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.

Sudden-onset headache due to reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by reversible segmental vasoconstriction of the cerebral arteries that spontaneously resolve within 3 months. Occurrence of RCVS peaks at around 40 years and the syndrome is common in women. Here, we report an adolescent boy case of RCVS.

Outcomes of discontinuing renin-angiotensin system inhibitors: a study protocol for conducting systematic review and meta-analysis.

INTRODUCTION: Renin-angiotensin system (RAS) plays a key role in various types of cardiovascular disease and many kinds of RAS inhibitors have been developed. The effect of discontinuation of RAS inhibitors on clinical outcomes is still controversial. This study aims to evaluate the effects of discontinuing RAS inhibitor medication on the clinical outcomes of patients continuously taking these agents. METHODS AND ANALYSIS: This article presents a systematic review protocol described in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will include randomised controlled trials in which the effects of RAS inhibitor withdrawal were evaluated. Initially, four authors will search for eligible studies in MEDLINE, EMBASE, the Cochrane Database Trial Register, European trial registry and ClinicalTrials.gov. Abstracts and full-text screenings will be performed by the four authors with data extraction performed by each author independently. We will include patients taking RAS inhibitors-including ACE inhibitor, angiotensin receptor blocker and angiotensin receptor neprilysin inhibitor and exclude the patients undergoing renal replacement therapy (RRT), adolescents (under 18 years of age) and patients with acute infectious diseases. Our search will be performed on 1 May 2023. Studies in which the patients discontinued RAS inhibitors due to any reason will be included. Patients who continuously took RAS inhibitors under conditions in which the intervention group discontinued these agents will be considered eligible as the comparison group. Death (any cause), Death (cardiovascular disease (CVD)) and CVD events will be set as primary outcomes. Secondary outcomes will be set as RRT, acute kidney injury, renal function (analysis of the change in estimated glomerular filtration rate), hyperkalaemia, proteinuria and blood pressure. ETHICS AND DISSEMINATION: Research ethics approval was not required in this study due to it being a systematic review, and any data belonging to individuals cannot be identified. The results of this study will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: PROSPERO CRD42022300777.

Kawasaki disease without changes in inflammatory biomarkers: A case report.

BACKGROUND: Kawasaki disease (KD) is diagnosed based on clinical features. Blood tests and other tests are auxiliary diagnostic tools. Since KD is a disease caused by arterial inflammation, many patients with KD have elevated levels of inflammatory biomarkers, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum amyloid A protein (SAA) in blood tests. We report our experience of a patient with KD who did not have elevated levels of inflammatory biomarkers. CASE SUMMARY: A 1-year-old boy presented with a 3-day history of fever. Five of the six symptoms of KD were observed, except for changes in the lips and oral cavity. Blood tests revealed no elevation in CRP, ESR, or SAA levels. Although the blood test results were atypical, the patient was diagnosed with KD based on clinical symptoms and was admitted to the hospital for treatment. The patient was administered intravenous immunoglobulin (IVIG) and aspirin. Despite commencing treatment, the fever persisted; therefore, additional IVIG was administered, the dosage of aspirin was increased, and ulinastatin was added. Three doses of IVIG were administered and the fever resolved on day 11 of KD symptoms started. Blood tests performed during hospitalization showed normal levels of inflammatory biomarkers. We examined leucine-rich alpha-2-glycoprotein 1 - a protein that is elevated during the acute phase of KD. The protein levels did not increase during hospitalization. CONCLUSION: This case suggests the need to identify criteria and biomarkers for detecting KD conditions that do not require KD treatment.

Remote sensing of vital signs by medical radar time-series signal using cardiac peak extraction and adaptive peak detection algorithm: Performance validation on healthy adults and application to neonatal monitoring at an NICU.

BACKGROUND AND OBJECTIVE: Continuous monitoring of vital signs plays a pivotal role in neonatal intensive care units (NICUs). In this paper, we present a system for monitoring fully non-contact medical radar-based vital signs to measure the respiratory rate (RR), heart rate (HR), I:E ratio, and heart rate variability (HRV). In addition, we evaluated its performance in a physiological laboratory and examined its adaptability in an NICU. METHODS: A non-contact medical radar-based vital sign monitoring system that includes 24 GHz radar installed in an incubator was developed. To enable reliable monitoring, an advanced signal processing algorithm (i.e., a nonlinear filter to separate respiration and heartbeat signals from the output of radar), template matching to extract cardiac peaks, and an adaptive peak detection algorithm to estimate cardiac peaks in time-series were proposed and implemented in the system. Nine healthy subjects comprising five males and four females (24 ± 5 years) participated in the laboratory test. To evaluate the adaptability of the system in an NICU setting, we tested it with three hospitalized infants, including two neonates. RESULTS: The results indicate strong agreement in healthy subjects between the non-contact system and reference contact devices for RR, HR, and inter-beat interval (IBI) measurement, with correlation coefficients of 0.83, 0.96, and 0.94, respectively. As anticipated, the template matching and adaptive peak detection algorithms outperformed the conventional approach. These showed a more accurate IBI close to the reference Bland-Altman analysis (proposed: bias of -3 ms, and 95% limits of agreement ranging from -73 to 67 ms; conventional: bias of -11 ms, and 95% limits of agreement ranging from -229 to 207 ms). Moreover, in the NICU clinical setting, the IBI correlation coefficient and 95% limit of agreement in the conventional method are 0.31 and 91 ms. The corresponding values obtained using the proposed method are 0.93 and 21 ms. CONCLUSION: The proposed system introduces a novel approach for NICU monitoring using a non-contact medical radar sensor. The signal processing method combining cardiac peak extraction algorithm with the adaptive peak detection algorithm shows high adaptability in detecting IBI the time series in various application settings.

