Pediatric early-phase anorexia nervosa without hypokalemia exhibiting acute tubular injury: a case report.

Anorexia nervosa can lead to kidney complications. Few studies reported kidney biopsy results in young adults, most of whom had chronic anorexia nervosa, and kidney biopsy findings in pediatric patients with early-phase anorexia nervosa are rarely reported. A 14-year-old girl who lost weight due to excessive exercise and reduced diet was admitted for kidney dysfunction. She was 147 cm tall and weighed 32.9 kg, with a body mass index of 15.2 kg/m2. She was 39 kg about a year earlier. Her heart rate and blood pressure were 30-40 beats/min and 108/68 mmHg, respectively. She had kidney dysfunction (estimated glomerular filtration rate, 56.6 mL/min/1.73 m2). Urine ß2-microglobulin was slightly elevated (393 µg/L), and percent tubular phosphate reabsorption was low (75.2%), suggesting tubular damage; however, hypokalemia was absent. Kidney dysfunction did not improve with fluid loading. Kidney biopsy revealed that all glomeruli were intact, with no vasculitis, interstitial inflammation or fibrosis on light microscopy. However, proximal tubular epithelial walls were flattened and the brush border was absent, suggesting acute tubular injury. Immunofluorescent staining was negative for immunoglobulins and complement proteins, and electron microscopy showed no significant electron-dense deposition. The patient's serum creatinine gradually declined, normalizing on the 17th day of admission. Unlike previous reports in young adults, kidney dysfunction was observed even in the absence of hypokalemia in the current pediatric patient with early-phase anorexia nervosa. Proximal tubular injury in early-phase anorexia nervosa may be caused by bradycardia without hypokalemia, leading to subsequent kidney dysfunction.

Intrapartum prophylactic efficacy of ampicillin versus clindamycin in preventing vertical transmission of group B Streptococcus.

AIM: To compare the prophylactic efficacy of ampicillin and clindamycin against vertical transmission of group B Streptococcus from mothers to their infants by evaluating the rates of group B Streptococcus colonisation. METHODS: We retrospectively extracted data for mothers who delivered at Showa University Northern Yokohama Hospital between 1 October 2017 and 31 March 2021 and tested positive for antepartum group B Streptococcus, and their infants. The chi-square test was used to compare the rates of group B Streptococcus colonisation, sepsis, and meningitis. We conducted a multivariate logistic regression analysis, including the time interval between membrane rupture and delivery, chorioamnionitis, and maternal intrapartum fever (≥38.0°C). RESULTS: Two hundred fifty-nine mothers and their infants were eligible. Ampicillin and clindamycin were administered to 150 and 109 mothers, respectively. In the ampicillin and clindamycin groups, 12.0% (18/150) and 37.6% (41/109) infants were group B Streptococcus positive, respectively. The rate of group B Streptococcus colonisation among infants was significantly lower in the ampicillin group (p < 0.001). Multivariate regression analysis showed similar results (p < 0.001). No sepsis or meningitis cases were observed in either group. CONCLUSION: Prophylactic efficacy of clindamycin against the vertical transmission of group B Streptococcus is lower than that of ampicillin.

Delayed diagnosis and exacerbation of hyperlipidemia in idiopathic nephrotic syndrome in children during the COVID-19 pandemic.

