Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). ...Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.
We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.
A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality.
One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients.
Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
An international study was performed by 26 experienced PCR laboratories from 14 countries to assess the performance of duplex quantitative real-time PCR (qPCR) strategies on the basis of TaqMan ...probes for detection and quantification of parasitic loads in peripheral blood samples from Chagas disease patients. Two methods were studied: Satellite DNA (SatDNA) qPCR and kinetoplastid DNA (kDNA) qPCR. Both methods included an internal amplification control. Reportable range, analytical sensitivity, limits of detection and quantification, and precision were estimated according to international guidelines. In addition, inclusivity and exclusivity were estimated with DNA from stocks representing the different Trypanosoma cruzi discrete typing units and Trypanosoma rangeli and Leishmania spp. Both methods were challenged against 156 blood samples provided by the participant laboratories, including samples from acute and chronic patients with varied clinical findings, infected by oral route or vectorial transmission. kDNA qPCR showed better analytical sensitivity than SatDNA qPCR with limits of detection of 0.23 and 0.70 parasite equivalents/mL, respectively. Analyses of clinical samples revealed a high concordance in terms of sensitivity and parasitic loads determined by both SatDNA and kDNA qPCRs. This effort is a major step toward international validation of qPCR methods for the quantification of T. cruzi DNA in human blood samples, aiming to provide an accurate surrogate biomarker for diagnosis and treatment monitoring for patients with Chagas disease.
Ataxia-Telangiectasia Mutated (ATM) is a cancer predisposition gene; carriers of germline pathogenic variants have an increased risk of developing malignancies, including breast, prostate, ...pancreatic, and ovarian cancer. Most ATM variants are of uncertain significance. Findings from genome-wide association studies (GWAS) suggest that ATM may be a low-risk melanoma susceptibility locus.
We report the case of a Hispanic family whose members who have presented cutaneous melanoma have been found to be carriers for the ATM pathogenic variant c.3747-1G>C (rs730881364), one of whom was diagnosed at 24 years old.
We describe for the first time the possible clinical association between ATM (c.3747-1G>C) and familial melanoma. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site, assuming a variant that entails loss of functionality that is probably pathogenic and related to oncogenesis. However, we cannot exclude that cutaneous melanoma in both members and at an early age is the result of chance, environmental interaction, other uncontrolled external factors, or the interaction of other genetic alterations other than the ATM variant described in this study.
Social influence can shape early childhood at different levels. We explored the association between social vulnerability and lifetime caregiver alcohol use with children’s psychiatric symptoms. ...Multivariable logistic regression assessed the association between child psychiatric symptoms and social vulnerability among 1275 preschool child-caregiver pairs with lifetime caregiver alcohol used as a control variable. Of the children, 15.78% (95% CI 15.17–16.42) had internalizing symptoms, 2.49% (95% CI 2.19–2.83) had externalizing symptoms, and 9.36% (95% CI 8.88–9.86) had internalizing/externalizing symptoms. High social vulnerability was positively correlated with internalizing (aRRR 1.54; 95% CI 1.41–1.68) and internalizing/externalizing symptoms (aRRR 1.77; 95% CI 1.58–2.00). Low family support was strongly associated with internalizing/externalizing symptoms (aRRR 2.60; 95% CI 2.20–3.10). Lifetime caregiver alcohol use was positively correlated with all three psychiatric symptoms (aRRR 1.33; 95% CI 1.18–1.51; aRRR 1.13; 95% CI 1.06–1.59; and aRRR 1.26; 95% CI 1.12–1.42). Their association with children’s mental health outcomes calls for social policy changes at the macrosystem level.
Abstract
Context
Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary ...aldosteronism (PA) is unknown.
Objective
We analyzed the effect of obesity on the characteristics of PA, and the association between obesity and RAAS components.
Methods
A retrospective study was conducted of the Spanish PA Registry (SPAIN-ALDO Registry), which included patients with PA seen at 20 tertiary centers between 2018 and 2022. Differences between patients with and without obesity were analyzed.
