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A cancer mass is composed of a heterogeneous group of cells, a small part of which constitutes the cancer stem cells since they are less differentiated and have a high capacity to develop cancer. Versican is an extracellular matrix protein located in many human tissues. The mRNA of versican has been shown to have "splicing patterns" as detected by RT-PCR, northern blot analysis, and cDNA sequencing. Based on this knowledge this study aims to reveal the splice variants of versican molecules, which are thought to be involved in the pathogenesis of the DU-145 human prostatic carcinoma cell line and prostatic cancer stem cells isolated from this cell line. In this study, RWPE-1 normal prostatic and DU-145 human prostate cancer cell lines have been used. Prostatic cancer stem cells and the remaining group of non-prostatic-cancer stem cells (bulk population) were isolated according to their CD133+/CD44+. RNA was isolated in all groups, and sequence analysis was accomplished for splicing variants by Illumina NextSeq 500 sequencing system. The results were analyzed by bioinformatic evaluation. As five isoforms of the versican gene in the differential transcript expression are analyzed, it was observed that a significant change was only found in the isoforms Versican 0 and Versican 1. In this study, we explored the function of this molecule which we think to be effective in cancer progression, and suggested that more valuable results can be obtained after the accomplishment of in vivo experiments.
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Antígeno AC133 , Receptores de Hialuranos , Células Madre Neoplásicas , Neoplasias de la Próstata , Versicanos , Humanos , Versicanos/genética , Versicanos/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Masculino , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genética , Antígeno AC133/metabolismo , Antígeno AC133/genética , Línea Celular Tumoral , Empalme Alternativo , Isoformas de ProteínasRESUMEN
Yin yang 1 (YY1), a transcription factor, plays crucial roles in cell fate specification, differentiation, and pluripotency during embryonic development. It is also involved in tumorigenesis, drug resistance, metastasis, and relapse caused by cancer stem cells (CSCs), particularly in prostate cancer (PCa). Targeting YY1 could potentially eliminate prostate CSCs (PCSCs) and provide novel therapeutic approaches. PCa tissues often exhibit elevated YY1 expression levels, especially in high-grade cases. Notably, high-grade PCa tissues from 58 PCa patients and CD133high/CD44high PCSCs isolated from DU145 PCa cell line by FACS both showed significantly increased YY1 expression as observed through immunofluorescence staining, respectively. To investigate the embryonic microenvironment impact on YY1 expression in CSC populations, firstly PCSCs were microinjected into the inner cell mass of blastocysts and then PCSCs were co-cultured with blastocysts. Next Generation Sequencing was used to analyze alterations in YY1 and related gene expressions. Interestingly, exposure to the embryonic microenvironment significantly reduced the expressions of YY1, YY2, and other relevant genes in PCSCs. These findings emphasize the tumor-suppressing effects of the embryonic environment by downregulating YY1 and YY1-related genes in PCSCs, thus providing promising strategies for PCa therapy. Through elucidating the mechanisms involved in embryonic reprogramming and its effects on YY1 expression, this research offers opportunities for further investigation into focused therapies directed against PCSCs, therefore enhancing the outcomes of PCa therapy. As a result, PCa tumors may benefit from YY1 and associated genes as a novel therapeutic target.
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Células Madre Neoplásicas , Neoplasias de la Próstata , Factor de Transcripción YY1 , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Microambiente Tumoral , Línea Celular Tumoral , AnimalesRESUMEN
How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.
