Evaluation of the behavioral, histopathological, and immunohistochemical effects resulting from ventriculosubcutaneous shunt obstruction in kaolin-induced hydrocephalus in rats.

PURPOSE: Hydrocephalus is a brain disease prevalent in the pediatric population that presents complex pathophysiology and multiple etiologies. The best treatment is still ventricular shunting. Mechanical obstruction is the most frequent complication, but the resulting pathological effects are still unknown. OBJECTIVE: Evaluation and comparison of clinical, histopathological, and immunohistochemical aspects in the acute phase of experimental hydrocephalus induced by kaolin, after treatment with adapted shunt, and after shunt obstruction and posterior disobstruction. METHODS: Wistar rats aged 7 days were used and divided into 4 groups: control group without kaolin injection (n = 6), untreated hydrocephalic group (n = 5), hydrocephalic group treated with ventriculosubcutaneous shunt (DVSC) (n = 7), and hydrocephalic group treated with shunt, posteriorly obstructed and disobstructed (n = 5). The animals were submitted to memory and spatial learning evaluation through the Morris water maze test. The rats were sacrificed at 28 days of age and histological analysis of the brains was performed with luxol fast blue, in addition to immunohistochemical analysis in order to evaluate reactive astrocytosis, inflammation, neuronal labeling, and apoptotic activity. RESULTS: The group with shunt obstruction had worse performance in memory tests. Reactive astrocytosis was more evident in this group, as was the inflammatory response. CONCLUSIONS: Obstruction of the shunt results in impaired performance of behavioral tests and causes irreversible histopathological changes when compared to findings in the group with treated hydrocephalus, even after unblocking the system. The developed model is feasible and efficient in simulating the clinical context of shunt dysfunction.

LioNeo project: a randomised double-blind clinical trial for nutrition of very-low-birth-weight infants.

We assessed the effectiveness of lyophilised banked human milk (HM) as a fortifier to feed very-low-birth-weight infants (VLBWI). This study aimed to evaluate the safety and tolerability of HM with HM lyophilisate as an additive compared with the standard additive (cows' milk protein). In this phase I double-blind randomised controlled clinical trial, set in the intensive and intermediate care units of a tertiary hospital, forty VLBWI were enrolled and allocated into two groups: HM plus HM lyophilisate (LioNeo) or HM plus commercial additive (HMCA). The inclusion criteria were preterm infants, birth weight 750-1500 g, small or adequate for gestational age, exclusively receiving donor HM, volume ≥ 100 ml/kg per d and haemodynamically stable. Participants were followed up for 21 consecutive days. The primary outcome measures were necrotising enterocolitis (NEC), late-onset sepsis (LOS), death, gastrointestinal (GI) bleeding or perforation, diarrhoea, regurgitation, vomiting and abdominal distension. The LioNeo and HMCA groups had similar weights at baseline. The regression models showed no differences between the groups in terms of the primary outcomes. Diarrhoea, GI perforation, NEC and LOS were absent in the LioNeo group (one LOS and one NEC in the HMCA group). Multiple regression analysis with the total volume of milk as a covariate did not show significant differences. The lyophilisation of donor HM was considered safe and tolerable for use in stable haemodynamically VLBWI.

Mild controlled hypothermia for necrotizing enterocolitis treatment to preterm neonates: low technology technique description and safety analysis.

