3 vs. 113.6±26.5) and to increase insulinemia (14.4±15.1 vs. 12.7±10.8) at intensities close to maximum oxygen uptake. CONCLUSIONS: The addition of PRO to a pre-exercise CHO beverage had no impact on running performance and related metabolic variables at a wide spectrum of exercise intensities.

Urinary Cysteinyl Leukotrienes as Biomarkers of Endothelial Activation, Inflammation and Oxidative Stress and Their Relationship with Organ Dysfunction in Human Septic Shock.

Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin-angiotensin-aldosterone system, and cardiac, renal, respiratory, and hepatic parameters in SS patients. Blood and spot-urine samples were collected at days 1-2 (admission), 3-4, and 5-8 in SS patients (n = 13) and at a single time point in controls (n = 22). Urinary CysLT (u-CysLT) and isoprostanes, plasma, and urinary angiotensinogen, serum myeloperoxidase, and IL-10 were quantified by ELISA. Serum intercellular-adhesion molecule-1, vascular cell-adhesion molecule-1, E-selectin, tumor necrosis factor-α, IL-1ß, and IL-6 were measured by multiplex immunoassays. Routine markers were evaluated using automated analyzers. At admission, SS patients had increased u-CysLT, endothelial activation, inflammation, oxidative stress, and plasma and urinary angiotensinogen, as well as cardiac, respiratory, hepatic, and renal injury/dysfunction. There were no changes in u-CysLT during hospitalization. Both correlation and multivariate analyses showed positive relationships of u-CysLT with endothelial activation, inflammation, oxidative stress, proteinuria, and hepatic injury/dysfunction markers. These results suggest that u-CysLT may be potential non-invasive biomarkers for monitoring the pathophysiological mechanisms underlying SS, as well as putative therapeutic targets.

Endothelitis profile in acute heart failure and cardiogenic shock patients: Endocan as a potential novel biomarker and putative therapeutic target.

Aims: Inflammation-driven endothelitis seems to be a hallmark of acute heart failure (AHF) and cardiogenic shock (CS). Endocan, a soluble proteoglycan secreted by the activated endothelium, contributes to inflammation and endothelial dysfunction, but has been scarcely explored in human AHF. We aimed to evaluate serum (S-Endocan) and urinary endocan (U-Endocan) profiles in AHF and CS patients and to correlate them with biomarkers/parameters of inflammation, endothelial activation, cardiovascular dysfunction and prognosis. Methods: Blood and spot urine were collected from patients with AHF (n = 23) or CS (n = 25) at days 1-2 (admission), 3-4 and 5-8 and from controls (blood donors, n = 22) at a single time point. S-Endocan, U-Endocan, serum IL-1ß, IL-6, tumour necrosis factor-α (S-TNF-α), intercellular adhesion molecule-1 (S-ICAM-1), vascular cell adhesion molecule-1 (S-VCAM-1) and E-selectin were determined by ELISA or multiplex immunoassays. Serum C-reactive protein (S-CRP), plasma B-type natriuretic peptide (P-BNP) and high-sensitivity troponin I (P-hs-trop I), lactate, urea, creatinine and urinary proteins, as well as prognostic scores (APACHE II, SAPS II) and echocardiographic left ventricular ejection fraction (LVEF) were also evaluated. Results: Admission S-Endocan was higher in both patient groups, with CS presenting greater values than AHF (AHF and CS vs. Controls, p < 0.001; CS vs. AHF, p < 0.01). Admission U-Endocan was only higher in CS patients (p < 0.01 vs. Controls). At admission, S-VCAM-1, S-IL-6 and S-TNF-α were also higher in both patient groups but there were no differences in S-E-selectin and S-IL-1ß among the groups, nor in P-BNP, S-CRP or renal function between AHF and CS. Neither endocan nor other endothelial and inflammatory markers were reduced during hospitalization (p > 0.05). S-Endocan positively correlated with S-VCAM-1, S-IL-6, S-CRP, APACHE II and SAPS II scores and was positively associated with P-BNP in multivariate analyses. Admission S-Endocan raised in line with LVEF impairment (p = 0.008 for linear trend). Conclusion: Admission endocan significantly increases across AHF spectrum. The lack of reduction in endothelial and inflammatory markers throughout hospitalization suggests a perpetuation of endothelial dysfunction and inflammation. S-Endocan appears to be a biomarker of endothelitis and a putative therapeutic target in AHF and CS, given its association with LVEF impairment and P-BNP and its positive correlation with prognostic scores.

