Continuous epileptiform discharges are associated with worse neurodevelopmental findings in a congenital Zika syndrome prospective cohort.

PURPOSE: This study aimed to identify continuous epileptiform discharges (CEDs) on electroencephalograms (EEG) and to determine their clinical significance in children with congenital Zika syndrome (CZS). METHODS: This prospective cohort study included 75 children diagnosed with CZS born from March 2015 and followed up until September 2018 (age up to 36 months). EEG was performed to detect CEDs up to 24 months old. Data on obstetric, demographic, and clinical signs; cranial computed tomography (CT); ophthalmology examination; anti-seizure medication; growth; and motor development were collected. Fisher's exact test was used to verify the associations between categorical variables, and the T- test was used to compare the mean z-scores of anthropometric measurements between the groups with and without CED. RESULTS: CEDs were identified in 41 (54.67 %) children. The mean age of CEDs identification was 12.24 ± 6.86 months. Bilateral CEDs were shown in 62.89 % of EEGs. CEDs were associated with severe congenital microcephaly, defined by z-score >3 standard deviation of head circumference (HC) below the mean for sex and age (p = 0.025), and worse outcomes, including first seizure before 6 months (p = 0.004), drug-resistant epilepsy (p < 0.001), chorioretinal scarring or mottling (p = 0.002), and severe CT findings (p = 0.002). The CED group had lower mean z-scores of HC up to 24 months of age. CONCLUSION: This is the first description of the prevalence and significance of CEDs that also remains during wakefulness in patients with CZS. New investigations may suggest that it is more appropriate to classify the EEG not as a CED, but as a periodic pattern. Anyway, CEDs may be a marker of neurological severity in children with CSZ.

Accuracy of the Verbal Autopsy questionnaire in the diagnosis of COVID-19 deaths in a Brazilian capital.

The Verbal Autopsy (VA) is a questionnaire about the circumstances surrounding a death. It was widely used in Brazil to assist in postmortem diagnoses and investigate excess mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. This study aimed to determine the accuracy of investigating acute respiratory distress syndrome (ARDS) using VA. This is a cross-sectional study with prospective data collected from January 2020 to August 2021 at the Death Verification Service of Sao Luis city, Brazil. VA was performed for suspected COVID-19 deaths, and one day of the week was randomly chosen to collect samples from patients without suspected COVID-19. Two swabs were collected after death and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection. Of the 250 cases included, the VA questionnaire identified COVID-19-related ARDS in 67.2% (52.98% were positive for COVID-19). The sensitivity of the VA questionnaire was 0.53 (0.45-0.61), the specificity was 0.75 (0.64-0.84), the positive predictive value was 0.81 (0.72-0.88), and the negative predictive value was 0.44 (0.36-0.53). The VA had a lower-than-expected accuracy for detecting COVID-19 deaths; however, because it is an easily accessible and cost-effective tool, it can be combined with more accurate methods to improve its performance.

Cyclin D1 expression in penile cancer.

The main goal of the present study was to analyze the expression profile of cyclin D1 in patients with PC, and to determine possible correlations with clinical and histopathological features. A survey was conducted with 100 patients diagnosed with PC, who were treated at two reference hospitals in São Luís, Maranhão, Brazil, between 2013 and 2017. A review of clinical, epidemiological, and histopathological data was performed, Human Papillomavírus (HPV) DNA was detected using polymerase chain reaction (PCR) and cyclin D1 expression analysis was performed using immunohistochemical techniques. The data revealed that the absence of cyclin D1 expression was significantly associated with HPV-positive histological subtypes (p = 0.001), while its expression was associated with high-grade tumors (p = 0.014), histological subtype (p = 0.001), presence of sarcomatoid transformation (p = 0.04), and perineural invasion (p = 0.023). Patients with cyclin D1 expression exhibited lower disease-free survival compared to the cyclin D1-negative group, although the difference was not statistically significant. The results suggest that cyclin D1 may be a potential biomarker for PC, especially for poorer prognosis.