We performed a quality improvement project to necrotizing enterocolitis (NEC) and published our results about the initiative in 2021. However, aspects on the safety of the cooling and how to do therapeutic hypothermia with low technology to preterm infants are not described in this previous reporter. Thus, we aim to describe the steps and management to apply hypothermia in preterm infants using low technology and present the safety aspects regarding the initiative. We performed a quality improvement project to NEC in a reference hospital for neonatology (intensive care unit). Forty-three preterm infants with NEC (modified Bell's stage II/III) were included: 19 in the control group (2015-2018) and 24 in the hypothermic group (2018-2020). The control group received standard treatments. The hypothermia group received standard treatment and underwent passive cooling (35.5 °C, used for 48 h after NEC diagnosis). We reported cooling safety to NEC, assessing hematological and gasometrical parameters, coagulation disorders, clinical instability, and neurological disorders. We described how to perform cooling to preterm infants using incubators' servo-control and the occurrence and management of dysthermia during the cooling. We turn-off the incubator and used the esophageal probe to monitor the temperature every 15 min; if the temperature dropped, the incubator was turned on with a rewarming speed of 0.5 °C/h. The participants' average weights and gestational ages were 1186 g and 32 weeks, respectively. There were no differences among hematological indices, serum parameters (sodium, potassium, creatinine, lactate, and bicarbonate), pH, pCO2, and pO2/FiO2 between the groups during treatment and after rewarming. We did not observe dysthermia, bradycardia, hemodynamic instability, apnea, seizure, bleeding, peri-intraventricular hemorrhage, or any alterations in ventilatory parameters due to the cooling technique in preterm babies. This simple technique was performed without intercurrences through a rigorous team evaluation, with a target cooling speed of 0.5 °C/h. The target temperature was successfully reached between the second and third hours of life with the incubator control in 21 children; ice bags were used in only three cases. The temperature was maintained at the expected level during the programmed cooling period. CONCLUSION: Mild controlled hypothermia for preterm infants with NEC is safe. The cooling of preterm infants could be performed through passive methods, using the servo-control of the incubators for temperature management. WHAT IS KNOWN: • Mild controlled hypothermia to NEC treatment is feasible and associated with a decrease in NEC surgery, short bowel, and death. • Mild controlled hypothermia to preterm is feasible and can be performed through low technology and passive cooling. WHAT IS NEW: • Mild controlled hypothermia to preterm is safe and does not associate with safety adverse effects during and after the cooling. • Preterm infants can be cooled through passive methods by just using the servo control of the incubator, presenting acceptable temperature variance, without dysthermia, achieving and remaining at the target temperature with a proper cooling speed. Mild controlled temperature for preterm infants does not need an additional cooling device.

Protective measures feasibility for infants of low income SARS-CoV-2 positive breastfeeding mothers: a prospective multicenter cohort study.

AIM: The aim was to evaluate the feasibility of protective measures for infants of low-income SARS-CoV-2 positive breastfeeding mothers. BACKGROUND: Breastfeeding mothers with SARS-CoV-2 positive should avoid exposing the infant through protective measures (PM), but it could be challenging in a low-income population. METHODS: A prospective, multicenter study was conducted between July and October 2020 (BRACOVID). The participants were recruited at birth and interviewed through a structured questionnaire at seven and 14 days in the home environment. The feasibility of PM during breastfeeding at home was defined by guidelines recommendations (mask using, handwashing, and distancing from newborn when not breastfeeding). Three groups according to the feasibility of guidelines: complete guidelines feasibility (CG): all PM; partial guidelines feasibility (PG): at least one PM feasible; no guidelines (NG): infeasibility to all of PM. Flu-like neonatal symptoms, mothers' breastfeeding practices. We evaluated the association between PM feasibility and socioeconomic factors. RESULTS: 117 infected mothers from 17 Brazilian hospitals were enrolled. 47 (40%) mothers followed all recommendations, 14 (11.9%) could not practice at least one recommendation, and 50 (42.7%) did not execute any of them. The breastfeeding rate was 98%. Factors associated with infeasibility were monthly family income < 92.7 dollars/person, high housing density (>1 inhabitant/room), teenage mothers, responsive feeding, and poor schooling. Regarding infants' flu-like symptoms, 5% presented symptoms at fourteen days (NG group). CONCLUSION: The guidelines were not applied to infants of SARs-CoV-positive mothers in 54.6% of the dyads since the recommendations were unviable in their environments. During pandemics, we should look for feasible and effective guidelines to protect neonates from low-income populations. IMPLICATIONS FOR NURSING MANAGEMENT: Poor socioeconomic conditions lead to the unfeasibility of protective measures for infants of low-income SARS-CoV-2 positive breastfeeding mothers during the isolation period in the pandemics. The orientations and the support provided to dyad should consider the socioeconomic factors to guide feasible measures in the home environment and promote adequate protections; only an individual approach will allow a safe environment for low-income infants.

