Methylprednisolone pulse and prednisolone for intensification of primary treatment in Kawasaki disease patients at high risk of treatment resistance: a multicenter prospective cohort study.

The purpose of this study is to determine whether adding intravenous methylprednisolone pulse (IVMP) to primary adjunctive prednisolone with intravenous immunoglobulin (IVIG) improves treatment resistance and coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) with a high risk of treatment resistance. This multicenter, prospective, observational study was conducted at 28 hospitals in Japan from October 2016 to June 2020. For patients predicted to be resistant to treatment based on a Kobayashi score ≥ 5 and total bilirubin ≥ 1.0 mg/dL, each hospital independently decided to add IVMP followed by prednisolone, prednisolone alone, or nothing to the primary IVIG therapy. In total, 2856 consecutive KD patients were enrolled; of these, 399 (14.0%) were predicted to be treatment resistant. Patients who were resistant to the primary treatment and required additional treatment comprised 59%, 20%, and 26% of the IVIG-alone group, IVIG-plus-prednisolone group, and IVIG-plus-IVMP group, respectively (P < .0001). The CAA incidence (Z score ≥ 2.5) at month 1 was similar among the treatment groups (6.7%, 4.8%, and 7.3%, respectively; P = .66). CAA occurred more frequently in patients who needed third- or later-line therapy.Conclusions: Primary adjunctive corticosteroid therapy improved the treatment response and suppressed inflammation. However, the study found no benefit of adding IVMP to prednisolone therapy. Patients receiving IVIG alone achieved coronary outcomes comparable to those of patients receiving primary adjunctive corticosteroid therapy although they were more likely to require additional rescue treatment. KD inflammation should be resolved no later than the third line of additional treatment to reduce the risk of CAA.Trial registration: University Hospital Medical Information Network Clinical Trials Registry in Japan ( https://www.umin.ac.jp/ctr/index.htm ) under code UMIN000024937.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Reference values for urinary protein, albumin, beta 2-microglobulin, and the alpha 1-microglobulin-to-creatinine ratio in Japanese children.

BACKGROUND: The importance of the ratio of creatinine to urinary protein, albumin, and low-molecular weight protein as a urinary marker in chronic kidney disease patients is widely recognized. However, no reference values have hitherto been established for these markers in Japanese children. The present study aimed to establish the reference values for these urinary markers in Japanese children. METHODS: The first morning urine was randomly collected from 1712 pupils aged ≥ 3 to < 18 years during school and kindergarten mass urinary screenings. The upper limit of the reference values was set at the 97.5th percentile of the creatinine ratio per marker. RESULTS: The urinary protein-to-creatinine ratio (PCR), urinary albumin-to-creatinine ratio (ACR), urinary beta 2-microglobulin-to-creatinine ratio (BMCR), and urinary alpha 1-microglobulin-to-creatinine ratio (AMCR) showed an age-related decrease at the 50th percentile reflecting an age-related increase in urinary creatinine. The appropriate reference value for the PCR and ACR was 0.12 g/gCr and 35 mg/gCr, respectively, in the entire cohort. The appropriate reference value for the BMCR was 0.5 µg /mgCr for age ≥ 3 to < 6 years and 0.35 µg/mgCr for age 6 years or older. The appropriate reference value for the AMCR was 5.0 µg/mgCr for age ≥ 3 to < 6 years and 3.5 µg /mgCr for age 6 years or older. CONCLUSION: The present study was the first to determine appropriate reference values for the PCR, ACR, BMCR, and AMCR based on an analysis of the first morning urine samples of a large number of children.

Understanding impacts of COVID-19 restrictions on glycemic control for patients with diabetes in Japan.

