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The aim of this randomised controlled study was to compare continuous subcutaneous insulin infusion using an insulin pump with the traditional continuous intravenous infusion method for tight glycaemic control. Sixty patients admitted to our University Hospital medical intensive care unit with an initial blood glucose level over 6.1 mmol/l, were enrolled and randomised into two treatment groups: the subcutaneous insulin group received continuous subcutaneous insulin infusion and the intravenous group received insulin by traditional intravenous infusion with infusers. Three patients died in the first 24 hours and were excluded from the final analysis. Insulin therapy was administered to both groups according to the previously designed and used protocol in the department. The target glucose level was 4.4 to 6.1 mmol/l. There was no significant difference in mortality between the groups. However mean blood glucose level was found to be lower (6.56+/-0.82 mmol/l vs. 7.85+/-1.6 mmol/l, P=0.00055) in the subcutaneous insulin group. According to Vogelzang's hyperglycaemic index, better glycaemic control was achieved in the subcutaneous insulin group while there was no significant difference in terms of hypoglycaemic events. Daily insulin bolus and infusion requirements were also significantly lower in the subcutaneous insulin group. Despite the small number of patients involved in this study in a medical intensive care unit, strict blood glucose control using a subcutaneous insulin pump was achieved more efficiently than the traditional intravenous infusion method without increasing hypoglycaemic events. [ABSTRACT FROM AUTHOR]

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is a genetic disease associated with renal, endocrine, neurological, skin and immune defects. SPLIS is caused by inactivating mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). SPL catalyzes the irreversible degradation of the bioactive sphingolipid sphingosine-1-phosphate (S1P), a key regulator of lymphocyte egress. The SPL reaction represents the only exit point of sphingolipid metabolism, and SPL insufficiency causes widespread sphingolipid derangements that could additionally contribute to immunodeficiency. Herein, we review SPLIS, the sphingolipid metabolic pathway, and various roles sphingolipids play in immunity. We then explore SPLIS-related immunodeficiency by analyzing data available in the published literature supplemented by medical record reviews in ten SPLIS children. We found 93% of evaluable SPLIS patients had documented evidence of immunodeficiency. Many of the remainder of cases were unevaluable due to lack of available immunological data. Most commonly, SPLIS patients exhibited lymphopenia and T cell-specific lymphopenia, consistent with the established role of the S1P/S1P1/SPL axis in lymphocyte egress. However, low B and NK cell counts, hypogammaglobulinemia, and opportunistic infections with bacterial, viral and fungal pathogens were observed. Diminished responses to childhood vaccinations were less frequently observed. Screening blood tests quantifying recent thymic emigrants identified some lymphopenic SPLIS patients in the newborn period. Lymphopenia has been reported to improve after cofactor supplementation in some SPLIS patients, indicating upregulation of SPL activity. A variety of treatments including immunoglobulin replacement, prophylactic antimicrobials and special preparation of blood products prior to transfusion have been employed in SPLIS. The diverse immune consequences in SPLIS patients suggest that aberrant S1P signaling may not fully explain the extent of immunodeficiency. Further study will be required to fully elucidate the complex mechanisms underlying SPLIS immunodeficiency and determine the most effective prophylaxis against infection., Competing Interests: Declaration of competing interest JDS is co-founder of Sphinxion Therapeutics Inc., which is developing gene therapy for individuals with SPLIS. JDS is an author on patent International Application Serial No. PCT/US2021/018613, “Adeno-Associated Viral (Aav)-Mediated SGPL1 Gene Therapy for Treatment of Sphingosine-1-Phosphate Lyase Insufficiency Syndrome (SPLIS)” published on 08/26/2021 and assigned publication number WO 2021/168140. All other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Despite its widespread use in patients undergoing organ transplantation or managing nephrotic syndrome, there is a lack of literature on the acute toxicity of cyclosporine A (CsA). This report presents a case of acute CsA toxicity resulting from an accidental overdose in a 2-year-old boy with steroid dependent nephrotic syndrome. Remarkably, despite