Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department.

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Prevalence, diagnostic utility, and clinical characteristics of ZnT8 antibody in children with type 1 diabetes in Northern Taiwan.

BACKGROUND: The ZnT8 autoantibody is used to independently diagnose type 1 diabetes (T1D) and as a prediction factor in high-risk populations. This is the first report in Taiwan on the prevalence, diagnostic utility, and clinical characteristics of zinc transporter 8 autoantibody (ZnT8A) in children with T1D. METHODS: We performed a retrospective analysis of 268 children (130 boys, 138 girls) newly diagnosed with T1D at three hospitals in North Taiwan from February 1994 to August 2021. RESULTS: ZnT8A was detected in 117 patients (43.7 %). The combined diagnostic rate of the four antibodies, including glutamic acid decarboxylase autoantibody (GADA), islet antigen 2 autoantibody (IA2A), insulin autoantibody (IAA), and ZnT8A, can reach 86.19 % while that of the original three antibodies is 84.3 %. IA2A (64.9 %) showed the highest positive rate, followed by GADA (64.2 %), ZnT8A (43.7 %), and IAA (22.0 %). Of the 268 patients, five (1.9 %) were only ZnT8A+. All antibodies were positive in 19 (7.1 %) people, whereas 37 others (13.8 %) had all antibodies negative. ZnT8A has the strongest relationship with IA2A. 5 patients had ZnT8A positive only. 5/(37 + 5) (about 12 %) T1D patients were diagnosed by ZnT8A testing. CONCLUSIONS: ZnT8A testing can diagnose up to 12 % more patients with T1D along with three other antibodies. Furthermore, since the ZnT8A titer decreased over time, it should be tested within six months of onset in Taiwanese patients with T1D.

Influencing factors for treatment escalation from metformin monotherapy in youth-onset type 2 diabetes in Northern Taiwan.

With the increasing prevalence of obesity, childhood type 2 diabetes (T2D) is a growing concern in Taiwan. Unlike its adult counterpart, T2D in children exhibits a more aggressive nature and earlier onset of complications. Metformin represents the first line of drug, but if blood sugar levels do not improve, other drugs are used. This retrospective cohort study endeavors to scrutinize and assess the pattern of treatment modification and associate factors among 79 young people with T2D in Taiwan. The study categorized participants into three distinct groups based on their treatment trajectory and outcomes: (1) those maintaining metformin (n = 34); (2) cases achieving remission (n = 7); and (3) individuals experiencing escalation through oral drugs or insulin (n = 38). The average follow-up period spanned 3.48 years. Findings from univariate analysis using a Cox proportional hazards model and propensity score weighting revealed that HbA1c and weight gain correlated with elevated risk of treatment escalation. Conversely, factors such as hypertension, high weight or body mass index (BMI) SDS, leptin levels, c-peptide concentrations, peak c-peptide values during glucagon stimulation test and LDL-cholesterol levels were associated with reduced risk of escalation. However, in multivariate analyses employing stepwise selection, the sole predictive factor for treatment escalation emerged as weight gain one year post-therapy (HR: 1.06, p < 0.001). This study underscores the interconnectedness between weight management and the trajectory toward either treatment escalation or disease remission. Furthermore, it highlights the cost-effective potential of intervening in younger populations. Ultimately, these insights accentuate the considerable opportunity for enhancing health care management strategies concerning pediatric T2D in Taiwan.