Decreasing Attacks and Improving Quality of Life through a Systematic Management Program for Patients with Hereditary Angioedema.

INTRODUCTION: Prevention of attacks is a major goal in management of patients with hereditary angioedema (HAE). We aimed to investigate the effects of a systematic intervention for HAE patients. METHODS: Thirty-three patients with HAE with C1-inhibitor deficiency, belonging to a single family, participated in a management program coordinated by an allergist/immunologist. Angioedema attacks before intervention were ascertained by interviews and emergency room charts and recorded prospectively by patients or caregivers after enrollment. Mean number of attacks/month was compared at 12 months preintervention and 8 and 14 months within intervention. Patient-reported outcome instruments were used to assess quality of life, including HAE Quality of Life (HAE-QoL) questionnaire, psychological conditions, and work impairment, at baseline and 8 and 14 months within intervention. Data were stored in REDCap platform and analyzed by adjusted Bayesian models of double Poisson regression. RESULTS: Mean number of attacks/month significantly decreased (95% credible interval [CrI] excluding 0) from 1.15 preintervention to 0.25 and 0.23, 8 and 14 months within intervention, with mean decreases of -0.89 (95% CrI: -1.21 to -0.58) and -0.92 (95% CrI: -1.22 to -0.60), respectively. HAE-QoL scores showed mean total increases of 15.2 (95% CrI: 1.23-29.77) and 26 (95% CrI: 14.56-39.02) at 8 and 14 months within the study, as compared to baseline, revealing marked improvement in quality of life. Significant increase in role-emotional and reduction of depression, stress, and anxiety were observed at 14 months. CONCLUSION: A systematic approach integrating HAE-specific care with effective handling of psychological issues decreased the number of attacks and improved quality of life, targets for best practice in HAE.

Evaluation of urine output, lactate levels and lactate clearance in the transitional period in very low birth weight preterm infants.

OBJECTIVE: To assess the association between urine output (UO), arterial lactate levels (LL) and lactate clearance with haemodynamic instability and death in very low birth weight (VLBW) preterm in the transitional period. STUDY DESIGN: Retrospective cohort study with VLBW newborns born in 2016 and 2017, excluding those with malformations and without data. We evaluated 254 preterm infants with a total of 482 lactate levels measured in the first 72 h. Areas under the curve (AUC) were calculated for receiver-operator characteristics (ROC) curves of UO and LL (alone and combined) and of lactate clearance for prediction of haemodynamic instability and death. RESULTS: All AUC were below 0.80. Sensitivity and specificity were also not very good. Although patients with poor outcomes had lactate levels higher than those with good outcomes, discrimination was poor. CONCLUSION: UO and LL and lactate clearance were not good predictors of haemodynamic instability or death within 10 days of life. What is Known • It is already established that blood pressure is not a good marker for haemodynamic stability in the preterm infant. • Others clinical parameters, albeit are largely used, are not fully reliable as well. What is New • In our study we tried to determine the sensibility and specificity of urine output and arterial lactate and also the lactate clearance. • All AUC were below 0.80. Sensitivity and specificity were also not very good. Although patients with poor outcomes had lactate levels higher than those with good outcomes, discrimination was poor.

Low technology, mild controlled hypothermia for necrotizing enterocolitis treatment: an initiative to improve healthcare to preterm neonates.

