SARS-CoV-2 in children with cancer in Brazil: Results of a multicenter national registry.

BACKGROUND: Strategies to mitigate the impact of COVID-19 in special populations are complex and challenging. Few studies have addressed the impact of COVID-19 on pediatric patients with cancer in low- and middle-income countries. METHODS: Multicenter observational cohort study with prospective records and retrospective analyses starting in April 2020 in 21 pediatric oncology centers distributed throughout Brazil. PARTICIPANTS: Patients under 18 years of age who are infected by the SARS-CoV-2 virus (confirmed diagnosis through reverse transcriptase-polymerase chain reaction [RT-PCR]) while under treatment at pediatric oncology centers. The variables of interest included clinical symptoms, diagnostic and therapeutic measures. The repercussions of SARS-CoV-2 infection on cancer treatment and general prognosis were monitored. RESULTS: One hundred seventy-nine patients were included (median age 6 [4-13] years, 58% male). Of these, 55.9% had acute leukemia and 34.1% had solid tumors. The presence of SARS-CoV-2 was diagnosed by RT-PCR. Various laboratory markers were analyzed, but showed no correlation with outcome. Children with low or high BMI for age had lower overall survival (71.4% and 82.6%, respectively) than those with age-appropriate BMI (92.7%) (p = .007). The severity of presentation at diagnosis was significantly associated with outcome (p < .001). Overall mortality in the presence of infection was 12.3% (n = 22). CONCLUSION: In children with cancer and COVID-19, lower BMI was associated with worse prognosis. The mortality in this group of patients (12.3%) was significantly higher than that described in the pediatric population overall (∼1%).

Neuropathic pain in patients with sickle cell disease: a cross-sectional study assessing teens and young adults.

Chronic pain conditions are little studied and may be underestimated in sickle cell disease (SCD). The aim of this study was to identify the occurrence and characteristics of neuropathic pain (NP) in SCD patients. A sample of 56 patients was chosen from a total of 554 patients submitted to the inclusion criteria between 2015 and 2016. The Leeds assessment of neuropathic symptoms and signs scale was used for detecting NP. The groups with and without NP were compared by sex, age, use of hydroxyurea, and sensory changes through Chi-square, Fisher's exact, ANOVA, and Kruskal-Wallis tests. The average age was 20.6 years (SD ± 4.6), 51.8% of the patients were male, and 14 patients (25%) suffered from NP. Most commonly, the pain was reported to be in the lower back area (53.6%). Age was positively related to NP: the average age in the group with NP was 22.7 years (SD ± 4.1) and in the group without NP was 19.8 years (SD ± 4.5), p < 0.05. Higher rates of NP occurred in patients aged 19 years or older, compared with that in teens (p < 0.01). There was a positive association between NP and the use of hydroxyurea (p < 0.05). An association was found between NP and sensitive neurological changes (p < 0.01). Therefore, screening for NP may result in faster and more effective diagnoses and consequently initiate appropriate treatment.

Use of ranitidine is associated with infections in newborns hospitalized in a neonatal intensive care unit: a cohort study.

BACKGROUND: The inhibition of gastric acid secretion with ranitidine is frequently prescribed off-label to newborns admitted to neonatal intensive care units (NICU). Some studies show that the use of inhibitors of gastric acid secretion (IGAS) may predispose to infections and necrotising enterocolitis (NEC), but there are few data to confirm this association. This study aimed to compare the rates of neonatal infections and NEC among preterm infants (<37 weeks gestation) hospitalised in a NICU exposed or not to treatment with ranitidine. METHODS: A retrospective cohort study was conducted with all consecutive preterm newborns admitted to a NICU between August-2014 and October-2015. The rates of infection, NEC, and death of newborns exposed or not to ranitidine were recorded. RESULTS: A total of 300 newborns were enrolled, of which 115 had received ranitidine and 185 had not. The two groups were similar with regard to the main demographic and clinical characteristics. Forty-eight (41.7%) of the 115 infants exposed to ranitidine and 49 (26.5%) of the 185 infants not exposed were infected (RR = 1.6, 95%CI 1.1-2.2, p = 0.006). The late onset (>48 h) blood culture positive infection rate was higher in the group exposed to ranitidine than in the untreated group (13.0% vs. 3.8%, p = 0.001). There was no significant association between the use of ranitidine and NEC (Bell stage >II) (p = 0.36). The mortality rate risk was 4-fold higher in infants receiving ranitidine (16.5% vs. 8.6%, p < 0.001). CONCLUSION: Ranitidine use in neonates was associated with an increased risk of infections and mortality, but not with NEC.

