Fibrinolytic Impairment and Mortality in Pediatric Septic Shock: A Single-Center Prospective Observational Study.

OBJECTIVES: Fibrinolytic shutdown is associated with poor prognosis in adult sepsis, but data in the pediatric population are sparse. This study aimed to identify the association between impaired fibrinolysis and mortality in pediatric septic shock. DESIGN: A prospective, observational study conducted between August 2019 and August 2020. SETTING: PICU at a pediatric tertiary hospital in Hanoi, Vietnam. PATIENTS: Fifty-six pediatric patients who met septic shock criteria were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Conventional coagulation tests and rotational thromboelastometry were performed at diagnosis. The fibrinolytic activity on extrinsic pathway thromboelastometry was negatively correlated with the Vasoactive-Inotropic Score at 24 hours post-PICU admission, peak lactate level during the first 24 hours, Pediatric Logistic Organ Dysfunction-2 score, and Pediatric Risk of Mortality-III score (all p < 0.05). Compared with patients with nonovert disseminated intravascular coagulation, dysfunction of less than two organs, and who survived, patients with overt disseminated intravascular coagulation, dysfunction of greater than two organs, and who died showed significantly lower fibrinolytic activity, represented by significantly higher lysis indexes (%) and lower maximum lysis (%) (all p < 0.05). The threshold values for prediction of mortality were lysis index 60 minutes greater than 97.5 (area under the curve = 0.86; sensitivity = 73%; specificity = 90%), maximum lysis less than 6.5 (area under the curve = 0.83; sensitivity = 73%; specificity = 87%), and lysis index 45 minutes greater than 99.5 (area under the curve = 0.83; sensitivity = 73%; specificity = 85%). Hypofibrinolysis was associated with prolonged PICU length of stay in survivors and with early mortality in nonsurvivors. CONCLUSIONS: Fibrinolytic shutdown in pediatric septic shock is associated with an increase in disease severity and mortality. This highlights the need for further investigations regarding whether fibrinolytic therapy improved the outcome of pediatric septic shock.

Pertussis Infants Needing Mechanical Ventilation and Extracorporeal Membrane Oxygenation: Single-Center Retrospective Series in Vietnam.

OBJECTIVES: Pertussis is an infectious disease that causes epidemics and outbreaks and is associated with a high mortality rate, especially in infants, in both developed and developing countries. We aimed to characterize infants with pertussis with respiratory failure and shock and investigated the factors related to mortality. DESIGN: A retrospective, observational study conducted between January 2015 and October 2020. SETTING: This study was conducted at the Vietnam National Children's Hospital, which is a government hospital that serves as a tertiary care center in Hanoi, Vietnam. PATIENTS: Children who fulfilled the following inclusion criteria were included: 1) admitted to the PICU, 2) less than 16 years old, 3) pertussis confirmed by real-time polymerase chain reaction, and 4) treated with mechanical ventilation due to respiratory failure and shock. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Seventy-three mechanically ventilated children (40 boys; median age, 56 d), whereas 19 patients received extracorporeal membrane oxygenation support. Twenty-six patients (36%) died including 12 who received extracorporeal membrane oxygenation. Those who received extracorporeal membrane oxygenation support had higher leukocyte counts upon admission and were more frequently diagnosed with pulmonary hypertension and stage 3 acute kidney injury. Compared with survivors, nonsurvivors showed increased heart rates, leukocyte and neutrophil counts, and lower systolic and diastolic blood pressure at admission. Increased Vasoactive-Inotropic Score, stage 3 acute kidney injury, fluid overload, the use of renal replacement therapy, and extracorporeal membrane oxygenation use were prevalent among nonsurvivors. CONCLUSIONS: In this study, around one third of mechanically ventilated patients with pertussis died. Those who received extracorporeal membrane oxygenation had higher leukocyte counts, a higher prevalence of pulmonary hypertension, and advanced stages of acute kidney injury. Higher Vasoactive-Inotropic Score and advanced stages of acute kidney injury were associated with a greater risk of mortality.

A New Technique in Alveolar Cleft Bone Grafting for Dental Implant Placement in Patients With Cleft Lip and Palate.