BACKGROUND: During the coronavirus disease-2019 (COVID-19) pandemic, there was a lack of access to outpatient facilities for other diseases. Conversely, few studies have reported changes in clinical features of idiopathic nephrotic syndrome (INS) in children before and after the COVID-19 pandemic. METHODS: Thirty-two children with primary INS, who were admitted to four Showa University-affiliated hospitals between January 2017 and December 2022, were enrolled in this retrospective study. Children were divided according to the onset of INS into a post-COVID-19 group (onset in 2020-2022, n = 25) and a pre-COVID-19 group (onset in 2017-2019, n = 32). We compared the clinical characteristics and features of initial INS between two groups. RESULTS: In the post-COVID-19 group, these patients had interval between noticing symptoms of INS, such as edema and INS diagnosis was significantly longer (7 days versus 3.5 days; p = 0.0047), and had significantly raised serum LDL cholesterol levels at the time of INS diagnosis than in the pre-COVID-19 group (314 mg/dL versus 260 mg/dL; p = 0.028). Likewise, steroid-resistant nephrotic syndrome was significantly more common in the post-COVID-19 group [32% (n = 8) versus 6% (n = 2); p = 0.016]. A correlation analysis revealed a moderate positive correlation between the interval from symptom to diagnosis and LDL cholesterol (r = 0.460015, p = 0.0003). CONCLUSIONS: Children with INS after the COVID-19 pandemic showed a longer time between noticing symptoms of INS and diagnosis, increased serum LDL cholesterol and more steroid resistance than before the pandemic.

Differences in the Clinical Characteristics of Kawasaki Disease Between Older and Younger Children (2015-2019): A Single-Center, Retrospective Study.

OBJECTIVE: The objective of this study was to investigate the differences in the clinical characteristics of Kawasaki disease between older and younger children. STUDY DESIGN: This retrospective study examined 405 children with Kawasaki disease admitted to Showa University Northern Yokohama Hospital between 2015 and 2019. RESULTS: Eligible patients were classified into the older (≥3.0 years of age, n = 169) and younger (<3.0 years of age, n = 236) groups. Skin rash was found in significantly fewer cases (112 [66.3%] vs 229 [97.0%], P < .001 in the younger group). Cervical lymphadenopathy was more common in older children (153 [90.5%] vs 165 [69.9%], P < .001) and in incomplete Kawasaki disease (3 or 4 findings) (34 [20.1%] vs 25 [10.6%], P = .0078). The diagnosis was more delayed in older children (median: 5.0 days vs 4.0 days, P = .003) than the younger group. Additionally, fever nonresponsive to a single intravenous immunoglobulin was more common, and the duration of fever was significantly longer in the older group (48 [28.4%] vs 47 [19.9%], P = .0479). CONCLUSIONS: Kawasaki disease should be suspected in children aged >3.0 years with cervical lymphadenopathy and fever, despite the absence of skin rash. Additionally, incomplete Kawasaki disease, fever unresolved by a single intravenous immunoglobulin infusion, and the tendency to delay treatment initiation are more common in children aged >3.0 years.

Sleep features of nocturnal enuresis: relationship between rapid eye movement sleep latency prolongation and nocturnal enuresis.

Nocturnal enuresis, or bed wetting, is the involuntary urination during sleep. One of its causes is difficulty awakening during sleep, suggesting a relationship between Nocturnal enuresis (NE) and sleep. However, no studies have yet clarified the relationship between NE and sleep, and the effects of sleep structure in NE children are not yet known. Assuming that changes in sleep structure are related to NE, there would be a difference in sleep structure between days with and without NE. We measured the sleep electroencephalograms of 27 at home patients aged 6-16 years, evaluated the differences between days with and without NE, and examined the NE-associated sleep characteristics associated. The evaluation items were total sleep time, sleep efficiency, the ratio of rapid eye movement (REM) to non-REM sleep, REM sleep latency, and non-REM sleep latency. Factors influencing NE were examined by logistic regression analysis, with NE presence/absence as the dependent variable and each evaluation item as the independent variable. Given that 2-6 measurements were made for each patient, Generalized Estimating Equations was used in the analysis. NE positively correlated with prolonged REM sleep latency, but no significant differences were found in other sleep structures. A positive correlation exists between NE and prolonged REM sleep latency. Changes in sleep structure in the early stages of sleep may lead to increased nocturnal urine volume and increased NE frequency.

Comparison of wireless and wired alarm devices for nocturnal enuresis treatment.