Objective: This study evaluated the changes in the status of glycemic control and lipid management in patients with diabetes under COVID-19 containment restrictions, in order to better understand the impacts of events causing lifestyle restrictions. Patient characteristics with worsened glycemic control were also assessed. Methods: We conducted a retrospective and observational cohort study using the electronic health records of 5,169 patients with diabetes seeking medical care in two healthcare centers. Laboratory test results including glycemic and lipid goal attainment rates were compared between pre-COVID-19 (January to December 2019) and the first wave of COVID-19 (February to June 2020). Multiple regression models were used to evaluate the association between glycated hemoglobin (HbA1c) at baseline and during the first wave with covariates such as concomitant medications and comorbidities. Results: The HbA1c goal achievement rate improved significantly from 39.0% to 43.1% (p < 0.0001) overall, and more patients reached their glycemic target during COVID-19 restrictions. No significant changes were observed in lipid control. An indexed change in HbA1c level showed that glycemic control improved in 2,230 patients and worsened in 1,619 patients. Administration of insulin, GLP-1, and sulfonylureas were each identified as factors correlated with elevated HbA1c, during the first wave of COVID-19. Conclusion: Although the glycemic control in patients with diabetes improved overall under COVID-19 restrictions, those on insulin, GLP-1, or sulfonylureas worsened. These findings suggest the need to better understand what drives differences in glycemic control to better support people with diabetes for future epidemiological outbreaks. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01302-5.

Analgesic efficacy of continuous wound infiltration compared with continuous intravenous fentanyl after gynaecological surgery: a non-inferiority, randomised controlled trial.

OBJECTIVE: The present trial aimed to prove the non-inferiority of the analgesic efficacy of continuous wound infiltration (CWI) to that of continuous intravenous fentanyl (IV) and to compare the safety of the two methods. METHODS: This trial was a prospective, single-centre, two-arm, non-inferiority, randomised controlled trial. Patients participating in the trial were randomised to a CWI group or an IV group. The VAS (visual analogue scale), additional analgesic usage and side effects were then compared between the groups. RESULTS: In total, 61 patients were enrolled; two in CWI were excluded, leaving 59 (30 in the CWI group and 29 in the IV group) for analysis. The difference in the VAS score at 24 h (CWI group - IV group) was -3.2 (95% confidence interval [CI] -14.7 to 8.2), which was less than the non-inferiority margin of 15. The mean amount of total fentanyl use at postoperative hour 48 was 1395 (95% CI 886-1903) µg in the CWI group and 3186 (95% CI 2716-3658) µg in the IV group. The amount of other analgesics and the incidence of adverse effects did not differ significantly between the groups. CONCLUSION: CWI was non-inferior to IV in terms of its analgesic effect, and has an opioid sparing effect in open gynaecological surgery.

Identifying Kawasaki Disease With a Low Coronary Artery Aneurysm Risk.

INTRODUCTION: Kawasaki disease (KD) patients with a high risk of coronary artery aneurysm (CAA) development are well characterized and targeted for intensified primary intravenous immunoglobulin (IVIG) treatment. However, the characteristics of KD patients with a low CAA risk are less well-known. METHODS: The present study was a secondary analysis of Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki disease (Post RAISE), a multicenter, prospective cohort study of KD patients in Japan. The target of the analysis was patients with a Kobayashi score <5 who were predicted to respond to IVIG. The incidence of CAA during the acute phase, the primary outcome, was assessed based on all echocardiographic evaluations performed between week 1 (days 5-9) and month 1 (days 20-50) after the start of primary treatment. Multivariable logistic regression was used to identify the independent risk factors of CAA during the acute phase, based on which a decision tree was created to identify a subpopulation of patients with KD with a low CAA risk. RESULTS: Multivariate analysis found that a baseline maximum Z score >2.5, age <12 months at fever onset, nonresponsiveness to IVIG, low neutrophils, high platelets and high C-reactive protein were independent predictors of CAA during the acute phase. The decision tree created by using these risk factors identified 679 KD patients who had a low incidence of CAA during the acute phase (4.1%) and no medium or large CAA. CONCLUSIONS: The present study identified a KD subpopulation with a low CAA risk comprising around a quarter of the entire Post RAISE cohort.

Analysis of Coronary Arterial Aneurysm Regression in Patients With Kawasaki Disease by Aneurysm Severity: Factors Associated With Regression.

