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The combination of signals from the T-cell receptor (TCR) and co-stimulatory molecules triggers transcriptional programs that lead to proliferation, cytokine secretion, and effector functions. We compared the impact of engaging the TCR with CD28 and/or CD43 at different time points relative to TCR engagement on T-cell function. TCR and CD43 simultaneous engagement resulted in higher CD69 and PD-1 expression levels than in TCR and CD28-stimulated cells, with a cytokine signature of mostly effector, inflammatory, and regulatory cytokines, while TCR and CD28-activated cells secreted all categories of cytokines, including stimulatory cytokines. Furthermore, the timing of CD43 engagement relative to TCR ligation, and to a lesser degree that of CD28, resulted in distinct patterns of expression of cytokines, chemokines, and growth factors. Complete cell activation was observed when CD28 or CD43 were engaged simultaneously with or before the TCR, but ligating the TCR before CD43 or CD28 failed to complete a cell activation program regarding cytokine secretion. As the order in which CD43 or CD28 and the TCR were engaged resulted in different combinations of cytokines that shape distinct T-cell immune programs, we analyzed their upstream sequences to assess whether the combinations of cytokines were associated with different sets of regulatory elements. We found that the order in which the TCR and CD28 or CD43 are engaged predicts the recruitment of specific sets of chromatin remodelers and TFSS, which ultimately regulate T-cell polarization and plasticity. Our data underscore that the combination of co-stimulatory molecules and the time when they are engaged relative to the TCR can change the cell differentiation program.

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ABSTRACT Introduction: Although still rare, pulmonary embolism (PE) in children has been increasing over the years. Data regarding this group of patients are still sparse, which contributes to the lack of standardized prophylaxis protocols and the misdiagnosis. This study aimed to determine the incidence of pediatric PE at a Brazilian tertiary hospital, describe clinical characteristics and identify possible risk factors. We also analyzed the diagnosis and management of PE. Methods: This was a retrospective review of tertiary Brazilian single-center data of all pediatric patients (0 - 18 years) with acute PE, diagnosed radiologically, from September 2009 to May 2019. Results: The incidence of PE was 3.3 cases per 10,000 hospitalized children. All the twenty-three cases had some risk factor identified and sixteen of them (69.5%) had more than one risk factor. The most important were central venous catheter (39.1%), malignancy (34.8%) and recent surgery (34.8%). Among the children with identifiable symptoms (69.5%), the most common was dyspnea (56.2%). Only one patient did not receive antithrombotic therapy because of the high bleeding risk and most patients (70.6%) were treated for 3 to 6 months. Among the nineteen patients alive at the end of the six-month follow-up, ten (52.6%) repeated the PE image control. Seven of them (70.0%) had complete or partial resolution of the thrombosis and none had worsening images. Conclusion: Our lower incidence than that of the current literature may reflect underdiagnosis due to low suspicion of PE. At least one risk factor was identified in all patients, which emphasizes the importance of increasing awareness of high-risk children.

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This study aimed to evaluate the impact of body condition score (BCS) at calving, parity, and the calving season on the performance of dairy cows and their offspring. Data from 521 Holstein cows that calved a female calf and had their BCS evaluated at calving from a single commercial farm located in Southern Brazil were used. Cows were categorized into five BCS classes: class 1: <3.0 (n = 19), class 2: 3.0-3.25 (n = 134), class 3: 3.5-3.75 (n = 160), class 4: 4.0-4.25 (n = 142), and class 5: >4.25 (n = 66). Data were also categorized by calving order (primiparous and multiparous dams) and by calving season. The study was designed as a prospective cohort study. Variables with normal distribution were analyzed by the MIXED procedure of SAS, while binary outcomes were analyzed by the GLIMMIX procedure of SAS. Daughters from primiparous dams were born lighter (39.1 ± 0.42 vs. 41.4 ± 0.29 kg, p < 0.01), but they had the same weights as the daughters from multiparous cows at weaning (121.5 ± 1.67 vs. 120.4 ± 1.58 kg, p = 0.20). As expected, primiparous cows showed lower (p < 0.01) 305-day milk yields than multiparous ones: 8633 ± 363 vs. 10,761 ± 249 kg, respectively. Regarding the calving season, cows that calved in the winter were the most productive ones, and those that calved in the fall had lower milk yields (p = 0.01). Calves born in the winter were heavier at birth (p < 0.01), calved younger (p = 0.04), and produced more milk at first lactation (p = 0.03). The BCS class had an impact (p < 0.01) on calf birth weights; daughters from Class 1 cows (BCS < 3.0) were lighter (38.0 ± 1.0 kg) than the calves from Class 5 cows with a BCS > 4.25 (41.9 ± 0.57 kg). Calves from dams with a BCS < 3 (Class 1) had a 31.8% culling rate until weaning, while calves from cows with a BCS of 3.0-3.25 (Class 2) had a 9.6% culling rate (p = 0.12). These results suggest that maternal and environmental factors, such as calving season and parity, in addition to the dams' body condition score at calving, are associated with different offspring performances.