Results
A total of 415 patients were included; 189 (45.5%) with obesity. Median age was 55 years (range, 47.3-65.2 years) and 240 (58.4%) were male. Compared to those without obesity, patients with obesity had higher rates of diabetes mellitus, chronic kidney disease, obstructive apnea syndrome, left ventricular hypertrophy, prior cardiovascular events, higher means of systolic blood pressure, and required more antihypertensive drugs. Patients with PA and obesity also had higher values of serum glucose, glycated hemoglobin A1c, creatinine, uric acid, and triglycerides, and lower levels of high-density lipoprotein cholesterol. Levels of blood aldosterone (PAC) and renin were similar between patients with and without obesity. Body mass index was not correlated with PAC nor renin. The rates of adrenal lesions on imaging studies, as well as the rates of unilateral disease assessed by adrenal vein sampling or I-6β-iodomethyl-19-norcholesterol scintigraphy, were similar between groups.
Conclusion
Obesity in PA patients involves a worse cardiometabolic profile, and need for more antihypertensive drugs but similar PAC and renin levels, and rates of adrenal lesions and lateral disease than patients without obesity. However, obesity implicates a lower rate of hypertension cure after adrenalectomy.
Soil conservation systems can achieve agricultural sustainability together with the integration and diversification of management activities, exploring the synergism of the system. The objective of ...this work was to evaluate in a temporal manner the physical attributes of the soil, under a crop-livestock-forest integration system, to verify possible contributions physical quality of the soil and system sustainability itself. The soil under study is a Typical Ultisol. The randomized block design was distributed in four respective treatments: crop-livestock integration, without the tree component (CLI), agrosilvipastoral system, with one eucalyptus (Eucalyptus ssp.) line of shading (AS1L), agrosilvipastoral system, with three eucalyptus lines of shading (AS3L), and exclusive culture of eucalyptus. The samples were collected from 2014 to 2018, in the 0-0.05, 0.05-0.1, and 0.1-0.2 m layers, to the water infiltration evaluations in soil, resistance to penetration, content of soil humidity. The results revealed that the systems that use integration improve or maintain physical quality of the soil, without compacting or negatively influencing water infiltration, highlighting the treatments CLI, AS1L e AS3L through time, which promotes its sustainability.
Preeclampsia (PE) is an often fatal pathology characterized by hypertension and proteinuria at the 20th week of gestation that affects 5-10% of the pregnancies. The problem is particularly important ...in developing countries in where the incidence of hypertensive disorders of pregnancy is higher and maternal mortality rates are 20 times higher than those reported in developed countries. Risk factors for the development of PE include obesity, insulin resistance and hyperlipidemia that stimulate inflammatory cytokine release and oxidative stress leading to endothelial dysfunction (ED). However, how all these clinical manifestations concur to develop PE is still not very well understood. The related poor trophoblast invasion and uteroplacental artery remodeling described in PE, increases reactive oxygen species (ROS), hypoxia and ED. Here we aim to review current literature from research showing the interplay between oxidative stress, ED and PE to the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation.
Objective
To analyze the evolution of the cardiometabolic profile of patients with primary hyperaldosteronism (PA) after the treatment with surgery and with mineralocorticoid receptor antagonists ...(MRA).
Design
Retrospective multicentric study of patients with PA on follow-up in twelve Spanish centers between 2018 and 2020.
Results
268 patients with PA treated by surgery (
n
= 100) or with MRA (
n
= 168) were included. At baseline, patients treated with surgery were more commonly women (54.6% vs 41.7%,
P
= 0.042), had a higher prevalence of hypokalemia (72.2% vs 58%,
P
= 0.022) and lower prevalence of obesity (37.4% vs 51.3%,
P
= 0.034) than patients treated with MRA. Adrenalectomy resulted in complete biochemical cure in 94.0% and clinical response in 83.0% (complete response in 41.0% and partial response in 42.0%). After a median follow-up of 23.6 (IQR 9.7–53.8) months, the reduction in blood pressure (BP) after treatment was similar between the group of surgery and MRA, but patients surgically treated reduced the number of antihypertensive pills for BP control more than those medically treated (∆antihypertensives: −1.3 ± 1.3 vs 0.0 ± 1.4,
P
< 0.0001) and experienced a higher increased in serum potassium levels (∆serum potassium: 0.9 ± 0.7 vs 0.6 ± 0.8mEq/ml,
P
= 0.003). However, no differences in the risk of the onset of new renal and cardiometabolic comorbidities was observed between the group of surgery and MRA (HR = 0.9 0.5–1.5,
P
= 0.659).