Simple determination of urine cefazolin concentration in pediatric patients with urinary tract infections using high-performance liquid chromatography.

Recently, global health concerns regarding increasing multidrug resistance have arisen. This study aimed to develop a simple, inexpensive and rapid high-performance liquid chromatography-ultraviolet (HPLC-UV) method for determining urinary concentrations of a first-generation cephem antibiotic in pediatric patients with urinary tract infections (UTIs). HPLC-UV was used to analyze urinary cefazolin concentrations at a detection wavelength of 254 nm. The assay used contained 10-fold diluted urine with an internal standard (cephapirin). The standard calibration curve for cefazolin was linear in the concentration range of 31.25-500 µg/ml (r2  > 0.999). The retention times of cefazolin and the internal standard were 4.2 and 4.9 min, respectively. The within- and between-day coefficients of variation were in the concentration ranges 1.2-15.2 and 5.5-19.2%, respectively. The urinary cefazolin concentration of a pediatric patient with a UTI was 1,476.6 µg/ml, which was over 700-fold higher than the minimum inhibitory concentration of cefazolin (≤2 µg/ml). The developed method is applicable to the confirmation of appropriate use for UTI treatment as therapeutic drug monitoring of cefazolin. Therefore, the findings of this study may contribute to the appropriate use of antibiotics to prevent antimicrobial resistance in pediatric patients with UTIs.

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.

A pediatric patient with hyponatremic hypertensive syndrome without persistent hypertension in acute phase: A case report and review of literature.

Hyponatremic hypertensive syndrome is characterized by hypertension, hyponatremia, and hypokalemia due to unilateral renal artery stenosis. We herein report a 1-year-old hyponatremic hypertensive syndrome infant without persistent hypertension in the acute phase. On the ninth hospital day, his systolic and diastolic blood pressure increased up to 154-160 and 70-84 mmHg, respectively. Acute gastroenteritis and dehydration might transiently mask his hypertension. By percutaneous transluminal balloon angioplasty for right renal artery, his blood pressure finally normalized without antihypertensive drugs. We reviewed 23 previously reported pediatric patients with hyponatremic hypertensive syndrome under the age of 15 years. Including our patient, there are only three reports on hyponatremic hypertensive syndrome without persistent hypertension in the acute phase. Hyponatremic hypertensive syndrome is curable with proper diagnosis and timely intervention. Therefore, pediatricians should pay attention to the signs and symptoms associated with hyponatremic hypertensive syndrome, even if persistent hypertension was absent in the acute phase.

Retrospective study of the renal function using estimated glomerular filtration rate and congenital anomalies of the kidney-urinary tract in pediatric Turner syndrome.

Although Turner syndrome (TS) is frequently associated with congenital anomalies of the kidney-urinary tract (CAKUT), which is a major cause of pediatric chronic kidney disease, renal function in TS is usually considered normal. The present study aimed to analyze the frequency of renal dysfunction and CAKUT in pediatric patients with TS. Our study included 122 patients with TS between the ages of 2 and 18 years from 30 hospitals across Japan. Clinical data related to renal function and CAKUT were retrospectively collected. The estimated glomerular filtration rate (eGFR) was calculated using the serum creatinine-based formula recommended by the Japanese Society for Pediatric Nephrology. An eGFR <90 mL/min/1.73 m2 for two consecutive years was defined as renal dysfunction. Fifteen (13.5%) of 122 patients had CAKUT, and four patients had renal dysfunction (3.2%, 95% confidence interval: 0%-6.7%). Three of the four did not have CAKUT. Of the CAKUT manifestations, horseshoe kidney, renal hypodysplasia, and multicystic dysplastic kidney were seen in nine, two, and one patient, respectively. Eight of the nine patients with horseshoe kidney had a normal renal function; however, the remaining patient with renal hypodysplasia had renal dysfunction. A small percentage of patients with pediatric TS may had an eGFR below 90 mL/min/1.73 m2 which was not necessarily associated with CAKUT.

