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Purpose@#The parents of adolescents with inflammatory bowel disease may experience impaired mental health and quality of life. This longitudinal study aimed to verify whether the mental health and quality of life of the parents of adolescents with inflammatory bowel disease declined when their children had active disease. @*Methods@#Sociodemographic data, parental anxiety, depression, and quality of life were analyzed using validated questionnaires for each variable. After the baseline survey, the second and follow-up surveys were conducted at 3 and 12 months, respectively. The active disease group comprised eight parents whose children had active disease during the baseline and second surveys. The remission group comprised 14 parents whose children remained in remission during both surveys. The improved group comprised nine parents whose children experienced active disease at baseline and remission during the second survey. Parental mental health and quality of life were compared among the groups. @*Results@#Significantly higher levels of anxiety were observed in the active disease group in all surveys (p<0.050). Although depression levels and quality of life did not differ significantly among the three groups, pairing the active disease group with other groups showed some large effect sizes. @*Conclusion@#Parents tended to experience decreased mental health and quality of life when their adolescents experienced active inflammatory bowel disease. Consequently, our hypothesis was partially verified. Therefore, parents need support when their children have active disease; this finding highlights the need for parental support systems.
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Purpose@#The development of assistive devices has allowed for the performance of capsule endoscopy in children. Anticipating the capsule’s transit time could affect the efficacy of the investigation and potentially minimize the fasting period. This study determined the predictors of small bowel transit time for small-bowel capsule endoscopy in children and adolescents with inflammatory bowel disease. @*Methods@#We retrospectively examined children and adolescents with inflammatory bowel disease who underwent capsule endoscopy by the age 18 at a Japanese tertiary care children’s hospital. Small bowel transit time predictors were analyzed using multiple regression with explanatory variables. @*Results@#Overall, 92 patients, aged 1–17 years, with inflammatory bowel disease (63 Crohn’s disease and 29 ulcerative colitis cases) were examined for factors affecting small bowel transit time. In the simple regression analysis, diagnosis, age, height, weight, serum albumin, general anesthesia, and small intestine lesions were significantly associated with small bowel transit time. In the multiple regression analyses, serum albumin (partial regression coefficient: −58.9, p=0.008), general anesthesia (partial regression coefficient: 127, p<0.001), and small intestine lesions (partial regression coefficient: 30.1, p=0.037) showed significant associations with small bowel transit time. @*Conclusion@#Hypoalbuminemia, the use of general anesthesia for endoscopic delivery of the capsule, and small intestine lesions appeared to be predictors of prolonged small bowel transit time in children and adolescents with inflammatory bowel disease. Expecting the finishing time may improve examination with a fasting period reduction, which benefits both patients and caregivers.
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BackgroundThe outcomes of coronavirus disease 2019 (COVID-19) treatment have improved due to vaccination and the establishment of better treatment regimens. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, and the corresponding changes in the characteristics of the disease present new challenges in patient management. This study aimed to analyze predictors of COVID-19 severity caused by the delta and omicron variants of SARS-CoV-2. MethodsWe retrospectively analyzed the data of patients who were admitted for COVID-19 at Yokohama City University Hospital from August 2021 to March 2022. ResultsA total of 141 patients were included in this study. Of these, 91 had moderate COVID-19, whereas 50 had severe COVID-19. There were significant differences in sex, vaccination status, dyspnea, sore throat symptoms, and body mass index (BMI) (p <0.0001, p <0.001, p <0.001, p=0.02, p< 0.0001, respectively) between the moderate and severe COVID-19 groups. Regarding comorbidities, smoking habit and renal dysfunction were significantly different between the two groups (p=0.007 and p=0.01, respectively). Regarding laboratory data, only LDH level on the first day of hospitalization was significantly different between the two groups (p<0.001). Multiple logistic regression analysis revealed that time from the onset of COVID-19 to hospitalization, BMI, smoking habit, and LDH level were significantly different between the two groups (p<0.03, p=0.039, p=0.008, p<0.001, respectively). The cut-off value for the time from onset of COVID-19 to hospitalization was four days (sensitivity, 0.73; specificity, 0.70). ConclusionsTime from the onset of COVID-19 to hospitalization is the most important factor in the prevention of the aggravation of COVID-19 caused by the delta and omicron SARS-CoV-2 variants. Appropriate medical management within four days after the onset of COVID-19 is essential for preventing the progression of COVID-19, especially in patients with smoking habits.