Persistent weight gain between 0 and 4 years of age is associated with higher dehydroepiandrosterone sulphate levels at 7 years old: Data from the Generation XXI birth cohort.

OBJECTIVE: To assess the influence of longitudinal weight gain from 0 to 4 years old on dehydroepiandrosterone sulphate (DHEAS) levels at 7 years old. DESIGN: DHEAS levels were measured at 7 years old in a subsample of 587 children from the Generation XXI birth cohort. Weight trajectories (0-4 years of age) were identified using model-based clustering and categorized as "normal weight gain," "weight gain during infancy," "weight gain during childhood" and "persistent weight gain." MEASUREMENTS: Differences in DHEAS levels at age 7 between the four weight trajectories were analysed through analysis of covariance (ANCOVA), adjusted for birth weight (BW) and body mass index (BMI). RESULTS: In the crude analysis, compared with the "normal weight gain" trajectory (5.53 (95% CI: 5.10-5.98] µmol/L), DHEAS levels were significantly higher in children in the "persistent weight gain" (8.75 [95% CI: 7.23-10.49] µmol/L, p < .001] and in children in the "weight gain during infancy" trajectories (7.68 [95% CI: 6.22-9.49] µmol/L, p = .021] and marginally significantly higher in children in the "weight gain during childhood" trajectory (6.89 (95% CI: 5.98-8.00) µmol/L; p = .052). In BW- and BMI-adjusted model, a statistically significant difference in DHEAS levels was found between the "persistent weight gain" (7.93 [95% CI: 6.43-9.86] µmol/L) and the "normal weight gain" trajectories ([5.75 [95% CI: 5.32-6.23] µmol/L; p = .039). CONCLUSION: Higher DHEAS levels are found in 7-year-old children following a trajectory of persistent weight gain from 0 to 4 years, independently of their BW or current BMI, highlighting the impact of exposure to overweight in the first years of life on prepubertal adrenal androgen production.

CA-125 variation in acute heart failure: a single-centre analysis.

AIMS: A decrease in carbohydrate antigen 125 (CA-125) predicts survival advantage in chronic heart failure (HF); the impact of its variation in acute HF is unknown. We studied the association of CA-125 decrease with prognosis in acute HF. METHODS AND RESULTS: We studied acute hospitalized HF patients. Predictors of admission and discharge CA-125 were determined by linear regression. Follow-up was 1 year; endpoint was all-cause death. The association of admission and discharge CA-125 with mortality was assessed using a Cox-regression analysis. A Cox-regression analysis was also used to assess the prognostic impact of CA-125 decrease during hospitalization. Analysis was stratified by length of hospital stay (LOS). We studied 363 patients, 51.5% male, mean age 75 ± 12 years, 51.5% ischaemic, 30.0% with preserved ejection fraction, and 57.3% with reduced ejection fraction; patients presented elevated comorbidity burden. Median LOS was 7 (5-11) days. In the subgroup of 262 patients with CA-125 measured both at admission and at discharge, we reported a significant increase in its levels: 56.0 (26.0-160.7) U/mL to 74.0 (32.3-195.0) U/mL. Independent predictors of admission CA-125 were higher BNP and lower creatinine. Predictors of discharge CA-125 were higher discharge BNP, lower discharge albumin, and younger age. Both admission and discharge CA-125 predicted mortality. During follow-up, 75 (31.8%) patients died. A decrease in CA-125 predicted a 68% reduction in the 1 year death risk only in patients with LOS > 10 days. CONCLUSIONS: Our results suggest that an early re-evaluation (>10 days) with CA-125 measurement after an acute HF hospitalization may be of interest in patient management.

Association of dehydroepiandrosterone sulfate, birth size, adiposity and cardiometabolic risk factors in 7-year-old children.