Steroid-induced ocular hypertensive response in children and adolescents with acute lymphoblastic leukemia and non-Hodgkin lymphoma.

The aim of this study was to evaluate intraocular pressure (IOP) associated with use of glucocorticoids in children and adolescents treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma. We carried out a prospective descriptive study with measurement of IOP before treatment (D0), 8th (D8), 14th (D14), and 28 h days (D28) of treatment. We examined 12 patients, with two cases of ocular hypertension, and it was found a statistically significant difference between the means of IOP between D0 versus D8 and D0 versus D14 (P = 0.013). The possibility of silent ocular hypertension with irreversible blindness indicates the need of IOP verification.

Levels of inflammatory markers are differentially expressed in sickle cell anemia and sickle cell trait.

Although sickle cell anemia (SCA) is related to inflammation, the profile of inflammatory markers in sickle cell trait (SCT) is poorly studied. This is a cross-sectional study of inflammatory biomarkers carried out involving adults with SCA in steady state, SCT and controls. The SCA group had higher levels of lactato dehydrogenase, IL-1ß, IL-6, IL-10, and tumor necrosis factor alpha than the others, while the SCT group had similar levels to control group. In addition, SCA group had lower IL-8/IL-10 and soluble triggering receptor expressed on myeloid cells-1/IL-10 ratios. These findings indicate that individuals with SCT do not have a chronic inflammatory profile and reinforce that cytokines are involved in the maintenance of the inflammatory state in SCA.

Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe, North-east Brazil.

OBJECTIVES: To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants. METHODS: Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti-T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti-T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year. RESULTS: Fifty-three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.4-8.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age. CONCLUSIONS: The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.

Natural products modulating interleukins and other inflammatory mediators in tumor-bearing animals: A systematic review.

BACKGROUND: Cancer is a group of diseases characterized by abnormal cell growth and proliferation. Natural products are a potentially important source for bioactive phytochemicals in the management of cancer, which regulate a broad range of biological events via the modulation of interleukins (ILs), pro- and anti-inflammatory modulators, and other cancer hallmark-mediated signaling pathways. PURPOSE: To systematically review the literature to identify in vivo studies investigating the anticancer properties of medicinal plants and natural molecules as modulators of ILs and their related pro- and anti-inflammatory signaling markers in tumor-bearing animals. METHODS: Articles published in English were searched, without any constraint in respect of countries. The electronic databases PubMed, Embase, Scopus, and Web of Science were used for the literature search for studies published between January 2010 and January 2022. The search terms used included medicinal plants, anticancer, antineoplasic agent, ILs, cytokine, and their combinations. A manual search to detect any articles not found in the databases was also made. The identified studies were then critically reviewed and relevant data were extracted and summarized. RESULTS: Natural products were found to modulate ILs, including IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-18, IL-23, and IL-12, and interferon gamma; increase tissue inhibitor metalloprotease; decrease vascular endothelial growth factor, tumor necrosis factor alpha, granulocyte macrophage colony-stimulating factor, and nuclear factor kappa B; augment immunity by increasing the major histocompatibility complexes II and CD4+, cluster of differentiation 8 + T cell and class II trans-activator expression; and heighten the action of antioxidant enzymes, which are involved in the detoxification of free radicals and reactive oxygen species. CONCLUSION: Natural products discussed in this review show great potential to regulate ILs and weaken associated pro- and anti-inflammatory signaling markers in tumor-bearing animals. Flavonoids, polyphenols, polysaccharides, alkaloids and tannins are important phytochemicals in the modulation of ILs, especially pro-inflammatory ones. However, in terms of future research, the importance of clinical trials to investigate their beneficial properties should be warranted.