Fatal Myocarditis following COVID-19 mRNA Immunization: A Case Report and Differential Diagnosis Review.

Carditis in childhood is a rare disease with several etiologies. We report a case of infant death due to pericarditis and myocarditis after the mRNA vaccine against COVID-19 (COVIDmRNAV). A 7-year-old male child received the first dose of the COVIDmRNAV and presented with monoarthritis and a fever non-responsive to oral antibiotics. The laboratory investigation showed signs of infection (leukocytosis, high levels of c-reactive protein). His condition rapidly deteriorated, and the patient died. The autopsy identified pericardial fibrin deposits, hemorrhagic areas in the myocardium, and normal valves. A diffuse intermyocardial inflammatory infiltrate composed of T CD8+ lymphocytes and histiocytes was identified. An antistreptolysin O (ASO) dosage showed high titers. The presence of arthritis, elevated ASO, and carditis fulfills the criteria for rheumatic fever. However, valve disease and Aschoff's nodules, present in 90% of rheumatic carditis cases, were absent in this case. The temporal correlation with mRNA vaccination prompted its inclusion as one of the etiologies. In cases of myocardial damage related to COVID-19mRNAV, it appears to be related to the expression of exosomes and lipid nanoparticles, leading to a cytokine storm. The potential effects of the COVID-19mRNAV must be considered in the pathogenesis of this disease, whether as an etiology or a contributing factor to a previously initiated myocardial injury.

Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review.

Large-scale COVID-19 vaccination has been one of the most effective strategies to control the spread of the SARS-CoV-2 virus. However, several cases of glomerular injury related to the COVID-19 vaccine have been described in the literature. We report two cases of a tip lesion variant of focal segmental glomerulosclerosis (FSGS), which presented with significant proteinuria and improved after immunosuppression. In our literature review, the tip lesion variant of FSGS is currently the most frequent variant associated with vaccination against COVID-19. Prognosis is favorable and without significant alterations in the tubulointerstitial or vascular compartments. Adverse effects of vaccines need to be recognized early and will help us to understand the immune and pathological mechanisms of kidney damage.

Equations for Prediction of Body Adiposity in Patients With Chronic Kidney Disease Undergoing Hemodialysis.

OBJECTIVES: The prevalence of obesity in the population has increased and excess body adiposity is one of the main nutritional disorders in patients with chronic kidney disease (CKD) on hemodialysis (HD). The objective of this study was to develop equations using anthropometric measurements to predict the total and abdominal body adiposity of patients with CKD on HD. METHODS: This is a cross-sectional study evaluating 323 patients with CKD on HD in city in northeastern Brazil. Measurements and anthropometric indicators were correlated with percentage of body fat (%BF) and visceral fat (VF, in kg) measured by dual energy X-ray absorptiometry. Multiple linear regression models based on different combinations of anthropometric measurements were adjusted to develop the equations, with subsequent cross-validation. RESULTS: Of the 323 patients, 62.2% were male and 46.5% were aged between 40 and 59 years. The equation selected to estimate %BF included weight, height, waist and hip circumferences, and triceps and suprailiac skin folds, presenting high predictive capacity (R2 = 0.771). The equation selected to estimate VF included weight, height, waist circumference, hip circumference, and sum of skin folds (R22 = 0.796). CONCLUSIONS: The proposed equations efficiently predicted the %BF and VF (kg) of patients with CKD on HD, thereby serving as viable indicators in clinical practice.

Malignant lung PEComa (clear cell tumor): rare case report and literature review.

Clear cell tumors of the lung (CCTL), or "sugar tumors" of lung, are very uncommon lesions and are mostly benign perivascular epithelioid cell (PEC) tumors with no specific morphologic features. Fewer than 100 cases have been reported; the aggressive nature demonstrated in sporadic reports has rarely been described in the literature. Although the course is generally described as benign, eight reported cases showed malignant behavior. We report a case of a PEC with a malignant presentation in a young man, correlating the main characteristics of the tumor with other cases reported in the literature to better elucidate this rare presentation. We also performed a literature review of reports on benign and malignant CCTL cases, with a focus on clinical, imaging, and immunohistochemical differentiation. CCTLs are rare tumors that require histopathological and immunohistochemical confirmation; to date, criteria that can predict malignant evolution are lacking.