Background Coronary arterial aneurysms (CAAs) associated with Kawasaki disease (KD) significantly affect prognosis. However, the clinical course of CAAs and factors associated with CAA regression have not been well analyzed. Methods and Results The cohort of the Z-Score 2nd Project Stage study, a multicenter, retrospective, cohort study involving 44 institutions in Japan including 1006 patients with KD, was examined. CAAs were classified by the z score of their internal diameter in the acute phase: small (z<5), medium (5≤z<10), and large (z≥10). The lower limit of small CAA was based on the Japanese Ministry of Health, Labour and Welfare criteria. In the right coronary artery, the CAA regression rates 10 years after diagnosis were 95.5% for small, 83.2% for medium, and 36.3% for large. In the proximal left anterior descending artery, the regression rates 10 years after diagnosis were 95.3% for small, 80.1% for medium, and 28.8% for large. Cox regression analysis showed that diagnosis under the age of 1 year and onset of KD in 2010 to 2012 for the right coronary artery and the left anterior descending artery, and female for the right coronary artery were significantly associated with a high regression rate, whereas large CAAs for the right coronary artery and the left anterior descending artery were significantly associated with a low regression rate. Conclusions The current study, the largest Japanese study of its kind, found that small aneurysm, recent onset, and diagnosis under the age of 1 year predict regression, and that even giant aneurysms could regress. These data may contribute to long-term management of coronary aneurysms. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000010606.

Urine alpha 1-microglobulin-to-creatinine ratio and beta 2-microglobulin-to-creatinine ratio for detecting CAKUT with kidney dysfunction in children.

BACKGROUND: The leading cause of advanced chronic kidney disease (CKD) in children is congenital anomalies of the kidney and urinary tract (CAKUT). However, the most appropriate parameters of biochemical urine analysis for detecting CAKUT with kidney dysfunction are not known. METHODS: The present observational study analyzed data on children with CAKUT (stage 2-4 CKD) and the general pediatric population obtained from school urine screenings. The sensitivity and specificity of urine alpha 1-microglobulin-, beta 2-microglobulin-, protein-, and the albumin-to-creatinine ratios (AMCR, BMCR, PCR, ACR, respectively) in detecting CAKUT with kidney dysfunction were compared with those of the conventional urine dipstick, and the most appropriate of these four parameters were evaluated. RESULTS: In total, 77 children with CAKUT and 1712 subjects in the general pediatric population fulfilled the eligibility criteria. Conventional dipstick urinalysis was insufficient due to its low sensitivity; even when the threshold of proteinuria was +/-, its sensitivity was only 29.7% for stage 2 and 44.1% for stage 3 CKD. Among the four parameters assessed, the AMCR and BMCR were adequate for detecting CAKUT in children with stage 3-4 CKD (the respective sensitivity and specificity of the AMCR for detecting CAKUT in stage 3 CKD was 79.4% and 97.5% while that of BMCR was 82.4% and 97.5%). These data were validated using national cohort data. CONCLUSION: AMCR and BMCR are superior to dipstick urinalysis, PCR, and ACR in detecting CAKUT with kidney dysfunction, particularly stage 3 CKD. However, for AMCR, external validation is required. A higher resolution version of the Graphical abstract is available as Supplementary information.

Impact of the COVID-19 pandemic on the glycemic control, eating habits, and body compositions of people with diabetes mellitus: A retrospective longitudinal observational study.

AIMS/INTRODUCTION: To evaluate the impact of the COVID-19 pandemic on the glycemic control, eating habits, and body composition of people with diabetes mellitus; to identify the determinants of worsening glycemic control in people with diabetes mellitus. MATERIALS AND METHODS: This retrospective, longitudinal observational study was performed in outpatients with diabetes mellitus who visited our hospital between April 2019 and March 2020 (pre-COVID-19 period) and continued for follow up from April 2020 to March 2021 (COVID-19 period). We compared the glycemic control, nutritional intakes, and body composition of people with diabetes mellitus between the two periods. The changes in the HbA1c values (ΔHbA1c) and other study variables were compared between the two periods. Logistic regression analysis was performed to identify the factors associated with the increase of HbA1c levels. RESULTS: A significant increase of HbA1c was observed during the COVID-19 period. The percent fat mass (FM) also increased, while the percent skeletal muscle mass (SMM) decreased during the COVID-19 period. After adjustments for age and sex, the ΔBMI (OR:2.33), ΔFM (OR:1.45), and ΔSMM (OR:0.51) were identified as being associated with elevated levels of HbA1c. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the glycemic control and body composition of people with diabetes mellitus. The increased body weight and FM and decreased SMM observed during the pandemic were associated with poor glycemic control in people with diabetes mellitus.

Early predictive factors for progression to kidney failure in infants with severe congenital anomalies of the kidney and urinary tract.

