Early Response, Long-Term Seizure Outcome, and Very-Low-Dose Adrenocorticotrophic Hormone Therapy for Infantile Epileptic Spasms Syndrome With Down Syndrome.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) with Down syndrome has good treatment response and good seizure outcomes with high-dose adrenocorticotrophic hormone (ACTH) therapy. We investigated the early treatment response of epileptic spasms (ES), long-term seizure outcome, and efficacy of very-low-dose ACTH therapy for IESS with Down syndrome. METHODS: We retrospectively investigated patients with Down syndrome and IESS between April 1983 and January 2023. We defined response to treatment as clinical remission and electrographic resolution of hypsarrhythmia after treatment for more than one month and early treatment as any treatment for ES within three months of initiation of treatment. Long-term seizure outcomes were determined by the presence of any type of seizure within one year of the last visit. We investigated the dosage and efficacy of very-low-dose ACTH therapy. RESULTS: Thirty patients were enrolled with a median follow-up period of 7.7 years (range: 1.3 to 19.1). The response and relapse rates in the early treatment were 83.3% and 16.0%, respectively. The seizure-free rate of long-term seizure outcomes was 80.0%. Long-term seizure outcomes correlated with early treatment response to ES. The response rate of very-low-dose ACTH therapy was 59.3%. The efficacy of ACTH therapy tended to be dose-dependent (P = 0.055). CONCLUSIONS: Early treatment response to ES may be useful in predicting long-term seizure outcomes of IESS with Down syndrome. Very-low-dose ACTH therapy was the most effective treatment for ES and could exhibit dose-dependent efficacy. Depending on the IESS etiology, the ACTH dose could be reduced to minimize its side effects.

1H, 13C and 15N backbone resonance assignments of hepatocyte nuclear factor-1-beta (HNF1ß) POUS and POUHD.

Hepatocyte nuclear factor 1ß (HNF1ß) is a transcription factor that plays a key role in the development and function of the liver, pancreas, and kidney. HNF1ß plays a key role in early vertebrate development and the morphogenesis of these organs. In humans, heterozygous mutations in the HNF1B gene can result in organ dysplasia, making it the most common cause of developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. Pathogenic variants in the HNF1B gene are known to cause various diseases, including maturity-onset diabetes of the young and developmental renal diseases. This study presents the backbone resonance assignments of HNF1ß POUS and POUHD domains, which are highly conserved domains required for the recognition of double-stranded DNA. Our data will be useful for NMR studies to verify the altered structures and functions of mutant HNF1B proteins that can induce developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. This study will provide the structural basis for future studies to elucidate the molecular mechanisms underlying how mutations in HNF1ß cause diseases.

Association between earthquakes and perinatal outcomes: A systematic review and meta-analysis.

BACKGROUND: Evidence for the association between earthquakes and adverse perinatal outcomes is limited. OBJECTIVES: To evaluate the association between earthquakes and perinatal outcomes including preterm birth and low birth weight. SEARCH STRATEGY: We searched studies using MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov on February 9, 2023. SELECTION CRITERIA: We included before-and-after studies that evaluated the associations between earthquakes and perinatal outcomes in women living in affected areas. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data. We calculated the pooled odds ratio (OR) with the random-effects model. We analyzed outcomes in subgroups of Asians and others. We evaluated the certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation system. MAIN RESULTS: We included 2 607 405 women in 13 studies. Earthquakes may not increase preterm birth (nine studies, 1 761 760 participants: OR 1.10, 95% confidence interval [CI] 0.98-1.24, low certainty of evidence) or low birth weight (seven studies, 1 753 891 participants: OR 1.10, 95% CI 0.94-1.28, low certainty of evidence). Subgroup analyses showed that earthquakes may be associated with an increase of preterm birth among populations in Asia (OR 1.44, 95% CI 1.07-1.95), but this was not evident in others (OR 0.93, 95% CI 0.83-1.05). CONCLUSIONS: Perinatal outcomes might not change after earthquakes. Further research on the association between earthquakes and perinatal outcomes, combined with an assessment of the characteristics of the region, is needed.