BACKGROUND: In monosymptomatic nocturnal enuresis (MNE) treatment, enuretic alarm devices are the first recommended treatment option. This study aimed to compare retrospectively the effectiveness of wearable wireless and wired alarm devices for MNE treatment in children aged 6-14 years. METHODS: All children aged 6-16 with MNE who underwent alarm therapy as outpatients were included. A wired alarm device was used from 2012 to 2015, and a wireless alarm device was used from 2016 to 2019. The primary outcomes were the dropout rates during therapy and at last follow up. The full response(14 consecutive dry nights) and the partial response rate during therapy were also assessed. RESULTS: Of the 173 patients enrolled, 75 and 98 used a wired and a wireless alarm device, respectively. The dropout rate at the last visit was significantly lower in the wireless alarm group than that in the wired alarm group (6.1% vs. 20.0%; P = 0.006). The full response(FR) rate was significantly higher in the wireless alarm group than these in the wired alarm group at 4, 12, 24 weeks (4 weeks: 11.2% vs. 1.3%, P = 0.011; 12 weeks: 31.9% vs. 13.5%, P = 0.005; 24 weeks: 72.9% vs. 39.7%, P < 0.0001). CONCLUSIONS: Wireless alarm therapy for MNE had lower attrition rates and a higher rate of FR than wired alarm therapy.

Meningitis due to Enterobacter aerogenes in the community associated with congenital dermal sinus in a Japanese infant.

Congenital dermal sinus is associated with meningitis caused by atypical pathogens. Although nosocomial infections with Enterobacter aerogenes in limited settings have been reported, community-acquired infections associated with congenital dermal sinus are rarely observed. We present the first non-neonatal case of a 3-month-old boy with meningitis due to Enterobacter aerogenes associated with congenital dermal sinus. The patient visited our hospital with fever and a skin dimple with lumbosacral hemangioma. He was diagnosed with meningitis based on cerebrospinal fluid (CSF) examination, which showed a cell count of 5717/µL. Subsequently, antimicrobial therapy with meropenem, cefotaxime (CTX), and vancomycin was initiated. His fever subsided, and the number of CSF cells decreased. Magnetic resonance imaging was performed for the dimple of the lumbosacral region, revealing the congenital dermal sinus. Enterobacter aerogenes was isolated from CSF and stool cultures, and treatment was adjusted to CTX alone based on susceptibility testing. However, the CSF culture remained positive. Although CTX was effective, the response to treatment was partial, and a switch to meropenem was required to achieve negative CSF cultures. In conclusion, Enterobacter aerogenes, although atypical, can cause community-acquired meningitis associated with congenital dermal sinus. Consistent with previous reports, in this case, a hemangioma on the back led to the diagnosis of congenital dermal sinus. Hence, systemic examination, including the back, is important. In addition, use of a third-generation cephalosporin (e.g., CTX) may not negate the CSF culture, even if it is effective. Thus, a switch to another drug (e.g., carbapenem) may be required.

Fecal impaction detected by imaging predicts recurrent urinary tract infection.

BACKGROUND: Few studies have evaluated the efficacy of ultrasonography (US) and abdominal radiography in assessing bladder and bowel dysfunction in children aged <24 months. We aimed to investigate the association between the risk of urinary tract infection (UTI) recurrence and fecal impaction using imaging findings. METHODS: The medical records of 121 children (aged <24 months) with initial febrile UTI (fUTI) who were admitted to the authors' institution from January 2004 to September 2019 were reviewed retrospectively. We evaluated the rectal diameters of children with suspected fecal impaction that were measured using transabdominal US, or the rectal diameters divided by the distance between the ischial spines that were measured using abdominal radiography. Based on previous reports, we defined fecal impaction as a transabdominal US score of >30 mm or an abdominal radiography score of >0.5. The definition of functional constipation was based on the child/adolescent Rome IV criteria - i.e., a maximum stool frequency of twice per week. RESULTS: The median age at initial fUTI diagnosis was 4 months. The occurrence of fecal impaction identified via imaging was significantly greater in patients with UTI recurrence than in those without recurrence: yes/no: 17/9 (65.4%) versus 35/60 (36.8%); P = 0.013. On the other hand, the occurrence rates of constipation based on stool frequency did not differ between the two groups. In multiple logistic analyses, fecal impaction detected via imaging was identified as an independent risk factor for fUTI recurrence. CONCLUSIONS: Fecal impaction observed via US and abdominal radiography may be useful in predicting the recurrence of fUTI in children.