BACKGROUND: Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined. METHODS: This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0 mg/dL during the first 3 days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3 days, and patients lacking sufficient data were excluded. RESULTS: Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3 days (Cr-day3-max) ≥ 2.5 mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5 mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up. CONCLUSIONS: Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Factors Associated With Time to Achieve Physical Functional Recovery in Patients With Severe Stoke After Inpatient Rehabilitation: A Retrospective Nationwide Cohort Study in Japan.

Objective: To describe characteristics of patient with severe stroke (FIM motor score [FIM motor] 20-49 at admission) and examine association between pre-specified factors (age, sex, modified Rankin Scale before stroke onset, body mass index, FIM motor, and FIM cognitive) and time to achieve FIM motor ≥70, that is, self-independent level. Design: Retrospective cohort study using a large database in Japan. Setting: Rehabilitation wards. Participants: Patients with severe stroke (N=1422) who received inpatient rehabilitation were included (median age: 76 years; interquartile range [IQR]: 68.0-84.0). A total of 54.6% were men, and 65.8% were ischemic stroke. Interventions: Not applicable. Main Outcome Measures: Time to achieve FIM motor ≥70. Results: After inpatient rehabilitation, 40.4% (N=575) achieved FIM motor ≥70 (admission FIM motor 20-29, 30-39 and 40-49: 18.6%, 33.6%, and 47.8%, respectively). Patients who achieved FIM motor ≥70 stayed median 81.0 days [IQR, 51.0-120.0]) and received median: 6.94 units per day [IQR, 5.48-7.78], 1 unit=20 minutes). Adjusted Fine-Gray regression revealed that shorter time to achieve FIM motor ≥70 was associated with higher admission FIM motor (hazard ratio [HR] 2.87 [95% confidence interval [CI] 2.27-3.62]: 20-29 vs 40-49), higher admission FIM cognitive (HR 1.81 [95% CI: 1.39-2.35]: 5-14 vs 25-35), and younger (HR 3.20 [95% CI: 2.32-4.42]: ≥85 years vs 20-69 years). Conclusions: Most patients with severe stroke did not achieve FIM motor ≥70 after inpatient rehabilitation. Older patients and patients with lower admission FIM motor require more attention. They should be prioritized for state-of-the-art rehabilitation therapy.

Epidemiology of biopsy-proven Henoch-Schönlein purpura nephritis in children: A nationwide survey in Japan.

BACKGROUND: Little is known about the epidemiology of Henoch-Schönlein purpura nephritis (HSPN). METHODS: We conducted a nationwide epidemiological survey of Japanese children aged 1 to 15 years with HSPN. Children who were newly diagnosed with HSPN by biopsy between January 2013 and December 2015 were eligible for the survey to clarify the incidence of HSPN. We also conducted an institutional survey on kidney biopsy criteria and treatment protocols. RESULTS: A total of 353 of 412 institutions (85.7%) responded to the questionnaire. Of the 353 institutions, 174 reported to perform kidney biopsies at their institutions, and 563 children were diagnosed with HSPN. Considering the collection rate, the estimated incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year. The median age at biopsy was 7.0 years, and the male-to-female ratio was 1.2:1. The kidney biopsy criteria and treatment protocols for HSPN were as follows. Patients with acute kidney injury underwent biopsy at least one month after onset. For patients without kidney dysfunction, the timing for biopsy was determined by the amount of proteinuria. Regarding the treatment of HSPN, there were certain commonalities among the treatment protocols, they eventually differed depending on the institutions involved. CONCLUSIONS: The incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year in Japan. The male-to-female ratio and date of diagnosis of HSPN were similar to those in previous studies. The kidney biopsy criteria and treatment protocols for HSPN varied among institutions. Further studies are warranted to establish an optimal treatment policy based on the prognosis.

Relationship Between Body Temperature and Heart Rate in Children With No Other Apparent Cause of Tachycardia.