Conclusion
In patients with PA, MRA and surgery offer a similar short-term cardiovascular protection, but surgery improves biochemical control and reduces pill burden more commonly than MRA, and lead to hypertension cure or improvement in up to 83% of the patients.
e12541 Background: Genomic assays have facilitated the decision-making of using chemotherapy and hormone therapy when incorporated into the care of patients with early-stage breast cancer. ...Mammaprint+Blueprint have been validated as a prognostic tool in cohorts around the world. However, to date, there hasn’t been a study that addresses the use of these assays on a large Mexican population and the description of clinical characteristics associated with genomic risk. Methods: We conducted a multicenter, retrospective, descriptive study from 2012 to 2023, including women who underwent surgery, aged ≥ 18 years with tumor size less than 5 cm, hormone receptor-positive evaluated through immunochemistry (IHC), 0 to 1-3 positive lymph nodes, in early stages (I-II), who underwent the Mammaprint+Blueprint at 20 institutions in Mexico. The primary goal was to describe the clinical and genomic characteristics of these patients and calculate the discordance rate between clinical risk and genomic risk. Results: This study included 1,673 patients, with a mean age of 57 ± 11 years. Of these, 649 (39%) were classified as high-risk, and 1,024 (61%) as low-risk through MammaPrint. A discordance rate of 49% was observed in the initially clinically classified high-risk group, which was reclassified as genomic low-risk through MammaPrint. On the other hand, 33% of patients in the clinically low-risk group were reclassified as genomic high-risk. The most common molecular subtype identified through Blueprint was Luminal A (61%), and the most prevalent histologic type was ductal (79%). The predominant tumor size stage was T1 (70%), with the majority presenting with no infiltrating lymph nodes at the testing time (N0, 88%). The most common tumor grade was 2 (65%) and the proliferation rate, assessed through Ki-67, was ≥ 20% in 43% of the patients. Conclusions: Our study showed a high rate of discordance between clinical and genomic risk, a rate of 49% between clinical high-risk and genomic high-risk patients, highlighting the importance of these assays in the decision-making of breast cancer patients. This represents the first cohort to evaluate MammaPrint+BluePrint in a Latin American population. A noteworthy result was identifying a significant proportion of our cohort as low-risk through genomic assay, sparing them from the toxic effects and expenses associated with chemotherapy. Using the combined insights from MammaPrint+BluePrint along with clinical factors provides a more complete basis for predicting prognosis and benefit from specific treatments. Finally, these assays emerge as a valuable tool, particularly in middle-income countries, offering a means to improve the accurate allocation of resources in the care of their population. Due to the retrospective nature of our study, its limitations are being addressed prospectively to evaluate survival rates, distant metastasis, and recurrent cancer.
Climate change may influence the incidence of infectious diseases including those transmitted by ticks. Rhipicephalus sanguineus complex has a worldwide distribution and transmits Rickettsial ...infections that could cause high mortality rates if untreated. We assessed the potential effects of climate change on the distribution of R. sanguineus in the Americas in 2050 and 2070 using the general circulation model CanESM5 and two shared socioeconomic pathways (SSPs), SSP2-4.5 (moderate emissions) and SSP2-8.5 (high emissions). A total of 355 occurrence points of R. sanguineus and eight uncorrelated bioclimatic variables were entered into a maximum entropy algorithm (MaxEnt) to produce 50 replicates per scenario. The area under the curve (AUC) value for the consensus model (>0.90) and the partial ROC value (>1.28) indicated a high predictive capacity. The models showed that the geographic regions currently suitable for R. sanguineus will remain stable in the future, but also predicted increases in habitat suitability in the Western U.S., Venezuela, Brazil and Bolivia. Scenario 4.5 showed an increase in habitat suitability for R. sanguineus in tropical and subtropical regions in both 2050 and 2070. Habitat suitability is predicted to remain constant in moist broadleaf forests and deserts but is predicted to decrease in flooded grasslands and savannas. Using the high emissions SSP5-8.5 scenario, habitat suitability in tropical and subtropical coniferous forests and temperate grasslands, savannas, and shrublands was predicted to be constant in 2050. In 2070, however, habitat suitability was predicted to decrease in tropical and subtropical moist broadleaf forests and increase in tropical and subtropical dry broadleaf forests. Our findings suggest that the current and potential future geographic distributions can be used in evidence-based strategies in the design of control plans aimed at reducing the risk of exposure to zoonotic diseases transmitted by R. sanguineus.
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