Revista De Investigacion Clinica-Clinical and Translational Investigation最新文献

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), triggers a pathophysiological process linked not only to viral mechanisms of infectivity, but also to the pattern of host response. Drug repurposing is a promising strategy for rapid identification of treatments for SARS-CoV-2 infection, and several attractive molecular viral targets can be exploited. Among those, 3CL protease is a potential target of great interest.

Objective: The objective of the study was to screen potential 3CLpro inhibitors compounds based on chemical fingerprints among anti-inflammatory, anticoagulant, and respiratory system agents.

Methods: The screening was developed based on a drug property prediction framework, in which the evaluated property was the ability to inhibit the activity of the 3CLpro protein, and the predictions were performed using a dense neural network trained and validated on bioassay data.

Results: On the validation and test set, the model obtained area under the curve values of 98.2 and 76.3, respectively, demonstrating high specificity for both sets (98.5% and 94.7%). Regarding the 1278 compounds screened, the model indicated four anti-inflammatory agents, two anticoagulants, and one respiratory agent as potential 3CLpro inhibitors.

Conclusions: Those findings point to a possible desirable synergistic effect in the management of patients with COVID-19 and provide potential directions for in vitro and in vivo research, which are indispensable for the validation of their results.

A large world population resides at moderate altitude. In the Valley of Mexico (2,240 m above sea level), its inhabitants, breathe approximately 29% more on average and have 10% increased hemoglobin concentrations compared to sea level residents, among other differences. These compensations reduce but not eliminate the impact of altitude hypoxemia. The objective of the manuscript is to review and describe the information available on health and disease at moderate altitudes, mainly with data in Spanish language from Latin-American countries. Young adults in Mexico City have an SaO2 between 92% and 94% versus 97% at sea level, frequently decreasing below 90% during sleep and intense exercise. It is likely that among the population living at this altitude, lung growth, and development during pregnancy and infancy are enhanced, and that after residing for several tens of thousands of years, more important adaptations in oxygen transport and utilization have developed, but we are not certain about it. For patients with respiratory diseases, residing at moderate altitudes implies increased hypoxemia and clinical deterioration, unless supplementary oxygen is prescribed or patients move to sea level. Hyperventilation increases exposure of residents to air pollutants compared to those living in cities with similar concentrations of pollutants, although at sea level. Humans evolved at sea level and lack the best-known adaptations to reside at moderate or high altitudes. Residents of moderate altitudes breathe deeply the city´s air with all its pollutants, and more often require supplementary oxygen.

Background: People living with HIV are at increased risk of cardiovascular disease. Cardiovascular risk (CVR) prediction scores are powerful tools for individualized assessment that inform decision-making about follow-up frequency, hypolipemiant treatment intensification, and choice antiretroviral therapy.

Objectives: The objectives of the study were to evaluate the performance of multiple cardiovascular assessment scores in predicting major adverse cardiovascular events (MACE) at 5 and 10 years. Framingham (2004, 2008, and Colombia-adjusted), SCORE, PROCAM, ASCVD, and D:A:D scores were included in the analysis.

Methods: Data were obtained from a medical registry of adults living with HIV attended by a teaching hospital in Colombia. All patients with complete information necessary for risk score calculations and determination of MACE at 5 and 10 years were included in the study. Receiver operating characteristic curves (ROC) were generated using calculations with all the aforementioned models for every individual. Differences between curves were compared with De- Long's test.

Results: A total of 808 patients were included in the analysis. Mean age was 35 years, and 12% were female. The majority of subjects had low and very low CVR. Eight MACE occurred during follow-up. Area under ROC curves were: Framingham (0.90), Framingham ATP3 (0.92), Framingham calibrated for Colombia (0.90), SCORE (0.92), PROCAM (0.92), ASCVD (0.89), and D:A:D (0.92), with no statistically significant differences.

Conclusions: The evaluated scores had an acceptable performance for HIV-infected patients in the studied cohort, especially for those in low and very low risk categories.

Background: CTHRC1 is highly expressed in various cancers.

Objectives: The aim of the study was to study the role of CTHRC1 played in lung adenocarcinoma (LUAD) development and its underlying biological functions.

Methods: Enriched pathways and upstream transcription factors of CTHRC1 were explored by bioinformatics analysis. Dual-luciferase assay and Chromatin immunoprecipitation assay were used to verify the binding relationship between CTHRC1 and HOXB9. CCK-8 was utilized to detect cell viability. Expression levels of CTHRC1, HOXB9, and angiogenesis-related genes were assessed by quantitative real time-polymerase chain reaction. Angiogenesis assay was used to detect angiogenesis ability. Quantitative analysis of metabolites were used to detect the accumulation of neutral lipids, the levels of free fatty acids (FAs), and glycerol. Western blot was conducted to measure expression of metabolic enzymes of FA.