Adult survivors of childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome treated with cyclosporine: a long-term single-center experience.

BACKGROUND: Although evidence has confirmed that cyclosporine (CS) is efficacious against childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome (SD/SRNS), some patients may continue to relapse during adulthood. However, predictive factors for adult active disease and kidney complications, such as chronic kidney disease (CKD) and hypertension, in this cohort remain unknown. METHODS: We conducted a retrospective study on the long-term outcomes of 81 young adults with childhood-onset SD/SRNS treated with CS. The primary endpoint was the probability of active disease into adulthood. The secondary endpoint was the probability of developing kidney complications. RESULTS: At the last follow-up (median age, 23.2 years; median disease duration, 15.8 years), 44 adult patients (54%) continued to have active disease, whereas 16 patients developed CKD or hypertension, respectively. The proportion of patients developing kidney complications was similar between the active disease and long-term remission groups. Young age at NS onset and history of relapse during the initial CS (median, 31 months) were independent predictive factors for active disease. Acute kidney injury at NS onset, focal segmental glomerulosclerosis, and irreversible CS nephrotoxicity were identified as risk factors for the development of CKD, whereas older age was identified as a risk factor for the development of CKD and hypertension. CONCLUSIONS: More than 50% of adult survivors treated with CS continued to have active disease, and each 20% developed CKD or hypertension. A long-term follow-up is necessary for patients with SD/SRNS to identify the development of kidney complications later in adulthood that can be attributed to prior disease and CS treatment in childhood, irrespective of disease activity. A higher resolution version of the Graphical abstract is available as Supplementary information.

Predictive factors of long-term disease remission after rituximab administration in patients with childhood-onset complicated steroid-dependent nephrotic syndrome: a single-center retrospective study.

BACKGROUND: Despite the fact that rituximab (RTX)-associated adverse events may be relatively frequent in younger patients, recent studies have reported RTX as a suitable first-line steroid-sparing agent for maintaining remission in children with steroid-dependent nephrotic syndrome (SDNS). However, the impact of age at RTX initiation on the long-term outcome remains unknown in this cohort. METHODS: We retrospectively reviewed the clinical course of 61 patients with complicated SDNS who received a single dose of RTX (375 mg/m2) followed by maintenance immunosuppressive agents (IS) from January 2008 to March 2021. In patients who achieved > 12 months of prednisolone-free remission, IS tapering within 6 months was tried to achieve. The primary endpoint was the probability of achieving long-term treatment-free remission at the last follow-up. RESULTS: After RTX initiation, 52 patients (85.2%) relapsed after a median of 665 days, and 44 patients (72.1%) received additional RTX doses (total, 226 infusions). At the last follow-up (median observation period, 8.3 years; median age, 18.3 years), 16 patients (26.2%) achieved long-term remission. Multivariate analysis showed that older age at RTX initiation was the independent predictive factor for achieving long-term remission (odds ratio, 1.25; p < 0.05). The proportion of those who achieved long-term remission was significantly higher in patients aged ≥ 13.5 years than in those aged < 13.5 years at RTX initiation (52.6 vs 14.3%, p < 0.05). Persistent severe hypogammaglobulinemia did not develop in older children (≥ 13.5 years) at RTX initiation. CONCLUSION: For older children with complicated SDNS, RTX appeared to be a suitable disease-modifying therapy without persistent adverse events.

Effectiveness and safety of Tolvaptan in infants with congenital heart disease.