COVID-19 in HSCT recipients: a collaborative study of the Brazilian Society of Marrow Transplantation (SBTMO).

In the COVID-19 scenario, patients undergoing hematopoietic stem cell transplantation (HSCT) infected with SARS-CoV-2 may have an increased risk of death. Through a national multicenter study, we aimed to describe the impact of COVID-19 on the survival of HSCT recipients in Brazil. Eighty-six patients with a confirmed diagnosis of SARS-CoV-2 (92% by RT-PCR) were included. There were 24 children and 62 adults receiving an autologous (n = 25) and allogeneic (n = 61) HSCT for malignant (n = 72) and non-malignant (n = 14) disorders. Twenty-six patients died, (10 on autologous (38%) and 16 patients (62%) on allogeneic group). The estimated overall survival (OS) at day 40 was 69%. Adults had decreased OS compared to children (66% vs 79%, p = 0.03). The severity of symptoms at the time of diagnosis, ECOG score, laboratory tests (C-reactive protein, urea values) were higher in patients who died (p < 0.05). In conclusion, HSCT recipients infected with SARS-CoV-2 have a high mortality rate mainly in adults and patients with critical initial COVID-19 presentation. These findings show the fragility of HSCT recipients with SARS-CoV-2 infection. Therefore, the importance of adherence to preventive measures is evident, in addition to prioritizing the vaccination of family members and the HSCT team.

Risk factors for acute chest syndrome in patients from low socioeconomic background: a cohort study from Sergipe, Brazil.

A prospective cohort study to assess the risk factors for acute chest syndrome (ACS) in individuals with sickle cell disease was carried out in a referral center from Sergipe, Brazil. A total of 168 SS homozygotic individuals (ages between 12 wk and 26 y) were followed for 12 months. There were 134 admissions of 81 patients. There were 50 events of ACS, which was the second most frequent cause of hospital admission (after pain crisis). One patient died of ischemic stroke during follow up. In bivariate analysis, the following variables showed statistically significant associations with the occurrence of ACS: age less than 5 years, living in rural area, history of previous hospital admission; white blood cell count greater than 10,000/dL; hemoglobin concentration less than 7 g/dL and oxygen saturation ≤ 95% on admission. After controlling for confounding in multivariate logistic regression, only a history of previous admission remained as an independent predictor of ACS (relative risk=4.20; 95% confidence interval: 1.79-9.87; P=0.001). Patients with a positive history of hospital admission are under increased risk and should be monitored closely for prevention and early detection of ACS.

Risk factors for acute chest syndrome in patients from low socioeconomic background: a cohort study from Sergipe, Brazil.

A prospective cohort study to assess the risk factors for acute chest syndrome (ACS) in individuals with sickle cell disease was carried out in a referral center from Sergipe, Brazil. A total of 168 SS homozygotic individuals (ages between 12 wk and 26 y) were followed for 12 months. There were 134 admissions of 81 patients. There were 50 events of ACS, which was the second most frequent cause of hospital admission (after pain crisis). One patient died of ischemic stroke during follow up. In bivariate analysis, the following variables showed statistically significant associations with the occurrence of ACS: age less than 5 years, living in rural area, history of previous hospital admission; white blood cell count greater than 10,000/dL; hemoglobin concentration less than 7 g/dL and oxygen saturation ≤95% on admission. After controlling for confounding in multivariate logistic regression, only a history of previous admission remained as an independent predictor of ACS (relative risk=4.20; 95% confidence interval: 1.79-9.87; P=0.001). Patients with a positive history of hospital admission are under increased risk and should be monitored closely for prevention and early detection of ACS.