BACKGROUND: Low birth size (BS) and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in childhood, insulin acting as a mediator, despite contradictory findings. To further explore these issues, we studied the associations between DHEAS, BS, adiposity, maternal characteristics, and cardiometabolic risk indicators, in participants of Generation XXI, a population-based birth cohort. METHODS: A sample of 700 children (mean age 7.1 yr) was randomly selected. Data on maternal characteristics, BS, body mass index (BMI), waist-to-height ratio, body fat (dual-energy X-ray absorptiometry), insulin, lipid profile, and high-sensitivity C-reactive protein were analyzed in relation to DHEAS. RESULTS: DHEAS was negatively associated with BS and positively associated with all adiposity indicators, with no sex differences. DHEAS was positively associated with insulinemia independently of the child's BS or BMI. No significant association was found between DHEAS, maternal characteristics, lipid profile, or high-sensitivity C-reactive protein. Including insulin in the model did not affect the association between BS and DHEAS but reduced the magnitude of the BMI effect by 24% for boys and 30% for girls. CONCLUSION: Higher DHEAS levels at 7 years old were associated with lower BS and higher adiposity. DHEAS levels were positively associated with insulinemia independently of BS or BMI. IMPACT: Low birth weight and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in prepuberty. Insulin has been suggested as a mediator, despite previous studies failing to show an association between DHEAS and insulin levels. In a randomly selected population of 700 7-year-old children from the Generation XXI birth cohort, higher DHEAS levels were associated with a lower birth size and higher adiposity, with no sex differences. DHEAS was positively related to insulinemia independently of the child's birth size or body mass index. No association was found between DHEAS and other cardiometabolic risk factors.

The Percentage of [-2]Pro-Prostate-Specific Antigen and the Prostate Health Index Outperform Prostate-Specific Antigen and the Percentage of Free Prostate-Specific Antigen in the Detection of Clinically Significant Prostate Cancer and Can Be Used as Reflex Tests.

CONTEXT.­: There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. OBJECTIVE.­: To evaluate the clinical utility of [-2]pro-prostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). DESIGN.­: Two hundred thirty-seven men (PSA: 2-10 ng/mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. RESULTS.­: Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: ≥1.25%) and PHI (cutoff: ≥27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: ≥1.12% and ≥24 for %[-2]proPSA and PHI, respectively). CONCLUSIONS.­: The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies.

Tumour markers in prostate cancer: The post-prostate-specific antigen era.

Although prostate-specific antigen-based prostate cancer screening had a positive impact in reducing prostate cancer mortality, it also led to overdiagnosis, overtreatment and a significant number of unnecessary biopsies. In the post-prostate-specific antigen era, new biomarkers have emerged that can complement the information given by prostate-specific antigen, towards a better cancer diagnostic specificity, and also allowing a better estimate of the aggressiveness of the disease and its clinical outcome. That means those markers have the potential to assist the clinician in the decision-making processes, such as whether or not to perform a biopsy, and to make the best treatment choice among the new therapeutic options available, including active surveillance in lower risk disease. In this article, we will review several of those more recent diagnostic markers (4Kscore®, [-2]proPSA and Prostate Health Index, SelectMDx®, ConfirmMDx®, Progensa® Prostate Cancer Antigen 3, Mi-Prostate Score, ExoDx™ Prostate Test, the Stockholm3 test and ERSPC risk calculators) and prognostic markers (OncotypeDX® Genomic Prostate Score, Prolaris®, Decipher® and ProMark®). We will also address some new liquid biopsy approaches - circulating tumour cells and cell-free DNA - with a potential role in metastatic castration-resistant prostate cancer and will briefly give some future perspectives, mostly outlooking epigenetic markers.

Comparison of Three Assays for Total and Free PSA Using Hybritech and WHO Calibrations.

