Cardiovascular biomarkers in sickle cell disease− clinical and echocardiographic correlations in a cross-sectional study with 126 patients

INTRODUCTION: Cardiac biomarkers can be useful in understanding the systemic and heart manifestations of sickle cell disease (SCD). Biomarkers reflect various aspects of heart disease (remodeling, injury and myocardial strain), with discriminatory potential for non-cardiac complications. Patients and METHODS: SCD patients (SS/Sß0) in steady state, were studied, correlating clinical manifestations and echo parameters (myocardial work - MW and speckle tracking), pre-MSCD severity score (integrating clinical and echo data), and cardiac biomarkers (high-sensitivity troponins ­ hs-cTn I and T, NT-pro-BNP, ST2s, and galectin-3 - GAL3). Quantitative characteristics were analyzed by Spearman tests, and qualitative characteristics by Mann-Whitney test. Hemolytic Index (HI) was calculated through Principal Component Analysis. Generalized linear Poisson models were generated for hs-cTn, and γ-distribution models were employed for other markers, with final models selected through the Stepwise Backward method. RESULTS: We studied 126 patients (mean age 37.2 ± 11.6 years), 42.1% male, and 80.2% SS. 47% were on hydroxyurea treatment and 30.2% on a chronic transfusion. NT-pro-BNP was elevated in 44% (> 160 ng/mL in 37%), correlated with female gender (p < 0.001), severity score (p = 0.001), uric acid (p = 0.017), HI (p < 0.001), Global Work Index (GWI) (p = 0.003), left atrial (LA) stiffness (p = 0.003), and ventricular mass (VM) (p = 0.02). ST2s were elevated in 11% and correlated with male gender (p > 0.001), HI (p > 0.001), cardiac index (p = 0.015), and LA strain reservoir function (p = 0.034). GAL3 was elevated in 42.8%, correlated with E/e'ratio (p = 0.006), uric acid (p = 0.005), and absence of chronic pain (p = 0.046). hs-cTn correlated with age (c-TnI p = 0.004; c-TnT p > 0.001), HI (p > 0.001), diastolic dysfunction (p > 0.001), left VM (p < 0.001), increased GWI (p < 0.001), and reduced MW efficiency (p < 0.001). hs-cTn I also correlated with increased LA reservoir function (p < 0.001) with reduced conduit function (p < 0.001). hs-cTn T correlated with uric acid (p = 0.001), and in univariate analysis was also correlated with severity score. The values of both hs-cTn correlated with increased GWI (p < 0.001) and reduced MW efficiency (p < 0.001). DISCUSSION: The biomarkers demonstrated various clinical and pathophysiological aspects of SCD. NT-pro-BNP is a routine marker with correlations similar to literature, except for higher values in females, also observed in non-SCD population. ST2 and GAL3 had limited correlations with echo findings, likely due to their production in extracardiac tissues affected by inflammation/vaso-occlusion. Both were linked to the HI, and the decrease in GAL3 in chronic pain can be attributed to chronic opioid use causing reduced synthesis of it. The elevation of hs-cTn was expected due to the analytical characteristics of high-sensitivity assays, but low in terms of the extent of heart involvement. hs-cTnT was more associated with general severity, like in the general population, where it is associated with overall mortality, while hs-cTnI is more connected to heart disease. MW in SCD is optimized to the maximum with a very low Global Work Wasted, and hs-cTn elevation is associated with reduced MW efficiency, indicating mecano-energetic uncoupling and subtle systolic dysfunction. CONCLUSION: Our study demonstrates that cardiac biomarkers can be used for clinical and pathophysiological evaluation, with NT-pro-BNP confirming its role in clinical stratification. ST2s and GAL3 may reveal new pathophysiological pathways in hemolysis and the interaction of opioids and chronic pain. Troponins are promising as prospective tool and may unveil ischemic damage resulting from myocardial mecano-energetic dissociation.

Detection of high-risk Avian Pathogenic Escherichia coli (APEC) isolated from broilers in São Paulo, Brazil.

Some high-risk Avian Pathogenic Escherichia coli (APEC) clones have been associated with increased economic losses caused by avian colibacillosis. They may represent an additional food consumption concern due to the potential zoonotic role causing urinary tract infections mainly related to E. coli ST73 and ST95 lineages. This study aimed to characterize APEC isolated from slaughterhouse carcasses presenting lesions compatible with avian colibacillosis. We analyzed about 6500 broilers carcasses, and 48 showed lesions consistent with colibacillosis. Forty-four strains of E. coli were isolated, with 77.27% (n = 34/44) classified as APEC. The isolates belonged to the phylogenetic groups B2 (41.17%, n = 14/34), G (20.59%, n = 7/34), A (17.65%, n = 6/34), B1 (8.82%, n = 3/34), and E (5.88%, n = 2/34). Determining the phylogenetic group of 5.88% (n = 2/34) of the strains was impossible. Moreover, 20.59% (n = 7/34) were positive to the clonal groups ST117, 8.82% (n = 3/34) to ST95, and 8.82% (n = 3/34) were classified as belonging to serogroup O78 by PCR screening. Strains of APEC from O78 serogroup and ST117 are considered high-risk clones for poultry, and our data reinforced the need for surveillance of these pathogens in poultry farms and slaughterhouses.

Oxaliplatin-related thrombocytopenia.

Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal cross-links in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used in other tumor types such as ovary, breast, liver and non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen during oxaliplatin treatment, occurring at any grade in up to 70% of patients and leading to delays or even discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia.

Presence of human immunodeficiency virus (HIV) and T-lymphotropic virus type I and II (HTLV-I/II) in a haemophiliac population in Belo Horizonte, Brazil, and correlation with additional serological results.

The aim of this study was to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus types I and II (HTLV-I/II) infections in 226 haemophiliac patients treated at Fundação Hemominas in Belo Horizonte, Minas Gerais State, Brazil, and to verify association with other serological results. Patients positive for HTLV-I/II had also a neurological, haematological and ophthalmological evaluation. Fundação Hemominas offers comprehensive care for all haemophiliac patients in Minas Gerais. Thirty-six (15.9%) of the 226 patients showed reactive results to HIV-1 [ELISA, Abbott, USA, confirmed by Western blot (WB), Cambridge Biotech, USA, and/or immunofluorescence, Fiocruz, Brazil] and 16 (7.1%) had reactive sera to HTLV-I/II (ELISA, Ortho). Eleven of these 16 (4.9%) were positive, 3/16 (1.3%) were indeterminate and 2/16 (0.9%) were negative in the HTLV WB (Cambridge Biotech). Neurological, haematological and ophthalmological examination of 9/16 patients revealed no abnormality suggestive of HTLV disease. Of the 16 patients reactive to HTLV-I/II ELISA test, six (37.5%) were also positive to HIV-1 (chi 2 = 5.92; P = 0.01). Seropositivity for HTLV-I/II and HIV-1 was associated with advancing age and positive results for hepatitis C virus (HCV), Chagas' disease (T. cruzi infection) and syphilis. No association between the presence of HTLV with type and severity of haemophilia and hepatitis B results was detected. The prevalence of antibodies against HIV-1 is approximately three times that of HTLV-I/II and a patient positive for HTLV-I/II had a significantly increased risk of being positive for HIV-1, HCV and T. cruzi.