Mental health and illness of medical students and newly graduated doctors during the pandemic of SARS-Cov-2/COVID-19.

INTRODUCTION: SARS-Cov-2 virus pandemic causes serious emotional consequences. It has occurred widespread medical courses suspension, and graduations were anticipated. Field hospitals, set up to treat patients with mild to moderate COVID-19, were the main workplaces of newly graduated doctors. OBJECTIVE: To assess the impact of SARS-Cov-2/COVID-19 pandemic on mental health of medical interns and newly graduated doctors. METHOD: This is a cross-sectional study performed using a digital platform. Links to forms were sent in two moments: moment 1 (M1), at the beginning of the pandemic, in the first half of April/2020 and moment 2 (M2), after six months of pandemic, in the second half of September/2020. All students from the medical internship and all doctors graduated since 2018 from the three medical schools in Sergipe-NE-Brazil were invited. RESULTS: 335 forms were answered in April and 148 in September. In M1 88.9% considered themselves exposed to excess of information about COVID-19, which was associated with anxiety symptoms (p = 0.04). Long family physical distance was also associated with these symptoms, as increased appetite (p = 0.01), feeling shortness of breath (p = 0.003) and sweating (p = 0.007). Fear of acquire COVID-19 was reported as intense by almost half of participants, and of transmitting by 85.7% in M1. In M2 41.2% reported the death of friends or relatives. Psychiatric illness was described by 38.5% and psychotropic drugs use by 30.1% in M1, especially those who lived alone (p = 0.03) and the single ones (p = 0.01). Alcohol intake was reported by 54.3%, and among doctors graduated in 2020 it increased from 50% in M1 to 85% in M2 (p = 0.04). CONCLUSION: The pandemic had a negative impact on the mental health of medical students and newly graduated doctors. Exposure to excessive COVID-19 information and family physical distance were associated to anxiety symptoms. Among doctors graduated in 2020, alcohol intake increased during pandemic evolution.

First Report of SARS-CoV-2 Detection in Cerebrospinal Fluid in a Child With Guillain-Barré Syndrome.

Underlying mechanisms on the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurologic complications are still poorly understood. Cases of Guillain-Barré Syndrome (GBS) have been linked to the SARS-CoV-2 infection as the result of dysregulated immune response with damage in neuronal tissues. In the current report, we present the first pediatric case of GBS with detection of SARS-CoV-2 in the cerebrospinal fluid (CFS). This unique case of COVID-19-associated GBS with detection of SARS-CoV-2 RNA in the CSF indicates direct viral involvement inducing peripheral nerve inflammation.

Estimating the post-neonatal prevalence of sickle cell disease in a Brazilian population.

SUMMARY OBJECTIVE: To estimate the prevalence of individuals with sickle cell disease (SCD) in Aracaju, Brazil, using the capture-recapture (CRC) method. SCD is a significant public health problem with long-term life-threatening complications. There are no reliable estimates of the number of individuals with this condition in Aracaju, north-east Brazil. The CRC method has been used to quantify other ubiquitous populations. METHOD: Three independent lists of individuals with homozygous (HbSS) SCD were constructed from patients attending the main specialist ambulatory service, all patients with SCD admitted to three government hospitals and a clinic providing specialist immunisation services to patients with SCD. Individuals were matched to ascertain whether they appeared in one, two or three lists, and population size was estimated using the log-linear model. RESULTS: The lists identified 374 individuals. Two hundred and one appeared in one, 99 in two and 74 in three lists with an estimated number 400 (95% CI 387-418) HbSS SCD individuals; 51.6% patients with SCD were men and age ranged from 1-62 years (median 14). CONCLUSION: The CRC method resulted in a smaller population estimate than expected. The causes of this discrepancy may include list dependence, high mortality with a survival cohort effect and the method of identifying the more severe cases. The CRC method has potential to estimate the size of this population and could supplement neonatal screening to further characterise the SCD population in this region.