Necrotizing enterocolitis (NEC) treatment remains unchanged for years. Data suggest that mild controlled hypothermia could potentially improve NEC outcomes. Our units presented unfavourable outcomes on NEC. The aim was to assess our experience with low technology, mild controlled hypothermia on NEC outcomes, and improve preterm infants' healthcare. This was a single-center quality improvement study with retrospective cohort design at the neonatal intensive care unit in the university hospital. Forty-three preterm infants with NEC (Modified Bell's Stage II/III) were included: 19 in the control group (2015-2018) and 24 in the hypothermia group (2018-2020). The control group received standard treatment (fasting, abdominal decompression, and broad-spectrum antibiotics). The hypothermia group underwent cooling to 35.5 °C for 48 h after NEC diagnosis, along with conventional treatment. The primary outcomes are intestinal perforation, need for surgery, duration of parenteral nutrition, death, and extensive resection of the small intestine. There was no statistical difference in the NEC score. The hypothermia group required less surgery (aRR 0.40; 95% CI 0.19-0.85), presented less bowel perforation (aRR 0.39; 95% CI 0.18; 0.83), had a shorter duration of parenteral nutrition (aHR 5.28; 95% CI 1.88-14.89), did not need extensive intestinal resection, (0 vs 15.7%), and did not experience any deaths (0 vs 31.6%).Conclusions: In our experience, low technology, mild controlled hypothermia was feasible, not related to adverse effects, and effective treatment for NEC Modified Bell's Stage II/III. It avoided surgery, bowel perforation, and extensive intestinal resection; reduced mortality; and shortened parenteral nutrition duration. What is Known: • New approaches have been proposed to avoid enterocolitis incidence; however, the treatment of enterocolitis stage 2 has been the same for decades, and unfavourable outcomes remain despite conventional management. • Studies suggest that hypothermia can be an alternative to enterocolitis treatment. What is New: • Mild controlled hypothermia can be an additional practice to treat enterocolitis stage 2, is feasible, and is not related to adverse effects to preterm infants. • It can decrease surgery needs, duration of parenteral nutrition, and death and avoids extensive intestinal resection in preterm infants.

Prevalence and Outcomes of Congenital Heart Disease in Very Low Birth Weight Preterm Infants: An Observational Study From the Brazilian Neonatal Network Database.

OBJECTIVES: To evaluate the prevalence of congenital heart disease and their outcomes in a Brazilian cohort of very low birth weight preterm infants. DESIGN: Post hoc analysis of data from the Brazilian Neonatal Network database, complemented by retrospective data from medical charts and a cross-sectional survey. SETTING: Twenty public tertiary-care university hospitals. PATIENTS: A total of 13,955 newborns weighing from 401 to 1,499 g and between 22 and 36 weeks of gestational age, born from 2010 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of congenital heart disease was 2.45% (95% CI, 2.20-2.72%). In a multivariate regression analysis, risk factors associated with congenital heart disease were maternal diabetes (relative risk, 1.55; 95% CI, 1.11-2.20) and maternal age above 35 years (relative risk, 2.09; 95% CI, 1.73-2.51), whereas the protection factors were maternal hypertension (relative risk, 0.54; 95% CI, 0.43-0.69), congenital infection (relative risk, 0.45; 95% CI, 0.21-0.94), and multiple gestation (relative risk, 0.73; 95% CI, 0.55-0.97). The pooled standardized mortality ratio in patients with congenital heart disease was 2.48 (95% CI, 2.22-2.80), which was significantly higher than in patients without congenital heart disease (2.08; 95% CI, 2.03-2.13). However, in multiple log-binomial regression analyses, only the presence of major congenital anomaly, gestational age (< 29 wk; relative risk, 2.32; 95% CI, 2.13-2.52), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20; relative risk, 3.76; 95% CI, 3.41-4.14) were independently associated with death, whereas the effect of congenital heart disease was spotted only when a conditional inference tree approach was used. CONCLUSIONS: The overall prevalence of congenital heart disease in this cohort of very low birth weight infants was higher and with higher mortality than in the general population of live births. The occurrence of a major congenital anomaly, gestational age (< 29 wk), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20) were significantly and independently associated with death, whereas the association of congenital heart disease and death was only evident when a major congenital anomaly was present.

IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection.