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Cadenas HLA-DRB1 , Humanos , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Lactante , Población Negra/genética , Vacunas contra Hepatitis B/inmunología , Sitios de Carácter Cuantitativo , Masculino , Femenino , Uganda , Formación de Anticuerpos/genética , Formación de Anticuerpos/inmunología , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/genética , Vacunación , Tos Ferina/prevención & control , Tos Ferina/inmunología , Tos Ferina/genéticaRESUMEN
Genetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities to functionally map genetic vulnerabilities. Here, we construct a second-generation map of cancer dependencies by annotating 930 cancer cell lines with multi-omic data and analyze relationships between molecular markers and cancer dependencies derived from CRISPR-Cas9 screens. We identify dependency-associated gene expression markers beyond driver genes, and observe many gene addiction relationships driven by gain of function rather than synthetic lethal effects. By combining clinically informed dependency-marker associations with protein-protein interaction networks, we identify 370 anti-cancer priority targets for 27 cancer types, many of which have network-based evidence of a functional link with a marker in a cancer type. Mapping these targets to sequenced tumor cohorts identifies tractable targets in different cancer types. This target prioritization map enhances understanding of gene dependencies and identifies candidate anti-cancer targets for drug development.
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Pruebas Genéticas , Neoplasias , Humanos , Fenotipo , Descubrimiento de Drogas , Neoplasias/genética , Neoplasias/patología , Línea Celular Tumoral , Sistemas CRISPR-CasRESUMEN
Mapping the functional human genome and impact of genetic variants is often limited to European-descendent population samples. To aid in overcoming this limitation, we measured gene expression using RNA sequencing in lymphoblastoid cell lines (LCLs) from 599 individuals from six African populations to identify novel transcripts including those not represented in the hg38 reference genome. We used whole genomes from the 1000 Genomes Project and 164 Maasai individuals to identify 8,881 expression and 6,949 splicing quantitative trait loci (eQTLs/sQTLs), and 2,611 structural variants associated with gene expression (SV-eQTLs). We further profiled chromatin accessibility using ATAC-Seq in a subset of 100 representative individuals, to identity chromatin accessibility quantitative trait loci (caQTLs) and allele-specific chromatin accessibility, and provide predictions for the functional effect of 78.9 million variants on chromatin accessibility. Using this map of eQTLs and caQTLs we fine-mapped GWAS signals for a range of complex diseases. Combined, this work expands global functional genomic data to identify novel transcripts, functional elements and variants, understand population genetic history of molecular quantitative trait loci, and further resolve the genetic basis of multiple human traits and disease.
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HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.
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ADN Helicasas , Proteínas de Unión al ADN , Variación Genética , Infecciones por VIH , VIH-1 , Carga Viral , Humanos , Línea Celular , ADN Helicasas/genética , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Infecciones por VIH/genética , VIH-1/crecimiento & desarrollo , VIH-1/fisiología , Carga Viral/genética , África , Cromosomas Humanos Par 1/genética , Alelos , ARN Largo no Codificante/genética , Replicación ViralRESUMEN
MOTIVATION: Identifying and prioritizing disease-related proteins is an important scientific problem to develop proper treatments. Network science has become an important discipline to prioritize such proteins. Multiple sclerosis, an autoimmune disease for which there is still no cure, is characterized by a damaging process called demyelination. Demyelination is the destruction of myelin, a structure facilitating fast transmission of neuron impulses, and oligodendrocytes, the cells producing myelin, by immune cells. Identifying the proteins that have special features on the network formed by the proteins of oligodendrocyte and immune cells can reveal useful information about the disease. RESULTS: We investigated the most significant protein pairs that we define as bridges among the proteins providing the interaction between the two cells in demyelination, in the networks formed by the oligodendrocyte and each type of two immune cells (i.e. macrophage and T-cell) using network analysis techniques and integer programming. The reason, we investigated these specialized hubs was that a problem related to these proteins might impose a bigger damage in the system. We showed that 61%-100% of the proteins our model detected, depending on parameterization, have already been associated with multiple sclerosis. We further observed the mRNA expression levels of several proteins we prioritized significantly decreased in human peripheral blood mononuclear cells of multiple sclerosis patients. We therefore present a model, BriFin, which can be used for analyzing processes where interactions of two cell types play an important role. AVAILABILITY AND IMPLEMENTATION: BriFin is available at https://github.com/BilkentCompGen/brifin.