BACKGROUND: Tolvaptan (TLV) is a selective vasopressin receptor 2 antagonist administered for congestive heart failure (CHF) after inadequate response to other diuretics. The effectiveness and safety of TLV have been evaluated well in adult patients. However, reports on its use in pediatric patients, especially infants, are scarce. METHODS: We retrospectively evaluated 41 children younger than 1 year of age who received TLV for CHF for congenital heart disease (CHD) between January 2010 and August 2021. We monitored the occurrence of adverse events, including acute kidney injury and hypernatremia, as well as laboratory data trends. RESULTS: Of the 41 infants included, 51.2% were male. The median age when TLV was initiated was 2 months, interquartile range (IQR) 1-4 months, and all infants had been administered other diuretics previously. The median dose of TLV was 0.1 mg/kg/day (IQR, 0.1-0.1). Urine output increased significantly after 48 h of treatment: baseline, 315 mL/day (IQR, 243-394); 48 h, 381 mL/day (IQR, 262-518) , p = 0.0004; 72 h, 385 mL/day (IQR, 301-569), p = 0.0013; 96 h, 425 mL/day (IQR, 272-524), p = 0.0006; and 144 h, 396 mL/day (IQR, 305-477), p = 0.0036. No adverse events were observed. CONCLUSIONS: Tolvaptan can be used safely and efficiently in infants with CHD. From the perspective of adverse effects, initiating administration at a lower dosage is preferable because this was found to be sufficiently effective.

Utility of a rapid assay for prostaglandin E-major urinary metabolite as a biomarker in pediatric ulcerative colitis.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6-16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts' histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group (P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR (P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER (P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.

Independent risk factors of rapid glomerular filtration rate decline in patients with type 2 diabetes with preserved kidney function and normoalbuminuria: A multicenter cohort study.

AIMS/INTRODUCTION: Research on the incidence and underlying mechanisms of rapid renal function decline in patients with type 2 diabetes mellitus with preserved renal function and normoalbuminuria is limited. This study aimed to investigate the involvement of hemoglobin level as a risk factor for rapid decliners among patients with type 2 diabetes with preserved renal function and normoalbuminuria. MATERIALS AND METHODS: This was a retrospective observational study of 242 patients with type 2 diabetes with a baseline estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 and normoalbuminuria (<30 mg/gCr), followed up for >1 year. The annual rate of estimated glomerular filtration rate decline during the follow-up period was calculated using least square regression analysis; rapid decliners defined at ≥3.3%/year. Risk factors associated with rapid decliners were identified using a logistic regression analysis of variables previously identified as risk factors of rapid decliners. RESULTS: The median follow-up period was 6.7 years, and 34 patients showed rapid decliners. On multivariate analysis, lower baseline hemoglobin level was a risk factor of rapid decliners (odds ratio 0.69, 95% confidence interval 0.47-0.99; P = 0.045). Furthermore, the baseline hemoglobin levels were correlated positively with iron and ferritin levels, implying that an impaired iron metabolism might cause lower hemoglobin levels in rapid decliners. CONCLUSIONS: In patients with type 2 diabetes with preserved renal function and normoalbuminuria, lower hemoglobin levels were a risk factor for rapid decliners, where disturbed iron metabolism might precede the development of diabetic kidney disease.

Medical and psychosocial outcomes in adolescents and young adults with childhood-onset end-stage kidney disease: a multicenter study in Japan.

BACKGROUND: Adolescents and young adults face various socio-emotional and behavioral challenges that can affect their medical and psychosocial outcomes. Pediatric patients with end-stage kidney disease (ESKD) often have extra-renal manifestations, including intellectual disability. However, limited data are available regarding the impact of extra-renal manifestations on medical and psychosocial outcomes among adolescents and young adults with childhood-onset ESKD. METHODS: Patients born between January 1982 and December 2006 that had developed ESKD in 2000 and later at age < 20 years were enrolled in this multicenter study in Japan. Data for patients' medical and psychosocial outcomes were retrospectively collected. Associations between extra-renal manifestations and these outcomes were analyzed. RESULTS: In total, 196 patients were analyzed. The mean age at ESKD was 10.8 years, and at last follow-up was 23.5 years. The first modality of kidney replacement therapy was kidney transplantation, peritoneal dialysis, and hemodialysis in 42, 55 and 3% of patients, respectively. Extra-renal manifestations were documented in 63% of patients and 27% had intellectual disability. Baseline height at kidney transplantation and intellectual disability significantly impacted final height. Six (3.1%) patients died, of which five (83%) had extra-renal manifestations. Patients' employment rate was lower than that in the general population, especially among those with extra-renal manifestations. Patients with intellectual disability were less likely to be transferred to adult care. CONCLUSIONS: Extra-renal manifestations and intellectual disability in adolescents and young adults with ESKD had considerable impacts on linear growth, mortality, employment, and transfer to adult care.

