Prevalence and outcomes of upper gastrointestinal bleeding in COVID-19: A systematic review and meta-analysis.

Upper gastrointestinal bleeding (UGIB) in COVID-19 presents challenges in patient management. Existing studies lack comprehensive review due to varied designs, samples, and demographics. A meta-analysis can provide valuable insights into the incidence, features, and outcomes of UGIB in COVID-19. A comprehensive literature search was carried out using several databases. We considered all appropriate observational studies from all over the world. Mantel-Haenszel odds ratios and associated 95% confidence intervals (CIs) were produced to report the overall effect size using random effect models. Besides, Random effects models were used to calculate the overall pooled prevalence. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 21 articles consisting of 26,933 COVID-19 patients were considered. The pooled estimate of UGIB prevalence in patients admitted with COVID-19 across studies was 2.10% (95% CI, 1.23-3.13). Similarly, the overall pooled estimate for severity, mortality, and rebleeding in COVID-19 patients with UGIB was 55% (95% CI, 37.01-72.68), 29% (95% CI, 19.26-40.20) and 12.7% (95% CI, 7.88-18.42) respectively. Further, UGIB in COVID-19 patients was associated with increased odds of severity (OR = 3.52, 95% CI 1.80-6.88, P = 0.001) and mortality (OR = 2.16, 95% CI 1.33-3.51, P = 0.002) compared with patients without UGIB. No significant publication bias was evident in the meta-analysis. The results of our study indicate that UGIB in individuals with COVID-19 is linked to negative outcomes such as severe illness, higher mortality rates, and an increased risk of re-bleeding. These findings highlight the significance of identifying UGIB as a significant complication in COVID-19 cases and emphasise the importance of timely clinical assessment and proper treatment.

Prevalence and clinical outcomes of COVID-19 in patients with pre-existing celiac disease: A systematic review and meta-analysis.

There is a scarcity of scientific evidence addressing the outcomes of COVID-19 in celiac disease (CD) patients. This systematic review and meta-analysis aimed to evaluate the correlation between pre-existing CD and COVID-19. A rigorous literature search was conducted using multiple databases. All eligible observational studies were included from around the globe. The random effect model calculated the pooled prevalence and associated 95% confidence intervals (CI). Mantel-Haenszel odds ratios were produced to report the overall effect size using random effect models for severity and mortality outcomes. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 11 articles consisting of 44,378 CD patients were obtained. Overall pooled random-effects estimate of SARS-CoV-2 infection in CD patients was 4.25% (95% CI, I2  = 98%). Our findings also indicated that pre-existing CD was not associated with an increased risk of hospitalisation with COVID-19 illness (OR = 1.04, 95% CI 0.87-1.24, I2  = 0%) and mortality due to illness (OR = 0.92, 95% CI 0.56-1.5, I2  = 45%) compared with patients without pre-existing CD. No significant publication bias was evident in the meta-analysis. The preliminary data from our analysis suggest that SARS-CoV-2 infection in patients with pre-existing CD is not associated with an increased risk of hospitalisation or mortality. Additional studies are required to overcome the restrictions of the limited data available at present.

Importance about use of high-throughput sequencing in pediatric: case report of a patient with Fanconi-Bickel syndrome.

BACKGROUND: Fanconi-Bickel syndrome is characterized by hepatorenal disease caused by anomalous glycogen storage. It occurs due to variants in the SLC2A2 gene. We present a male patient of 2 years 7 months old, with failure to thrive, hepatomegaly, metabolic acidosis, hypophosphatemia, hypokalemia, hyperlactatemia. RESULTS: Exome sequencing identified the homozygous pathogenic variant NM_000340.2(SLC2A2):c.1093 C > T (p.Arg365Ter), related with Fanconi-Bickel syndrome. He received treatment with bicarbonate, amlodipine, sodium citrate and citric acid solution, enalapril, alendronate and zolendronate, and nutritional management with uncooked cornstarch, resulting in an improvement of one standard deviation in weight and height. CONCLUSIONS: The importance of knowing the etiology in rare genetic disease is essential, not only to determine individual and familial recurrence risk, but also to establish the treatment and prognosis; in this sense, access to a new genomic technology in low- and middle-income countries is essential to shorten the diagnostic odyssey.