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Esclerosis Múltiple , Humanos , Leucocitos Mononucleares , Oligodendroglía/fisiología , Neuronas , Vaina de MielinaRESUMEN
A limitation of pooled CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes arising from copy-number-amplified genomics regions. To solve this issue, we previously developed CRISPRcleanR: a computational method implemented as R/python package and in a dockerized version. CRISPRcleanR detects and corrects biased responses to CRISPR-Cas9 targeting in an unsupervised fashion, accurately reducing false-positive signals while maintaining sensitivity in identifying relevant genetic dependencies. Here, we present CRISPRcleanR WebApp , a web application enabling access to CRISPRcleanR through an intuitive interface. CRISPRcleanR WebApp removes the complexity of R/python language user interactions; provides user-friendly access to a complete analytical pipeline, not requiring any data pre-processing and generating gene-level summaries of essentiality with associated statistical scores; and offers a range of interactively explorable plots while supporting a more comprehensive range of CRISPR guide RNAs' libraries than the original package. CRISPRcleanR WebApp is available at https://crisprcleanr-webapp.fht.org/.
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Sistemas CRISPR-Cas , Genoma , Sistemas CRISPR-Cas/genética , Genómica/métodos , Programas InformáticosRESUMEN
Interferon-γ (IFN-γ) signaling mediates host responses to infection, inflammation and anti-tumor immunity. Mutations in the IFN-γ signaling pathway cause immunological disorders, hematological malignancies, and resistance to immune checkpoint blockade (ICB) in cancer; however, the function of most clinically observed variants remains unknown. Here, we systematically investigate the genetic determinants of IFN-γ response in colorectal cancer cells using CRISPR-Cas9 screens and base editing mutagenesis. Deep mutagenesis of JAK1 with cytidine and adenine base editors, combined with pathway-wide screens, reveal loss-of-function and gain-of-function mutations, including causal variants in hematological malignancies and mutations detected in patients refractory to ICB. We functionally validate variants of uncertain significance in primary tumor organoids, where engineering missense mutations in JAK1 enhanced or reduced sensitivity to autologous tumor-reactive T cells. We identify more than 300 predicted missense mutations altering IFN-γ pathway activity, generating a valuable resource for interpreting gene variant function.
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Neoplasias Hematológicas , Neoplasias , Humanos , Interferón gamma/genética , Interferón gamma/metabolismo , Edición Génica , Neoplasias/genética , Mutación , Transducción de Señal/genética , Sistemas CRISPR-CasRESUMEN
BACKGROUND: Data on intoxication patients with shock and acute organ failure is valuable for the prediction of the tailored scale prognosis of the patients in the emergency department. METHODS: : Our study was designed prospectively as a cross-sectional and observational over the course of four years. The patients over 18 years of age were included and the epidemiological data related to development of shock and acute organ failure, the treatments, and the outcome were recorded. The organic phosphate severity score was also calculated for all patients. RESULTS: A total of 89 patients with shock and/or acute organ failure 72 (80.9%) of the patients were males. Methanol (51 patients, 57.3%) was the most common cause of intoxications followed by cardiovascular agents. Thirty (33.7%) patients died despite all treatments and mortality was found to be higher in patients with hypotension (p = 0.031) at the time of admission to the emergency department and in those with a high organic phosphate poisoning severity index (p = 0.001). High levels of WBC, creatine, lactate, base excess and low bicarbonate and blood pH were associated with mortality. The discharge rates of patients who received extracorporeal treatment were statistically higher than those who did not receive this treatment (p = 0.001). DISCUSSION: The organic phosphate poisoning severity score can partially help us to predict the prognosis in all poisoning patients at the time of the first presentation. Emergency physicians may consider the development of hypotension, high creatine, lactate, base excess, low bicarbonate, and blood pH to be associated with a poor prognosis in the first hours of admission in acute poisoning patients. In these patients, it was predicted that the addition of selected extracorporeal methods without delay, in addition to the treatments that should be applied, may increase the survival rate.