Depression and health-related quality of life in adolescents and young adults with childhood-onset end-stage kidney disease: a multicenter study in Japan.

BACKGROUND: Patient survival and physical outcomes among children with end-stage kidney disease (ESKD) have significantly improved, and recent research has focused on long-term depression symptoms and health-related quality of life (HRQOL). However, no studies have been conducted among adolescents and young adults with childhood-onset ESKD in Japan. METHODS: This multicenter study included 45 adolescents and young adults aged 16-39 years who developed ESKD at age < 20 years. Depression symptoms were measured using the Beck Depression Inventory (BDI)-II. The Short Form-36 Health Survey (SF-36) was used to assess HRQOL. Factors associated with depression and HRQOL were analyzed. RESULTS: Depression (BDI-II score ≥ 14) was observed in 13 (29%) patients. Patient's SF-36 physical component summary (PCS) and mental component summary (MCS) scores were comparable with those for the general population. Lower estimated glomerular filtration rate, higher BDI-II scores, and lower body mass index were associated with lower PCS scores. BDI-II scores were negatively correlated with MCS scores. We observed a trend that unemployment was associated with lower MCS scores. CONCLUSIONS: Depression is frequently observed among adolescents and young adults with childhood-onset ESKD. Regular screening for psychosocial concerns, maintaining stable graft functions, and achieving optimal nutritional status may contribute to improved well-being among these patients.

Comparison of the characteristics and factors influencing hospital visits among children with nocturnal enuresis in Japan: The Hirakata-Urayasu population-based cohort study.

OBJECTIVES: The aim of this study was to compare the demographic characteristics of school-aged children with nocturnal enuresis and factors influencing hospital visits between two regions in Japan. METHODS: A cross-sectional survey was conducted in Hirakata City, Osaka Prefecture, and Urayasu City, Chiba Prefecture. An anonymous online questionnaire was administered to all public elementary and junior high school students (aged 6-16 years) or their guardians. Questions included age, gender, perinatal history, frequency of nocturnal enuresis, frequency of bowel movements, comorbidities, and hospital visits for nocturnal enuresis. RESULTS: The survey response rates were 15.4% in Hirakata City and 37.0% in Urayasu City. In total, 426 children with nocturnal enuresis in Hirakata City and 270 in Urayasu City were included in the final analysis. In both cities, the boy-girl ratio was approximately 2:1, and the prevalence of nocturnal enuresis gradually decreased with age. Multivariate analysis revealed that children aged ≥11 years had a significantly higher proportion of hospital visits (OR, 2.61; 95% CI: 1.49-4.56; p = 0.001; OR, 2.72; 95% CI: 1.12-6.64; p = 0.027, respectively). However, the frequency of nocturnal enuresis did not affect hospital visits. CONCLUSIONS: The findings of this study suggest that parents with school-aged children have low awareness that nocturnal enuresis is a health problem and therefore subject to medical consultation. Although the proportion of hospital visits increases for children aged ≥11 years, children and families suffering from nocturnal enuresis should be encouraged to see a doctor instead of adopting a "wait and see attitude," even at a young age.

Survival analysis among pediatric patients receiving kidney replacement therapy: a Japanese nationwide cohort study.

