Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

IntroductionSARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators.MethodsA sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array.ResultsIn the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester.Discussion and conclusionFrom an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women

Preeclampsia: the role of tissue factor and tissue factor pathway inhibitor

Preeclampsia (PE) is a multi-system disorder of human pregnancy, whose etiology remains poorly understood. Preeclamptic women are known to have an increased hypercoagulable state that result in excess fibrin deposition in several organs, which compromises their function. Tissue factor (TF) is the main physiological initiator of blood coagulation and its activity is regulated by a specific inhibitor known as Tissue factor pathway inhibitor (TFPI). Based on the important role of TF and TFPI in hemostasis, we hypothesize that their levels may change in the severe PE contributing to exacerbate hypercoagulable state. Some studies have assessed the balance between TF and TFPI in preeclamptic women, but results are inconsistent. Therefore, the aim of this study was to examine these inconsistencies and to assess TF and TFPI plasma levels in three groups of age matched women; pregnant with severe PE (n = 60), normotensive pregnant (n = 50) and normotensive non-pregnant women (n = 50). There was not significantly different among the three groups for TF plasma levels; severe PE women: 338.4 pg/mL (248.1-457.6), normotensive pregnant women: 301.5 pg/mL (216.4-442.9) and normotensive non-pregnant women 393 pg/mL (310.3-522.9). TFPI plasma levels were higher in severe PE comparing to normotensive pregnant women and normotensive non-pregnant women, 115.8 ng/mL (75-149.8); 80.3 ng/mL (59.6-99.7) and 74.5 ng/mL (47.1-98.0), respectively No difference was found between normotensive pregnant women and normotensive non-pregnant women. As for gestational age, a significant difference in TFPI levels was found between severe PE and normotensive pregnant women up to the 33rd week of pregnancy (p = 0.001), and severe PE and non-pregnant women up to the 34th (p = 0.01). In summary, our results indicated that TF plasma levels did not vary in the studied groups, while TFPI plasma levels were significantly increased in severe PE compared to normotensive pregnant and normotensive non-pregnant women. So, our data do not explain the exacerbated hypercoagulability state observed in severe PE. Further studies evaluating genes expression, TF activity and antigen, total and free TFPI and TFPI-2, both in plasma and obstetric tissues, throughout the pregnancy in PE (mild and severe forms) are required

Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients

Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients

Longitudinal assessment of D-dimer and plasminogen activator inhibitor type-1 plasma levels in pregnant women with risk factors for preeclampsia

Objective: Investigating D-Dimer/D-Di and plasminogen activator inhibitor type-1/PAI-1 levels throughout gestation in women with preeclampsia/PE risk factors. Methods: D-Di and PAI-1 plasma levels were determined in 28 women at 12–19, 20–29, 30–34 and 35–40 weeks of gestation. Results: D-Di was lower at 12–19 weeks and higher at 30–34 weeks in women who developed PE versus who did not develop it. D-Di increased throughout gestation in both groups, peaking earlier in pregnant women who developed PE versus who did not develop it. PA1-1 increased across gestation, but it didn’t differ between groups. Conclusion: D-Di was able to discriminate these groups of women at 12–19 and 30–34 weeks of gestation.</p

Pediatric chronic kidney disease: blood cell count indexes as inflammation markers

Abstract Introduction: Chronic kidney disease (CKD) is defined as a progressive decline of kidney functions. In childhood, the main triggering factors are congenital anomalies of the kidneys and urinary tract (CAKUT) and glomerulopathies. Inflammatory responses present challenges for diagnosis and staging, which justifies studies on biomarkers/indexes. Aim: To define blood cell count indexes and verify their association with pediatric CKD etiology and staging. The included indexes were: Neutrophil-Lymphocyte Ratio (NLR), Derived Neutrophil-Lymphocyte Ratio (dNLR), Lymphocyte-Monocyte Ratio (LMR), Systemic Inflammation Response Index (SIRI), Aggregate Index of Systemic Inflammation (AISI), and Systemic Immune-Inflammation Index (SII). Methods: We determined the indexes in 52 pediatric CKD patients and 33 healthy controls by mathematical calculation. CKD patients were separated in five groups based on the etiology and staging: Group IA: glomerulopathies at stage 1 or 2; IB: glomerulopathies at stage 3 or 4; IIA: CAKUT at stage 1 or 2; IIB: CAKUT at stage 3 or 4; and III: stages 3 or 4 of other etiologies. In addition, we combined all patients with CKD in one group (IV). Group V was a healthy control group. Results: Lower values of LMR were observed for groups IB and IIB compared to group V (p = 0.047, p = 0.031, respectively). Increased values of SIRI were found for group III versus group V (p = 0.030). There was no difference for other indexes when the groups were compared two by two. Conclusion: The LMR and SIRI indexes showed promising results in the evaluation of inflammation, as they correlated with CKD etiologies and specially staging in these patients

Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients

Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients

Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

Substance use disorder is one of the major social and public health problems in the world.The present study analyzed the pharmacoepidemiological profile of patients treated at thePsychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) fortreatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcoholand cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitativeand descriptive data and was based on the evaluation of medical records of patients attendedfrom January to December 2016. After analyzing 295 medical records, the majority of studyparticipants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %),complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol(23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine(42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowingthe pharmacoepidemiological profile of CAPS-AD patients is extremely important for makingdecisions regarding which medicines to make available to the population

Estrogen receptor-alpha gene XbaI A &gt; G polymorphism influences short-term cognitive decline in healthy oldest-old individuals Polimorfismo XbaI A &gt; G no gene do receptor do estrogênio-alfa influencia o declínio cognitivo em curto prazo em idosos muito id

Global aging is a challenging reality of this century. In 2010, there were 576 million people aged 65 years and over, worldwide. The expectation for 2050 is that this number will triple, reaching 1.5 billion people 1 . It is important to note that the highest population aging rates occur in developing countries. It is expected that between 2010 and 2050 the number of older people in developing countries will grow around 250%, while in developed countries the rate will be 71% 1 . Notably, the change in aging is rising: a child born in Brazil in 2015 has a life expectancy 20 years longer than Brazilians who were born just 50 years ago 2 . The maintenance of cognitive skills is fundamental for preservation of autonomy and quality of life among elderly individuals. Age-associated cognitive decline is characterized by changes in attention regulation, processing speed and memory capacity Results: The XbaI -351 AA genotype was more common among cognitive decliners, while -351G allele carriers showed cognitive stability or improvement. Conclusion: These results suggest that ESR-1 could be associated with one-year cognitive decline in healthy oldest-old individuals, since the estrogen pathway may be involved with neuroprotection, even in healthy brain aging. Keywords: estrogen receptor alpha; polymorphism, genetic; aging; cognition. Resultados: O genótipo XbaI -351 AA foi mais comum entre indivíduos que apresentaram declínio cognitivo, enquanto carreadores do alelo -351G demonstraram estabilidade ou melhora cognitiva. Conclusão: Estes resultados sugerem que ESR-1 poderia estar associado ao declínio cognitivo em curto prazo em idosos saudáveis, possivelmente por meio de propriedades neuroprotetoras do estrogênio, mesmo em cérebros idosos saudáveis. RESUMO Palavras-chave: receptor alfa de estrogênio; polimorfismo genético; envelhecimento; cognição