BACKGROUND: Mechanisms influencing severity of acute lower respiratory infection (ALRI) in children are not established. We aimed to assess the role of inflammatory markers and respiratory viruses in ALRI severity. METHODS: Concentrations of interleukin(IL)-33, soluble suppression of tumorigenicity (sST)2, IL-1ß, tumor necrosis factor α, IL-4, IL-6 and IL- 8 and types of respiratory viruses were evaluated in children at the first and fifth days after hospital admission. Disease severity was defined as need for mechanical ventilation. RESULTS: Seventy-nine children <5 years-old were included; 33(41.8%) received mechanical ventilation. No associations between virus type, viral load or co-detections and severity of disease were observed. Detection of IL-33 and sST2 in nasopharyngeal aspirates (NPA) on admission were associated with higher risk for mechanical ventilation (RR = 2.89 and RR = 4.57, respectively). IL-6 and IL-8 concentrations were higher on Day 5 in mechanically ventilated children. IL-6 NPA concentrations decreased from Day 1 to Day 5 in children who did not receive mechanical ventilation. Increase in sST2 NPA concentrations from Day 1 to Day 5 was associated with longer hospital length of stay (p < 0.01). CONCLUSIONS: An exacerbated local activation of the IL-33/ST2 axis and persistently high sST2 concentrations over time were associated with severity of viral ALRI in children.

Assessment of late anthracycline-induced cardiotoxicity by 123I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence.

PURPOSE: The goal of this study was to evaluate late cardiotoxic effects of anthracyclines (ATC) by evaluating cardiac sympathetic activity in a cohort of asymptomatic patients previously treated with ATC for childhood cancers. METHODS: We studied 89 asymptomatic patients previously treated with ATC with a normal echocardiogram (49 men and 40 women) and a control group of 40 healthy individuals (26 men and 14 women). Both groups underwent planar myocardial 123I-meta-iodobenzylguanidine scintigraphy (123I-mIBG). From these images, the early and late heart-to-mediastinum (H/M) ratio and washout rate (WR) were assessed. RESULTS: The mean survival at the time of the 123I-mIBG scintigraphy was 5.3 ± 3.4 years. Patients treated with ATC had a lower but clinical normal left ventricular ejection fraction (LVEF) compared to controls (60.44 ± 6.5 vs 64.1 ± 6.0%, P < 0.01). Both the late H/M ratio and WR were not able to discriminate ATC treated patients from controls. The cumulative ATC dose was the only independent predictor of the LVEF, explaining approximately 12% of the variation in LVEF (P = 0.01). CONCLUSIONS: Although the pathophysiology behind ATC cardiotoxicity is most likely multifactorial, myocardial sympathetic activity is not associated with a reduction in LVEF 5-years after completion of chemotherapy.

Incidence, Risk Factors, and Morbidity of Acquired Postnatal Cytomegalovirus Infection Among Preterm Infants Fed Maternal Milk in a Highly Seropositive Population.

BACKGROUND: In preterm infants cytomegalovirus (CMV) infection acquired through maternal milk has been related to morbidity. However, infants who may receive higher titers of protective antibodies from highly seropositive mothers have not been studied in detail. METHODS: A cohort of 188 ≤30-week-old infants was monitored from admission to discharge. CMV-DNA, hematology, liver enzymes, neutralizing antibodies, and CMV-DNA-lactia were tested periodically. RESULTS: Mothers of 157 infants (83.5%) were CMV-seropositive. A total of 24/157 (15.3%) infants became infected (95% confidence interval [CI], 9.8-22.6), particularly those of lower gestational age (GA; relative risk [RR], 2.32; 95% CI, 1.01-5.34 for 23-26 weeks). Low (<1:64) neutralizing antibody titers were similarly detected in CMV-infected and uninfected infants. Mean DNA-lactia in mothers was higher in CMV-infected than in uninfected infants (5.34 log vs 4.60 log). Clinical findings suggestive of CMV disease were similar in CMV-infected (50.0%) and CMV-uninfected (51.1%) infants. Although transitory, >2 laboratory test abnormalities occurred more frequently among CMV-infected (39.1%) than CMV-uninfected (2.1%) infants. More severe stages of retinopathy of prematurity (ROP) were found among CMV-infected infants (adjusted RR, 2.51; 95% CI, 1.07-5.91). Although deaths were more frequent among infected infants, none of the deaths could be directly attributed to CMV. CONCLUSIONS: Postnatal CMV infection acquired by exposure to raw maternal milk is very frequent among extremely premature newborns, being facilitated by high DNA-lactia and lower GA, regardless of maternally acquired neutralizing antibody levels. The association with advanced stages of ROP is a concern and needs to be further explored in larger studies.