a tenfold overdose and elevated trough levels, the patient remained asymptomatic, and the CsA trough level normalized within 48 h with rapid intervention, including discontinuation of CsA, intravenous hydration, and cytochrome P450 induction. This case emphasizes the critical importance of prompt and appropriate management to prevent serious consequences in such scenarios., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Sports dentistry aims to prevent and manage orofacial injuries, tooth fractures, tooth loss, and soft tissue trauma during sport activities. Mouthguards are appliances that protect athletes from dental trauma during contact sports. The video-sharing platform YouTube has a large number of informative videos about mouthguards. This study aimed to analyze the quality, accuracy, and reliability of YouTube videos about mouthguards, investigate the relationship between the features and the quality of mouthguard videos on YouTube, and provide suggestions for future informative content about mouthguards and sports dentistry., Materials and Methods: The first 100 videos for each keyword from YouTube were collected using the keywords "mouthguard," "sports mouthguard," and "mouthguard and dental trauma." Videos meeting the inclusion criteria were categorized based on publisher (dental professionals and nonprofessionals) and type (animation/slideshow, interview, and product introduction). Video features were recorded. Video content quality, reliability, and accuracy were measured by the Video Information and Quality Index (VIQI), the Journal of the American Medical Association (JAMA) benchmarks, the DISCERN Instrument, the Global Quality Scale (GQS), and the usefulness score. Data were analyzed using SPSS (IBM 29.0) at a 95% statistical significance level (p = 0.05)., Results: Out of 300 videos, 80 videos were included. Most of the videos were uploaded by dental professionals (n = 49). The average values of the VIQI, JAMA, DISCERN, and GQS scores were 15.33 out of 20.0, 1.38 out of 4.00, 49.24 out of 80.0, and 2.99 out of 5.00, respectively. Videos uploaded by dental professionals had significantly higher scores in VIQI, JAMA, DISCERN, GQS, and usefulness scores but exhibited a lower number of likes, comments, and views (p < 0.05). Of all included videos, 51% (n = 41) were categorized as "moderately useful" and 10% (n = 8) as "very useful.", Conclusions: Mouthguard videos uploaded by dental professionals are more useful, accurate, and of higher quality. Therefore, patients should consider the information shared by dental professionals. Greater participation from dentists in sharing high-quality content would be beneficial., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and objectives: As one of the most popular beverages in the world, coffee has long been known to affect bowel functions such as motility, secretion, and absorption. Recent evidence obtained in human and animal studies suggests that coffee has modulating impacts on gut microbiota. We aim to present an overview of the specific effects of coffee on gut microbiota composition, diversity, and growth. We will also critically review the impacts of coffee on bowel functions in health and diseases and discuss whether gut microbiota play a role in the coffee-associated functional changes in the gastrointestinal tract. Methods: We searched the literature up to June 2024 through PubMed, Web of Science, and other sources using search terms such as coffee, caffeine, microbiota, gastrointestinal infection, motility, secretion, gut-brain axis, absorption, and medication interaction. Clinical research in patients and preclinical studies in rodent animals were included. Results: A majority of the studies found that moderate consumption of coffee (<4 cups a day) increased the relative abundance of beneficial bacterial phyla such as Firmicutes and Actinobacteria and decreased Bacteroidetes. Moderate coffee consumption also increased Bifidobacterium spp. and decreased the abundance of Enterobacteria. Coffee consumption is reported to increase gut microbiota diversity. Although the effects of coffee on bowel functions have been known for a long time, it is not until recently that we have recognized that some of the effects of coffee may be partly due to its impacts on microbiota. Conclusions: The current literature suggests that moderate coffee consumption has beneficial effects on oral and gut microbiota and motility function. However, excessive coffee intake (>5 cups a day) is implicated in reflux disorders, periodontal diseases, and progression of Crohn's disease. Further research in the field is needed, as there are many conflicting results regarding the impacts of coffee in the gastrointestinal tract.