Clinical, pathological, and genetic characteristics of cases with asymptomatic proteinuria not manifesting nephrotic syndrome at onset: a single-center retrospective study.

BACKGROUND: Cases with asymptomatic proteinuria (ASP) not manifesting nephrotic syndrome often pathologically show focal segmental glomerulosclerosis (FSGS). However, characteristics of those cases had not been intensively studied so far. METHODS: We retrospectively reviewed clinical, pathological, and genetic characteristics of 37 children (median age, 9.3 years) who underwent renal biopsy for persistent isolated proteinuria (urine protein-to-creatinine ratio: UP/C, > 0.2 g/g) between 2003 and 2019. Targeted next-generation sequencing (NGS) was utilized for all patients with FSGS, excluding those with secondary FSGS. RESULTS: At biopsy, all patients with FSGS (N = 14) had UP/C ≥ 0.5 g/g and the median UP/C was significantly higher in those with FSGS than those with minor glomerular abnormalities (MGA) (N = 23) (1.49 vs. 0.53 g/g, P < 0.001). Causative variants were found in seven patients with FSGS (TRPC6, WT1, ACTN4, and INF2 in 3, 2, 1, and 1 patient, respectively): all gene variants were in genes manifesting autosomal dominant inheritance mode. The proportion of the perihilar variant was significantly higher in the genetic FSGS patients than in the non-genetic FSGS patients (4/7 vs. 0/7, P < 0.05). Kaplan-Meier analysis showed that the renal survival rate after ASP diagnosis was significantly lower in the genetic FSGS patients than in the non-genetic FSGS and the MGA patients (P < 0.001). CONCLUSIONS: UP/C was a simple and useful predictive parameter for the diagnosis of FSGS. APS without nephrotic syndrome at onset may be associated with autosomal dominant causes of FSGS, especially in those with the perihilar variant.

Safety of vancomycin in patients with moderate and severe renal dysfunction.

AIM: The new guidelines in Japan do not recommend a vancomycin (VCM) loading dose for patients with an estimated glomerular filtration rate (eGFR) 30 < and ≤ 80 mL×min-1×1.73m-2 (moderate renal dysfunction) or administration to those with the eGFR < 30 mL×min-1×1.73m-2 (severe renal dysfunction). We investigated the safety and efficiency of VCM in patients with moderate and severe renal dysfunction based on the new guidelines. MATERIALS AND METHODS: The study involved patients admitted to our hospital between April 2014 and March 2018 with an eGFR < 80 mL×min-1×1.73m-2 and treated with VCM. VCM trough concentration and pre- and post-administration renal function were investigated retrospectively. The primary endpoints were the proportion of patients who achieved an effective trough concentration of 10 - 20 µg/mL and rate of acute kidney injury (AKI). RESULTS: We included 64 patients (32 moderate, 32 severe). The mean VCM trough concentration achieved for the first time was 9.3 and 11.6 µg/mL in the moderate and severe renal dysfunction groups, respectively (p = 0.91). The effective trough concentration endpoint was achieved by 50% and 43% of the patients in the severe and moderate renal dysfunction groups, respectively, and no significant difference was found in the AKI rate. The serum creatinine change was significantly different between the groups - the moderate group showed a slight deterioration and the severe renal dysfunction group an improvement. CONCLUSION: It may be necessary to increase the dose for these patients with severe renal dysfunction while implementing a VCM loading dose and monitoring trough concentrations and adverse effects.

Distribution of serum adiponectin isoforms in pediatric patients with steroid-sensitive nephrotic syndrome.

BACKGROUND: Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. METHODS: We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. RESULTS: The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 µg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. CONCLUSIONS: In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.

Comparison of trough concentration and area under the curve of vancomycin associated with the incidence of nephrotoxicity and predictors of a high trough level.