Ferritin as an Effective Predictor of Neurological Outcomes in Children With Acute Necrotizing Encephalopathy.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a fulminant disease with poor prognosis. Cytokine storm is the important phenomenon of ANE that affects the brain and multiple organs. The study aimed to identify whether hyperferritinemia was associated with poor prognosis in patients with ANE. METHODS: All patients with ANE had multiple symmetric lesions located in the bilateral thalami and other regions such as brainstem tegmentum, cerebral white matter, and cerebellum. Neurological outcome at discharge was evaluated by pediatric neurologists using the Pediatric Cerebral Performance Category Scale. All risk factors associated with poor prognosis were further analyzed using receiver operating characteristic curve analysis. RESULTS: Twenty-nine patients with ANE were enrolled in the current study. Nine (31%) patients achieved a favorable neurological outcome, and 20 (69%) patients had poor neurological outcomes. results The group of poor neurological outcome had significantly higher proportion of shock on admission and brainstem involvement. Based on multivariate logistic regression analysis, ferritin, aspartate aminotransferase (AST), and ANE severity score (ANE-SS) were the predictors associated with outcomes. The appropriate cutoff value for predicting neurological outcomes in patients with ANE was 1823 ng/mL for ferritin, 78 U/L for AST, and 4.5 for ANE-SS. Besides, comparison analyses showed that higher level of ferritin and ANE-SS were significantly correlated with brainstem involvement (P < 0.05). CONCLUSIONS: Ferritin may potentially be a prognostic factor in patients with ANE. Hyperferritinemia is associated with poor neurological outcomes in patients with ANE and ferritin levels more than 1823 ng/mL have about eightfold increased risk of poor neurological outcome.

Diastolic blood pressure impact on pediatric refractory septic shock outcomes.

BACKGROUND: Septic shock is the progression of sepsis, defined as cardiovascular dysfunction during systemic infection, and it has a mortality rate of 40 %-80 %. Loss of vascular tone is an important pathophysiological feature of septic shock. Diastolic blood pressure (DBP) was reported to be associated with vascular tone. This study aimed to identify the associations of several hemodynamic indices, especially DBP, with outcome in pediatric septic shock to allow for timely interventions. METHODS: Children with persistent catecholamine-resistant shock had a pulse index continuous cardiac output (PiCCO®) system implanted for invasive hemodynamic monitoring and were enrolled in the current study. Serial cardiac index, systemic vascular resistance index (SVRI), systolic blood pressure (SBP), mean arterial pressure (MAP), and DBP were recorded during the first 24 h following PiCCO® initiation. All hemodynamic parameters associated with 28-day mortality were further analyzed using receiver operating characteristic curve analysis. RESULTS: Thirty-three children with persistent catecholamine-resistant shock were enrolled. The median age was 12 years and the youngest children were 5 years old. Univariate analysis noted that SVRI, SBP, MAP, and DBP were significantly higher, and shock index was significant lower, in survivors compared with non-survivors (p < 0.05). In the multivariate analysis, only SVRI and DBP remained independent predictors of 28-day mortality. DBP had the best correlation with SVRI (r = 0.718, n = 219, p < 0.001). The area under the receiver operating characteristic curves of SVRI and DBP for predicting 28-day mortality during the first 24 h of persistent catecholamine-resistant shock were >0.75, indicating a good prediction for mortality. CONCLUSIONS: DBP correlated well with SVRI and it can serve as a predictor for mortality in pediatric septic shock. Furthermore, DBP was a superior discriminator of mortality when compared with SBP and MAP. A lower DBP was an independent hemodynamic factor associated with 28-day mortality.

Predictors of disease severity and outcomes in pediatric patients with croup and COVID-19 in the pediatric emergency department.

BACKGROUND: Croup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited. The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). POPULATION AND METHOD: Patients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. RESULT: In total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥3 was 0.895 (0.842-0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711-0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. CONCLUSION: NLR is correlated with WS and is a reliable, easy-to-use, and cheap biomarker for the early screening and prognosis of croup severity in the PED. A higher NLR may indicate severe croup and the need for further treatment. And the WS score remains reliable for estimating the severity of croup caused by SARS-CoV-2 and the risk of intensive care.

Risk Factors for Tracheobronchomalacia in Preterm Infants With Bronchopulmonary Dysplasia.

