22q11 Copy Number Variations in a Brazilian Cohort of Children with Congenital Heart Disorders.

Introduction: Congenital heart disease (CHD) is the most common type of congenital defect reported to be one of the leading causes of mortality in the first year of life. Microdeletion and microduplication syndromes (MMS) are associated with cardiac malformations. Understanding which genetic factors are involved in these conditions directly impacts treatment decisions. We aimed to identify the occurrence of genetic alterations and their association with MMS in CHD pediatric patients evaluated in a reference service of Southern Brazil. Methods: Participants were recruited during 2010 in the intensive care unit of a pediatric hospital. MMs and regions of chromosome 22 were screened by SALSA MLPA Probemix P245 Microdeletion Syndromes-1A kit for detection of copy number variations (CNVs). Results: MMS were detected in 11 from 207 patients (5.3%). Heterozygous deletion in the 22q11.2 chromosome region was the most prevalent CNV (5 from 11 patients). Also, atypical RTDR1 deletion and 22q11.2 duplication were detected. MLPA was able to reveal microdeletions in SNRPN and NF1 genes in patients with a normal karyotype and FISH. Conclusion: Our study reports the prevalence and variability of genomic alterations associated with MMS in CHD pediatric patients. The results by MLPA are of great help in planning and specialized care.

Longer length of stay, days between discharge/first readmission, and pulmonary involvement ≥50% increase prevalence of admissions in ICU in unplanned readmissions after COVID-19 hospitalizations.

Hospital readmissions due to COVID-19 are one of the main concerns for the health system due to risks to the patient's life and increased use of health resources. Studies focusing on this issue are important to understand the risk factors and create strategies to avoid readmissions. We evaluated the readmission of patients with confirmed COVID-19 in a private hospital in southern Brazil, between March 2020 and 2021. Also, the characteristics and clinical outcomes of patients admitted to the intensive care unit (ICU) and nonadmitted were compared. Poisson regression models with prevalence ratio (PR) with 95% confidence intervals (95% CIs) were applied to confirm the association between variables and ICU admission. Of the 2084 hospitalized patients with COVID-19, 1806 were discharged alive. Among them, 106 were readmitted for unplanned reasons during one year. Early hospital readmission (≤30 days) occurred in 52.8% of the cases. The main reasons were respiratory, gastroenterological, kidney, and cardiac disease. The median age was 73.0 years old and women correspond to 52.8%. The presence of at least one comorbidity was detected in 87.7% of patients. Hypertension, diabetes, cardiac, and lung disease were more frequent. The ICU admitted patients (n = 43; 40.5%) mostly had 4-5 comorbidities, pulmonary involvement ≥50%, length of stay (LOS), and days between discharge and first readmission. Longer LOS (PR: 3.46; 95% CI: 1.24-5.67), days between discharge/first readmission (PR: 2.21; 95% CI: 1.15-5.88), and pulmonary involvement (≥50%; PR: 1.59; 95% CI: 1.11-3.54) were independently associated with ICU admission. Longer LOS, longer days between discharge/first readmission, and pulmonary involvement (≥50%) were associated with ICU admission in readmitted patients. Readmissions evaluation is pivotal and may help in ensuring safe care transition and postdischarge follow-up.

ABC2-SPH risk score for in-hospital mortality in COVID-19 patients: development, external validation and comparison with other available scores.

OBJECTIVES: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. METHODS: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients. RESULTS: Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). CONCLUSIONS: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.

GATA 4 Deletions Associated with Congenital Heart Diseases in South Brazil.

The normal development of the heart comprises a highly regulated machinery of genetic events, involving transcriptional factors. Congenital heart disease (CHD), have been associated with chromosomal abnormalities and copy number variants (CNVs). Our goal was to investigate through the multiplex ligation-dependent probe amplification (MLPA) technique, the presence of CNVs in reference genes for normal cardiac development in patients with CHD. GATA4 , NKX2-5 , TBX5 , BMP4 , and CRELD1 genes and 22q11.2 chromosome region were analyzed in 207 children with CHD admitted for the first time in a cardiac intensive care unit from a pediatric hospital. CNVs were detected in seven patients (3.4%): four had a 22q11.2 deletion (22q11DS) (1.9%), two had a GATA4 deletion (1%) and one had a 22q11.2 duplication (0.5%). No patients with CNVs in the NKX2-5 , TBX5 , BMP4 , and CRELD1 genes were identified. GATA4 deletions appear to be present in a significant number of CHD patients, especially those with septal defects, persistent left superior vena cava, pulmonary artery abnormalities, and extracardiac findings. GATA4 screening seems to be more effective when directed to these CHDs. The investigation of CNVs in GATA4 and 22q11 chromosome region in patients with CHD is important to anticipating the diagnosis, and to contributing to family planning.