BACKGROUND/AIM: Lack of interchangeability between prostate-specific antigen (PSA) assays could have a clinical impact. We compared PSA assays from different manufacturers and calibrations. PATIENTS AND METHODS: A total of 233 men who underwent prostate biopsy (PSA: 2-10 ng/ml; Beckman Coulter Access® Hybritech® as reference) were enrolled. Total (tPSA) and free PSA (fPSA) were also measured using the Roche cobas® and the Abbott Architect® methods. RESULTS: Roche tPSA values were ≈1% higher than Beckman, while Abbott values were ≈5% lower. Roche had the highest diagnostic sensitivity (92%) compared to Beckman Coulter (87%) and Abbott (85%). Roche fPSA was ≈3% lower and Abbott ≈17% higher than that of Beckman. For the percentage of fPSA, Roche had the highest sensitivity (98%). CONCLUSION: Roche cobas® and Beckman Coulter Access® Hybritech® tPSA were almost interchangeable. While the agreement was acceptable for tPSA, this did not happen with fPSA and greater efforts for harmonization are required.

Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications.

Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer, but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in patients with AML at diagnosis and explored the mechanisms involved using the syngeneic MLL-AF9-induced AML mouse model. We found that AML is a disorder with a unique iron profile, not associated with inflammation or transfusion, characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that the AML-induced loss of erythroblasts is responsible for iron redistribution and increased TSAT. We also show that AML progression is delayed in mouse models of systemic iron overload and that elevated TSAT at diagnosis is independently associated with increased overall survival in AML. We suggest that TSAT may be a relevant prognostic marker in AML.

Forecasting COVID-19 Severity by Intelligent Optical Fingerprinting of Blood Samples.

Forecasting COVID-19 disease severity is key to supporting clinical decision making and assisting resource allocation, particularly in intensive care units (ICUs). Here, we investigated the utility of time- and frequency-related features of the backscattered signal of serum patient samples to predict COVID-19 disease severity immediately after diagnosis. ICU admission was the primary outcome used to define disease severity. We developed a stacking ensemble machine learning model including the backscattered signal features (optical fingerprint), patient comorbidities, and age (AUROC = 0.80), which significantly outperformed the predictive value of clinical and laboratory variables available at hospital admission (AUROC = 0.71). The information derived from patient optical fingerprints was not strongly correlated with any clinical/laboratory variable, suggesting that optical fingerprinting brings unique information for COVID-19 severity risk assessment. Optical fingerprinting is a label-free, real-time, and low-cost technology that can be easily integrated as a front-line tool to facilitate the triage and clinical management of COVID-19 patients.

Pericardial NT-Pro-BNP and GDF-15 as Biomarkers of Atrial Fibrillation and Atrial Matrix Remodeling in Aortic Stenosis.

AIMS: This study aimed to evaluate the association of GDF-15 and NT-pro-BNP in two different biological matrices with AF in severe aortic stenosis patients undergoing aortic valve replacement surgery (AVR), its association with atrial matrix remodeling, as well as with 30-day postoperative outcomes. MAIN METHODS: One hundred and twenty-six patients between 2009 and 2019 with severe aortic stenosis undergoing AVR surgery in a tertiary hospital were assessed. KEY FINDINGS: pericardial fluid GDF-15 and pericardial fluid and serum NT-pro-BNP were increased in AF patients with aortic stenosis. COL1A1 and COL3A1 gene expression increased when pericardial fluid NT-pro-BNP values were higher. TIMP4 was positively correlated with pericardial fluid GDF-15. SIGNIFICANCE: GDF-15 and NT-pro-BNP in the pericardial fluid are biomarkers of atrial fibrillation in aortic stenosis and correlate with atrial matrix remodeling. AKI is predicted by both serum and pericardial fluid GDF-15.

The prostate health index and the percentage of [-2]proPSA maintain their diagnostic performance when calculated with total and free PSA from different manufacturers.

