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

Background: Rheumatoid arthritis (RA) diagnosis is a challenge in the initial phases of the disease when clinical symptoms are only starting to develop. Early diagnosis and treatment can promote long-term remission, reduce disability, and improve cardiovascular outcomes. Autoantibodies can help in the diagnosis and identification of RA patients in the early phases of the disease, but scarce information has been reported for the Mexican population.

Objective: To study anti-citrullinated peptide antibodies (anti-CCP) and anti-carbamylated protein antibodies (anti-CarP) in Mexican patients with RA and individuals at high risk of developing the disease.

Methods: Serum samples from long-standing and early RA patients, first-degree relatives (FstD) of RA patients, and healthy individuals were analyzed for anti-CCP and anti-CarP using enzyme-linked immunosorbent assay.

Results: Anti-CCP and anti-CarP levels were higher in the RA groups than in the FstD and healthy groups. The odds ratio (OR) for antiCCP for RA groups was 29.7 (95% confidence interval [CI] 14.2-61.9), significantly higher than the OR for anti-CarP 11.07 (95% CI 5.4-22.8). The sensitivity of anti-CCP was 85% (95% CI 76-93) higher than for anti-CarP (42.1%, 95% CI 31-54). The specificity of anti-CarP was 93.8% (95% CI 90-97) and the specificity of anti-CCP was 83.4% (95% CI 78-88). Using both tests in parallel increased sensitivity to 91%, while a sequential approach increased sensitivity to 98%.

Conclusion: Anti-CCP outperformed anti-CarP in Mexican RA patients, demonstrating greater sensitivity, while anti-CarP showed higher specificity. Combining these tests, either simultaneously or sequentially, could enhance diagnostic accuracy. (.

Background: MiR-155 plays a role in inflammatory pathways and cardiovascular diseases, though its relationship with inflammation, atherosclerosis, and outcomes in ST-elevation myocardial infarction (STEMI) is not well established.

Objective: To investigate associations between miR-155 levels, inflammation, atherosclerotic burden, and major adverse cardiovascular events (MACE) in STEMI patients.

Methods: Sixty-nine STEMI patients and 16 healthy controls were recruited from a specialized university-affiliated cardiovascular center. MiR-155 expression and serum interleukin (IL)-1β, IL-6, and tumor necrosis factor levels were measured. Patients were grouped into tertiles based on miR-155 expression. Clinical data, atherosclerotic burden (through cardiac catheterization), and in-hospital MACE were recorded.

Results: MiR-155 levels were significantly lower in STEMI patients compared to controls (median 54.2, vs. 152.8 arbitrary units; p = 0.003). Higher miR-155 tertiles were associated with a greater prevalence of three-vessel occlusion (34% vs. 13% vs. 4%; p = 0.007) and increased incidence of pulmonary edema (13% vs. 0% vs. 0%; p = 0.030). No significant correlation was found between miR-155 and inflammatory or myocardial markers.

Conclusion: Dysregulated miR-155 expression in STEMI patients may influence disease severity and MACE risk, independent of inflammation or myocardial damage markers.

Background: There is currently no prognostic scale for patients with Guillain-Barré syndrome (GBS) in the Mexican population.

Objective: The objective of the study was to examine the factors associated with functional prognosis by proposing short-term and long-term prognostic scales.

Methods: Prospective cohort of patients with GBS at an academic medical center, with neuroconduction study and 6-month follow-up. Through logistic regression, we evaluated clinical and paraclinical variables, and the results are expressed as odds ratios 95% confidence intervals [CIs]). We used a scale to predict poor functional prognosis. The performance of the scale was assessed using the area under the curve (AUC).

Results: A total of 259 patients (age 46.1 +- 16.1 years) were included in the study; 38.6% had a history of diarrhea, and 42.8% had an axonal variant. The rates of poor functional prognosis were 36.6% and 22.7% at 3 and 6 months of follow-up, respectively. The following variables were included in the univariate logistic regression: age >- 70 years, history of diarrhea, axonal variant, and Medical Research Council score. We performed a prognostic scale (0-9 points), with AUC of 0.81 (95% CI: 0.75-0.86) at 3 months, and 0.82 (95% CI: 0.76-0.87) at 6 months, which was higher than the modified Erasmus Guillain-Barré Outcome Score scale at admission (AUC: 0.75. 95% CI: 0.69-0.81 and AUC: 0.78. 95% CI: 0.72-0.83).

Conclusion: The proposed prognostic scale performs well in discerning poor functional prognosis in short- and long-term frames among Mexican patients.

Background: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer (BC), characterized by a dismal prognosis. Dysregulated long non-coding RNA LINC01614 might be a potential biomarker for BC as previously reported. Nevertheless, its functions and mechanism in TNBC cells are unclear.

Objectives: The study aimed to study the effects of LINC01614 on TNBC cell migration, invasion, and epithelial-mesenchymal transition (EMT) process as well as the related mechanism.

Methods: Reverse transcription quantitative polymerase chain reaction was performed to detect the expression of LINC01614 and SP1 in TNBC cells and tissues. The cellular localization of LINC01614 was determined by subcellular fraction assays. Cell counting kit-8 and Transwell invasion assays were conducted for measurement of TNBC cell viability and invasive ability. Cell migration was performed using wound healing assays and Transwell migration assays. Chromatin immunoprecipitation assays and luciferase reporter assays were used to explore the interaction between SP1 and LINC01614. Western blotting was used to assess protein levels of factors involved in EMT process and Wnt/ß-catenin signaling in TNBC cells.