BACKGROUND: Limited data are available on the survival and causes of death in pediatric patients with chronic kidney disease (CKD) stage 5 receiving kidney replacement therapy (KRT) in Asia. METHODS: Data were obtained from the Japanese nationwide cross-sectional CKD stage 5 survey on pediatric patients (<20 years of age) who started KRT from 2006 to 2013. The cohort was divided into three groups according to age at the start of KRT: <1, 1-5, and 6-19 years. RESULTS: Among the 701 children who were included, 59.3% were boys. Peritoneal dialysis was the most common initial modality of KRT (60.3%). Median age at KRT initiation was 10.2 years. Infants (<1 year old) accounted for 16.0% of the total cohort. Overall survival at 1 and 5 years was 97.2% and 92.5%, respectively. Infants had significantly lower survival rates than the other groups (hazard ratio, 5.35; 95% CI, 2.60-11.03; P < 0.001). In contrast, after the age of 1 year, the survival rate improved and did not differ from that of other age groups. The most common causes of death were infection (35.9%) and sudden death (15.4%). CONCLUSIONS: The overall survival rate of pediatric patients with CKD stage 5 in Japan is like that in other high-income countries. Age at initiation of KRT is an important factor affecting survival since the poorest survival rate was observed in infants. Further improvement in infant dialysis therapy is still needed to improve survival of the youngest children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Lack of clinical evidence of antiviral therapy for human monkeypox: A scoping review.

Since May 2022, many human monkeypox cases have been reported from non-endemic countries. This systematic review aimed to evaluate and summarize the existing research on the efficacy and safety of tecovirimat, brincidofovir, and cidofovir for patients with monkeypox. We searched studies that reported the efficacy and adverse events of tecovirimat, brincidofovir, or cidofovir for patients with human monkeypox in several databases including preprint servers. Only five studies were included. The efficacy and adverse events were assessed in only five and four patients, respectively. Regarding tecovirimat, all two patients recovered from monkeypox. One had no adverse event and the other has no description of an adverse event. Regarding brincidofovir, all three patients recovered from monkeypox but all of them had increased alanine transaminase, and one had nausea and abdominal discomfort. There was no study on treatment with cidofovir. Based on past studies and our results, tecovirimat might be the best choice due to ease of administration (oral drug), fewer side effects, and past treatment results for human monkeypox administration. However, very few studies were included in this scoping review. Therefore, further studies are needed to assess their efficacy and safety as possible treatments for human monkeypox.

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.

Cumulative Dialytic Glucose Exposure is a Risk Factor for Peritoneal Fibrosis and Angiogenesis in Pediatric Patients Undergoing Peritoneal Dialysis Using Neutral-pH Fluids.

Introduction: Neutral-pH dialysate has been reported to be beneficial to prevent the peritoneal pathological changes in adult peritoneal dialysis (PD) patients, but its use is controversial in pediatric PD patients. In addition, the impact of cumulative dialytic glucose exposure has not been examined. Methods: Pediatric PD patients using conventional fluids (conventional group, n = 31) or those using neutral-pH fluids (neutral-pH group, n = 33) were compared. Clinical risk factors for peritoneal pathological changes in the neutral-pH group were analyzed using generalized linear modeling. Furthermore, the mechanisms of peritoneal pathological changes were explored using immunohistochemical studies and cultured cells. Results: The median (interquartile range) duration of dialysis was 3.2 (1.7-5.3) years in overall patients. After propensity score matching, the conventional group showed increased thickening of the submesothelial compact (SMC) zone and lower luminal-to-vessel diameter (L/V) ratio than the neutral-pH group. In the neutral-pH group, the cumulative dialytic glucose exposure was an independent risk factor for greater thickness of the SMC zone (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.16-2.05) and higher submesothelial microvessel density (OR, 1.29; 95% CI, 1.01-1.64). Immunohistochemical study showed that cumulative dialytic glucose exposure correlated with the proportion of the tissue expressing hypoxia inducible factor -1α (HIF-1α) and vascular endothelial growth factor-α (VEGF-α). In human peritoneal mesothelial cells, high glucose significantly increased HIF-1α and VEGF-α expressions. Conclusion: Cumulative dialytic glucose exposure is an independent risk factor for peritoneal fibrosis and angiogenesis in pediatric patients undergoing PD using neutral-pH fluids, which might be associated with greater VEGF-α production by myofibroblasts implying a hypoxic response.