OBJECTIVE: The aim of the study was to investigate the normal heart rate range for each body temperature in patients visiting the emergency department (ED) with no other, apparent, coexisting factors causing tachycardia. METHODS: This was an observational study conducted in the ED at a single children's hospital between April 1, 2014, and March 31, 2017. Data on all visits were extracted from the electronic triage system and were excluded if they indicated the presence of factors other than body temperature potentially increasing the heart rate. We created age-dependent heart rate percentile curves for body temperature in 6 age categories: 0 to younger than 3 months, 3 to younger than 12 months, 1 to younger than 2 years, 2 to younger than 5 years, 5 to younger than 10 years, and 10 years or older. The curves were created for the body temperatures of 36.0°C to 38.0°C for the 0 to younger than 3 months age group and for body temperatures of 36.0°C to 40.5°C for the other age groups. RESULTS: Of the 113,242 patients included, 61,321 were analyzed. The percentile curves across all age groups were similar despite differences in the baseline heart rate. Heart rate increase was steepest between 37.0°C and 38.0°C at a rate of approximately 20 beats per minute per degree Celsius for all groups. Compared with previous studies in the outpatient setting, including the ED, heart rate was lower in younger patients and was similar among older patients. CONCLUSIONS: We created new, age-dependent heart rate percentile curves for body temperature for use in the ED setting. In outpatients, the effect of coexisting factors affecting heart rate, such as crying, may be higher among younger patients.

Ultrasonographic reference values and a simple yet practical formula for estimating average kidney length in Japanese children.

BACKGROUND: The assessment of kidney size is essential for treating kidney disease. However, there are no reliable and sufficiently robust ultrasonographic reference values or prediction formulas for kidney length in Japanese children, based on a sufficient number of participants. METHODS: We retrospectively analyzed kidney measurements by ultrasonography in children aged 18 years or younger from eight facilities throughout Japan between January 1991 and September 2018. Detailed reference values were developed by aggregating the left and right kidneys of boys and girls separately. Simple and practical reference values were developed by combining all the data from left and right kidneys and boys and girls. The estimation formulas for the average value and lower limit of the normal range for kidney length were developed based on regression analysis. RESULTS: Based on the aggregated kidney length data of 1984 participants (3968 kidneys), detailed reference values and simple reference values for kidney length were determined. From the regression analysis, the formula for calculating the average kidney length was generated as "kidney length (cm) = body height (m) × 5 + 2", and that for predicting the lower limit of normal kidney length in children under 130 cm was calculated as "lower limit (cm) = 0.85 × [body height (m) × 5 + 2]". CONCLUSION: Detailed ultrasonographic reference values of kidney length for Japanese children and simple reference values and estimation formulas for daily practice have been established.

Risk Factors of Coronary Artery Aneurysms in Kawasaki Disease with a Low Risk of Intravenous Immunoglobulin Resistance: An Analysis of Post RAISE.

OBJECTIVE: To detect risk factors of coronary artery aneurysm (CAA) development in patients with Kawasaki disease determined to have a low risk for resistance to primary intravenous immunoglobulin (IVIG) treatment based on the Kobayashi score. STUDY DESIGN: This study included 1757 predicted IVIG responders from Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki disease (Post RAISE), a large-scale, multicenter, prospective cohort study of Kawasaki disease in Japan. Predicted IVIG responders were defined as patients with Kawasaki disease with a Kobayashi score of <5, a predictive scoring system for IVIG resistance created in Japan. The primary outcome was CAA development at 1 month after disease onset. CAA was defined as a Z score of ≥2.5. Multivariable logistic regression was used to identify the independent risk factors of CAA. The variables for inclusion were identified based on univariate analysis results and previously reported risk factors of CAA. RESULTS: Among 1632 patients who had complete coronary outcome data, CAA developed in 90 patients (5.5%) at 1 month after disease onset. Multivariable analysis found that a baseline maximum Z score of >2.5, age of <12 months at fever onset, and nonresponsiveness to IVIG were significant, independent risk factors of CAA development at 1 month after disease onset. Among the risk factors, a baseline maximum Z score of >2.5 was most strongly associated with CAA development (OR, 7.1; 95% CI, 4.1-12.2; P ≤ .001). CONCLUSIONS: Predicted IVIG responders with CAA risk factors identified in this study may be candidates for future clinical trials of intensified primary IVIG treatment with prednisolone, cyclosporine or infliximab.

Follow-Up Duration of Echocardiography in Patients with Kawasaki Disease with No Initial Coronary Aneurysms.