Results: LINC01614 expression was elevated in TNBC tissues and cells. LINC01614 knockdown inhibited cell viability as well as migratory and invasive abilities of TNBC cells. LINC01614 knockdown also obstructed EMT process, as shown by E-cadherin upregulation and vimentin downregulation in TNBC cells. SP1 directly bound to the promoter of LINC01614 and activated LINC01614 expression. SP1 overexpression reversed the suppressive effect of LINC01614 knockdown on TNBC cell migration, invasion, and EMT process. Protein levels of Wnt and ß-catenin were diminished by LINC01614 knockdown, and the trend was partially rescued by SP1 overexpression.

Conclusion: SP1-induced LINC01614 promoted malignant behavior of TNBC cells by activating the Wnt/ß-catenin signaling pathway.

Background: The leading cause of spontaneous intracerebral hemorrhage (ICH) is hypertensive arteriolopathy. In addition to age and hypertension history, patients usually present other comorbidities that potentially increase morbimortality. Ancillary studies other than non-contrast computerized tomography (NCCT) may help clarify the diagnosis and increase the detection of potentially modifiable vascular risk factors. Unfortunately, their use is not routinely performed.

Objective: The study aimed to determine the frequency of ancillary studies performed in patients with hypertensive ICH.

Methods: We performed a retrospective analysis of three Latin American cerebrovascular registries from academic medical centers, analyzing the results with descriptive statistics focusing on diagnosis and short-term outcomes.

Results: We analyzed a total of 1,324 patients (mean age 64 years). Hypertension and obesity were the most prevalent risk factors. Only 14% underwent MRI, 10.3% extracranial ultrasonography, and 6.7% echocardiography. Among the three registries, the Latin America Stroke Registry performed more ancillary studies. Most of the patients presented a poor clinical outcome and in-hospital death.

Conclusions: The use of ancillary studies in the diagnostic workup of ICH was poor in the three registries, and mortality was high. The lack of ancillary studies performed may negatively impact outcomes.

Background: Several models have been developed to assess bleeding risk in patients with venous thromboembolism, such as HAS-BLED, but their external validity has not been adequately assessed.

Objective: The objective of the study was to evaluate the discriminative ability and calibration of the HAS-BLED scale for predicting 1-month bleeding risk in patient's anticoagulated for venous thromboembolism.

Materials and methods: External validation study of a prediction model based on a retrospective cohort of patients with venous thromboembolism treated between November 2019 and January 2022. Calibration of the HAS-BLED scale was evaluated using the Hosmer-Lemeshow test and the ratio of observed to expect events within each risk category. Discriminatory ability was assessed using the area under the curve (AUC) of a receiver operating characteristic curve.

Results: We included 735 patients (median age 64 years, female sex 55.2%), pulmonary embolism was diagnosed in most patients (60.7%), and 4.9% presented bleeding events. Regarding calibration, the HAS-BLED scale systematically underestimates the risk both in the general population (ROE 3.76, p < 0.001) and in cancer patients (ROE 4.16). The Hosmer-Lemeshow test rejected the hypothesis of adequate calibration (p < 0.001). Discriminatory ability was limited both in the general population (AUC = 0.57, 95% confidence interval [CI]: 0.48-0.66) and in the subgroup with active cancer (AUC = 0.53, 95% CI: 0.36-0.69).

Conclusion: The HAS-BLED scale in patients with venous thromboembolism underestimates the risk of bleeding at 1 month and has a low ability to discriminate high-risk patients. Cautious interpretation of the scale is recommended until additional evidence is available.

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. Curzerene is a sesquiterpene and component of Curcuma rhizomes and has anti-tumor and anti-inflammatory properties.

Objective: The study aimed to investigate the effects of curzerene on the malignant phenotypes and tumor growth in HCC.

Methods: Various concentrations of curzerene were used to treat human HCC cells (Huh7 and HCCLM3). Cell viability, apoptosis, cell cycle, invasion, and migration were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, Transwell, and wound healing assays. Cell cycle-, apoptosis-, and signaling pathway-related proteins were analyzed by Western blot analysis. A mouse xenograft model was established to analyze the anti-tumor effects of curzerene in vivo.

Results: Curzerene repressed the proliferation, invasion, and migration of Huh7 and HCCLM3 cells. Curzerene also induced G2/M cycle arrest and cell apoptosis. Curzerene downregulated the CDK1, cyclin B1, PCNA, Bcl-2, matrix metallopeptidases (MMP)2, and MMP9 protein expression and upregulated the Bax, cleaved caspase3, and cleaved poly ADPribose polymerase protein expression in HCC cells. Curzerene restrained the phosphorylation of PI3K, AKT, and the Mammalian target of rapamycin (mTOR) in Huh7 and HCCLM3 cells. The in vivo data revealed that curzerene inhibited HCC tumor growth and decreased the expression of phosphorylated mTOR in xenograft mouse models.

Conclusion: Curzerene inhibited cell malignancy in vitro and tumor growth in vivo in HCC, suggesting that curzerene may be a candidate agent for anti-HCC therapy.

Background: The 5^th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed.

Objectives: To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoidproliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated.

Materials and methods: HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data.

Results: We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related.

Conclusion: IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.