ANCA-associated glomerulonephritis and lupus nephritis following COVID-19 vaccination: a case report and literature review.

With the coverage of COVID-19 vaccination, it has been possible to observe the potential side effects of SARS-CoV-2 vaccines, with the most common ones being fever, myalgia, headache, and fatigue. However, an association has been observed between new and recurrent kidney injuries, mainly glomerulonephritis and lupus nephritis associated with ANCA, with the Pfizer-BioNTech, Moderna, Sinovac, and AstraZeneca vaccines, although the relationship between them is not clear. We report a case of ANCA-related vasculitis and lupus glomerulonephritis after the second dose of the AstraZeneca vaccine. The elderly patient presented significant worsening of kidney function after immunosuppression and complications after a new onset COVID-19 infection that led to death. We provide a literature review about kidney damage related to ANCA vasculitis after COVID-19 vaccine, aiming for a better understanding of the pathophysiological mechanism of kidney injury, its presentation, and treatment.

Characteristics associated with drug resistant epilepsy in children up to 36 months old with Congenital Zika Syndrome.

OBJECTIVES: To verify characteristics associated with drug resistant epilepsy in children up to 36 months of age with Congenital Zika Syndrome (CZS). METHODS: This is a prospective cohort study with children aged up to 36 months diagnosed with CZS. Obstetric, demographic, phenotype and other clinical signs, cranial tomography, growth and motor development of the children were collected. RESULTS: Of a total of 109 children diagnosed with CZS, 100 (91.7%) had epilepsy and 68 (68%) with drug resistant seizures. The types of seizures associated with drug resistant epilepsy were focal seizures from the occipital lobe, generalized tonic and generalized tonic-clonic seizures. There was an association between drug resistant epilepsy and microcephaly at birth, severe microcephaly at birth, excess nuchal skin, ventriculomegaly, reduced brain parenchyma volume, and hypoplasia or malformation of the cerebellum. Difficulty sleeping, irritability, continuous crying, dysphagia and gross motor function were clinical signs associated with drug resistant epilepsy, as were the presence of ocular abnormalities, low head circumference in the first year of life and low weight in the first six months. CONCLUSIONS: The prevalence of drug resistant epilepsy in children up to 36 months with CZS was 62.4% and was associated with the severity of the child's neurological damage, with emphasis on the reduction of brain parenchyma volume and damage to the cerebellum.

Decline in head circumference growth and associated factors in congenital Zika syndrome.

Little is known about the evolution of head circumference (HC) in children with congenital Zika syndrome (CZS). This study aims to evaluate HC growth in children with CZS in the first three years of life and identify associated factors. HC data obtained at birth and in neuropediatric consultations from 74 children with CZS were collected from the Child's Health Handbook, parents' reports, and medical records. Predictors of HC z-score were investigated using different mixed-effects models; Akaike's information criterion was used for model selection. The HC z-score decreased from -2.7 ± 1.6 at birth to -5.5 ± 2.2 at 3 months of age, remaining relatively stable thereafter. In the selected adjusted model, the presence of severe brain parenchymal atrophy and maternal symptoms of infection in the first trimester of pregnancy were associated with a more pronounced reduction in the HC z-score in the first three years of life. The decrease of HC z-score in CZS children over the first three months demonstrated a reduced potential for growth and development of the central nervous system of these children. The prognosis of head growth in the first 3 years of life is worse when maternal infection occurs in the first gestational trimester and in children who have severe brain parenchymal atrophy.

Collapsing Glomerulopathy: A Review by the Collapsing Brazilian Consortium.