SPATIAL DISTRIBUTION OF NEWBORNS WITH SICKLE CELL TRAIT IN SERGIPE, BRAZIL.

OBJECTIVE: To use the spatial distribution of the sickle cell trait (SCT) to analyze the frequency of hemoglobin S (HbS) carriers in Sergipe. METHODS: The sample consisted of all individuals born in Sergipe from October 2011 to October 2012 who underwent neonatal screening in the public health system. Tests were carried out in basic health units and forwarded to the University Hospital laboratory, where they were analyzed. We used spatial autocorrelation (Moran's index) to assess the spatial distribution of heterozygous individuals with hemoglobinopathies. RESULTS: Among 32,906 newborns, 1,202 showed other types of hemoglobin besides Hemoglobin A. We found a positive correlation between the percentage of black and multiracial people and the incidence of SCT. Most SCT cases occurred in the cities of Aracaju (n=273; 22.7%), Nossa Senhora do Socorro (n=102; 8.4%), São Cristóvão (n=58; 4.8%), Itabaiana (n=39; 4.2%), Lagarto (n=37; 4.01%), and Estância (n=46; 4.9%). CONCLUSIONS: The spatial distribution analysis identified regions in the state with a high frequency of HbS carriers. This information is important health care planning. This method can be applied to detect other places that need health units to guide and care for sickle cell disease patients and their families.

Temporal trend of cancer mortality in a Brazilian state with a medium Human Development Index (1980-2018).

Emerging economy countries in epidemiological transition have been especially challenged in the fight against cancer. This was an ecological study that aimed to describe the temporal trend of cancer mortality in a Brazilian northeastern state with a medium Human Development Index using official Brazilian mortality data from 1980 to 2018. We calculated the mortality crude rate (CR) and age-standardized rate (ASR) based on official population counts and estimates. The Joinpoint Regression Program, National Cancer Institute, USA, was used to calculate time trends of cancer mortality. There were 34,214 deaths from cancer, excluding nonmelanoma skin cancer, in Sergipe. The overall cancer mortality ASR was 70.1 and 57.9 per 100,000 men and women, respectively. For the last five years, the leading causes of cancer deaths were prostate (21.3), trachea, bronchus and lung (11.7), stomach (6.5), oral cavity (5.4) and liver and intrahepatic bile ducts (5.1) in males and breast (13.8), trachea, bronchus and lung (6.6), cervix (6.4), colon/rectum (5.8) and central nervous system (3.6) in females. In addition, there was a significant reduction in deaths from ill-defined causes in the series. Our results show that although there has been an increase in cancer mortality rates associated with Western lifestyles, such as prostate, breast and colon/rectum, high rates of cancer related to poverty and infections, such as stomach and cervix, still persist in Sergipe.

Trends in cervical cancer and its precursor forms to evaluate screening policies in a mid-sized Northeastern Brazilian city.

Cervical cancer is a health issue that disproportionately affects developing countries, where the Papanicolaou test (Pap smear) remains an important screening tool. Brazilian government recommendations have focused screening on the female population aged from 25 to 64 years old. In this study, we examined the incidence and mortality rates of invasive cervical cancer lesions and the incidence rates of in situ precancerous cervical lesions, aiming to calculate their respective statistics over time in a mid-sized Brazilian city, Aracaju. The 1996-2015 database from the Aracaju Cancer Registry and Mortality Information System was used to calculate age standardized rates for all invasive cervical tumors (International code of diseases, ICD-10: C53) and preinvasive cervical lesions (ICD-10: D06) in the following patient age ranges; ≤ 24, 25-34, 35-44, 45-54, 55-64 and ≥ 65 years old. We identified 1,030 cancer cases, 1,871 in situ lesions and 334 deaths. Using the Joinpoint Regression Program, we calculated the annual percentage incidence changes and our analyses show that cervical cancer incidence decreased up to 2008, increased up to 2012 and decreased again thereafter, a significant trend in all age groups from 25 years. The incidence of precursor lesions increased from 1996 to 2005 and has since decreased, a result significant in all age groups until 64 years. Cervical cancer mortality has decreased by 3.8% annually and trend analysis indicates that Pap smears have been effective in decreasing cancer incidence and mortality. However, recent trends shown here show a decreasing incidence of in situ lesions and may indicate either a real decrease or incomplete catchment. Thus, we suggest health policies should be re-considered and include sufficient screening and HPV vaccination strategies to avoid cervical cancer resurgence in the population.