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Hipotensión , Choque , Masculino , Humanos , Adolescente , Adulto , Femenino , Bicarbonatos , Estudios Transversales , Creatina , Ácido LácticoRESUMEN
Objectives: In this study, we aimed to investigate whether quality of life (QoL) before intensive care unit (ICU) admission could predict ICU mortality in critically ill patients. Patients and methods: Between January 2019 and April 2019, a total of 105 ICU patients (54 males, 51 females; mean age: 58 years; range, 18 to 91 years) from two ICUs of a tertiary care hospital were included in this cross-sectional, prospective study. Pre-admission QoL was measured by the Short Form (SF)-12- Physical Component Scores (PCS) and Mental Component Scores (MCS) and EuroQoL five-dimension, five-level scale (EQ-5D-5L) within 24 h of ICU admission and mortality rates were estimated. Results: The overall mortality rate was 28.5%. Pre-admission QoL was worse in the non-survivors independent from age, sex, socioeconomic and education status, and comorbidities. During the hospitalization, the rate of sepsis and ventilator/hospital-acquired pneumonia were similar among the two groups (p>0.05). Logistic regression analysis adjusted for sex, age, education status, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores showed that pre-admission functional status as assessed by the SF-12 MCS (odds ratio [OR]: 14,2; 95% confidence interval [CI]: 2.5-79.0), SF-12 PCS (OR: 10.6; 95% CI: 1.8-62.7), and EQ-5D-5L (OR: 8.0; 95% CI: 1.5-44.5) were found to be independently associated with mortality. Conclusion: Worse pre-admission QoL is a strong predictor of mortality in critically ill patients. The SF-12 and EQ-5D-5L scores are both valuable tools for this assessment. Not only the physical status, but also the mental status before ICU admission should be evaluated in terms of QoL to better utilize ICU resources.
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BACKGROUND: CRISPR-Cas9 genome-wide screens are being increasingly performed, allowing systematic explorations of cancer dependencies at unprecedented accuracy and scale. One of the major computational challenges when analysing data derived from such screens is to identify genes that are essential for cell survival invariantly across tissues, conditions, and genomic-contexts (core-fitness genes), and to distinguish them from context-specific essential genes. This is of paramount importance to assess the safety profile of candidate therapeutic targets and for elucidating mechanisms involved in tissue-specific genetic diseases. RESULTS: We have developed CoRe: an R package implementing existing and novel methods for the identification of core-fitness genes (at two different level of stringency) from joint analyses of multiple CRISPR-Cas9 screens. We demonstrate, through a fully reproducible benchmarking pipeline, that CoRe outperforms state-of-the-art tools, yielding more reliable and biologically relevant sets of core-fitness genes. CONCLUSIONS: CoRe offers a flexible pipeline, compatible with many pre-processing methods for the analysis of CRISPR data, which can be tailored onto different use-cases. The CoRe package can be used for the identification of high-confidence novel core-fitness genes, as well as a means to filter out potentially cytotoxic hits while analysing cancer dependency datasets for identifying and prioritising novel selective therapeutic targets.
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Sistemas CRISPR-Cas , Neoplasias , Benchmarking , Genes Esenciales , Humanos , Neoplasias/genéticaRESUMEN
BACKGROUND: There are limited data on the long-term outcomes of COVID-19 from different parts of the world. AIMS: To determine risk factors of 90-day mortality in critically ill patients in Turkish intensive care units (ICUs), with respiratory failure. STUDY DESIGN: Retrospective, observational cohort. METHODS: Patients with laboratory-confirmed COVID-19 and who had been followed up in the ICUs with respiratory failure for more than 24 hours were included in the study. Their demographics, clinical characteristics, laboratory variables, treatment protocols, and survival data were recorded. RESULTS: A total of 421 patients were included. The median age was 67 (IQR: 57-76) years, and 251 patients (59.6%) were men. The 90-day mortality rate was 55.1%. The factors independently associated with 90-day mortality were invasive mechanical ventilation (IMV) (HR 4.09 [95% CI: [2.20-7.63], P < .001), lactate level >2 mmol/L (2.78 [1.93-4.01], P < .001), age ≥60 years (2.45 [1.48-4.06)], P < .001), cardiac arrhythmia during ICU stay (2.01 [1.27-3.20], P = .003), vasopressor treatment (1.94 [1.32-2.84], P = .001), positive fluid balance of ≥600 mL/day (1.68 [1.21-2.34], P = .002), PaO2/FiO2 ratio of ≤150 mmHg (1.66 [1.18-2.32], P = .003), and ECOG score ≥1 (1.42 [1.00-2.02], P = .050). CONCLUSION: Long-term mortality was high in critically ill patients with COVID-19 hospitalized in intensive care units in Turkey. Invasive mechanical ventilation, lactate level, age, cardiac arrhythmia, vasopressor therapy, positive fluid balance, severe hypoxemia and ECOG score were the independent risk factors for 90-day mortality.