Collapsing glomerulopathy (CG) is a clinicopathologic entity characterized by segmentar or global collapse of the glomerulus and hypertrophy and hyperplasia of podocytes. The Columbia classification of 2004 classified CG as a histological subtype of focal segmental glomerulosclerosis (FSGS). A growing number of studies have demonstrated a high prevalence of CG in many countries, especially among populations with a higher proportion of people with African descent. The present study is a narrative review of articles extracted from PubMed, Medline, and Scielo databases from September 1, 2020 to December 31, 2021. We have focused on populational studies (specially cross-sectional and cohort articles). CG is defined as a podocytopathy with a distinct pathogenesis characterized by strong podocyte proliferative activity. The most significant risk factors for CG include APOL1 gene mutations and infections with human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. CG typically presents with more severe symptoms and greater renal damage. The prognosis is notably worse than that of other FSGS subtypes.

Decline in head circumference growth and associated factors in congenital Zika syndrome / Declínio no crescimento do perímetro cefálico e fatores associados à síndrome congênita associada à infecção pelo vírus Zika / Disminución del crecimiento del perímetro cefálico y factores asociados en el síndrome congénito del Zika

Little is known about the evolution of head circumference (HC) in children with congenital Zika syndrome (CZS). This study aims to evaluate HC growth in children with CZS in the first three years of life and identify associated factors. HC data obtained at birth and in neuropediatric consultations from 74 children with CZS were collected from the Child's Health Handbook, parents' reports, and medical records. Predictors of HC z-score were investigated using different mixed-effects models; Akaike's information criterion was used for model selection. The HC z-score decreased from -2.7 ± 1.6 at birth to -5.5 ± 2.2 at 3 months of age, remaining relatively stable thereafter. In the selected adjusted model, the presence of severe brain parenchymal atrophy and maternal symptoms of infection in the first trimester of pregnancy were associated with a more pronounced reduction in the HC z-score in the first three years of life. The decrease of HC z-score in CZS children over the first three months demonstrated a reduced potential for growth and development of the central nervous system of these children. The prognosis of head growth in the first 3 years of life is worse when maternal infection occurs in the first gestational trimester and in children who have severe brain parenchymal atrophy.

Pouco se sabe sobre a evolução do perímetro cefálico (PC) em crianças com síndrome congênita associada à infecção pelo vírus Zika (SCZ) em acompanhamentos contínuos. Este estudo buscou avaliar o crescimento do PC em crianças com SCZ nos primeiros três anos de suas vidas e identificar os fatores associados a ele. Os dados do PC ao nascimento e obtidos em consultas neuropediátricas de 74 crianças com SCZ foram coletados no Cartão da Criança, nos laudos paternos e em seus prontuários. Os preditores de escore-z para PC foram investigados utilizando-se diferentes modelos de efeitos mistos. O critério de informação de Akaike foi utilizado para selecionar os modelos usados. O escore-z de PC diminuiu de -2,7 ± 1,6 ao nascimento para -5,5 ± 2,2 aos 3 meses de idade, mas permaneceu relativamente estável desde então. No modelo ajustado selecionado, a presença de atrofia parênquimal cerebral grave e sintomas maternos de infecção no primeiro trimestre de sua gravidez estiveram associados a uma redução mais acentuada no escore-z de PC nos primeiros três anos de vida dos participantes. A diminuição do escore-z de PC em crianças com SCZ nos primeiros 3 meses de sua vida monstra o potencial reduzido de crescimento e desenvolvimento do sistema nervoso central dessas crianças. O prognóstico de crescimento do perímetro cefálico nos primeiros 3 anos de vida é pior quando a infecção materna ocorreu no primeiro trimestre gestacional e em crianças que tiveram atrofia parênquimal grave.