Experience with enteral sulfonylurea monotherapy for extremely low birth weight infants with hyperglycemia.

Limited data are available on the effects of enteral sulfonylurea (SU) monotherapy in extremely low birth weight infants (ELBWIs) with hyperglycemia. Therefore, we report our experience with enteral SU monotherapy for hyperglycemic ELBWIs. We retrospectively evaluated 11 hyperglycemic ELBWIs (seven male infants, median gestational age = 24.9 wk) who received SU between January 2016 and December 2019. Blood glucose (BG) levels were monitored before and after SU initiation and evaluated for the occurrence of adverse effects. We administered SU at a median of 15 d (interquartile range [IQR]: 12-20 d) after birth, with the median maximum dose of 0.2 mg/kg/d (IQR: 0.125-0.3 mg/kg/d). Hyperglycemia improved in all patients, and the target BG levels were achieved without severe side effects at a median of 6 d (IQR: 4-8.5 d) after initiation of treatment. The incidence of hypoglycemia during SU treatment was observed in 18 events per 1000 patient hours; however, the patients were asymptomatic. Based on these results, enteral SU monotherapy may be considered as an option for hyperglycemic ELBWIs.

Clinicopathologic Features of Mitochondrial Nephropathy.

Introduction: The clinicopathologic characteristics of nephropathy associated with mitochondrial disease (MD) remain unknown. We retrospectively analyzed a cohort of patients with proteinuria, decreased glomerular filtration rate, or Fanconi syndrome who had a genetic mutation confirmed as the cause of MD, defined as mitochondrial nephropathy. Methods: This nationwide survey included 757 nephrology sections throughout Japan, and consequently, data on 81 cases of mitochondrial nephropathy were collected. Results: The most common renal manifestation observed during the disease course was proteinuria. Hearing loss was the most common comorbidity; a renal-limited phenotype was observed only in mitochondrial DNA (mtDNA) point mutation and COQ8B mutation cases. We found a median time delay of 6.0 years from onset of renal manifestations to diagnosis. Focal segmental glomerular sclerosis (FSGS) was the most common pathologic diagnosis. We then focused on 63 cases with the m.3243A>G mutation. The rate of cases with diabetes was significantly higher among adult-onset cases than among childhood-onset cases. Pathologic diagnoses were more variable in adult-onset cases, including diabetic nephropathy, nephrosclerosis, tubulointerstitial nephropathy, and minor glomerular abnormalities. During the median observation period of 11.0 years from the first onset of renal manifestations in patients with m.3243A>G, renal replacement therapy (RRT) was initiated in 50.8% of patients. Death occurred in 25.4% of the patients during the median observation period of 12.0 years. The median estimated glomerular filtration rate (eGFR) decline was 5.4 ml/min per 1.73 m2/yr in the cases, especially 8.3 ml/min per 1.73 m2/yr in FSGS cases, with m.3243A>G. Conclusion: Here, we described the clinicopathologic features and prognosis of mitochondrial nephropathy using large-scale data.

The effectiveness of intravenous benzodiazepine for status epilepticus in Dravet syndrome.