Background/aims: The preservation of avulsed teeth is critical in dental trauma management, necessitating effective storage media to ensure viable tooth reimplantation. The urgent need for accurate information has led both professional and non-professional individuals to increasingly seek guidance from video-sharing platforms such as YouTube™ and TikTok™. These platforms have become key resources for advice on such dental emergencies, but the reliability and accuracy of this information have not yet been systematically evaluated. This study aimed to assess the quality, accuracy, and reliability YouTube™ and TikTok™ of videos regarding storage solutions for avulsion injuries., Material and Methods: A search was conducted on YouTube™ and TikTok™ on February 4th, 2023, using terms related to traumatic dental injuries, and 53 videos were included. Video demographics such as platform, duration, type, upload date, likes, and comments were recorded. Video content quality, reliability, and accuracy were measured using the Global Quality Scale (GQS), Journal of the American Medical Association (JAMA) benchmarks, and Video Information and Quality Index (VIQI). Research data were analyzed using SPSS IBM 24.0 at a 95% confidence interval., Results: In total, 53 videos were examined. The average scores were JAMA: 1.70/4.00, modified DISCERN: 54.3/80.00, GQS: 3.88/5.00, and VIQI: 13.8/20.00. According to the modified DISCERN index, there were no "very poor" or "poor" quality videos, 49.05% were "moderate," 22.6% were "good," and 28.3% were "very good." No difference was found between YouTube™ and TikTok™ videos in terms of the modified DISCERN index, JAMA scores, GQS, and VIQI scoring (p > .05)., Conclusions: Traumatic dental injuries are a common problem among children, and evaluating the reliability of available contents is becoming crucial for appropriate intervention. The study reveals that despite being sourced mainly from dental professionals, the overall quality of videos on avulsed tooth management was mediocre, underscoring the risks associated with misleading or incomplete information in such critical situations., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: In the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups., Methods: This multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5-18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV., Results: Median (Q1-Q3) age of the patients was 6.0 (2.0-10.0) years, 56% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89% had PKD1 and 11% had PKD2 mutations. Non-missense mutations were 73% in PKD1 and 75% in PKD2. Twenty patients (27%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117 ml/m, p  = 0.0003). LIC stratification revealed Classes A (38.7%), B (28%), C (24%), and D + E (9.3%). All children in class D + E and 94% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes ( p  > 0.05 for all)., Discussion: This study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yilmaz, Saygili, Canpolat, Akgun-Dogan, Yuruk Yildirim, Cicek-Oksuz, Oner, Aksu, Akyel, Oguzhan-Hamis, Dursun, Yavuz, Cicek, Akinci, Karabag Yilmaz, Agbas, Nayir, Konukoglu, Kurugoglu, Sever and Caliskan.)

Background: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study., Methods: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI., Results: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001)., Conclusions: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: Autosomal recessive polycystic kidney disease (ARPKD) is associated with pathogenic variants in the PKHD1 gene. Autosomal dominant polycystic kidney disease (ADPKD) is mainly associated with pathogenic variants in PKD1 or PKD2. The present study aimed to identify the clinical and genetic features of Turkish pediatric ARPKD and ADPKD patients., Methods: This multicenter, retrospective cohort study included 21 genetically confirmed ARPKD and 48 genetically confirmed ADPKD patients from 7 pediatric nephrology centers. Demographic features, clinical, and laboratory findings at presentation and during 12-month intervals were recorded., Results: The median age of the ARPKD patients at diagnosis was lower than the median age of ADPKD patients (10.5 months [range: 0-15 years] vs. 5.2 years [range: 0.1-16 years], respectively, [p = 0.014]). At the time of diagnosis, the median eGFR in the ARPKD patients was lower compared to that of ADPKD patients (81.6 [IQR: 28.7-110.5] mL/min/1.73 m2 and 118 [IQR: 91.2-139.8] mL/min/1.73 m2, respectively, [p = 0.0001]). In total, 11 (52.4%) ARPKD patients had malnutrition; 7 (33.3%) patients had growth retardation at presentation; and 4 (19%) patients had both malnutrition and growth retardation. At diagnosis, 8 (16.7%) of the ADPKD patients had malnutrition, and 5 (10.4%) patients had growth retardation. The malnutrition, growth retardation, and hypertension rates at diagnosis were higher in the ARPKD patients than the ADPKD patients (p = 0.002, p = 0.02, and p = 0.0001, respectively). ARPKD patients with malnutrition and growth retardation had worse renal survival compared to the patients without (p = 0.03 and p = 0.01). Similarly, ADPKD patients with malnutrition had worse renal survival compared to the patients without (p = 0.002). ARPKD patients with truncating variants had poorer 3- and 6-year renal outcome than those carrying non-truncating variants (p = 0.017)., Conclusion: Based on renal survival analysis, type of genetic variant, growth retardation, and/or malnutrition at presentation were observed to be factors associated with progression to chronic kidney disease (CKD). Differentiation of ARPKD and ADPKD, and identification of the predictors of the development of CKD are vital for optimal management of patients with ARPKD or ADPKD., (© 2023 S. Karger AG, Basel.)