OBJECTIVES: To evaluate the diagnostic performance of the prostate health index (PHI) and of the percentage of [-2]proPSA (%[-2]proPSA) calculated with total and free PSA from non-Beckman Coulter manufacturers (Roche and Abbott), and compare it with the fully Beckman Coulter [-2]proPSA derivatives. METHODS: In this study, 237 men (PSA: 2-10 µg/L) scheduled for prostate biopsy were enrolled. %[-2]proPSA and PHI were calculated with total and free PSA from three manufacturers. Beckman Coulter PSA and [-2]proPSA were performed on the Access 2 analyzer (Hybritech calibration). Roche PSA was performed on the cobas e411 and the Abbott PSA on the Architect i2000sr. Statistical analysis was performed, considering prostate cancer (PCa) as the outcome. RESULTS: Univariate analysis showed that all indices were predictors of cancer, irrespective of the manufacturer (p<0.001). The AUC was similar for all manufacturers, both for %[-2]proPSA (Beckman Coulter: 0.756; Roche: 0.770; Abbott: 0.756) and PHI (Beckman Coulter: 0.776; Roche: 0.785; Abbott: 0.778). When considering the cutoffs that allowed 90% sensitivity, [-2]proPSA derivatives calculated with Roche and Abbott PSA had similar specificities and predictive values when compared to Beckman Coulter. The percentage of missed cancers (8-9%) was the same between manufacturers. The percentage of spared biopsies was significantly higher with Roche's PHI (21.0%) and Abbott's PHI (20.6%) than with Beckman Coulter's PHI (17.2%). CONCLUSIONS: In the PSA range between 2 and 10 µg/L, [-2]proPSA derivatives maintain their diagnostic performance in PCa detection when calculated with PSA from Roche and Abbott. This can lead to a broader implementation of these indices in clinical laboratories worldwide.

The prostate health index (PHI) density: Are there advantages over PHI or over the prostate-specific antigen density?

BACKGROUND AND AIMS: Overdiagnosis of prostate cancer (PCa) should be minimized. We wanted to evaluate the diagnostic performance of the prostate health index density (PHID) and compare it with that of the prostate health index (PHI) alone and of the prostate-specific antigen density (PSAD). MATERIALS AND METHODS: 232 men scheduled for a prostate biopsy (prostate-specific antigen level: 2-10 µg/L), were enrolled. PHI, PHID and PSAD were evaluated considering PCa and clinically significant PCa (csPCa) as the outcomes. RESULTS: For PCa, the area under the curve (AUC) was higher for PHID (0.823) than for PHI (0.779) and PSAD (0.776). For csPCa, the AUC was also higher for PHID (0.851) but closer to that of PSAD (0.819) and PHI (0.813). For equal sensitivities (90%) for PCa, PHID and PSAD offered the highest specificities (37%), missing the same number of cancers (n = 11). Considering csPCa, PHI and PHID had similar specificities. PSAD reached the highest specificity (50.0%), sparing 32.8% of biopsies, while missing 9 cases of csPCa. CONCLUSIONS: PHID has a better diagnostic performance than PHI for overall PCa detection, but very close to the PSAD performance. Considering csPCa, PHI and PHID perform almost equally, but PSAD has a better diagnostic performance.

Are Proinflammatory Cytokines Relevant for the Diagnosis of Prostate Cancer?

BACKGROUND/AIM: Inflammation plays an important role in prostate cancer (PCa). We evaluated proinflammatory cytokines regarding differential diagnosis of PCa in men with PSA levels between 2-10 ng/ml. PATIENTS AND METHODS: Serum samples of 79 men (PSA 2-10 ng/ml) were analyzed for 10 proinflammatory cytokines (IL-6, IL-8, TNF-α, IFN-γ, IL-10, IL-1ß, IL-2, IL-4, IL-12p70, IL-13) and results were evaluated regarding presence of PCa and disease severity. RESULTS: Significant differences between PCa patients and controls were found for IL-6 (p=0.002), IL-8 (p=0.030), and TNF-α (p=0.009), although they were not predictors of PCa in a logistic regression analysis. In addition, IL-6 and TNF-α levels were significantly higher in patients with high-risk PCa (p<0.05). No significant differences were observed regarding the other cytokines. CONCLUSION: In patients with PSA levels between 2-10 ng/ml, IL-6, IL-8, and TNF-α are associated with PCa, and IL-6 and TNF-α are associated with high-risk PCa.

Relevance of Circulating Nucleosomes, HMGB1 and sRAGE for Prostate Cancer Diagnosis.