PURPOSE: We aimed to evaluate choice and efficacy of intravenous antiepileptic drugs (AEDs) for status epilepticus (SE) in Dravet syndrome and to find predictable clinical features demonstrating the effectiveness of benzodiazepine (BZD) for SE. METHODS: We retrospectively investigated the medical records in patients with Dravet syndrome and evaluated the effectiveness rate of intravenous AEDs and the rate of adverse effects. To find the clinical features of BZD-effective SE, we divided the SE episodes into the following two groups: BZD effective group and BZD non-effective group. The choice of treatment was dependent on physicians' discretion according to the protocol for SE in our institution. RESULTS: Sixty-eight SE episodes in 10 patients were assessed. The median age at SE was 31 months. Of 68 episodes, 42 episodes (61.8%) were in the BZD effective group and 26 (38.2%) in the BZD non-effective group. There were no significant differences in clinical features. In the BZD non-effective group, the effective rates of continuous midazolam, phenobarbital, phenytoin/fosphenytoin were 9/9 episodes (100%), 14/17 (82.4%), and 2/5 (40.0%), respectively. Adverse effects were identified in 19/68 episodes (27.9%), including 11/42 episodes in the BZD effective group and 8/26 in the BZD non-effective group, which was no statistical difference between the two groups. Respiratory suppression was found in all 19 episodes and the incidence of endotracheal intubation in the BZD non-effective group (15.4%) was higher than that in the BZD effective group (2.4%) (p = 0.046). CONCLUSION: BZD may be used as first choice, and phenobarbital prior to continuous midazolam as second choice for SE with Dravet syndrome. There might be no predictable clinical features showing that BZD will be effective.

Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent.

Mizoribine may be a safe and effective treatment for children with steroid-dependent nephrotic syndrome (SDNS). However, predictors of treatment response and long-term outcomes after mizoribine discontinuation remain unknown. We retrospectively reviewed the clinical course of 22 children aged ≤ 10 years (median age, 5.3 years) with SDNS who received high-dose mizoribine as the initial steroid-sparing agent (SSA). Mizoribine was administered at a single daily dose of 10 mg/kg (maximum, 300 mg/day) after breakfast. The dose was adjusted to maintain 2-h post-dose mizoribine levels of > 3 µg/mL and was tapered off after 12 months of steroid-free remission. Patients who regressed to SDNS were switched from mizoribine to other SSAs. The primary endpoint was probability of survival without regression to SDNS after mizoribine initiation. Ten patients were able to discontinue SDNS (response group), whereas twelve were switched from mizoribine to other SSAs (non-response group) during a median observation period of 6.0 years after mizoribine. The steroid-dependent dose prior to mizoribine was significantly lower in the response group than in the non-response group (p < 0.05). The Kaplan-Meier analysis revealed that the probability of regression-free survival was significant higher in patients with steroid-dependent dose of < 0.25 mg/kg/day than in those with steroid-dependent dose of ≥ 0.25 mg/kg/day (p < 0.05). During a median follow-up of 5.5 years after mizoribine discontinuation, all but one patient did not develop SDNS. High-dose mizoribine may be an attractive treatment option as initial SSA in young children with low steroid-dependent dose for improved long-term outcomes.

Risk factors for hyperglycemia in extremely low birth weight infants during the first 14 days.

BACKGROUND: There are limited data regarding the risk factors for hyperglycemia in extremely low birth weight infants (ELBWIs). The aim of this observational study was to investigate the incidence of hyperglycemia among ELBWIs during the first 14 days of life and identify independent risk factors for hyperglycemia development. METHODS: We retrospectively evaluated 55 ELBWIs (32 male infants) between January 2015 and March 2020. Hyperglycemia was diagnosed when the glucose level was ≥180 mg/dL. Demographic and clinical data were extracted from the patients' medical records. The risk factors associated with the onset of hyperglycemia were identified by Cox proportional hazards regression analysis with variables that had previously been identified as risk factors for hyperglycemia. RESULTS: Hyperglycemia developed in 23 patients (41.8%) within the first 14 days of life. Gestational age, chorioamnionitis, postnatal intravenous glucocorticoids, and probiotic type were included in the analysis. The results indicated that hyperglycemia was significantly associated with gestational age (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48-0.87; P = 0.004). Further, Bifidobacterium breve (B. breve M-16V) use was related to hyperglycemia in ELBWIs (HR, 2.95; 95% CI, 1.10-7.87; P = 0.031). CONCLUSION: Hyperglycemia was strongly associated with lower gestational age and B. breve M-16V use in our study population. Although probiotic supplementation may be beneficial for preterm infants to reduce the incidence of necrotizing enterocolitis, the dextrin used as an excipient in B. breve M-16V may lead to an undesirable carbohydrate load in ELBWIs.