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COVID-19/complicaciones , COVID-19/mortalidad , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/virología , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , COVID-19/terapia , Cuidados Críticos , Enfermedad Crítica , Femenino , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Pronóstico , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Turquía/epidemiologíaRESUMEN
Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (Covid-19), which has been declared as a pandemic by the World Health Organization. The aim of the study described here was to determine the severity of pneumonia and the clinical parameters related to a modified lung ultrasound score (mLUS) in patients with COVID-19 pneumonia. The study included 44 patients with proven COVID-19 pneumonia. Patients were divided into three groups on the basis of pneumonia severity: mild/moderate pneumonia (group I), severe pneumonia (group II) and critically ill patients (group III). It was determined that mLUS values in groups I-III were 6.51 ± 4.12, 23.5 ± 5.9 and 24.7 ± 3.9, respectively. mLUS values were significantly higher in group II and III patients than in group I patients. There was a positive relationship between mLUS and age and N-terminal pro-brain natriuretic peptide level and a negative relationship with PaO2/FiO2 (pâ¯=â¯0.032, ßâ¯=â¯0.275 vs. pâ¯=â¯0.012, ßâ¯=â¯0.315 vs. pâ¯=â¯0.001, ßâ¯=â¯-0.520, respectively). In patients with COVID-19 pneumonia, mLUS increases significantly with the severity of the disease.
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COVID-19/diagnóstico , Pulmón/diagnóstico por imagen , SARS-CoV-2 , Ultrasonografía/métodos , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
CRISPR-Cas9 viability screens are increasingly performed at a genome-wide scale across large panels of cell lines to identify new therapeutic targets for precision cancer therapy. Integrating the datasets resulting from these studies is necessary to adequately represent the heterogeneity of human cancers and to assemble a comprehensive map of cancer genetic vulnerabilities. Here, we integrated the two largest public independent CRISPR-Cas9 screens performed to date (at the Broad and Sanger institutes) by assessing, comparing, and selecting methods for correcting biases due to heterogeneous single-guide RNA efficiency, gene-independent responses to CRISPR-Cas9 targeting originated from copy number alterations, and experimental batch effects. Our integrated datasets recapitulate findings from the individual datasets, provide greater statistical power to cancer- and subtype-specific analyses, unveil additional biomarkers of gene dependency, and improve the detection of common essential genes. We provide the largest integrated resources of CRISPR-Cas9 screens to date and the basis for harmonizing existing and future functional genetics datasets.
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Neoplasias/genética , Biomarcadores de Tumor , Sistemas CRISPR-Cas , Línea Celular Tumoral , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Variaciones en el Número de Copia de ADN , Genes Esenciales/genética , Genómica/métodos , Humanos , ARN Guía de Kinetoplastida/genéticaRESUMEN
Hybrid sterility maintains reproductive isolation between species by preventing them from exchanging genetic material1. Anti-recombination can contribute to hybrid sterility when different species' chromosome sequences are too diverged to cross over efficiently during hybrid meiosis, resulting in chromosome mis-segregation and aneuploidy. The genome sequences of the yeasts Saccharomyces cerevisiae and Saccharomyces paradoxus have diverged by about 12% and their hybrids are sexually sterile: nearly all of their gametes are aneuploid and inviable. Previous methods to increase hybrid yeast fertility have targeted the anti-recombination machinery by enhancing meiotic crossing over. However, these methods also have counteracting detrimental effects on gamete viability due to increased mutagenesis2 and ectopic recombination3. Therefore, the role of anti-recombination has not been fully revealed, and it is often dismissed as a minor player in speciation1. By repressing two genes, SGS1 and MSH2, specifically during meiosis whilst maintaining their mitotic expression, we were able to increase hybrid fertility 70-fold, to the level of non-hybrid crosses, confirming that anti-recombination is the principal cause of hybrid sterility. Breaking this species barrier allows us to generate, for the first time, viable euploid gametes containing recombinant hybrid genomes from these two highly diverged parent species.