Intramuscular Anti-D treatment for immune thrombocytopenia: A single centre experience.

Intravenous Anti-Rhesus-D immunoglobulin (Anti-D) is a first-line treatment option for immune thrombocytopenia in non-splenectomised and RhD-positive patients. In this report, we retrospectively review our experience with intramuscular (IM) Anti-D treatment in 74 adult patients between 1990 and 2018. We found that 73% of patients showed a response; almost all of them had complete responses (68.9%), and 26% achieved complete responses sustained at least 6 months after treatment discontinuation. [Correction added on 02 December 2022, after first online publication: In the preceding sentence, '(68.89%)' has been corrected to '(68.9%)' in this version.] No significant side effects were observed with no cases of acute haemolysis or anaemia reported. We conclude from this study that IM Anti-D is an effective and safe treatment for immune thrombocytopenia.

Low-risk HPLLs/ABC score patients with splenic marginal zone lymphoma can be safely managed without treatment: Results from a prospective Spanish study.

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.

The association between hypoalbuminemia and microcirculation, endothelium, and glycocalyx disorders in children with sepsis.

OBJECTIVE: The objective of this study was to evaluate the association between serum albumin levels and microcirculation changes, glycocalyx degradation, and the clinical outcomes of interest. METHODS: Observational, prospective study in children with sepsis. The primary outcome was the association between hypoalbuminemia and microcirculation disorders, endothelial activation and glycocalyx degradation using a perfused boundary region (PBR) (abnormal >2.0 µm on sublingual video microscopy) or plasma biomarkers (syndecan-1, angiopoietin-2). RESULTS: A total of 125 patients with sepsis were included. The median age was 2.0 years (IQR 0.5-12.5). Children with hypoalbuminemia had more abnormal microcirculation with a higher PBR (2.16 µm [IQR 2.03-2.47] vs. 1.92 [1.76-2.28]; p = .01) and more 4-6 µm capillaries recruited (60% vs. 40%; p = .04). The low albumin group that had the worst PBR had the most 4-6 µm capillaries recruited (rho 0.29; p < .01), 48% higher Ang-2 (p = .04), worse annexin A5 (p = 0.03) and no syndecan-1 abnormalities (p = .21). Children with hypoalbuminemia and a greater percentage of blood volume in their capillaries needed mechanical ventilation more often (56.3% vs. 43.7%; aOR 2.01 95% CI 1.38-3.10: p < .01). CONCLUSIONS: In children with sepsis, an association was found between hypoalbuminemia and microcirculation changes, vascular permeability, and greater endothelial glycocalyx degradation.

Pathogen inactivation methods to prevent transfusion-transmissible arboviruses: A systematic review and meta-analysis.

OBJECTIVE: Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different PIMs, according to the blood product they are used on and the arbovirus targeted. METHODS: Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main PIMs (amotosalen + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods. RESULTS: We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral load-mean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating Chikungunya virus, Dengue virus and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine). CONCLUSION: Not all PIMs achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the PIMs. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated PIMs and be logistically prepared to implement these techniques quickly.

Prognostic value of novel serum biomarkers, including C-reactive protein to albumin ratio and fibrinogen to albumin ratio, in COVID-19 disease: A meta-analysis.