OBJECTIVE: To evaluate 2 iliac corticocancellous-block grafting techniques for dental implant placement in residual alveolar clefts. DESIGN: Nonrandomized prospective clinical trial between March 2010 and December 2014. SETTING: National Hospital of Odonto-Stomatology, Hanoi, Vietnam. PARTICIPANTS: Thirty-two patients (23 female, 9 male; mean age, 21.28 years; range, 16-31 years) with unilateral complete alveolar cleft after reconstructive surgery for cleft lip and palate (CLP). INTERVENTIONS: Harvested iliac crest bone was cut into 2 corticocancellous blocks. The smaller block was adapted against the sutured nasal mucoperiosteum and overlaid with cancellous bone; the larger one overlapped the labial cleft margin and was fixed with screws. Endosteal dental implants were placed after 4 to 6 months, and final restorations were delivered 6 months later. MAIN OUTCOME MEASURES: Flap statuses were assessed clinically. Bone formation was assessed using the Enemark scale. Cone-beam computed tomography was used for graft height and width measurements. Implant health was assessed by the Misch criteria. RESULTS: The mean postgrafting follow-up period was 36.7 ± 10.4 (range, 18-53) months. Three patients (9.4%) showed flap dehiscence but no infection 7 days after bone grafting. Twenty-nine patients (90.6%) had 75% to 100% bone fill (Enemark score of 1). The mean graft height and width were 11.4 ± 2.4 and 6.1 ± 1.0 mm, respectively. Sufficient bone for implant placement was noted in 29 patients (90.6%); the others required partially fixed prostheses. All implants functioned for at least 18 months. CONCLUSION: The proposed technique is reliable to reconstruct the alveolar cleft for implant placement in CLP patients.

Neonatal neural networks predict children behavioral profiles later in life.

This study aimed to examine heterogeneity of neonatal brain network and its prediction to child behaviors at 24 and 48 months of age. Diffusion tensor imaging (DTI) tractography was employed to construct brain anatomical network for 120 neonates. Clustering coefficients of individual structures were computed and used to classify neonates with similar brain anatomical networks into one group. Internalizing and externalizing behavioral problems were assessed using maternal reports of the Child Behavior Checklist (CBCL) at 24 and 48 months of age. The profile of CBCL externalizing and internalizing behaviors was then examined in the groups identified based on the neonatal brain network. Finally, support vector machine and canonical correlation analysis were used to identify brain structures whose clustering coefficients together significantly contribute the variation of the behaviors at 24 and 48 months of age. Four meaningful groups were revealed based on the brain anatomical networks at birth. Moreover, the clustering coefficients of the brain regions that most contributed to this grouping of neonates were significantly associated with childhood internalizing and externalizing behaviors assessed at 24 and 48 months of age. Specially, the clustering coefficient of the right amygdala was associated with both internalizing and externalizing behaviors at 24 months of age, while the clustering coefficients of the right inferior frontal cortex and insula were associated with externalizing behaviors at 48 months of age. Our findings suggested that neural organization established during fetal development could to some extent predict individual differences in behavioral-emotional problems in early childhood. Hum Brain Mapp 38:1362-1373, 2017. © 2016 Wiley Periodicals, Inc.

Adenovirus Type 7 Pneumonia in Children Who Died from Measles-Associated Pneumonia, Hanoi, Vietnam, 2014.

During a 2014 measles outbreak in Vietnam, postmortem pathologic examination of hospitalized children who died showed that adenovirus type 7 pneumonia was a contributory cause of death in children with measles-associated immune suppression. Adenovirus type 7 pneumonia should be recognized as a major cause of secondary infection after measles.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes.

Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine-phosphate-guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine-phosphate-guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.

Reference Value Fibrin Monomer in Healthy Children: A Cross-Sectional Study.

The objective of this study is to determine the fibrin monomer reference intervals in healthy children. This cross-sectional study was conducted in the Hematology Department at Vietnam National Children's Hospital (April 2023 to March 2024). Children without prior history of clotting disorders or anticoagulants use hospitalized in preparation for orthopedic surgery or inguinal hernia surgery were enrolled in the study. The fibrin monomer test method was the quantitative fibrin monomer test on the STA-R system (Diagnostica Stago™, France). Eighty-six children (58 males and 28 females) were enrolled in the study. The median (interquartile range, 2.5th-97.5th) fibrin monomer value of the study subjects was 2.56 (0.11-5.93) µg/mL, with no statistically significant difference in fibrin monomer values among the age groups of 1 month to 3 years, 3 years to 13 years, and 13 years to 18 years. This is the first study conducted in Vietnam to determine reference values of fibrin monomer in children. This information can help in the diagnosis and treatment of early hypercoagulation stage and disseminated intravascular coagulation in children.