BACKGROUND/AIM: Evasion from cell death occurs in prostate cancer (PCa). We verified whether serum levels of cell death markers can have diagnostic value in PCa. PATIENTS AND METHODS: A total of 233 men scheduled for prostate biopsy [prostate specific antigen (PSA) level: 2-10 ng/ml] were enrolled. Serum nucleosomes, nucleosomes containing the H3 histone (H3), high mobility group box 1 (HMGB1), and soluble receptor for advanced glycation end products (sRAGE) were analyzed by enzyme immunoassays. RESULTS: There were no differences (p>0.05) in nucleosomes, H3, and sRAGE levels between patients with and without PCa or clinically significant PCa (csPCa). HMGB1 had lower levels in PCa patients (p=0.023) and was a predictor of PCa (p=0.047), but not of csPCa (p=0.180). CONCLUSION: In patients with critical PSA levels between 2-10 ng/ml, HMGB1 had some diagnostic value for overall PCa detection, but it was not predictive of csPCa. Nucleosomes, H3 and sRAGE did not discriminate between PCa or csPCa and controls.

Inflammatory Response Assessment in Patients with COVID-19 Under Extracorporeal Membrane Oxygenation Support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO), could be extremely helpful in the management of COVID-19 patients with refractory hypoxemic respiratory failure; however, to date, evidence on the true effecttiveness of ECMO in the COVID19 setting still hangs in the balance. METHODS: This was a prospective cohort study of 39 COVID-19 patients admitted to the intensive care unit (ICU) in an experienced ECMO center at a tertiary hospital during March/April 2020. Among the recruited participants, 10 (25.6%) required ECMO (ICU-ECMO group) and 29 (74.4%) did not have ECMO support (ICU group). Immunological parameters were assessed both at ICU admission and on a daily basis for 7 consecutive days. RESULTS: The absolute lymphocyte count increased significantly in the ICU-ECMO group compared to the ICU group in which it remained relatively stable: ß for the time variable was 127.1 [95% CI 68.9 - 185.3], p < 0.001 and for the interaction term -141.36 [-208.95 - -73.77], p < 0.001. On the other hand, globally, no significant differences were observed over time for the lymphocyte percentage, although it was higher in the ICU patients. Neutrophil counts were overall higher in the ICU-ECMO group (ß -4,275.38 [-6,845.21 - 1,705.55], p = 0.001). In regard to neutrophil percentage, a significant decrease over time was reported (ß -1.76 [-3.16 - -0.36], p = 0.014), namely in the ICU-ECMO group (ß for the interaction 2.09 [0.45 - 3.73], p = 0.013). CONCLUSIONS: Herein, we found ECMO support seems to provide a less aggressive immune response in COVID-19 patients with severe and refractory respiratory dysfunction.

Serum lipids and prostate cancer.

BACKGROUND: Conflicting results are found in the literature relating serum lipids levels and prostate cancer. Some results imply a relationship between them; others contradict this association. The purpose of this study was to investigate a possible association between serum lipids levels and prostate cancer, at time of diagnosis. METHODS: We measured serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in 237 patients submitted to a prostate biopsy, with PSA between 2 and 10 ng/ml. Patients without cancer at biopsy were used as controls, and the others were considered as cases. No information about lipid-lowering therapy, including statins, was available neither in cases nor in controls. Cases were divided into risk groups, according to the disease severity, based on staging. Lipids levels were compared between groups, using parametric and nonparametric tests. Logistic regression analysis and odds ratios were calculated. RESULTS: LDL and total cholesterol levels were lower in patients with cancer, with the difference being statistically significant for LDL cholesterol (p = 0.010) and borderline for total cholesterol (p = 0.050). No significant differences were found between the several risk groups. Odds ratios for low LDL cholesterol (<130 mg/dl) and low total cholesterol (<200 mg/dl), with prostate cancer as the outcome, were 1.983 and 1.703, respectively. There were no significant differences between cases and controls for the other lipids. CONCLUSION: Lower LDL cholesterol (<130 mg/dl) and lower total cholesterol (<200 mg/dl) serum levels seem to associate with prostate cancer, at time of diagnosis.

Dynamics of a Dual SARS-CoV-2 Lineage Co-Infection on a Prolonged Viral Shedding COVID-19 Case: Insights into Clinical Severity and Disease Duration.

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (>900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient's mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.