Se conoce poco sobre la evolución del perímetro cefálico (PC) en niños con síndrome de Zika congénito (SZC) en los seguimientos continuos. El objetivo del estudio fue evaluar el crecimiento del PC en niños con SZC en los primeros 3 años de vida e identificar los factores asociados. Se recogieron datos del PC al nacimiento y obtenidos en las consultas de neuropediatría de 74 niños con SZC a partir de la Tarjeta del Niño, los informes de los padres y los registros médicos. Se investigaron los predictores de la puntuación Z del PC mediante diferentes modelos de efectos mixtos; se utilizó el criterio de información de Akaike para la selección del modelo. La puntuación Z del PC disminuyó de -2,7 ± 1,6 al nacer a -5,5 ± 2,2 a los 3 meses de edad, pero a partir de entonces se mantuvo relativamente estable. En el modelo ajustado seleccionado, la presencia de atrofia grave del parénquima cerebral y los síntomas maternos de infección en el primer trimestre del embarazo se asociaron con una reducción más pronunciada de la puntuación Z del PC en los primeros 3 años de vida. La disminución de la puntuación Z del PC en los niños con SZC durante los primeros 3 meses demuestra el menor potencial de crecimiento y desarrollo del sistema nervioso central de estos niños. El pronóstico del crecimiento de la cabeza en los primeros 3 años de vida es peor cuando la infección materna se produjo en el primer trimestre gestacional y en los niños que tenían una atrofia grave del parénquima cerebral.

Excess deaths from all causes and by COVID-19 in Brazil in 2020.

OBJECTIVE: To estimate the 2020 all-cause and COVID-19 excess mortality according to sex, age, race/color, and state, and to compare mortality rates by selected causes with that of the five previous years in Brazil. METHODS: Data from the Mortality Information System were used. Expected deaths for 2020 were estimated from 2015 to 2019 data using a negative binomial log-linear model. RESULTS: Excess deaths in Brazil in 2020 amounted to 13.7%, and the ratio of excess deaths to COVID-19 deaths was 0.90. Reductions in deaths from cardiovascular diseases (CVD), respiratory diseases, and external causes, and an increase in ill-defined causes were all noted. Excess deaths were also found to be heterogeneous, being higher in the Northern, Center-Western, and Northeastern states. In some states, the number of COVID-19 deaths was lower than that of excess deaths, whereas the opposite occurred in others. Moreover, excess deaths were higher in men aged 20 to 59, and in black, yellow, or indigenous individuals. Meanwhile, excess mortality was lower in women, in individuals aged 80 years or older, and in whites. Additionally, deaths among those aged 0 to 19 were 7.2% lower than expected, with reduction in mortality from respiratory diseases and external causes. There was also a drop in mortality due to external causes in men and in those aged 20 to 39 years. Moreover, reductions in deaths from CVD and neoplasms were noted in some states and groups. CONCLUSION: There is evidence of underreporting of COVID-19 deaths and of the possible impact of restrictive measures in the reduction of deaths from external causes and respiratory diseases. The impacts of COVID-19 on mortality were heterogeneous among the states and groups, revealing that regional, demographic, socioeconomic, and racial differences expose individuals in distinct ways to the risk of death from both COVID-19 and other causes.

Delay in death reporting affects timely monitoring and modeling of the COVID-19 pandemic.

This study describes the COVID-19 death reporting delay in the city of São Luís, Maranhão State, Brazil, and shows its impact on timely monitoring and modeling of the COVID-19 pandemic, while seeking to ascertain how nowcasting can improve death reporting delay. We analyzed COVID-19 death data reported daily in the Epidemiological Bulletin of the State Health Secretariat of Maranhão and calculated the reporting delay from March 23 to August 29, 2020. A semi-mechanistic Bayesian hierarchical model was fitted to illustrate the impact of death reporting delay and test the effectiveness of a Bayesian Nowcasting in improving data quality. Only 17.8% of deaths were reported without delay or the day after, while 40.5% were reported more than 30 days late. Following an initial underestimation due to reporting delay, 644 deaths were reported from June 7 to August 29, although only 116 deaths occurred during this period. Using the Bayesian nowcasting technique partially improved the quality of mortality data during the peak of the pandemic, providing estimates that better matched the observed scenario in the city, becoming unusable nearly two months after the peak. As delay in death reporting can directly interfere with assertive and timely decision-making regarding the COVID-19 pandemic, the Brazilian epidemiological surveillance system must be urgently revised and notifying the date of death must be mandatory. Nowcasting has proven somewhat effective in improving the quality of mortality data, but only at the peak of the pandemic.