First confirmed case of infant botulism caused by Clostridium botulinum type A(B) in a 10-month-old infant in Hanoi, Vietnam.

Infant botulism is a rare but sometimes life-threatening toxemia caused by ingestion of Clostridium botulinum spores. Although cases of infant botulism have probably occurred in Vietnam in the past, they have never been diagnosed and reported. Herein, we report the isolation of C. botulinum type A(B) from the stool of a 10-month-old infant during hospitalization.

Hypocoagulable Tendency on Thromboelastometry Associated With Severity and Anticoagulation Timing in Pediatric Septic Shock: A Prospective Observational Study.

Objective: To identify whether coagulation profiles using thromboelastometry are associated with outcomes in pediatric septic shock. The primary outcomes were the development of disseminated intravascular coagulation (DIC) and the severity of the pediatric intensive care unit (PICU) existing scoring systems, while the secondary outcome was hospital mortality. This study aimed to contribute to current findings of the limitations of conventional tests in determining the optimal timing of anticoagulation in sepsis. Design: A prospective, observational study conducted between August 2019 and August 2020. Setting: PICU at a pediatric tertiary hospital in Hanoi, Vietnam. Patients: Fifty-five pediatric patients who met the septic shock criteria were enrolled. Measurements and Main Results: Fifty-five patients with septic shock were recruited. At the time of diagnosis, thromboelastometry revealed normocoagulability, hypercoagulability, and hypocoagulability in 29, 29, and 42% of the patients, respectively (p > 0.05); however, most patients in the overt DIC and non-survival groups progressed to hypocoagulability (82 and 64%, respectively). The overt DIC, PELOD-2 > 8, PRISM-III > 11, and non-survival group had a significant hypocoagulable tendency according to thromboelastometry parameters [prolonged clotting time (CT) and clot formation time (CFT); and reduced α-angle (α), maximum clot firmness (MCF), thrombodynamic potential index (TPI)] compared to the non-overt DIC, PELOD-2 ≤ 8, PRISM-III score ≤ 11 and survival group (p < 0.05). Conventional parameters between the normocoagulable and hypercoagulable groups were not different (p > 0.05). Hypocoagulability was characterized by lower platelet count and fibrinogen level, higher prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), and higher D-dimer level than in hypercoagulability (p < 0.05). Hypocoagulable tendency on thromboelastometry had a higher hazard at a PT > 16.1 s [area under the curve (AUC) = 0.747, odds ratio (OR) = 10.5, p = 0.002], INR > 1.4 (AUC = 0.754, OR = 6.9, p = 0.001), fibrinogen <3.3 g/L (AUC = 0.728, OR = 9.9, p = 0.004), and D-dimer > 3,863 ng/mL (AUC = 0.728, OR = 6.7, p = 0.004). Conclusions: Hypocoagulable tendency using thromboelastometry is associated with the severity of septic shock. Conventional coagulation tests may fail to detect hypercoagulability, which is crucial in determining anticoagulation timing.

Pediatric Acute Myocarditis With Short-Term Outcomes and Factors for Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study in Vietnam.