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Hibridación Genética , Meiosis/genética , Recombinación Genética , Saccharomyces cerevisiae/genética , Saccharomyces/genética , Aneuploidia , Segregación Cromosómica , Proteína 2 Homóloga a MutS/genética , RecQ Helicasas/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
BACKGROUND: There is no study evaluating the Tpeak-Tend (Tpe) interval, Tpe/QT ratio, and Tpe/QTc ratio to assess cardiac arrhythmias in patients with COVID-19. OBJECTIVE: We aimed to examine whether there is a change in QT, QTc, Tpe interval, Tpe/QT ratio, and Tpe/QTc ratio in patients with COVID-19. METHODS: The study included 90 patients with COVID-19 infection and 30 age-and-sex-matched healthy controls. QT, QTc, Tpe interval, Tpe/QT ratio, and Tpe/QTc ratio were measured. The participants included in the study were divided into the following 4 groups: healthy controls (group I), patients with COVID-19 without pneumonia (group II), patients with COVID-19 and mild pneumonia (group III), and patients with COVID-19 and severe pneumonia (group IV). Statistical significance was set at p < 0.05. RESULTS: It was found that baseline heart rate, presence of hypertension and diabetes, white blood cell count, blood urea nitrogen, creatinine, potassium, aspartate aminotransferase, alanine aminotransferase, NT-proBNP, high sensitive C reactive protein, D-dimer, hs-cTnI, Tpe, Tpe/QT, and Tpe/QTc increased from group I to group IV, and they were significantly higher in all patients in group IV (p < 0.05). Systolic-diastolic blood pressure, hemoglobin, and calcium levels were found to be lowest in group IV and significantly lower than in other groups (< 0.05). QT and QTc intervals were similar between groups. It was determined that increased heart rate, calcium, D-dimer, NT-proBNP and hs-CRP levels were significantly related to Tpe, Tpe/QT, and Tpe/QTc. CONCLUSIONS: In patients with COVID-19 and severe pneumonia, Tpe, Tpe/QT ratio, and Tpe/QTc ratio, which are among ventricular repolarization parameters, were found to be increased, without prolonged QT and QTc intervals. In this study, we cannot definitively conclude that the ECG changes observed are directly related to COVID-19 infection or inflammation, but rather associated with severe COVID-19 scenarios, which might involve other causes of inflammation and comorbidities. (Arq Bras Cardiol. 2020; 115(5):907-913).