With COVID-19 still hovering around and threatening the lives of many at-risk patients, an effective, quick, and inexpensive prognostic method is required. Few studies have shown fibrinogen to albumin ratio (FAR) and C-reactive protein to albumin ratio (CAR) to be promising as prognostic markers for COVID-19 disease. However, their implications remain unclear. This meta-analysis aimed to elucidate the prognostic role of FAR and CAR in COVID-19 disease. A systematic literature search was undertaken using PubMed and Embase till April 2022. Inverse variance standardised mean difference (SMD) was calculated to report the overall effect size using random effect models. The generic inverse variance random-effects method was used to pool the area under the curve (AUC) values. All statistical analyses were performed on Revman and MedCalc Software. A total of 23 studies were included. COVID-19 non-survivors had a higher CAR on admission compared with survivors (SMD = 1.79 [1.04, 2.55]; p < 0.00001; I2  = 97%) and patients with a severe COVID-19 infection had a higher CAR on admission than non-severe patients (SMD = 1.21 [0.54, 1.89]; p = 0.0004; I2  = 97%). Similarly, higher mean FAR values on admission were significantly associated with COVID-19 mortality (SMD = 0.55 [0.32, 0.78]; p < 0.00001; I2  = 82%). However, no significant association was found between mean FAR on admission and COVID-19 severity (SMD = 0.54 [-0.09, 1.18]; p = 0.09; I2  = 91%). The pooled AUC values found that CAR had a good discriminatory-power to predict COVID-19 severity (AUC = 0.81 [0.75, 0.86]; p < 0.00001; I2  = 80%) and mortality (AUC = 0.81 [0.74, 0.87]; p < 0.00001; I2  = 86%). FAR had a fair discriminatory-power to predict COVID-19 severity (AUC = 0.73 [0.64, 0.82]; p < 0.00001; I2  = 89%). Overall, CAR was a good predictor of both severity and mortality associated with COVID-19 infection. Similarly, FAR was a satisfactory predictor of COVID-19 mortality but not severity.

Maternal and foetal-neonatal outcomes of dengue virus infection during pregnancy.

OBJECTIVE: Given that women of reproductive age in dengue-endemic areas are at risk of infection, it is necessary to determine whether dengue virus (DENV) infection during pregnancy is associated with adverse outcomes. The aim of this systematic review and meta-analysis is to investigate the consequences of DENV infection in pregnancy on various maternal and foetal-neonatal outcomes. METHODS: A systematic literature search was undertaken using PubMed, Google Scholar, and Embase till December 2021. Mantel-Haenszel risk ratios were calculated to report overall effect size using random effect models. The pooled prevalence was computed using the random effect model. All statistical analyses were performed on MedCalc Software. RESULT: We obtained data from 36 studies involving 39,632 DENV-infected pregnant women. DENV infection in pregnancy was associated with an increased risk of maternal mortality (OR = 4.14 [95% CI, 1.17-14.73]), stillbirth (OR = 2.71 [95% CI, 1.44-5.10]), and neonatal deaths (OR = 3.03 [95% CI, 1.17-7.83]) compared with pregnant women without DENV infection. There was no significant statistical association established between maternal DENV infection and the outcomes of preterm birth, maternal bleeding, low birth weight in neonates, and risk of miscarriage. Pooled prevalences were 14.9% for dengue shock syndrome, 14% for preterm birth, 13.8% for maternal bleeding, 10.1% for low birth weight, 6% for miscarriages, and 5.6% for stillbirth. CONCLUSION: DENV infection in pregnant women may be associated with adverse outcomes such as maternal mortality, stillbirth, and neonatal mortality. Hence, pregnant women should be considered an at-risk population for dengue management programmes.

Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19.

INTRODUCTION: Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. METHODS: This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, ß2 microglobulin and albumin levels pre/post-dialysis and on 1st-2nd week. We compared levels among both techniques and control group (HD without COVID-19). RESULTS: We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and ß2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. DISCUSSION: Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. CONCLUSION: HDx appears to provide better clearance for TNFα and ß2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

Antiretroviral Therapy-Induced Dysregulation of Gene Expression and Lipid Metabolism in HIV+ Patients: Beneficial Role of Antioxidant Phytochemicals.

Human immunodeficiency virus (HIV) infection has continued to be the subject of study since its discovery nearly 40 years ago. Significant advances in research and intake of antiretroviral therapy (ART) have slowed the progression and appearance of the disease symptoms and the incidence of concomitant diseases, which are the leading cause of death in HIV+ persons. However, the prolongation of ART is closely related to chronic degenerative diseases and pathologies caused by oxidative stress (OS) and alterations in lipid metabolism (increased cholesterol levels), both of which are conditions of ART. Therefore, recent research focuses on using natural therapies to diminish the effects of ART and HIV infection: regulating lipid metabolism and reducing OS status. The present review summarizes current information on OS and cholesterol metabolism in HIV+ persons and how the consumption of certain phytochemicals can modulate these. For this purpose, MEDLINE and SCOPUS databases were consulted to identify publications investigating HIV disease and natural therapies and their associated effects.