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BackgroundTherapeutic effects of steroids on acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) have been reported. However, predictive indicators of early weaning from MV post-treatment have not yet been defined, making treating established ARDS challenging. Interleukin (IL)-6 has been associated with the pathogenesis of ARDS. ObjectiveOur aim was to clarify clinical utility of IL-6 level in ventilated patients with established ARDS. MethodsClinical, treatment, and outcome data were evaluated in 119 invasively ventilated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated ARDS. Plasma levels of IL-6 and C-reactive protein (CRP) were measured on days 1, 4, and 7 after intubation. ResultsFifty-two patients were treated with dexamethasone (steroid group), while the remaining 67 patients were not (non-steroid group). Duration of MV use was significantly shorter in the steroid group compared to non-steroid group (11.5{+/-}0.6 vs. 16.1{+/-}1.0 days, P = 0.0005, respectively) along with significantly decreased levels of IL-6 and CRP. Even when restricted to the steroid group, among variables post-MV, IL-6 level on day 7 was most closely correlated with duration of MV use (Spearmans rank correlation coefficient [{rho}] = 0.73, P < 0.0001), followed by CRP level on day 7 and the percentage change in IL-6 or CRP levels between day 1 and day 7. Moreover, among these variables, IL-6 levels on day 7 showed the highest accuracy for withdrawal from MV within 11 days (AUC: 0.88), with optimal cutoff value of 20.6 pg/mL. Consistently, the rate of MV weaning increased significantly earlier in patients with low IL-6 ([≤] 20.6 pg/mL) than in those with high IL-6 (> 20.6 pg/mL) (log-rank test P < 0.0001). ConclusionsIn invasively ventilated patients with established ARDS due to SARS-CoV-2, plasma IL-6 levels served as a predictor of early withdrawal from MV after dexamethasone administration.
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Acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after the peak of viral load has passed; however, its underlying mechanisms remain unclear. In the present study, analysis of the alveolar tissue injury markers and epithelial cell death markers in patients with COVID-19 revealed that COVID-19-induced ARDS was characterized by alveolar epithelial necrosis at an early disease stage. Serum levels of HMGB-1, one of DAMPs released from necrotic cells, were also significantly elevated in these patients. Further analysis using mouse model mimicking COVID-19-induced ARDS showed that the alveolar epithelial cell necrosis involved two forms of programmed necrosis, namely necroptosis and pyroptosis. Finally, the neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model. Collectively, necrosis, including necroptosis and pyroptosis, is the predominant form of alveolar epithelial cell death at an early disease stage and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS.
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Purpose@#Golimumab (GLM) is an anti-tumor necrosis factor (TNF)-α antibody preparation known to be less immunogenic than infliximab (IFX) or adalimumab. Few reports on GLM in pediatric patients with ulcerative colitis (UC) are available. This study aimed to review the long-term durability and safety of GLM in a pediatric center. @*Methods@#The medical records of 17 pediatric patients (eight boys and nine girls) who received GLM at the National Center for Child Health and Development were retrospectively reviewed. @*Results@#The median age at GLM initiation was 13.9 (interquartile range 12.0–16.3) years.Fourteen patients had pancolitis, and 11 had severe disease (pediatric ulcerative colitis activity index ≥65). Ten patients were biologic-naïve, and 50% achieved corticosteroid-free remission at week 54. Two patients discontinued prior anti-TNF-α agents because of adverse events during remission. Both showed responses to GLM without unfavorable events through week 54. However, the efficacy of GLM in patients who showed primary nonresponse or loss of response to IFX was limited. Four of the five patients showed non-response at week 54. Patients with severe disease had significantly lower corticosteroid-free remission rate at week 54 than those without severe disease. No severe adverse events were observed during the study period. @*Conclusion@#GLM appears to be safe and useful for pediatric patients with UC. Patients with mild to moderate disease who responded to but had some adverse events with prior biologics may be good candidates for GLM. Its safety and low immunogenicity profile serve as favorable options for selected children with UC.
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Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.