PURPOSE: A high vancomycin trough concentration during therapy is associated with increased nephrotoxicity, and the recent guidelines for therapeutic monitoring of vancomycin recommend target of the ratio of area under the curve (AUC) to minimum inhibitory concentration. We aimed to determine vancomycin trough concentration and AUC that induce nephrotoxicity and evaluate predictive factors associated with a high serum vancomycin trough level according to the initial dosing strategy. METHODS: We conducted a retrospective cohort study in patients administered intravenous vancomycin from June 2013 to February 2017. Totally, 346 patients were included. RESULTS: 38 experienced nephrotoxicity during therapy. The both trough level and AUC were significant risk factors for the occurrence of vancomycin induced-nephrotoxicity (p < 0.001, p = 0.001). The exposure-response analysis revealed that the trough level of 15 µg/mL was associated with 12.0% nephrotoxicity incidence and AUC of 600 was associated with 12.9% nephrotoxicity incidence. During the treatment, 90 patients had an initial trough concentration of ≥15 µg/mL, and 124 patients had AUC of ≥600 µg h/mL. The multiple logistic regression analysis revealed body weight (p = 0.001), serum creatinine level (p = 0.028), daily vancomycin dose (p = 0.001), and ICU (p = 0.015) were independent predictive factors for a high trough concentration. And same factors were selected for the high AUC. CONCLUSION: The risk factors for vancomycin induced nephrotoxicity were comparable in both trough concentration and AUC. The incidence of nephrotoxicity can be reduced by controlling vancomycin trough concentration similarly AUC and promoting antimicrobial stewardship.

Evaluation of prognosis following early disease progression in peripheral T-cell lymphoma.

Recently, progression of disease within 24 months (POD24) has been demonstrated as a strong prognostic indicator in various types of malignant lymphoma. Peripheral T-cell lymphoma (PTCL) has an aggressive course and poor clinical outcomes. In this multicenter retrospective study, 111 consecutively registered patients with newly diagnosed PTCL were analyzed. Of these patients, 72 (64.9%) experienced POD24 (POD24 group), and the other 39 patients (35.1%) were analyzed as the no POD24 group. In the POD24 group, overall survival (OS) was significantly inferior to all patients, and in the no POD24 group, subsequent OS was significantly superior to the POD24 group, although the clinical characteristics between the POD24 group and no POD24 group were not significantly different. Twenty-three patients (20.7%) showed primary refractory disease to first-line therapy, and the prognosis was poor. The International Prognostic Index score and POD24 were identified as independent predictors in multivariate analysis for OS in all patients, and only performance status was an independent prognostic factor for OS in the POD24 group in multivariate analysis. In conclusion, the clinical significance of assessing POD24 in PTCL and the poor prognosis in patients with early disease progression were demonstrated.

A multi-center retrospective analysis of patients with relapsed/refractory follicular lymphoma after third-line chemotherapy.

The overall outcome of patients with advanced-stage follicular lymphoma (FL) has improved significantly. However, some patients still develop multiple relapsed/refractory FL (RRFL). To address the still-limited data on this population, we performed this multi-center retrospective study. We analyzed 41 patients who received third-line treatment for RRFL at 8 institutes. The median age at diagnosis was 59 years (range, 38-70). The median progression-free survival (PFS) and probability of PFS at 2 years were 1.61 years and 39.4%, respectively, after third-line chemotherapy, and 0.45 years and 19.0%, respectively, after fourth-line chemotherapy. Objective response (OR) after third-line chemotherapy was achieved in 24 patients (53.7%). Bendamustine (Ben)-based regimens were associated with a significantly higher OR rate than other regimens (77.8% vs. 40.0%, respectively, P = 0.025). The median overall survival (OS) and probability of OS at 2 years were 4.71 years and 65.9%, respectively, after third-line chemotherapy, and 1.01 year and 45.1%, respectively, after fourth-line chemotherapy. In conclusion, this study had a small sample size and retrospective design, but it was able to demonstrate poor response rate and duration in patients with multiple RRFL, particularly after fourth-line chemotherapy. The optimal treatment strategy in this population should be clarified, including possibly hematopoietic stem cell transplantation.