Cyclophosphamide (CP) is an alkylating chemotherapeutic agent commonly used in cancer treatments. In this study, we aimed to investigate the effects of 4-Hydroperoxy cyclophosphamide (4-HC), which is active form of CP, on glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phospho-protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (p-PERK), phospho-inositol-requiring enzyme 1 alpha (p-IRE1α), eukaryotic translation initiation factor 2 alpha (eIF2α), and caspase-3 messenger ribonucleic acids (mRNAs) and proteins that play roles in the ER stress pathway and apoptosis in U87 and T98 human glioblastoma cell lines. U87 and T98 human glioblastoma cell lines were divided into control and 4-HC-treated groups. Cell viability assay was used to detect the half maximal inhibitory concentration (IC50) for 24 hours of 4-HC. Immunocytochemistry and quantitative polymerase chain reaction (qPCR) methods were used to evaluate the levels of proteins and their mRNAs. The IC50 values of U87 and T98 cells were calculated as 15.67±0.58 μM and 19.92±1 μM, respectively. The levels of GRP78, ATF6, p-PERK, p-IRE1α, eIF2α, and caspase-3 protein expressions in the 4-HC-treated group compared to that in the control group. These increased protein expressions also were correlated with the mRNA levels. The ER stress signal pathway could be active in 4-HC-induced cell death. Further studies of ER-related stress mechanisms in anticancer treatment would be important for effective therapeutic strategies.

Background: Compared with the general population, the immune response to COVID-19 mRNA vaccines is lower in adult kidney transplant recipients (KTRs). However, data is limited for pediatric KTRs. In this study, we aimed to assess humoral and cellular immune responses to the COVID-19 mRNA vaccine in pediatric KTRs., Methods: This multicenter, prospective, case-control study included 63 KTRs (37 male, aged 12-21 years), 19 dialysis patients, and 19 controls. Humoral (anti-SARS-CoV2 IgG, neutralizing Ab (nAb)) and cellular (interferon-gamma release assay (IGRA)) immune responses were assessed at least one month after two doses of BNT162b2 mRNA vaccine., Results: Among COVID-19 naïve KTRs (n = 46), 76.1% tested positive for anti-SARS-CoV-2 IgG, 54.3% for nAb, and 63% for IGRA. Serum levels of anti-SARS-CoV-2 IgG and nAb activity were significantly lower in KTRs compared to dialysis and control groups (p < 0.05 for all). Seropositivity in KTRs was independently associated with shorter transplant duration (p = 0.005), and higher eGFR (p = 0.007). IGRA titer was significantly lower than dialysis patients (p = 0.009). Twenty (43.4%) KTRs were positive for all immune parameters. Only four of 11 seronegative KTRs were IGRA-positive. COVID-19 recovered KTRs had significantly higher anti-SARS-CoV-2 IgG and nAb activity levels than COVID-19 naïve KTRs (p = 0.018 and p = 0.007, respectively)., Conclusions: The humoral and cellular immune responses to SARS-CoV-2 mRNA BNT162b2 vaccine are lower in pediatric KTRs compared to dialysis patients. Further prospective studies are required to demonstrate the clinical efficacy of the mRNA vaccine in KTRs. This prospective study was registered in ClinicalTrials.gov (NCT05465863, registered retrospectively at 20.07.2022). A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

We performed dual immunohistochemistry for CD163/CD34 and CD68/CD34 in 108 renal transplant indication biopsies to investigate the presence and distribution of macrophages in various renal compartments. All Banff scores and diagnoses were revised according to the Banff 2019 classification. CD163 and CD68 positive cell counts (CD163pos and CD68pos) were evaluated in the interstitium, glomerular mesangium, and, within glomerular and peritubular capillaries. The diagnosis was antibody-mediated rejection (ABMR) in 38 (35.2%), T-cell mediated rejection (TCMR) in 24 (22.2%), mixed rejection in 30 (27.8%), and no rejection in 16 (14.8%). Banff lesion scores t , i , and ti were correlated with both CD163 and CD68 interstitial inflammation scores ( r > 0.30; P < 0.05). Glomerular total CD163pos was correlated to Banff lesion scores g and cg ( r > 0.30; P < 0.05). Glomerular total, mesangial, and intracapillary CD68pos were correlated with g ( r > 0.30; P < 0.05). Both glomerular total and peritubular capillary CD68pos were correlated with peritubular capillaritis ( r > 0.30; P < 0.05). Glomerular CD163pos were significantly higher in ABMR compared with no rejection, in mixed rejection compared with no rejection and TCMR. CD163pos in peritubular capillaries was significantly higher in mixed rejection compared with no rejection. Glomerular CD68pos was significantly higher in ABMR compared with no rejection. CD68pos per peritubular capillary was higher in mixed rejection, ABMR, and TCMR compared with no rejection. In conclusion, compared with CD68 positive macrophages, localization of CD163 positive macrophages in various renal compartments seems to be different among rejection subtypes and their glomerular infiltration seems to be more specific for the presence of ABMR component., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI., Methods: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI., Results: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive., Conclusions: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Recently, recessive