Maple syrup urine disease: Characteristics of diagnosis and treatment in 45 patients in Chile.

Maple urine syrup disease (MSUD) is an autosomal recessive disorder characterized by deficient activity of the branched-chain alpha ketoacid dehydrogenase (BCKAD) enzymatic complex due to biallelic variants in the alpha (BCKDHA) or beta (BCKDHB) subunits or the acyltransferase component (DBT). Treatment consists in leucine (LEU), isoleucine (ILE), and valine (VAL) (branched-chain amino acids) dietary restriction and strict metabolic control. to determine the characteristics of the Chilean cohort with MSUD currently in follow-up at Instituto de Nutrición y Tecnología de los Alimentos, during the 1990-2017 period Retrospective analytical study in 45 MSUD cases. Measured: biochemical parameters (LEU, ILE, and VAL), anthropometric evaluation, and neurocognitive development. In 18 cases undergoing genetic study were analyzed according to the gene and protein location, number of affected alleles, and type of posttranslational modification affected. Then, 45 patients with MSUD diagnosis were identified during the period: 37 were alive at the time of the study. Average diagnosis age was 71 ± 231 days. Average serum diagnosis LEU concentrations: 1.463 ± 854.1 µmol/L, VAL 550 ± 598 µmol/L and ILE 454 ± 458 µmol/L. BCKDHB variants explain 89% cases, while BCKDHA and DBT variants explain 5.5% of cases each. Variants p.Thr338Ile in BCKDHA, p.Pro240Thr and p.Ser342Asn in BCKDHB have not been previously reported in literature. Average serum follow-up LEU concentrations were 252.7 ± 16.9 µmol/L in the <5 years group and 299 ± 123.2 µmol/L in ≥5 years. Most cases presented some degree of developmental delay. Early diagnosis and treatment is essential to improve the long-term prognosis. Frequent blood LEU measurements are required to optimize metabolic control and to establish relationships between different aspects analyzed.

Small bowel occlusion secondary to a giant abdominal solitary fibrous tumor.

A 30-year-old male with no medical history was admitted to the hospital with abdominal pain, vomiting, and inability to pass gas through the rectum. In the physical examination a non-mobile, smooth, firm mass was palpated in the lower abdominal quadrants. An abdominal mass was detected by a CT scan. Thus, the patient underwent laparotomy and the mass was excised together with a bowel segment, and a terminal anastomosis was performed. No peritoneal or liver seeding was observed, and the patient recovered uneventfully.

Risk transfer from a megacity to a peri-urban agricultural community: wastewater reuse and effects on groundwater quality.

Urban wastewater is a resource that can be reused, but its management must be carefully executed, considering its potential impact on public and environmental health. Unfortunately, marked differences in the quality of treatment, management, collection, and the monitoring of wastewater exist among low-, middle-, and high-income countries. This is the case of the Mezquital Valley, a semi-rural area that is composed of agricultural and industrial communities on the outskirts of Mexico City. For over 100 years, wastewater from Mexico City and its areas of conurbation has been sent to the Mezquital Valley, with few studies having been conducted to assess the existence and severity of bacterial and pathogen infiltration into the local aquifer. In this research, we present an assessment of wastewater infiltration transported from Mexico City, used for irrigation, with potential infiltration into the Mezquital Valley aquifer. We utilized stable isotope analysis of deuterium and oxygen-18 to determine whether a mixture of untreated wastewater from the Mexico City Metropolitan Area (MCMA) flows into the Mezquital aquifer. Also, tests for adenovirus, rotavirus, fecal coliform, fecal enterococci, Giardia lamblia, and Cryptosporidium parvum were employed to determine the presence of fecal indicators and pathogens in different water sources in the study area. The results show the presence of indicators and pathogens in local wells used as water supply in Mezquital Valley. The presence of such indicators suggests that pathogens can reach the water consumed by the inhabitants, posing a hazard to persons exposed to these waters during their normal daily-life activities.