Aim: To identify the risk factors associated with the development of tracheobronchomalacia (TBM) in preterm infants with bronchopulmonary dysplasia (BPD). Methods: This was a retrospective cohort study using chart reviews of preterm infants born at ≤ 36 week's gestation who underwent flexible fiberoptic bronchoscopy in a tertiary pediatric referral center between January 2015 and January 2020. Indications for the bronchoscopy examination included lobar atelectasis on plain chest film, persistent CO2 retention, recurrent extubation failure, or abnormal breathing sounds such as wheeze or stridor. Optimal cutoff values for each risk factor were also determined. Results: Fifty-eight preterm infants with BPD were enrolled, of whom 29 (50%) had TBM. There were no significant differences in gestational age and birth weight between those with and without TBM. Significantly more of the patients with TBM had severe BPD compared to those without TBM (68.9 vs. 20.6%, p < 0.001). Clinical parameters that were significantly different between the two groups were included in multivariate analysis. Among these factors, severe BPD was the most powerful risk factor for the development of TBM (odds ratio 5.57, 95% confidence interval 1.32-23.5, p = 0.019). The areas under the receiver operating characteristic curves for peak inspiratory pressure (PIP) and the duration of intubation were 0.788 and 0.75, respectively. The best predictive cutoff values of PIP and duration of intubation for TBM were 18.5 mmHg and 82 days, respectively. Conclusion: Preterm infants with severe BPD are at high risk for the development of TBM, and the risk is even higher in those who receive a higher PIP or are intubated for longer. Bronchoscopy examinations should be considered for the early diagnosis and management of TBM in infants with these risk factors.

Vascular Reactivity Index as an Effective Predictor of Mortality in Children With Refractory Septic Shock.

BACKGROUND: Vasoplegia is vascular hyporesponsiveness to vasopressors and is an important phenomenon in children with refractory septic shock. This study aimed to develop an objective formula correlated with vasoplegia and evaluate the predictive power for mortality in children with refractory septic shock. MATERIALS AND METHODS: We retrospectively analyzed children with refractory septic shock admitted to a pediatric intensive care unit (PICU) and monitored their hemodynamics via a pulse index continuous cardiac output (PiCCO) system. Serial hemodynamic data including cardiac index (CI), systemic vascular resistant index (SVRI) and vasoactive-inotropic score (VIS) were recorded during the first 72 hours after PICU admission. We defined vascular reactivity index (VRI) as SVRI/VIS and analyzed the effect of VRI in predicting mortality in children with refractory septic shock. RESULTS: Thirty-three children with refractory septic shock were enrolled. The SVRI was lower in the mortality group compared to the survival group (P < .05). The average area under the receiver operating characteristic curve of VRI within the first 72 hours was 0.8 and the serial values of VRI were significantly lower in the mortality group during the period from 0 to 48 hours (P < .05). However, there were no significant differences in serial CI values between the survival and mortality groups. CONCLUSIONS: Vasoactive-inotropic score may potentially be used to quantify the severity of vasoplegia based on the clinical response of vessels after resuscitation with vasopressors. Lower VRI levels may indicate a higher risk of mortality in children with septic shock.

Factors Associated With In-hospital Mortality of Children With Acute Fulminant Myocarditis on Extracorporeal Membrane Oxygenation.