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties.

BACKGROUND: Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities. PURPOSE: We reviewed whether essential oils and their bioactive compounds of plant origin could modulate cytokines' immune responses and improve asthma therapy in experimental systems in vitro and in vivo. METHODS: Electronic and manual search of articles in English available from inception up to November 2018 reporting the immunomodulatory activity of essential oils and their bioactive compounds for the management of asthma. We used PubMed, EMBASE, Scopus and Web of Science. Publications reporting preclinical experiments where cytokines were examined to evaluate the consequence of anti-asthmatic therapy were included. RESULTS: 914 publications were identified and 13 were included in the systematic review. Four articles described the role of essential oils and their bioactive compounds on bronchial asthma using cell lines; nine in vivo studies evaluated the anti-inflammatory efficacy and immunomodulating effects of essential oil and their secondary metabolites on cytokines production and inflammatory responses. The most important immunopharmacological mechanisms reported were the regulation of cytokine production, inhibition of reactive oxygen species accumulation, inactivation of eosinophil migration and remodeling of the airways and lung tissue, modulation of FOXP3 gene expression, regulation of inflammatory cells in the airways and decreasing inflammatory mediator expression levels. CONCLUSION: Plant derived essential oils and related active compounds have potential therapeutic activity for the treatment of asthma by modulating the release of pro-inflammatory (TNF-α, IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10), Th1 (IFN-γ, IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines and the suppression of inflammatory cell accumulation.

Brazilian pediatricians' adherence to food allergy guidelines-A cross-sectional study.

Food allergy is an emerging clinical condition in pediatrics, so recommendations on its management have been widely published. Studying pediatricians' adherence to these clinical practice guidelines (CPG) and understanding the reasons for their non-compliance can help to promote better management of this condition. A cross-sectional study was conducted by a survey among Brazilian pediatricians, randomly selected during the 38th Brazilian Congress of Pediatrics, which took place in October, 2017. A validated questionnaire with 16 questions addressing knowledge and practice on food allergy, as well as self-reported adherence to international guidelines was applied. Of the total of 415 pediatricians from all regions of the country who were surveyed, only 69 (16.7%) had a satisfactory adherence rate (≥80%). Adequate adherence to the guidelines was associated with the variables: 'evaluating more than 10 children with suspected cow's milk allergy (CMA) per month'; 'having read the Brazilian consensus'; or 'being aware of any international food allergy guideline'. In 8 of the 10 questions that assessed conscious adherence, a minority of those surveyed (20.3-42.3% variation) stated that they knew that their response was in line with the guidelines. This finding was statistically significant (p<0.05) in 7 of these 8 questions. The self-reported adherence of Brazilian pediatricians to international food allergy guidelines was low. Pediatricians who evaluated a higher number of children with suspected CMA or who were aware of the recommendations, had a higher rate of adherence. The results of the survey found that lack of resource was the major reported barrier to guideline adherence but lack of awareness must be a relevant non perceived barrier. This study shows the pediatricians´ self-reported adherence to food allergy guidelines in a widely overview for the first time in Brazil. More studies are necessary to investigate adherence to guidelines by pediatricians in other countries and to develop strategies to improve adherence.