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INTRODUCTION: Although still rare, pulmonary embolism (PE) in children has been increasing over the years. Data regarding this group of patients are still sparse, which contributes to the lack of standardized prophylaxis protocols and the misdiagnosis. This study aimed to determine the incidence of pediatric PE at a Brazilian tertiary hospital, describe clinical characteristics and identify possible risk factors. We also analyzed the diagnosis and management of PE. METHODS: This was a retrospective review of tertiary Brazilian single-center data of all pediatric patients (0 - 18 years) with acute PE, diagnosed radiologically, from September 2009 to May 2019. RESULTS: The incidence of PE was 3.3 cases per 10,000 hospitalized children. All the twenty-three cases had some risk factor identified and sixteen of them (69.5%) had more than one risk factor. The most important were central venous catheter (39.1%), malignancy (34.8%) and recent surgery (34.8%). Among the children with identifiable symptoms (69.5%), the most common was dyspnea (56.2%). Only one patient did not receive antithrombotic therapy because of the high bleeding risk and most patients (70.6%) were treated for 3 to 6 months. Among the nineteen patients alive at the end of the six-month follow-up, ten (52.6%) repeated the PE image control. Seven of them (70.0%) had complete or partial resolution of the thrombosis and none had worsening images. CONCLUSION: Our lower incidence than that of the current literature may reflect underdiagnosis due to low suspicion of PE. At least one risk factor was identified in all patients, which emphasizes the importance of increasing awareness of high-risk children.

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This study assessed the technical performance of a rapid lateral flow immunochromatographic assay (LFIA) for the detection of anti-SARS-CoV-2 IgG and compared LFIA results with chemiluminescent immunoassay (CLIA) results and an in-house enzyme immunoassay (EIA). To this end, a total of 216 whole blood or serum samples from three groups were analyzed: the first group was composed of 68 true negative cases corresponding to blood bank donors, healthy young volunteers, and eight pediatric patients diagnosed with other coronavirus infections. The serum samples from these participants were obtained and stored in a pre-COVID-19 period, thus they were not expected to have COVID-19. In the second group of true positive cases, we chose to replace natural cases of COVID-19 by 96 participants who were expected to have produced anti-SARS-CoV-2 IgG antibodies 30-60 days after the vaccine booster dose. The serum samples were collected on the same day that LFIA were tested either by EIA or CLIA. The third study group was composed of 52 participants (12 adults and 40 children) who did or did not have anti-SARS-CoV-2 IgG antibodies due to specific clinical scenarios. The 12 adults had been vaccinated more than seven months before LFIA testing, and the 40 children had non-severe COVID-19 diagnosed using RT-PCR during the acute phase of infection. They were referred for outpatient follow-up and during this period the serum samples were collected and tested by CLIA and LFIA. All tests were performed by the same healthcare operator and there was no variation of LFIA results when tests were performed on finger prick whole blood or serum samples, so that results were grouped for analysis. LFIA's sensitivity in detecting anti-SARS-CoV-2 IgG antibodies was 90%, specificity 97.6%, efficiency 93%, PPV 98.3%, NPV 86.6%, and likelihood ratio for a positive or a negative result were 37.5 and 0.01 respectively. There was a good agreement (Kappa index of 0.677) between LFIA results and serological (EIA or CLIA) results. In conclusion, LFIA analyzed in this study showed a good technical performance and agreement with reference serological assays (EIA or CLIA), therefore it can be recommended for use in the outpatient follow-up of non-severe cases of COVID-19 and to assess anti-SARS-CoV-2 IgG antibody production induced by vaccination and the antibodies decrease over time. However, LFIAs should be confirmed by using reference serological assays whenever possible.

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OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

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BACKGROUND/AIMS: Obesity leads to increased risk of thromboembolic events in adults, but few studies have addressed the relationship between obesity and thrombogenic risk during childhood. The aim of this study was to evaluate the prothrombotic state of obese children in comparison with healthy children. METHODS: Thrombin generation, fibrinogen, and D-dimer levels, along with metabolic parameters, were measured in 72 prepubertal children, of which 47 were obese and 25 eutrophic. RESULTS: A significant increase in thrombin generation, fibrinogen, and dyslipidemia was found among obese patients. CONCLUSION: A prothrombotic state develops in childhood obesity during the prepubertal phase.

