Hydroxychloroquine in the treatment of COVID-19 disease: a systematic review and meta-analysis

BACKGROUND Given the urgency of finding a specific treatment for coronavirus disease 2019 (COVID-19), several approaches have been carried out, including the use of chloroquine (CQ) and hydroxychloroquine (HCQ). This study was aimed to systematically evaluate the available evidence on the effectiveness of HCQ in the treatment of COVID-19 disease. METHODS We searched 3 databases (PubMed, Google Scholar, and ClinicalTrials) until May 31, 2020 for clinical studies in patients diagnosed with COVID-19 comparing conventional treatment with and without HCQ combined with or without azithromycin. The risk of bias assessment and quality evaluation was carried out according to the Cochrane recommendations. RESULTS 5 articles (1 randomized clinical trial [RCT], 1 non-RCT, and 3 cohort studies) were included. The main outcome measure in 2 articles was the virological conversion determined by reverse transcription-polymerase chain reaction; however, the findings of both studies were contrary. The main objective of the other studies was to determine the effects of HCQ on COVID-19 mortality, and the studies showed similar results. In general, the studies showed methodological limitations, risk of bias, and variable quality. A meta-analysis from 2,041 patients showed the odds ratio of mortality for patients having HCQ and standard care was 1.38 (95% CI 0.93–2.04). CONCLUSIONS Considering the limited data available and the very low-to-moderate quality of the studies included in this systematic review, the evidence suggests that the HCQ administration does not decrease the risk of death from COVID-19

Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis

Characterization and understanding of gut microbiota has recently increased representing a wide research eld, especially in autoimmune diseases. Gut microbiota is the major source of microbes which might exert benecial as well as pathogenic effects on human health. Intestinal microbiome’s role as mediator of inammation has only recently emerged. Microbiota has been observed to differ in subjects with early rheumatoid arthritis compared to controls, and this nding has commanded this study as a possible autoimmune process. Studies with intestinal microbiota have shown that rheumatoid arthritis is characterized by an expansion and/or decrease of bacterial groups as compared to controls. In this review, we present evidence linking intestinal dysbiosis with the autoimmune mechanisms involved in the development of rheumatoid arthritis

Management of traumatic popliteal vascular injuries in a level I trauma center: A 6-year experience

Popliteal vascular trauma remains a challenging entity, and carries the greatest risk of limb loss among the lower extremity vascular injuries. Operative management of traumatic popliteal vascular injuries continues to evolve. We aim at describing our experience with such complex injuries, with associated patterns of injury, diagnostic and therapeutic challenges, and outcomes. From January 2006 to September 2011, 191 adult trauma patients presented to an urban level I trauma center in Miami, Florida with traumatic lower extremity vascular injuries. Variables collected included age, gender, mechanism of injury, and clinical status at presentation. Surgical data included vessel injury, technical aspects of repair, associated complications and outcomes. Forty-seven (24.6%) patients were diagnosed with traumatic popliteal vascular injuries. Mean age was 38.1 ± 16.1 years, and the majority of patients were males (43 patients, 91.4%). There were 21 (44.7%) penetrating injuries, and 26 (55.3%) blunt injuries. Vascular repair with saphenous venous interposition graft and PTFE (polytetrafluoroethylene) grafting were performed in 36 (70.7%) and 2 (3.9%) patients, respectively. Blunt popliteal injuries were significantly more associated with major tissue loss, and length of hospital and intensive care unit (ICU) stays. The risk for amputation is increased with longer ICU stays and the use of PTFE grafting for vascular repair. The overall mortality rate in this series was 8.5%. Blunt popliteal vascular injuries are associated with increased morbidity compared to penetrating trauma. Early restoration of blood perfusion, frequent use of interposition grafts with autogenous saphenous vein, and liberal use of fasciotomies play important role to achieve acceptable outcomes

Asociación entre parámetros hematológicos y fenotipos metabólicamente poco saludables en niños y adolescentes: Association between hematological parameters and metabolically unhealthy phenotypes in children and adolescents.