FUNDAMENTO: Não há estudos avaliando o intervalo Tpico-Tfim (Tpe), a relação Tpe/QT e a relação Tpe/QTc para avaliar arritmias cardíacas em pacientes com COVID-19. OBJETIVO: Visamos investigar se há alterações nos intervalos QT, QTc e Tpe e nas relações Tpe/QT e Tpe/QTc em pacientes com COVID-19. MÉTODOS: O estudo incluiu 90 pacientes com infecção por COVID-19 e 30 controles saudáveis pareados por sexo e idade. Foram aferidos os intervalos QT, QTc e Tpe e as relações Tpe/QT e Tpe/QTc. Os participantes incluídos no estudo foram divididos nos seguintes 4 grupos: controles saudáveis (grupo I), pacientes com COVID-19 sem pneumonia (grupo II), pacientes com COVID-19 e pneumonia leve (grupo III) e pacientes com COVID-19 e pneumonia grave (grupo IV). Significância estatística foi definida por valor p < 0,05. RESULTADOS: Verificou-se que a frequência cardíaca basal, a presença de hipertensão e diabetes, a contagem de leucócitos, o nitrogênio ureico no sangue, a creatinina, o potássio, o aspartato aminotransferase, a alanina aminotransferase, o NT-proBNP, a proteína C reativa de alta sensibilidade, o dímero-D, a TncI-as, o intervalo Tpe, a relação Tpe/QT e a relação Tpe/QTc aumentaram do grupo I para o grupo IV e foram significativamente mais altos em todos os pacientes do grupo IV (p < 0,05). A pressão arterial sistólica, a hemoglobina e os níveis de cálcio eram menores no grupo IV e significativamente menores em comparação com os demais grupos (< 0,05). Os intervalos QT e QTc eram semelhantes entre grupos. Determinou-se que os níveis elevados de frequência cardíaca, cálcio, dímero-D, NT-proBNP e PCR-as eram significativamente relacionados a Tpe, Tpe/QT e Tpe/QTc. CONCLUSÕES: Em pacientes com COVID-19 e pneumonia grave, o intervalo Tpe, a relação Tpe/QT e a relação Tpe/QTc, que estão entre os parâmetros de repolarização ventricular, foram aumentados, sem prolongação dos intervalos QT e QTc. A partir deste estudo, não podemos definitivamente concluir que as alterações eletrocardiográficas observadas estão diretamente relacionadas à infecção por COVID-19 ou à inflamação, mas sim associadas a cenários graves de COVID-19, que podem envolver outras causas de inflamação e comorbidades.
Asunto(s)
Arritmias Cardíacas , COVID-19 , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/virología , COVID-19/complicaciones , Estudios de Casos y Controles , Electrocardiografía , Ventrículos Cardíacos/fisiopatología , Humanos , Pandemias , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
Resumo Fundamento: Não há estudos avaliando o intervalo Tpico-Tfim (Tpe), a relação Tpe/QT e a relação Tpe/QTc para avaliar arritmias cardíacas em pacientes com COVID-19. Objetivo: Visamos investigar se há alterações nos intervalos QT, QTc e Tpe e nas relações Tpe/QT e Tpe/QTc em pacientes com COVID-19. Métodos: O estudo incluiu 90 pacientes com infecção por COVID-19 e 30 controles saudáveis pareados por sexo e idade. Foram aferidos os intervalos QT, QTc e Tpe e as relações Tpe/QT e Tpe/QTc. Os participantes incluídos no estudo foram divididos nos seguintes 4 grupos: controles saudáveis (grupo I), pacientes com COVID-19 sem pneumonia (grupo II), pacientes com COVID-19 e pneumonia leve (grupo III) e pacientes com COVID-19 e pneumonia grave (grupo IV). Significância estatística foi definida por valor p < 0,05. Resultados: Verificou-se que a frequência cardíaca basal, a presença de hipertensão e diabetes, a contagem de leucócitos, o nitrogênio ureico no sangue, a creatinina, o potássio, o aspartato aminotransferase, a alanina aminotransferase, o NT-proBNP, a proteína C reativa de alta sensibilidade, o dímero-D, a TncI-as, o intervalo Tpe, a relação Tpe/QT e a relação Tpe/QTc aumentaram do grupo I para o grupo IV e foram significativamente mais altos em todos os pacientes do grupo IV (p < 0,05). A pressão arterial sistólica, a hemoglobina e os níveis de cálcio eram menores no grupo IV e significativamente menores em comparação com os demais grupos (< 0,05). Os intervalos QT e QTc eram semelhantes entre grupos. Determinou-se que os níveis elevados de frequência cardíaca, cálcio, dímero-D, NT-proBNP e PCR-as eram significativamente relacionados a Tpe, Tpe/QT e Tpe/QTc. Conclusões: Em pacientes com COVID-19 e pneumonia grave, o intervalo Tpe, a relação Tpe/QT e a relação Tpe/QTc, que estão entre os parâmetros de repolarização ventricular, foram aumentados, sem prolongação dos intervalos QT e QTc. A partir deste estudo, não podemos definitivamente concluir que as alterações eletrocardiográficas observadas estão diretamente relacionadas à infecção por COVID-19 ou à inflamação, mas sim associadas a cenários graves de COVID-19, que podem envolver outras causas de inflamação e comorbidades.