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Abstract Introduction: Little attention is given to thrombosis associated with pediatric acute promyelocytic leukemia (APL). This study describes the thrombotic and hemorrhagic manifestations of APL in pediatric patients and evaluates their hemostasis, based on coagulation tests. Methods: Inclusion criteria were age 0-18 years and APL diagnosis between April 2005 and November 2017. Patients who had received blood transfusion prior to coagulation tests were excluded. Baseline coagulation tests, hematologic counts, and hemorrhagic/thrombotic manifestations were evaluated. Results: Median age was 10.7 years (1-15 years). The initial coagulation tests revealed a median Hgb of 8.3 g/dL (4.7-12.9 g/dL), median leucocyte count of 10.9 × 109/L (1.1-95.8 × 109/L), median platelet count of 31.8 × 109/L (2.0-109.0 × 109/L), median activated partial thromboplastin time (aPTT) of 31.7 s (23.0-50.4 s), median aPTT ratio of 1.0 (0.78-1.6), median thromboplastin time (PT) of 17.5 s (13.8-27.7 s), median PT activity of 62% (25-95 %), and median fibrinogen of 157.7 mg/dL (60.0-281.0 mg/dL). Three patients (13%) had thrombosis. At diagnosis, 21 patients (91.3%) had bruising, one patient (4.3%) had splenic vein and artery thrombosis and one patient (4.3%) presented without thrombohemorrhagic manifestations. During treatment, two patients (8.6%) had thrombosis. Conclusion: Knowledge of thrombosis in pediatric APL is important to determine its risk factors and the best way to treat and prevent this complication.

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The acrosome reaction (AR) is an exocytotic process essential for mammalian fertilization. It involves diverse physiological changes (biochemical, biophysical, and morphological) that culminate in the release of the acrosomal content to the extracellular medium as well as a reorganization of the plasma membrane (PM) that allows sperm to interact and fuse with the egg. In spite of many efforts, there are still important pending questions regarding the molecular mechanism regulating the AR. Particularly, the contribution of acrosomal alkalinization to AR triggering physiological conditions is not well understood. Also, the dependence of the proportion of sperm capable of undergoing AR on the physiological heterogeneity within a sperm population has not been studied. Here, we present a discrete mathematical model for the human sperm AR based on the physiological interactions among some of the main components of this complex exocytotic process. We show that this model can qualitatively reproduce diverse experimental results, and that it can be used to analyze how acrosomal pH (pH a ) and cell heterogeneity regulate AR. Our results confirm that a pH a increase can on its own trigger AR in a subpopulation of sperm, and furthermore, it indicates that this is a necessary step to trigger acrosomal exocytosis through progesterone, a known natural inducer of AR. Most importantly, we show that the proportion of sperm undergoing AR is directly related to the detailed structure of the population physiological heterogeneity.

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BACKGROUND: Kidney transplantation is the gold standard treatment for children with end-stage chronic kidney disease. Graft thrombosis is an important cause of graft failure, with high morbidity, mortality, and impact on quality of life and to the health system. The role of thromboprophylaxis in this setting is still uncertain. We describe the demographic characteristics and thrombotic risk factors in pediatric renal transplant recipients, determining the rate of renal graft thrombosis, and discuss the role of thromboprophylaxis. METHODS: This retrospective study reviewed 96 pediatric renal transplantations between 2008 and 2017 in a single hospital. Patients were assigned to one of two groups: children who did not receive thromboprophylaxis after transplantation and those who did. We reported their characteristics, comparing the incidence of graft thrombosis and hemorrhagic complications between the groups. RESULTS: Forty-nine patients (51%) received thromboprophylaxis. Thrombosis occurred in 5 patients who did not receive thromboprophylaxis (5.2%) compared with none in the group that did (p = .025). In all patients, renal graft thrombosis resulted in early graft loss. Thirteen patients had hemorrhagic complications. Seven were unrelated to pharmacological thromboprophylaxis (2 major, 1 moderate, and 4 minor bleeding, which either did not receive thromboprophylaxis or had bleeding prior to thromboprophylaxis), while six occurred during heparinization (2 major, 1 moderate, and 3 minor bleeding). There was no significant difference in the rate of hemorrhagic complications between the groups (p = .105). CONCLUSIONS: The rate of renal graft thrombosis was 5.2%. Thrombosis remains an important cause of early graft loss. Thromboprophylaxis was associated with a reduction in graft thrombosis without increased risk of bleeding.