Objective. Metabolic syndrome has been associated with changes in the composition of circulating blood cells. Hematologic indices can be used to identify the subjects at risk of metabolically unhealthy phenotype (MUP). This study investigated whether hematological indices can serve as biomarkers to distinguish metabolically healthy phenotype (MHP) from MUP in children and adolescents. Methods. Two hundred ninety-two children and adolescents were enrolled in a cross-sectional study. The MUP was diagnosed using consensus-based criteria proposed by Damanhoury et al. Group comparisons were performed using one-way ANOVA. To examine if sex, age group, nutritional status, puberty, hematological parameters, and insulin resistance were associated with MUP, we used multiadjusted logistic regression analysis with metabolic status as the dependent variable.    Results. The subject's age mean was 11 years (SD: 2.61). RDW values were significantly lower in children with metabolically unhealthy normal weight (MUNW) compared to children with metabolically unhealthy obesity (MUO) (12.33 ± 0.90 vs. 13.67 ± 0.52; p = 0.01), and in metabolically healthy obesity (MHO) compared to MUO (13.15 ± 0.53 vs. 13.67 ± 0.52; p = 0.04). In adolescents, the PLR was higher for the MHNW group, with a mean value of 152.60 (SD 62.97) compared to 111.16 (SD 44.12) for the MHO group. After adjusting for age, nutritional status, and puberty, hematological indices were not associated with MUP.   Conclusions. The study demonstrates that hematological indices are not independently associated with the metabolically unhealthy phenotype. Hematologic indices are unlikely to represent reliable biomarkers of MU phenotype in the pediatric population.    Objetivo. El síndrome metabólico se ha asociado con cambios en la composición de las células sanguíneas circulantes. Los índices hematológicos  pueden ser utilizados para identificar a los sujetos con un fenotipo metabólicamente no saludable (MUP). Este estudio investigó  si los índices hematológicos pueden servir como biomarcadores para distinguir el fenotipo metabólicamente saludable (MHP) del fenotipo no saludable (MUP) en niños y adolescentes. Métodos. Doscientos noventa y dos niños y adolescentes participaron en un estudio transversal. La MUP se diagnosticó utilizando los criterios consensuados propuestos por Damanhoury et al. Las comparaciones de grupos se realizaron mediante ANOVA de una vía. Para examinar si el sexo, el grupo de edad, el estado nutricional, la pubertad, los parámetros hematológicos y la resistencia a la insulina estaban asociados con la MUP, utilizamos un análisis de regresión logística multiajustado con el estado metabólico como variable dependiente. Resultados. La media de edad de los participantes fue de 11 años (±2.61). Los valores de RDW fueron significativamente más bajos en niños con peso normal metabólicamente no saludables (MUNW) en comparación con niños con obesidad metabólicamente no saludable (MUO) (12,33 ± 0,90 vs. 13,67 ± 0,52; p = 0,01), y en niños con obesidad y metabólicamente saludable (MHO) en comparación con MUO (13,15 ± 0,53 frente a 13,67 ± 0,52; p = 0,04). En adolescentes, el PLR fue mayor para el grupo MHNW, con un valor medio de 152,60 (±62,97) en comparación con 111.16 (±44,12) para el grupo MHO. Después de ajustar por edad, estado nutricional y pubertad, los índices hematológicos no se asociaron con MUP.   Conclusiones. El estudio demuestra que los índices hematológicos no están asociados de forma independiente con el fenotipo metabólicamente poco saludable. Es poco probable que los índices hematológicos representen biomarcadores fiables del fenotipo MU en la población pediátrica. &nbsp

Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis

Characterization and understanding of gut microbiota has recently increased representing a wide research eld, especially in autoimmune diseases. Gut microbiota is the major source of microbes which might exert benecial as well as pathogenic effects on human health. Intestinal microbiome’s role as mediator of inammation has only recently emerged. Microbiota has been observed to differ in subjects with early rheumatoid arthritis compared to controls, and this nding has commanded this study as a possible autoimmune process. Studies with intestinal microbiota have shown that rheumatoid arthritis is characterized by an expansion and/or decrease of bacterial groups as compared to controls. In this review, we present evidence linking intestinal dysbiosis with the autoimmune mechanisms involved in the development of rheumatoid arthritis

Pregnant women infected with pandemic H1N1pdm2009 influenza virus displayed overproduction of peripheral blood CD69+ lymphocytes and increased levels of serum cytokines.