OBJECTIVE: To evaluate the optimal duration of echocardiographic follow-up in patients with Kawasaki disease without an initial coronary aneurysm. STUDY DESIGN: In this single-center, retrospective, observational study, we reviewed the results of follow-up echocardiography in children with Kawasaki disease enrolled in the Prospective Observational Study on Stratified Treatment with Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease from a children's hospital. The main enrollment criterion was the absence of coronary aneurysms, defined as a maximum z-score (Zmax) ≥2.5, in the proximal right coronary artery and the proximal left anterior descending artery within 9 days from treatment initiation. The primary outcome was Zmax on follow-up echocardiography at up to 5 years. RESULTS: Among 386 patients, 106 (27.5%) received prednisolone with intravenous immunoglobulin for first-line therapy, and 57 (14.8%) showed a poor response. Echocardiography at 1 month detected 9 patients with a Zmax ≥2, including 3 (0.8%) with coronary aneurysms requiring additional antithrombotic treatment and observation. Of 7 patients (1.8%) with normal echocardiographic findings at 1 month but a Zmax ≥2 later, 2 were lost to follow-up and 5 experienced spontaneous resolution, but none of the 7 patients required any change in management. CONCLUSIONS: The optimal duration of echocardiographic follow-up may be 1 month in patients with no initial coronary aneurysms and a Zmax <2 at 1 month. Coronary artery abnormalities observed after 1 month are rare and mostly benign in this category of patients.

Perinatal factors contributing to intellectual impairment in a cohort of Japanese children with very low birth weight.

BACKGROUND: To determine whether prematurity, intrauterine growth restriction (IUGR), or neonatal stress affects intellectual impairment in children with very low birth weight (VLBW). METHODS: This national historical cohort study evaluated children with VLBW cared for in perinatal medical centers throughout Japan. Factors assessed included three latent variables (prematurity, IUGR, and stress during the neonatal period) and eight observed variables during perinatal period. The primary endpoint was intellectual or developmental quotient (IQ/DQ) at age ≥3 years. Structural equation model (SEM) was used to examine factors associated with IQ/DQ. RESULTS: The study included 248 VLBW children, who were of mean age 5.7±2.0 years and mean IQ/DQ of 85.5 at last encounter. SEM showed that stress during the neonatal period (ß=-0.37) contributed more to IQ/DQ than intrauterine malnutrition (ß=0.25) and prematurity (ß=0.15) and that the duration of mechanical ventilation was an important contributor to stress during the neonatal period. CONCLUSIONS: Neonatal stress was more harmful to future intellectual impairment of VLBW neonates, with IUGR contributing more than prematurity. Duration of mechanical ventilation was an important risk factor in neonatal stress. Neonatologists should minimize neonatal stress in VLBW neonates, and obstetricians should monitor fetal growth restriction to prevent intellectual impairment in later life.

Superiority of urgent vs early endoscopic hemostasis in patients with upper gastrointestinal bleeding with high-risk stigmata.

BACKGROUND: Guidelines recommend that all patients with upper gastrointestinal bleeding (UGIB) undergo endoscopy within 24 h. It is unclear whether a subgroup may benefit from an urgent intervention. We aimed to evaluate the influence of endoscopic hemostasis and urgent endoscopy on mortality in UGIB patients with high-risk stigmata (HRS). METHODS: Consecutive patients with suspected UGIB were enrolled in three Japanese hospitals with a policy to perform endoscopy within 24 h. The primary outcome was 30-day mortality. Endoscopic hemostasis and endoscopy timing (urgent, ≤6 h; early, >6 h) were evaluated in a regression model adjusting for age, systolic pressure, heart rate, hemoglobin, creatinine, and variceal bleeding in multivariate analysis. A propensity score of 1:1 matched sensitivity analysis was also performed. RESULTS: HRS were present in 886 of 1966 patients, and 35 of 886 (3.95%) patients perished. Median urgent-endoscopy time (n = 769) was 3.0 h (interquartile range [IQR], 2.0-4.0 h) and early endoscopy (n = 117) was 12.0 h (IQR, 8.5-19.0 h). Successful endoscopic hemostasis and urgent endoscopy were significantly associated with reduced mortality in multivariable analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09-0.52; P = 0.0006, and OR, 0.37; 95% CI, 0.16-0.87; P = 0.023, respectively). In a propensity-score-matched analysis of 115 pairs, adjusted comparisons showed significantly lower mortality of urgent vs early endoscopy (2.61% vs 7.83%, P < 0.001). CONCLUSIONS: A subgroup of UGIB patients, namely those harboring HRS, may benefit from endoscopic hemostasis and urgent endoscopy rather than early endoscopy in reducing mortality. Implementing triage scores that predict the presence of such lesions is important.