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INTRODUCTION: Little attention is given to thrombosis associated with pediatric acute promyelocytic leukemia (APL). This study describes the thrombotic and hemorrhagic manifestations of APL in pediatric patients and evaluates their hemostasis, based on coagulation tests. METHODS: Inclusion criteria were age 0-18 years and APL diagnosis between April 2005 and November 2017. Patients who had received blood transfusion prior to coagulation tests were excluded. Baseline coagulation tests, hematologic counts, and hemorrhagic/thrombotic manifestations were evaluated. RESULTS: Median age was 10.7 years (1-15 years). The initial coagulation tests revealed a median Hgb of 8.3 g/dL (4.7-12.9 g/dL), median leucocyte count of 10.9 × 109/L (1.1-95.8 × 109/L), median platelet count of 31.8 × 109/L (2.0-109.0 × 109/L), median activated partial thromboplastin time (aPTT) of 31.7 s (23.0-50.4 s), median aPTT ratio of 1.0 (0.78-1.6), median thromboplastin time (PT) of 17.5 s (13.8-27.7 s), median PT activity of 62% (25-95 %), and median fibrinogen of 157.7 mg/dL (60.0-281.0 mg/dL). Three patients (13%) had thrombosis. At diagnosis, 21 patients (91.3%) had bruising, one patient (4.3%) had splenic vein and artery thrombosis and one patient (4.3%) presented without thrombohemorrhagic manifestations. During treatment, two patients (8.6%) had thrombosis. CONCLUSION: Knowledge of thrombosis in pediatric APL is important to determine its risk factors and the best way to treat and prevent this complication.

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Ensiling corn for longer periods is a strategy used to increase rumen bacteria access to starch. In fact, when corn is ensiled for insufficient periods, starch digestibility decreases, as evidenced by excreted starch. This study investigates the effects of corn silage ensiling time on starch digestibility of dairy cows through fecal starch analysis. The trial was conducted during the spring of 2013 and the fall of 2014 on twenty dairy herds located in the state of Paraná, southern Brazil. Total mixed ration (TMR), whole-plant corn silage (WPCS) and fecal samples were collected for determination of dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF), lignin and starch. Apparent total tract starch digestibility (ATTSD) was calculated using equations developed by Fredin et al. (2014) and Bal et al. (1997). Data were analyzed using the CORR, REG and GLM procedures of SAS. Spring and fall WPCS were ensiled for 260 and 132 days, respectively (p < 0.01). There was no difference (p > 0.05) in ATTSD-Fredin from season to season though there was a trend (p = 0.11) towards greater ATTSD-Bal for spring samples. ATTSD-Bal was positively correlated with ensiling days (r = 0.31). Starch digestibility was not negatively affected by WPCS harvesting maturity. Differences in post-ruminal starch digestion, variation between farms in DM intake and diets, limitations of the equations, influence of uncontrolled factors, and the small number of experimental units might have contributed to the absence of significant results. Overall, Bal et al. (1997) equation was more efficient in distinguishing ATTSD from different ensiling periods.(AU)

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Ensiling corn for longer periods is a strategy used to increase rumen bacteria access to starch. In fact, when corn is ensiled for insufficient periods, starch digestibility decreases, as evidenced by excreted starch. This study investigates the effects of corn silage ensiling time on starch digestibility of dairy cows through fecal starch analysis. The trial was conducted during the spring of 2013 and the fall of 2014 on twenty dairy herds located in the state of Paraná, southern Brazil. Total mixed ration (TMR), whole-plant corn silage (WPCS) and fecal samples were collected for determination of dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF), lignin and starch. Apparent total tract starch digestibility (ATTSD) was calculated using equations developed by Fredin et al. (2014) and Bal et al. (1997). Data were analyzed using the CORR, REG and GLM procedures of SAS. Spring and fall WPCS were ensiled for 260 and 132 days, respectively (p 0.05) in ATTSD-Fredin from season to season though there was a trend (p = 0.11) towards greater ATTSD-Bal for spring samples. ATTSD-Bal was positively correlated with ensiling days (r = 0.31). Starch digestibility was not negatively affected by WPCS harvesting maturity. Differences in post-ruminal starch digestion, variation between farms in DM intake and diets, limitations of the equations, influence of uncontrolled factors, and the small number of experimental units might have contributed to the absence of significant results. Overall, Bal et al. (1997) equation was more efficient in distinguishing ATTSD from different ensiling periods.