Prevalence of viral load suppression, predictors of virological failure and patterns of HIV drug resistance after 12 and 48 months on first-line antiretroviral therapy: a national cross-sectional survey in Uganda.

OBJECTIVES: We implemented the WHO cross-sectional survey protocol to determine rates of HIV viral load (VL) suppression (VLS), and weighted prevalence, predictors and patterns of acquired drug resistance (ADR) in individuals with virological failure (VF) defined as VL ≥1000 copies/mL. METHODS: We enrolled 547 and 1064 adult participants on first-line ART for 12 (±3) months (ADR12) and ≥48 months (ADR48), respectively. Dried blood spots and plasma specimens were collected for VL testing and genotyping among the VFs. RESULTS: VLS was 95.0% (95% CI 93.4%-96.5%) in the ADR12 group and 87.9% (95% CI 85.0%-90.9%) in the ADR48 group. The weighted prevalence of ADR was 96.1% (95% CI 72.9%-99.6%) in the ADR12 and 90.4% (95% CI 73.6-96.8%) in the ADR48 group, out of the 30 and 95 successful genotypes in the respective groups. Initiation on a zidovudine-based regimen compared with a tenofovir-based regimen was significantly associated with VF in the ADR48 group; adjusted OR (AOR) 1.96 (95% CI 1.13-3.39). Independent predictors of ADR in the ADR48 group were initiation on a zidovudine-based regimen compared with tenofovir-based regimens, AOR 3.16 (95% CI 1.34-7.46) and ART duration of ≥82 months compared with <82 months, AOR 1.92 (95% CI 1.03-3.59). CONCLUSIONS: While good VLS was observed, the high prevalence of ADR among the VFs before they underwent the recommended three intensive adherence counselling (IAC) sessions followed by repeat VL testing implies that IAC prior to treatment switching may be of limited benefit in improving VLS.

Epstein-Barr virus-induced gene 3 (EBI3) single nucleotide polymorphisms and their association with central obesity and risk factors for cardiovascular disease: The GEA study.

Obesity, a chronic low-grade inflammation metabolic abnormality, is related to high proinflammatory cytokines concentrations. Epstein-Barr virus-induced gene 3 (EBI3) encodes for the EBI3 beta subunit that constitutes interleukin (IL) 27 and 35. Our objective was to assess the association of three EBI3 single nucleotide polymorphisms (SNPs) with the presence of central obesity in a group of Mexican subjects. The rs428253, rs4740, and rs4905 EBI3 SNPs were genotyped in 1323 individuals (1092 central obese and 231 non-central obese). We also analyzed IL-6, IL-27, and IL-35 concentrations. Under different models, the rs4740 (OR = 0.384, Precessive = 0.010; OR = 0.404, Pcodominant 2 = 0.019) and rs4905 (OR = 0.380, Precessive = 0.009; OR = 0.404, Pcodominant 2 = 0.018) were related with a low risk of central obesity. In central obese subjects, the SNPs were related to lower risk of hypoalphalipoproteinemia (rs4740) and with high IL-6 concentrations (rs428253, rs4740, and rs4905), whereas in non-central obese individuals, the rs428253 was related with low risk of increased visceral abdominal fat and hypertriglyceridemia. Interleukin-6, IL-27 and IL-35 concentrations were similar in both groups and no relation was noticed with the studied genotypes. Our results suggest an association of EBI3 SNPs with a low risk of central obesity and with a few risk factors for cardiovascular disease in individuals with and without central obesity.