Quality of Life Assessment in Patients with Surgically Treated Parasagittal Meningiomas.

AIM: To assess quality of life (QoL) in patients with parasagittal meningiomas (PSM), and to identify the risk factors for different levels of QoL. MATERIAL AND METHODS: Patients were contacted and interviewed via telephone. A total of 136 patients with PSM underwent surgery at our institution between 1984 and 2020. Among them, 45 had agreed to participate in the research. The scales utilized included the Functional Assessment of Cancer Therapy General (FACT-G), Brain (FACT-Br), and Meningioma (FACT-MNG). Medical records were also reviewed. RESULTS: The mean KPS was 93.3 (70-100). Overall, the mean scores for the FACT-G, FACT-Br, and FACT-MNG scales were 98.4/108 (55-108; SD: 12.9), 179.3/200 (98-200; SD: 22.4), and 219.3 (119-248; SD: 29.7). Considerable variability in scales scores was observed among those with the same KPS score. Preoperative KPS score was significantly associated with both FACT-Br [-21.64; 95% CrI (-34.04, -9.59)] and FACT-MNG [-31.88; 95% CrI (-47.24, -15.25)]. Preoperative KPS was identified as a risk factor for QoL impairment. CONCLUSION: Variability in the scale scores among those with the same KPS score highlights the importance of structured assessment. Moreover, KPS may overlook impairments in QoL. To date, this has been the first study to assess QoL in PSM patients.

High Incidence Rates of Early-onset Bacterial Sepsis in Infants Born in Two Brazilian Maternities: A 15-Year Retrospective Analysis.

BACKGROUND: Data on the burden and etiology of neonatal early-onset bacterial sepsis (EOBS) in low-to-middle-income countries are scarce. Surveillance is critical for optimizing prevention and treatment strategies. We aimed to estimate the incidence of EOBS in 2 large Brazilian cohorts of neonates. METHODS: Data were retrospectively obtained from 33,794 neonates born between 2009 and 2017 at low-risk (n = 17,981) and high-risk maternity centers (n = 15,813). Blood cultures were taken within 72 hours of life from neonates with perinatal risk factors for EOBS or suspected EOBS. A positive blood culture for a pathogenic microorganism and a compatible clinical evolution confirmed the diagnosis of EOBS. RESULTS: One-third of the infants born from high-risk and 18.5% from low-risk maternities were investigated for EOBS. Overall, EOBS was more incident in neonates born in the high-risk facilities [66 cases or 4.2/1000 (95% CI: 3.2-5.3)] than in the low-risk facilities [24 cases or 1.3/1000 (95% CI: 0.9-2.0)]. The incidence rate of EOBS increased with decreasing gestational age (<32 weeks: 20.5/1000; 32-36 weeks: 5.6/1000; ≥37 weeks: 1.5/1000). Group B Streptococcus (GBS) was the agent more frequently identified in high-risk and low-risk maternities: 1.8/1000 (95% CI: 1.1-2.4) and 0.4/1000 (95% CI: 0.2-0.9), respectively. EOBS's overall case fatality rate was 17.8% for all the agents and 22% for GBS. CONCLUSIONS: EOBS remains unacceptably high and is frequently fatal in preterm and term infants cared for in high- or low-risk maternities. Because GBS has emerged as the most frequent causative agent, preventive strategies are urgently needed.

Development and Evaluation of a Mixed Reality Model for Training the Retrosigmoid Approach.