Results: CTHRC1 was enriched in FA metabolic pathway, which was positively correlated and bound with HOXB9. CTHRC1 and HOXB9 expression was remarkably up-regulated in LUAD cells. Overexpression of CTHRC1 promoted FA metabolic pathway and angiogenesis, and FA inhibitor Orlistat restored it to NC group level. Meanwhile, CTHRC1 affected LUAD angiogenesis by activating HOXB9 to regulate FA metabolism.

Conclusions: This study found that activation of CTHRC1 by HOXB9 induces angiogenesis by mediating FA metabolism. CTHRC1 may be a potential target for LUAD diagnosis.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening.

Objectives: The objective of the study was to study TL changes in patients at early disease onset and after follow-up.

Methods: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant.

Results: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001).

Conclusions: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.

Background: Relatively low SARS-CoV-2 reinfection rates have been reported in vaccinated individuals, but updates considering the Omicron variant are lacking.

Objectives: The objective of the study was to provide a current estimate of the SARS-CoV-2 reinfection rate in a highly immunized population.

Methods: A prospective cohort of Mexican hospital workers was followed (March 2020-February 2022). Reinfection was defined as the occurrence of two or more episodes of COVID-19 separated by a period of ≥ 90 days without symptoms. The reinfection rate was calculated as the number of reinfection episodes per 100,000 persons per day.

Results: A total of 3732 medical consultations were provided to 2700 workers, of whom 1388 (51.4%) were confirmed COVID-19 cases. A total of 73 reinfection cases were identified, of whom 71 (97.3%) had completed their primary vaccination series and 22 (30.1%) had had a booster dose before the second episode. The overall reinfection rate was 23.1 per 100,000 persons per day (as compared to a rate of 1.9 per 100,000 persons per day before the Omicron wave).

Conclusions: The SARS-CoV-2 reinfection rate rose significantly during the Omicron wave despite a high primary vaccination coverage rate. Almost one-third of reinfected workers had a vaccine booster ≥ 14 days before the last COVID-19 episode.

Abstract: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a wide range of clinical presentations. Lupus nephritis (LN) is a frequent complication of SLE, representing a significant cause of morbidity and mortality in these patients. In addition, LN diagnosis remains suboptimal in most clinical contexts. The current gold standard for LN clinical diagnosis is a renal biopsy. Still, the invasiveness of this technique is an obstacle to the early detection of renal involvement and further monitoring of treatment results. Consequently, there are different areas for improvement in the field of LN, such as the search for novel non-invasive clinical biomarkers with an adequate correlation between clinical manifestations and actual histological damage. Although urine component-related studies are promising, the more robust blood/serum biomarkers may still be helpful in developing point-of-care systems that can be adapted to most clinical scenarios. Therefore, this brief review aims to highlight and summarize some of the most recently reported non-classical serum/blood potential LN biomarkers. (Rev Invest Clin. 2022;74(5):227-31).

Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with chronic kidney disease vulnerable to suffering more severe COVID-19 disease and worse outcomes have been identified.

Objectives: Our study's aim was to determine the incidence, characteristics, and outcomes of SARS-CoV-2 infection in patients of hemodialysis (HD) units in Mexico and to describe the availability of confirmatory testing.

Methods: This study was multicentric study of 19 HD units, conducted between March 2020 and March 2021.

Results: From a total of 5779 patients, 955 (16.5%) cases of suspicious COVID-19 were detected; a SARS-CoV-2 reverse transcription polymerase chain reaction test was done in only 50.6% of patients. Forty-five percentages were hospitalized and 6% required invasive mechanical ventilation (IMV). There was no significant difference in mortality between confirmed (131/483) and suspicious (124/472) cases (p = 0.74). The percentage of patients in need of hospitalization, IMV, and deceased was greater than in the rest of the study population.

Conclusions: The study revealed that 49.4% of the cases were not confirmed, a worrisome observation given that this is a highly vulnerable population (higher probability of contagion and worse outcomes), in which 100% of patients should have a confirmatory test.

Background: While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date.

Objectives: The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF.

Methods: In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction < 50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals.

Results: In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p < 0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF.

Conclusions: These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia. (Rev Invest Clin. 2022;74(5):276-83).

Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied.

Objectives: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19.

Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed.

Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01).

Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV. (Rev Invest Clin. 2022;74(5):268-75).