Chia (Salvia hispanica)-supplemented diet ameliorates non-alcoholic fatty liver disease and its metabolic abnormalities in humans.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a public health problem lacking an approved pharmacological treatment. Omega-3 fatty acids have shown to reverse NAFLD. Chia is a seed rich in α-linolenic acid (ALA), antioxidants, and fiber; therefore, it could be useful to treat NAFLD. METHODS: In a single arm experimental design study, the effect of 25 g/day of milled chia was assessed in 25 patients with NAFLD. After two weeks of dietary stabilization (basal condition) and eight weeks of a chia-supplemented isocaloric diet, liver:spleen attenuation index and visceral abdominal fat (VAF) were measured by computed tomography. Lipids, lipoproteins, free fatty acids (FFA), and ALA plasma concentrations were also determined. RESULTS: Dietary chia supplementation induced an increase in plasma ALA concentration (75%) and dietary fiber (55%) consumption. After chia supplementation, VAF (9%), body weight (1.4%), total cholesterol (2.5%), non-high density lipoprotein cholesterol (3.2%), and circulating FFA (8%) decreased. Furthermore, NAFLD regressed in 52% of the treated patients (P < 0.05 for all). CONCLUSIONS: The results of the present study show that 25 g/day of milled chia ameliorates NAFLD. Chia is an accessible vegetal source of omega-3 fatty acids, antioxidants, and fiber, which could have the potential to prevent metabolic abnormalities in NAFLD patients. Considering that there is no pharmacological treatment approved for NAFLD, the findings of the present study suggest that a chia-supplemented diet could be an innovative alternative to control this disease. RETROSPECTIVELY REGISTERED: https://clinicaltrials.gov/show/NCT03942822.

CORONARY ARTERY CALCIUM IS ASSOCIATED WITH LPA GENE VARIANT RS7765803-C IN MEXICAN MESTIZO POPULATION. THE GEA PROJECT.

BACKGROUND: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. METHODS: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. RESULTS: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. CONCLUSIONS: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

[New mutation in FOXP3 gene identified in an infant with chronic diarrhea as manifestation of autoinmune enteropathy - IPEX syndrome]. / Nueva mutación identificada en el gen FOXP3 en lactante menor con diarrea crónica como manifestación de enteropatía autoinmune - Síndrome IPEX.

INTRODUCTION: The IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syn drome is caused by the mutations of the FOXP3 gene, characterized by persistent diarrhea, endo crine disorders, and dermatitis. The treatment is the administration of immunosuppressive drugs, where hematopoietic stem cell transplantation is the only potential cure. OBJECTIVE: To describe a new FOXP3 gene mutation, as well as the findings and evolution of a patient with IPEX syndrome. CLINICAL CASE: Male infant presenting at one month of age with chronic diarrhea, intestinal failure, and recurrent infections. Lab tests and intestinal biopsy suggested autoimmune enteropathy. During follow-up, the patient presented resistance to immunosuppressive treatment with corticosteroids, cyclosporine, and tacrolimus, dying at 7 months of age due to vascular complications. He had a ma ternal family history of multiple deaths of men under 1 year of age. IPEX syndrome was suspected therefore a trio whole-exome sequencing was performed that showed a probably pathogenic FOXP3 gene mutation. CONCLUSION: A new FOXP3 gene mutation is reported in a patient with IPEX syndro me. Despite the low prevalence of this disease, it is important to recognize non-specific but suggestive symptoms for its diagnosis.

Mesenchymal stromal cell-derived exosomes improve mitochondrial health in pulmonary arterial hypertension.

Secreted exosomes are bioactive particles that elicit profound responses in target cells. Using targeted metabolomics and global microarray analysis, we identified a role of exosomes in promoting mitochondrial function in the context of pulmonary arterial hypertension (PAH). Whereas chronic hypoxia results in a glycolytic shift in pulmonary artery smooth muscle cells (PASMCs), exosomes restore energy balance and improve O2 consumption. These results were confirmed in a hypoxia-induced mouse model and a semaxanib/hypoxia rat model of PAH wherein exosomes improved the mitochondrial dysfunction associated with disease. Importantly, exosome exposure increased PASMC expression of pyruvate dehydrogenase (PDH) and glutamate dehydrogenase 1 (GLUD1), linking exosome treatment to the TCA cycle. Furthermore, we show that although prolonged hypoxia induced sirtuin 4 expression, an upstream inhibitor of both GLUD1 and PDH, exosomes reduced its expression. These data provide direct evidence of an exosome-mediated improvement in mitochondrial function and contribute new insights into the therapeutic potential of exosomes in PAH.