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The objective of this study was to assess the accuracy of the content of total mixed rations (TMR) offered to high-producing cows from 20 dairy herds of Castro, Paraná State, Brazil. The average milk yield during the sample collection period was 38.0±6.8 kg/day, with 3.47±0.25% milk fat and 3.05±0.18% milk protein. The particle size distribution of samples of fresh diet and leftovers was evaluated using the Penn State Particle Separator (PSPS) and chemical analysis was also conducted. The TMR homogeneity was estimated by the coefficient of variation (CV) of particles retained on the two intermediary sieves (1.18 mm), in which a CV higher than 5% indicated a poorly mixed TMR. The TMR offered exceeded the formulated TMR only for NDF (+7.3%) and was lower than the formulated TMR for CP (−6.5%), ADF (−10.1%), and ash (−18.6%) contents. These differences are due to daily variations in feed quality, mixing equipment, and ingredient mixing order, mostly for forage. Differences between leftovers and TMR offered were substantial: −9.4% for CP, +25.1% for NDF, +31.6% for ADF, and +13.1% for ash, suggesting a feed sorting effect against long forage particles and in favor of small concentrate particles. The proportion of the offered TMR retained in the top PSPS sieve showed positive correlations with NDF (r = 0.58) and ADF (r = 0.54) contents of the refusals, which indicates that cows sort against long particles. Positive correlations were also found between the CV in the second sieve and NDF (r = 0.56) and ADF (r = 0.47) contents of refusals, suggesting that poorly mixed diets are more easily sorted by cows. Therefore, evaluating the chemical and physical properties of TMR, especially for forage, is extremely important for providing a consistent diet.

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OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

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OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

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OBJECTIVE: To report a single-center experience with thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in preterm neonates with severe thrombotic events, in terms of thrombus resolution and bleeding complications. STUDY DESIGN: This retrospective study included 21 preterm neonates with severe venous thrombotic events admitted to the neonatal intensive care unit, identified in our pharmacy database from January 2001 to December 2016, and treated with rt-PA until complete or partial clot lysis, no-response or bleeding complications. Our primary outcome was thrombus resolution. RESULTS: Twenty-one preterm neonates were treated with rt-PA for an average of 2.9 cycles. Seventeen patients (80.9%) had superior vena cava thrombosis and superior vena cava syndrome. All patients had a central venous catheter, parenteral nutrition, mechanical ventilation, and sepsis. Fifteen patients (71.4%) were extremely preterm, 11 (52.4%) were extremely low birth weight, and seven (33.3%) were very low birth weight. The patency rate was 85.7%, complete lysis occurred in 11 (52.4%) patients, and partial lysis in seven (33.3%). Minor bleeding occurred in five (23.8%) patients, three patients (14.2%) had clinically relevant nonmajor bleeding events, and major bleeding occurred in six (28%) patients. CONCLUSION: In this study, the rate of thrombus resolution in preterm neonates treated with rt-PA were similar to the percentages reported in children and adolescents, with a high rate of bleeding. Therefore, rt-PA thrombolytic therapy should only be considered as a treatment option for severe life-threatening thrombosis in premature neonates for whom the benefits of the thrombolytic treatment outweigh the risks of bleeding.

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Hepatitis A vaccine is recommended for all individuals with hemophilia, although patients with bleeding disorders should avoid intramuscular (IM) injections. To date, only few studies showed subcutaneous (SC) route immunogenicity is comparable with the IM route. Therefore, this randomized study compared immunogenicity, long term protection and safety of hepatitis A vaccine administered by SC route with the IM route in 78 children and adults with hemophilia and other bleeding disorders. Thirty-eight patients had serology performed after first vaccine dose, determining seroconversion rates of 83.3% and 90.0% for the SC and the IM group, respectively (p = 0.5). Median IgG CO/OD value for the SC group was almost the double compared with the IM group (4.4 vs 2.6, p = 0.2). After second vaccine dose, seroconversion rates for the SC group was 97.5% and for the IM group was 97.4% (p = 1.0). Of the two patients who did not have seroconversion, interval between vaccine dose and serology was only one and two days for the SC and the IM group, respectively and in the following routine antibody dosage they presented seroconversion (100% for both groups). Median IgG CO/OD value for the SC group was greater than the IM group (72.5 vs. 58.0, p = 0.2). In a median of nine years after second vaccine dose, median IgG S/CO value for the SC group was slightly greater than the IM group (7.6 vs. 7.4, p = 0.8). There were no serious adverse events in both groups. Five (12.5%) patients of the SC group and seven (18.4%) of the IM group presented adverse events (p = 0.5). Twice as many patients of the IM group had clotting factor concentrates need for adverse events (15.8% vs. 7.5%, p = 0.3). Therefore, hepatitis A vaccine administered subcutaneously is as immunogenic, long term protective and even safer than the intramuscular route.

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