BACKGROUND: The use of simulation has the potential to accelerate the learning curves and increase the efficiency of surgeons. However, there is currently a scarcity in models dedicated to skull base surgical approaches. Thus, the objective of this study was to develop a cost-effective mixed reality system consisting of an ultrarealistic physical model and augmented reality and evaluate its use in training surgeons on the retrosigmoid approach. METHODS: The virtual models were developed from images of patients with vestibular schwannoma. The tumor was mirrored to allow bilateral approaches and the model has drawers for repositioning structures, allowing reuse of the material and cost reduction. Pre and posttest assessments were applied to 10 residents and young neurosurgeons, divided into control and test groups. Only the control group was exposed to the model. The difference in scores obtained by participants before and after exposure to the models was considered for analysis and participants in the control group answered self-satisfaction questionnaires. RESULTS: The mean differences were 4.80 in the control group (95% credibility intervals=1.08-9.79) and 5.43 in the test group (95% credibility intervals=1.67-8.20). The average score of the self-satisfaction questionnaires was 24.0 (23-25). CONCLUSIONS: The ultrarealistic model efficiently allowed retromastoid access to the cerebellopontine angle. A tendency toward greater gains in performance in the group exposed to the model was verified. Scores from the self-satisfaction questionnaires demonstrated that participants considered the model relevant for neurosurgical training and increased confidence among surgeons.

Personalized lung care: Bronchopulmonary dysplasia risk prediction tool tailored for neonates born in resource-limited settings.

PURPOSE: Predicting bronchopulmonary dysplasia (BPD) to assess the risk-benefit of therapy is necessary considering the side effects of medications. We developed and validated an instrument for predicting BPD and compared it with an instrument currently used for neonates born in a Brazilian hospital. METHODS: This was a retrospective cohort study of patients born between 2016 and 2020 with a gestational age (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of component variable selection collected on the 14th day of life; 70% of the sample was randomly selected for the construction of risk prediction equations and the remaining 30% for their validation, application, and comparison with the National Institute of Child Health and Human Development (NICHD) instrument. The sensitivity, specificity, and predictive values of the equations were calculated. RESULTS: The equation that used variables with p < 5% in Fisher's exact test presented the best results: specificity of 98% and positive predictive value of 93% and could be used for BPD prediction of all small-for-gestational-age (SGA) infants. The NICHD calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to extremely SGA infants. CONCLUSION: Our tool can predict the risk of BPD on the 14th day of life, has higher specificity and positive predictive value to our population than the NICHD instrument, and can be suitable for SGA infants. The results must be confirmed by applying it to other populations to validate our tool.

Chronic neutropenia in childhood: experience of a tertiary center.

OBJECTIVE: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. METHODS: Retrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %. RESULTS: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. CONCLUSION: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist.

Cytomegalovirus Active Infection in Critically Ill Children.

OBJECTIVE: To describe the epidemiology, clinical characteristics and outcomes of children with cytomegalovirus (CMV) active infection in the pediatric intensive care unit (PICU) and to investigate risk factors for mortality. METHODS: This was a retrospective cohort study of patients who had CMV DNA detected in blood samples and/or tracheal aspirates by polymerase chain reaction (PCR) during stay at 2 PICUs of a university hospital. Suspected cases without etiological confirmation and patients with laboratory-confirmed CMV infection before PICU admission were excluded. RESULTS: Demographic, clinical and outcome data were collected from medical records. From January 1, 2012, to December 31, 2019, 4748 children were admitted to the PICUs. Thirty-five (0.74%; 95% CI 0.51%-1.02%) had laboratory-confirmed CMV active infection; 71.4% were immunocompromised and 11 (31.4%) died. Patients who died were older than those who survived (median age 65 vs. 5.5 months, respectively; P = 0.048), and they received antiviral therapy for a shorter time (median 12 vs. 23 days, respectively; P = 0.001). The main causa mortis was septic shock (82%) and in most deceased patients (73%) the last CMV PCR before death was positive. PELOD score >6 was a risk factor for death (RR 2.96; 95% CI 1.07-8.21). Viral load in blood had a poor ability for the prediction of death (area under the receiver operating characteristic curve 0.62; 95% CI 0.37-0.84). CONCLUSIONS: The incidence of CMV active infection during PICU stay was 0.74% in an upper-middle income country with a high CMV seroprevalence. PELOD score higher than 6 was a risk factor for death. No association was observed between CMV viral load and mortality.