Bacteriuria With CTX-M-8 Extended-Spectrum ß-Lactamase-Producing Escherichia coli in a Patient With Incomplete Kawasaki Disease.

We report the case of a 2-month-old infant with incomplete Kawasaki disease that presented as an apparent urinary tract infection. The patient's fever persisted despite antibiotic treatment. Intravenous immunoglobulin and aspirin therapy cured both the incomplete Kawasaki disease and bacterial pyuria. Renal sonography, voiding cystourethrography, and renal parenchyma radionuclide scanning did not detect any abnormalities. Temporary dilation of the coronary artery was noted. In a urine specimen obtained through transurethral catheterization, the growth of 105 colony-forming units/mL of extended-spectrum ß-lactamase-producing Escherichia coli was detected. Polymerase chain reaction analysis revealed that the enzyme genotype was CTX-M-8, which is a rare type in Japan. In conclusion, attention should be paid to a misleading initial presentation of fever and pyuria, which might be interpreted as urinary tract infection in patients with Kawasaki disease. Furthermore, pediatricians should consider incomplete Kawasaki disease when patients present with fever and pyuria, which are consistent with urinary tract infection, but do not respond to antibiotic treatment.

A review of clinical characteristics and genetic backgrounds in Alport syndrome.

Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype-phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype-phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.

Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.

A Novel Mutation in a Japanese Family with X-linked Alport Syndrome.

We herein report a novel mutation in a Japanese family with an X-linked Alport syndrome (AS) mutation in COL4A5. Patient 1 was a 2-year-old Japanese girl. She and her mother (patient 2) had a history of proteinuria and hematuria without renal dysfunction, deafness, or ocular abnormalities. Pathological findings were consistent with AS, and a genetic analysis revealed that both patients had a heterozygous mutation (c.2767G>C) in exon 32. In summary, the identification of mutations and characteristic pathological findings was useful in making a diagnosis of AS. For a close long-term follow-up, the early detection and treatment of women with X-linked AS are important.

Validation of Cefazolin as Initial Antibiotic for First Upper Urinary Tract Infection in Children.

To validate the policy of administering cefazolin (CEZ) as a first-line antibiotic to children who are hospitalized with their first febrile urinary tract infection (UTI), we evaluated microbial susceptibility to CEZ and the efficacy of CEZ. The 75 enrolled children with febrile UTI were initially treated with CEZ. Switching CEZ was not required in 84% of the patients. The median fever duration, prevalence of bacteremia, prevalence of UTI caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli, and median duration of hospitalization were significantly higher in the CEZ-ineffective group. The risks of vesicoureteral reflux, indication of operation, and renal scarring are not increased, even when CEZ is ineffective as a first-line antibiotic. CEZ is effective in more than 80% of pediatric patients with their first febrile UTI, but it should be switched to appropriate antibiotics considering sepsis or the ESBL-producing Enterobacteriaceae pathogen, when fever does not improve within 72 hours.

AICAR Attenuates TNFα-Induced Inappropriate Secretion of Monocyte Chemoattractant Protein-1 and Adiponectin in 3T3-L1 Adipocytes.

AIM: The increase in monocyte chemoattractant protein-1 (MCP-1) and the decrease in adiponectin production from hypertrophic adipocytes are associated with adipose tissue inflammation and its metabolic complications. The aim of this study was to determine whether 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR), an adenosine monophosphate-activated protein kinase (AMPK) activator, modulates these adipocytokine productions in tumor necrosis factor-α (TNFα)-treated adipocytes. METHODS: AICAR and/or other reagents were added to the culture medium, and then, TNFα was added to fully differentiated 3T3-L1 adipocytes. The MCP-1 and adiponectin production in the culture supernatant was measured by ELISA. AMPK, phosphatidylinositol 3-kinase (PI3K), and nuclear factor-κB (NF-κB) activities were also assayed. RESULTS: Treatment with TNFα increased MCP-1 and decreased adiponectin secretion dose-dependently in the 3T3-L1 adipocytes, and AICAR significantly inhibited these TNFα-mediated changes. Interestingly, metformin, another AMPK activator, did not have such effects on these adipocytokines. Both the AMPK and PI3K systems in the cells were significantly activated by the AICAR treatment, but the effects of AICAR on adipocytokines were not weakened by the addition of dorsomorphin, an AMPK inhibitor, or LY294002, a PI3K inhibitor. Pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, showed protective effects similar to those as AICAR. AICAR, but not metformin, significantly inhibited the TNFα-stimulated activation of NF-κB, and dorsomorphin did not change AICAR's effect. CONCLUSION: AICAR attenuates the TNFα-induced secretion of MCP-1 and adiponectin in 3T3-L1 adipocytes. The observed effects of AICAR seem to be mainly due to the inhibition of NF-κB activation rather than the activation of the AMPK pathway, at least in TNFα-treated adipocytes.