Objective: Data on the management and outcomes of acute myocarditis treated with extracorporeal membrane oxygenation (ECMO) among low- and middle-income countries are limited. This study aimed to determine the short-term outcomes and also identify factors associated with ECMO use among children with acute myocarditis at a tertiary children's hospital in Vietnam. Methods: A single-center, retrospective observational study was conducted between January 2016 and February 2021. Pediatric patients with acute myocarditis, aged 1 month to 16 years, were included. Results: In total, 54 patients (male, 46%; median age, 7 years) with acute myocarditis were included; 37 of them received ECMO support. Thirty percent (16/54) of the patients died, and 12 of them received ECMO. Laboratory variables that differed between survivors and non-survivors included median left ventricular ejection fraction (LVEF) at 48 h (42 vs. 25%; p = 0.001), platelet count (304 g/L [interquartile range (IQR): 243-271] vs. 219 g/L [IQR: 167-297]; p = 0.014), and protein (60 g/dl [IQR: 54-69] vs. 55 [IQR: 50-58]; p = 0.025). Among patients who received ECMO, compared with the survivors, non-survivors had a low LVEF at 48 h (odds ratio (OR), 0.8; 95% confidence interval (CI): 0.6-0.9; p = 0.006) and high vasoactive-inotropic score (OR, 1.0; 95% CI: 1.0-1.0; p = 0.038) and lactate (OR, 2.8; 95% CI, 1.2-6.1; p = 0.013) at 24 h post-ECMO. Conclusions: The case fatality rate among children with acute myocarditis was 30 and 32% among patients requiring ECMO support. Arrhythmia was an indicator for ECMO in patients with cardiogenic shock.

Hippocampal-cortical structural connectivity disruptions in schizophrenia: an integrated perspective from hippocampal shape, cortical thickness, and integrity of white matter bundles.

Disruptions in the hippocampal-cortical functional connectivities have been implicated in schizophrenia but less is known about their anatomical disconnectivities and association with clinical symptoms. We assessed the anatomical relationships between hippocampal shape, cortical thickness, and integrity of white matter bundles interconnecting them in this study. A brain mapping technique, large deformation diffeomorphic metric mapping, was used to analyze structural magnetic resonance imaging and diffusion tensor imaging scans of 126 schizophrenia patients and 77 matched healthy controls. We found that schizophrenia patients had surface inward-deformation in bilateral anterior hippocampi and cortical thinning in the regions of bilateral prefrontal, temporal, and occipital cortices compared with healthy controls. Anterior hippocampal shape deformity was associated with cortical thinning in the brain regions involved in visuo-spatial and verbal memory pathways. Canonical analysis revealed that greater disruptions in the hippocampal-cortical connectivity were associated with more severe negative symptoms in schizophrenia. Furthermore, fractional anisotropy in the fornix and cingulum bundles were reduced indicating abnormal integration of white matter between hippocampus and cortex in schizophrenia. Our findings suggested that aberrant structural hippocampal-cortical connectivities may serve as a marker of the illness and provide further structural evidence to support the notion of schizophrenia as a disorder of brain connectivity.

Adaptation of brain functional and structural networks in aging.

The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

COMT haplotypes modulate associations of antenatal maternal anxiety and neonatal cortical morphology.

OBJECTIVE: Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development. METHOD: A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy. RESULTS: Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that among rs737865-val158met-rs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex. CONCLUSIONS: These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.

Inattention and hyperactivity predict alterations in specific neural circuits among 6-year-old boys.

OBJECTIVE: Assessment of inattention and hyperactivity in preschoolers is highly dependent upon parental reports. Such reports are compromised by parental attitudes and mental health. Our study aimed to examine associations of inattention and hyperactivity/impulsivity from maternal reports on the Conners' Parent Rating Scale (CPRS) with brain morphology assessed using structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in 6-year-old boys. METHOD: Large deformation diffeomorphic metric brain mapping was used to assess brain morphology on MRI and DTI in 96 six-year-old boys, including cortical thickness, subcortical shapes, and fractional anisotropy (FA) of deep white matter tracts (DWMTs). Linear regression examined associations between these measures of brain structures and mothers' CPRS ratings of their child's inattention and hyperactivity/impulsivity. RESULTS: Our results revealed that temporal and parietal cortices, as well as posterior white matter and callosal tracts are associated with inattention and hyperactivity/impulsivity symptoms among six-year-old boys. Inattention and hyperactivity/impulsivity symptoms share common neural circuits, but hyperactivity/impulsivity ratings associate with more extensive cortical areas, such as frontal regions, and with white matter tracts emphasizing executive control. There were no associations detected between inattention (or hyperactivity/impulsivity) and the shape of subcortical structures. CONCLUSIONS: Our results suggested specific rather than widespread neural circuits involved in inattention and hyperactivity/impulsivity in young children, which is congruent with existing findings in older children and adolescents, and in adults with attention-deficit/hyperactivity disorder (ADHD). Hence, our study supported the dimensional view of ADHD, that is, that symptoms of inattention and hyperactivity/impulsivity lie on a continuum.