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Purpose@#A change in diagnosis from ulcerative colitis (UC) to Crohn's disease (CD) has been reported in pediatric inflammatory bowel disease; however, only a few clinical characteristics and predictors of this diagnostic change have been reported. We aimed to describe the clinical characteristics of patients with UC who underwent a change in diagnosis to CD and identify variables associated with the change. @*Methods@#The medical records of pediatric patients with UC who were followed up at the National Center for Child Health and Development between 2006 and 2019 were retrospectively reviewed. Clinical data on disease phenotype, laboratory parameters, endoscopic findings, and treatment of patients whose diagnosis changed to CD (cCD) were compared to those of patients whose diagnosis remained UC (rUC). @*Results@#Among the 111 patients initially diagnosed with UC, 11 (9.9%) patients were subsequently diagnosed with CD during follow-up. There was no significant difference between the cCD and rUC groups in terms of sex, age at initial diagnosis, and the extent and severity of disease at initial diagnosis. Albumin and hemoglobin levels were significantly lower in the cCD group than in the rUC group. The proportion of patients who required biologics was significantly higher in the cCD group than in the rUC group (p<0.05). @*Conclusion@#Approximately 10% children initially diagnosed with UC were subsequently diagnosed with CD. Hypoalbuminemia and anemia at initial diagnosis and use of biologics could be predictors of this diagnostic change.
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Purpose@#The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. @*Methods@#This retrospective study included 20 children with UC who were administered IFX. @*Results@#For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. @*Conclusion@#IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.
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Purpose@#A change in diagnosis from ulcerative colitis (UC) to Crohn's disease (CD) has been reported in pediatric inflammatory bowel disease; however, only a few clinical characteristics and predictors of this diagnostic change have been reported. We aimed to describe the clinical characteristics of patients with UC who underwent a change in diagnosis to CD and identify variables associated with the change. @*Methods@#The medical records of pediatric patients with UC who were followed up at the National Center for Child Health and Development between 2006 and 2019 were retrospectively reviewed. Clinical data on disease phenotype, laboratory parameters, endoscopic findings, and treatment of patients whose diagnosis changed to CD (cCD) were compared to those of patients whose diagnosis remained UC (rUC). @*Results@#Among the 111 patients initially diagnosed with UC, 11 (9.9%) patients were subsequently diagnosed with CD during follow-up. There was no significant difference between the cCD and rUC groups in terms of sex, age at initial diagnosis, and the extent and severity of disease at initial diagnosis. Albumin and hemoglobin levels were significantly lower in the cCD group than in the rUC group. The proportion of patients who required biologics was significantly higher in the cCD group than in the rUC group (p<0.05). @*Conclusion@#Approximately 10% children initially diagnosed with UC were subsequently diagnosed with CD. Hypoalbuminemia and anemia at initial diagnosis and use of biologics could be predictors of this diagnostic change.
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Purpose@#The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. @*Methods@#This retrospective study included 20 children with UC who were administered IFX. @*Results@#For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. @*Conclusion@#IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.
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SARS-CoV-2 neutralizing antibodies confer protective immunity against reinfection. We have developed a rapid test for screening SARS-CoV-2 neutralization antibodies using genome-free virus-like particles incorporated with a small luciferase peptide, HiBiT. Their entry into LgBiT-expressing target cells reconstitutes NanoLuc luciferase readily detected by a luminometer. This newly developed HiBiT-tagged Virus-like particle-based Neutralization Test (hiVNT) can readily quantify SARS-CoV-2 neutralizing antibodies within three hours with a high-throughput in a low biosafety setting. Moreover, the neutralizing activity obtained from hiVNT was highly consistent with that measured by the conventional neutralization test using authentic SARS-CoV-2. Furthermore, antibody responses to both viral spike and nucleocapsid proteins correlated with the neutralization activity assessed by hiVNT. Our newly-developed hiVNT could be instrumental to survey individuals for the presence of functional neutralizing antibody against SARS-CoV-2.
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Genome-wide association studies have identified various genetic variants associated with complex disorders. However, these studies have commonly been conducted in a cross-sectional manner. Therefore, we performed a longitudinal exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify genetic variants that confer susceptibility to hypertension using ~244 000 single-nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals who underwent annual health check-ups for several years. After quality control, the association of hypertension with SNVs was tested using a generalized estimating equation model. Finally, our longitudinal EWAS detected seven hypertension-related SNVs that passed strict criteria. Among these variants, six SNVs were densely located at 12q24.1, and an East Asian-specific motif (haplotype) ‘CAAAA’ comprising five derived alleles was identified. Statistical analyses showed that the prevalence of hypertension in individuals with the East Asian-specific haplotype was significantly lower than that in individuals with the common haplotype ‘TGGGT’. Furthermore, individuals with the East Asian haplotype may be less susceptible to the adverse effects of smoking on hypertension. The longitudinal EWAS for the recessive model showed that a novel SNV, rs11917356 of COL6A5, was significantly associated with systolic blood pressure, and the derived allele at the SNV may have spread throughout East Asia in recent evolutionary time.