Abstract Background: There is no study evaluating the Tpeak-Tend (Tpe) interval, Tpe/QT ratio, and Tpe/QTc ratio to assess cardiac arrhythmias in patients with COVID-19. Objective: We aimed to examine whether there is a change in QT, QTc, Tpe interval, Tpe/QT ratio, and Tpe/QTc ratio in patients with COVID-19. Methods: The study included 90 patients with COVID-19 infection and 30 age-and-sex-matched healthy controls. QT, QTc, Tpe interval, Tpe/QT ratio, and Tpe/QTc ratio were measured. The participants included in the study were divided into the following 4 groups: healthy controls (group I), patients with COVID-19 without pneumonia (group II), patients with COVID-19 and mild pneumonia (group III), and patients with COVID-19 and severe pneumonia (group IV). Statistical significance was set at p < 0.05. Results: It was found that baseline heart rate, presence of hypertension and diabetes, white blood cell count, blood urea nitrogen, creatinine, potassium, aspartate aminotransferase, alanine aminotransferase, NT-proBNP, high sensitive C reactive protein, D-dimer, hs-cTnI, Tpe, Tpe/QT, and Tpe/QTc increased from group I to group IV, and they were significantly higher in all patients in group IV (p < 0.05). Systolic-diastolic blood pressure, hemoglobin, and calcium levels were found to be lowest in group IV and significantly lower than in other groups (< 0.05). QT and QTc intervals were similar between groups. It was determined that increased heart rate, calcium, D-dimer, NT-proBNP and hs-CRP levels were significantly related to Tpe, Tpe/QT, and Tpe/QTc. Conclusions: In patients with COVID-19 and severe pneumonia, Tpe, Tpe/QT ratio, and Tpe/QTc ratio, which are among ventricular repolarization parameters, were found to be increased, without prolonged QT and QTc intervals. In this study, we cannot definitively conclude that the ECG changes observed are directly related to COVID-19 infection or inflammation, but rather associated with severe COVID-19 scenarios, which might involve other causes of inflammation and comorbidities. (Arq Bras Cardiol. 2020; 115(5):907-913)
Asunto(s)
Humanos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/virología , Infecciones por Coronavirus/complicaciones , Índice de Severidad de la Enfermedad , Estudios de Casos y Controles , Electrocardiografía , Pandemias , Betacoronavirus , Ventrículos Cardíacos/fisiopatologíaRESUMEN
Background/aim: Critically ill patients are at risk of developing gastrointestinal (GI) bleeding due to stress causing mucosal damage. Aim of the study was to determine the effect of oral/enteral nutrition with or without concomitant pantoprazole on upper GI bleeding in low risk critically ill patients. Materials and methods: This was a prospective, randomized, open-label, multicenter study conducted with intensive care unit (ICU) patients receiving oral/enteral nutritional support. Patients were randomly assigned into two groups including intervention group (received oral/EN plus pantoprazole) and control group (received only oral/EN). Results: A total of 300 patients (intervention group: 152, control group: 148) participated in the study. Overall, 226 (75%) patients were fed by orally and 74 (25%) patients fed by enteral tube feeding. Median duration of nutritional support 4 (range: 233) days. Overt upper GI bleeding was noted only in one patient (0.65%) who was in the intervention group. The overall length of ICU stay of 4 (2105) days, while ICU stay was significantly longer in the intervention group than in the control group (P = 0.006). Conclusions: Our findings seems to indicate that in patients who are at low risk for GI bleeding and under oral/enteral nutritional support, the use of PPIs may not reduce the risk of bleeding, however these results are imprecise because of low event (GI bleeding) rate and limited power.