The first pandemic of the 21st century occurred in 2009 and was caused by the H1N1pdm influenza A virus. Severe cases of H1N1pdm infection in adults are characterized by sustained immune activation, whereas pregnant women are prone to more severe forms of influenza, with increased morbi-mortality. During the H1N1pdm09 pandemic, few studies assessed the immune status of infected pregnant women. The objective of this study was to evaluate the behavior of several immune markers in 13 H1N1pdm2009 virus-infected pregnant (PH1N1) women, in comparison to pregnant women with an influenza-like illness (ILI), healthy pregnant women (HP) and healthy non-pregnant women (HW). The blood leukocyte phenotypes and the serological cytokine and chemokine concentrations of the blood leukocytes, as measured by flow cytometry, showed that the CD69+ cell counts in the T and B-lymphocytes were significantly higher in the PH1N1 group. We found that pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines and some chemokines (CXCL8, CXCL10), which are typically at lower levels during pregnancy, were substantially increased in the women in the ILI group. Our findings suggest that CD69 overexpression in blood lymphocytes and elevated levels of serum cytokines might be potential markers for the discrimination of H1N1 disease from other influenza-like illnesses in pregnant women

Human Mesenchymal Stem/Stromal Cells from Umbilical Cord Blood and Placenta Exhibit Similar Capacities to Promote Expansion of Hematopoietic Progenitor Cells In Vitro

Mesenchymal stem/stromal cells (MSCs) from bone marrow (BM) have been used in coculture systems as a feeder layer for promoting the expansion of hematopoietic progenitor cells (HPCs) for hematopoietic cell transplantation. Because BM has some drawbacks, umbilical cord blood (UCB) and placenta (PL) have been proposed as possible alternative sources of MSCs. However, MSCs from UCB and PL sources have not been compared to determine which of these cell populations has the best capacity of promoting hematopoietic expansion. In this study, MSCs from UCB and PL were cultured under the same conditions to compare their capacities to support the expansion of HPCs in vitro. MSCs were cocultured with CD34+CD38−Lin− HPCs in the presence or absence of early acting cytokines. HPC expansion was analyzed through quantification of colony-forming cells (CFCs), long-term culture-initiating cells (LTC-ICs), and CD34+CD38−Lin− cells. MSCs from UCB and PL have similar capacities to increase HPC expansion, and this capacity is similar to that presented by BM-MSCs. Here, we are the first to determine that MSCs from UCB and PL have similar capacities to promote HPC expansion; however, PL is a better alternative source because MSCs can be obtained from a higher proportion of samples

Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested

Gut Microbiota and Endothelial Dysfunction Markers in Obese Mexican Children and Adolescents

Obesity is a metabolic disease characterized by low-grade inflammation and accompanied by dyslipidemia and up-regulation of other bioactive molecules, creating a predisposition to endothelial dysfunction and metabolic syndrome. We studied the association between gut microbiota diversity and endothelial dysfunction (EDF) markers in obese Mexican children and adolescents. We examined clinical data including metabolic factors and EDF markers in blood samples. Gut bacterial diversity was characterized by high-throughput sequencing of V3-16S rDNA libraries. Triglycerides, insulin, homeostasis model assessment-insulin resistant (HOMA-IR), leptin, C-reactive protein (CRP), and EDF marker intercellular adhesion molecule 1 (ICAM-1) were significantly higher in obese children and adolescents. Multivariate analysis showed statistically significant positive associations between vascular cell adhesion molecule 1 (VCAM-1) and Veillonellaceae, and between ICAM-1 and Ruminococcus in obese children. In obese adolescents, there was a statistically significant positive association between total cholesterol and Ruminococcus, and between ICAM-1 and Bacteroides. LEfSe analysis showed that the genus Lactobacillus and family Coriobacteriaceae were enriched in children, and genera Collinsella and Prevotella were enriched in obese adolescents. Obese children and adolescents had higher levels of insulin resistance and metabolic syndrome. These results suggest that obese Mexican children and adolescents had increased levels of CRP and a reduction of adiponectin, which causes higher expression of EDF markers, affecting endothelial function and associating with changes in the gut microbiota