Aim: To analyze the factors associated with in-hospital mortality of children with acute fulminant myocarditis on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods: This was a retrospective cohort study using chart reviews of patients diagnosed with acute fulminant myocarditis at the pediatric intensive care unit of two tertiary medical centers between January 1, 2005 and December 31, 2017. The inclusion criteria for this study were: (1) age from 1 month to 18 years; (2) diagnosed with acute myocarditis; (3) cardiogenic shock and need vasoactive-inotropic score ≥20 within 48 h after the use of vasoactive-inotropic agents; and (4) the need for ECMO placement. Results: Thirty-three children with acute fulminant myocarditis who needed ECMO were included. Clinical parameters were retrospectively reviewed. The overall survival rate was 69.6%. Higher levels of pre-ECMO troponin-I and pre-ECMO lactate, and lower post-ECMO left ventricular ejection fraction (LVEF) were significantly associated with in-hospital mortality in univariate analysis. Only higher pre-ECMO lactate and lower post-ECMO LVEF remained as predictors for in-hospital mortality in multivariate analysis. The areas under the curve of pre-ECMO lactate and post-ECMO LVEF in predicting survival were 0.848 (95% CI, 0.697-0.999, p = 0.002) and 0.824 (95% CI, 0.704-0.996, p = 0.01), respectively. A pre-ECMO lactate level of 79.8 mg/dL and post-ECMO LVEF of 39% were appropriate cutoff points to predict mortality. Conclusion: Pre-ECMO lactate level was associated with mortality in children with acute fulminant myocarditis, with an optimal cutoff value of 79.8 mg/dL. After VA-ECMO implantation, post-ECMO LVEF was associated with mortality, with an optimal cutoff value of 39%. The use of LVADs or urgent heart transplantation should be considered if the post-ECMO LVEF does not improve.

Comparison of Predictive Powers for Mortality between Systemic Vascular Resistance Index and Serum Lactate in Children with Persistent Catecholamine-Resistant Shock.

Persistent catecholamine-resistant shock in children causes severe morbidity and mortality. We aimed to analyze the association between hemodynamics and serum lactate at different time points and 28-day mortality in children with persistent catecholamine-resistant shock. Methods. Twenty-six children with persistent catecholamine-resistant shock were enrolled, and their hemodynamics were monitored using the pulse index continuous cardiac output. Serial cardiac index (CI), systemic vascular resistant index (SVRI), and vasoactive-inotropic score (VIS) were analyzed for the first 24 hours. Associations between hemodynamics, serum lactate, and 28-day mortality were analyzed. Results. The 28-day mortality rate was 53.8%. SVRI and VIS were independent predictors of 28-day mortality. The mortality group had lower serial SVRI and higher VIS than the survival group (p < 0.05). Serial SVRI had the highest area under the receiver operating characteristic curve (AUC) for predicting mortality during the first 24 hours of persistent catecholamine-resistant shock. Three important hemodynamic parameters, CI, SVRI and perfusion pressure (MAP-CVP), were significantly correlated with lactate, of which SVRI had the best correlation (r = -0.711, p < 0.001). According to the AUC, SVRI was a more powerful predictor of mortality than lactate in persistent catecholamine-resistant shock. After 24 hours of treatment for persistent catecholamine-resistant shock, an SVRI lower than 1284 dyn·s·cm-5·m2 was associated with 28-day mortality. Conclusions. SVRI was an early factor associated with mortality in the pediatric patients with persistent catecholamine-resistant shock potentially and had the good correlation with serum lactate. An SVRI more than 1284 dyn·s·cm-5·m2 during the first 24 hours of persistent catecholamine-resistant shock was associated with favorable outcomes. The result should be used with caution due to the small sample size.

Clinical Significance of Nadir Hemoglobin in Predicting Neurologic Outcome in Infants With Abused Head Trauma.

Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality and is categorized as abusive head trauma (AHT) and accidental head injury. A retrospective chart review of 124 children aged <1 year diagnosed with TBI were analyzed. Outcomes were evaluated at discharge and 6 months later by using the Pediatric Cerebral Performance Category (PCPC) Scale. The receiver operating characteristic (ROC) curve was applied to determine the cutoff values for hemoglobin (HB) levels. In the study, 50 infants (40.3%) achieved a favorable neurologic outcome (PCPC ≦ 2) and 74 (59.7%) had poor neurologic outcomes (PCPC ≧ 3). Infants with poor neurologic outcomes had lower HB on admission and nadir HB (p < 0.05). Based on multivariate logistic regression analysis, the nadir HB was a predictor of poor neurologic outcomes at discharge and 6 months later in both AHT and accidental head injury. Nadir HB had the largest area under the ROC curve for predicting poor neurologic outcomes. We determined the appropriate cutoff value of nadir HB as 9.35 g/dl for predicting neurologic outcomes in infants with TBI. Furthermore, the cutoff value of nadir HB in predicting poor neurologic outcomes in infants caused by AHT and accidental head injury were taken as 9.36 and 8.75 g/dl, respectively.