A data-driven approach to manage type 2 diabetes mellitus through digital health: The Klivo Intervention Program protocol (KIPDM).

BACKGROUND: Digital therapeutics, an emerging type of medical approach, is defined as evidence-based therapeutic interventions through qualified software programs that help prevent, manage, or treat chronic diseases such as type 2 diabetes mellitus (T2DM), which has high social and economic burden. Klivo, a startup certified by the Brazilian Society of Diabetes, developed the first digital therapeutic product for managing T2DM in Brazil, reaching 21 of 24 states. Klivo has continuously been improving its model of behavior change on the basis of an intensive lifestyle intervention method that addresses individuals' needs-the Klivo Intervention Program for T2DM (KIPDM). To test the most recent version of the KIPDM, we will evaluate the ongoing management of daily life habits in patients with T2DM by measuring clinically significant outcomes. To improve the transparency of further results, here we will present the study protocol and detail the plan for the research project, including the study design and the analysis strategies. METHODS: The KIPDM will be sponsored by health plans and healthcare provider organizations and will be free for patients (adults aged ≥ 18 years and <65 years; and glycated hemoglobin ≥ 7%). The program will be based on a 6-month management process that will supervise patients remotely. The program will include educational classes via the Klivo app, text messages, or e-mails. Evaluation will include objectively assessing clinical, laboratory, and behavioral outcomes such as health-related quality of life, mental health, medication adherence, and healthcare utilization. For this, validated electronic questionnaires will be available through the Klivo app. The primary outcome will be glycated hemoglobin (HbA1c) values. The secondary outcome will be time in target blood glucose range (TIR) estimated by capillary glycemia. Other outcomes of interest will be evaluated at baseline and stipulated time points (3 and 6 months after the start of the program). EXPECTED OUTCOMES: KIPDM patients should present improved HbA1c and TIR along the intervention as compared to baseline values. Findings from this study will provide insights into the health improvement of T2DM and other cardiometabolic conditions such as hypertension, dyslipidemia, and obesity by using a digital therapeutic strategy. By analyzing the patient's health over time, this study will also contribute to understanding comorbidities associated with this chronic condition in the Brazilian population.

Continuous interstitial glucose monitoring for term newborns: analysis of the first day of life.

OBJECTIVE: Glycaemia in newborns changes significantly after birth; however, little is known about these changes. The objective was to describe continuous interstitial glucose values in term newborns who were exclusively breast fed on the first day of life. DESIGN: We studied 159 newborns with appropriate weights for gestational age, who were exclusively breast fed on the first day of life, using a continuous glucose monitoring device that calculates interstitial glucose every 5 min. The device was removed after 24 hours, and the results were analysed using the R program, which provides the minimum, maximum, median and a standard curve with centiles. RESULTS: At the second hour of life, the moment in which the sensor started to identify the newborn's glycaemia, interstitial glucose levels were 2.59-4.43 mmol/L (46.7-79.9 mg/dL). The median interstitial glucose level of the newborns during the first day of life was 3.33±0.48 mmol/L (60±8.6 mg/dL). Interstitial glucose levels dropped until the sixth hour of life, reaching 2.19-3.95 mmol/L (39.5-71.1 mg/dL), and then increased again. The maximum values were found at the 20th and 21st hours of life, which were 2.81-4.64 mmol/L (50.6-83.6 mg/dL). CONCLUSION: The interstitial glucose during the first 24 hours of life declined until the sixth hour of life, then increased around the 20th hour and remained stable until the end of the first day of life.