Prevalence and factors associated with covid-19 vaccine hesitancy in Maranhão, Brazil.

OBJECTIVES: To estimate the prevalence and factors associated with hesitancy in getting the vaccine against SARS-CoV-2 in Maranhão, Brazil. METHODS: This is a cross-sectional population-based study conducted from October 19 to 30, 2020. The estimates were calculated based on clustering, stratification, and non-response. A three-stage sampling was adopted, considering stratum, census tracts, and domicile. After systematic analysis, thirty sectors were selected in each stratum, totaling 150 sectors. Each sector contained a fixed number of 34 households, thus totaling 5,100 households. One individual within each household (resident for at least six months and aged one year or more) was selected by a simple random sampling. We questioned participants about their vaccination intention. Univariate association between independent variables and the outcome were verified using descriptive analysis (weighted frequencies) and Pearson's chi-square test (p < 0.05). Robust multivariate analysis was performed using a three-level hierarchical model. RESULTS: We found 17.5% (95%CI 16.1-19.1%) of the 4,630 individuals interviewed to report hesitancy to be vaccinated against covid-19. After final model adjustment, vaccination hesitancy was statistically higher among residents of the cities of Imperatriz (24.0%; RP = 1.48; IC95% 1.09-2.02) and municipalities of the Grande Ilha de São Luís (20.7%; RP = 1.34; 95%CI 1.02-1.76), female individuals (19.8%; RP = 1.44; 95%CI 1.20-1.75), older adults (22.8%; RP = 1.79; IC95% 1.30-2.46), evangelicals (24.1%; RP = 1.49; 95%CI 1.24-1.79), and those without reported symptoms (18.6%; RP = 1.24; 95%CI 1.02-1.51). We found no statistical differences for other socioeconomic and demographic characteristics, as well as variables related to the labor market, behaviors, and health conditions of the interviewees. CONCLUSION: The prevalence of vaccine hesitancy in Maranhão and its association with individual, contextual, and clinical factors enable us to identify the groups and contexts of greatest resistance, requiring special attention from public strategies to ensure wide vaccination.

Is splenectomy an option for multiple relapses in a child with visceral leishmaniasis? A case report.

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania spp. The recurrence of the disease occurs, in general, in patients with decreased or loss of T-cell function, whether due to the use of corticosteroids, immunosuppressive disease, or another cause. In some cases, splenectomy may be a therapeutic option. However, the effectiveness of splenectomy is not well defined. This report describes the evolution of a pediatric patient with seven recurrences of VL, who relapsed post-surgery after drug therapy and splenectomy.

Congenital Zika syndrome: Growth, clinical, and motor development outcomes up to 36 months of age and differences according to microcephaly at birth.

BACKGROUND: Little is known regarding the developmental consequences of congenital Zika syndrome (CZS) without microcephaly at birth. Most previously published clinical series were descriptive and they had small sample sizes. STUDY DESIGN: We conducted a cohort study to compare the growth, clinical, and motor development outcomes for 110 children with CZS born with and without microcephaly up to their third birthday. Ninety-three had their head circumference (HC) at birth abstracted and they did not have hypertensive hydrocephalus at birth, where 61 were born with microcephaly and 32 without. RESULTS: The HC z-scores decreased steeply from birth to six months of age, i.e., from -3.77 to -6.39 among those with microcephaly at birth and from -1.03 to -3.84 among those without. Thus, at 6 months of age, the mean HC z-scores for children born without microcephaly were nearly the same as those for children born with microcephaly. Children born without microcephaly were less likely to have brain damage, ophthalmic abnormalities, and drug-resistant epilepsy, but the differences in many conditions were not statistically significant. CONCLUSIONS: Children born without microcephaly were only slightly less likely to present severe neurologic impairment and to develop postnatal-onset microcephaly, and some of the original differences between the groups tended to dissipate with age.