Improved Production of Spores and Bioactive Metabolites from Bacillus amyloliquefaciens in Solid-state Fermentation by a Rapid Optimization Process.

A dipicolonic acid fluorimetry assay was used instead of plate counting for the assessment of spore yields for enhanced optimization efficiency. The associated parameters, including the ratio of solid substrates, composition of liquid substrates, and cultivation conditions, were systematically optimized in a shake-flask culture. The maximum spore yield of 7.24 × 1010 CFU/g of wet substrate was achieved. The optimization process produced a 25.7-fold increase in spore yields compared with those before optimization. In addition, the maximum release of bioactive metabolites during spore accumulation was subsequently obtained with 573.0 U/g of protease, 188.8 U/g of amylase, 186.8 U/g of cellulase, and 3.45 mg/g of acid-soluble protein. The experiment provides a methodological basis for the rapidly optimized production of Bacillus spores in pure solid-state fermentation.

Strong correlation between doppler snuffbox resistive index and systemic vascular resistance in septic patients.

PURPOSE: To compare systemic vascular resistance index (SVRI) as measured by invasive transpulmonary indicator dilution (TPID) and non-invasive Doppler-derived resistive index in septic patients. METHODS: We measured the snuffbox resistive index (SBRI) in both hands of septic patients who received hemodynamic monitoring by TPID prospectively. RESULTS: Thirty-six patients with septic shock were enrolled (median acute physiology and chronic health evaluation II score: 23; median age: 64 years). Four SBRI values were measured in each patient, for a total of 96 patient days and 951 ultrasound measurements. The correlation coefficients between SVRI and the four SBRI values were all higher than 0.87 (p < .001). A higher SVRI was associated with sharp waveforms and reversed diastolic flow. A resistive index (RI) of 0.97 was the lower limit of normal SVRI (1700 dyn*s*cm-5*m2), and an RI of 1.1 was the upper limit of normal SVRI (2400 dyn*s*cm-5*m2). CONCLUSIONS: Using ultrasound to measure RI is a noninvasive, inexpensive, reliable method to evaluate peripheral vascular resistance in septic patients, and it is highly correlated with SVRI. In addition, SBRI can be used to evaluate peripheral circulatory disturbances in septic patients.

Rapid optimization of spore production from Bacillus amyloliquefaciens in submerged cultures based on dipicolinic acid fluorimetry assay.

Some optimization techniques have been widely applied for spore fermentation based on the plate counting. This study optimized the culture medium for the spore production of Bacillus amyloliquefaciens BS-20 and investigated the feasibility of using a dipicolonic acid (DPA) fluorimetry assay as a simpler alternative to plate counting for evaluating spore yields. Through the single-factor experiment, the metal ions and agro-industrial raw materials that significantly enhanced spore production were determined. After conducting a response surface methodology (RSM) analysis of several metal ions, the combined use of optimum concentrations of Mn2+, Fe2+, and Ca2+ in culture media produced a 3.4-fold increase in spore yields. Subsequently, supplementing soybean meal and corn meal with optimum concentrations determined by another RSM analysis produced an 8.8-fold increase. The final spore concentration from a culture medium incorporating optimum concentrations of the metal ions and raw materials mentioned above was verified to reach (8.05 ± 0.70) × 109 CFU/mL by both DPA fluorimetry and plate counting. The results suggest that the use of DPA fluorescence intensity as an alternative value to colony counting provides a general method for assessing spore yields with less work and shorter time.