mutations in SGPL1 (sphingosine-1-phosphate lyase), which encodes the final enzyme of sphingolipid metabolism, have been reported to cause steroid-resistant nephrotic syndrome, adrenal insufficiency, and many other organ/system involvements. We aimed to determine the clinical and genetic characteristics, and outcomes in patients with SGPL1 mutations., Methods: The study included 6 patients with bi-allelic SGPL1 mutation. Clinical, genetic, and laboratory characteristics, and outcomes of the patients were evaluated retrospectively. We also reviewed previously reported patients with SGPL1 mutations and compared them to the presented patients., Results: The median age at kidney presentation was 5 months. Four patients (67%) were diagnosed before age 1 year. Kidney biopsy showed focal segmental glomerulosclerosis in 2 patients and diffuse mesangial sclerosis in one patient. Steroids were given to 3 patients, but they did not respond. All 6 patients progressed to chronic kidney disease; 5 required kidney replacement therapy (KRT) at a median age of 6 months. Deceased kidney transplantation was performed in one patient. All 6 patients had adrenal insufficiency, of which 5 were diagnosed at age < 6 months. Three patients had hypothyroidism, 2 had ichthyosis, 4 had immunodeficiency, 5 had neurological findings, and 2 had genitourinary system anomalies. Four patients died at a median age of 30.5 months. Two patients are being followed up with KRT. One patient had a novel mutation., Conclusions: Patients with SGPL1 mutations have a poor prognosis, and many types of extrarenal organ/system involvement beyond adrenal insufficiency can be seen. Genetic diagnosis of such patients is important for treatment, genetic counseling, and screening for comorbid conditions. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Our aim was to identify acute kidney injury (AKI) and subacute kidney injury using both KDIGO criteria and urinary biomarkers in children with mild/moderate COVID-19., Methods: This cross-sectional study included 71 children who were hospitalized with a diagnosis of COVID-19 from 3 centers in Istanbul and 75 healthy children. We used a combination of functional (serum creatinine) and damage (NGAL, KIM-1, and IL-18) markers for the definition of AKI and subclinical AKI. Clinical and laboratory features were evaluated as predictors of AKI and subclinical AKI., Results: Patients had significantly higher levels of urinary biomarkers and urine albumin-creatinine ratio than healthy controls (p < 0.001). Twelve patients (16.9%) developed AKI based on KDIGO criteria, and 22 patients (31%) had subclinical AKI. AKI group had significantly higher values of neutrophil count on admission than both subclinical AKI and non-AKI groups (p < 0.05 for all). Neutrophil count was independently associated with the presence of AKI (p = 0.014)., Conclusions: This study reveals that even children with a mild or moderate disease course are at risk for AKI. Association between neutrophil count and AKI may point out the role of inflammation in the development of AKI., Impact: The key message of our article is that not only children with severe disease but also children with mild or moderate disease have an increased risk for kidney injury due to COVID-19. Urinary biomarkers enable the diagnosis of a significant number of patients with subclinical AKI in patients without elevation in serum creatinine. Our findings reveal that patients with high neutrophil count may be more prone to develop AKI and should be followed up carefully. We conclude that even children with mild or moderate COVID-19 disease courses should be evaluated for AKI and subclinical AKI, which may improve patient outcomes., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Automated peritoneal dialysis (APD) is increasingly preferred worldwide. By using a software application (Homechoice with Claria sharesource system (CSS)) with a mod-M added to the APD device, details of the home dialysis treatment become visible for PD nurses and physicians, allowing for close supervision. We aimed to evaluate the perceptions of patients/caregivers, PD nurses, and physicians about the advantages and disadvantages of CSS., Methods: Three different web-based questionnaires for patients/caregivers, nurses, and physicians were sent to 15 pediatric nephrology centers with more than 1 year of experience with CSS., Results: Respective questionnaires were answered by 30 patients/caregivers, 22 pediatric nephrologists, and 15 PD nurses. Most of the nurses and physicians (87% and 73%) reported that CSS improved patient monitoring. A total of 73% of nurses suggested that CCS is not well known by physicians, while half of them reported reviewing CSS data for all patients every morning. Sixty-eight percent of physicians thought that CSS helps save time for both patients/caregivers and healthcare providers by reducing visits. However, only 20% of patients/caregivers reported reduced hospital visits. A total of 90% of patients/caregivers reported that being under constant monitoring made them feel safe, and 83% stated that the patient's sleep quality improved., Conclusions: A remote monitoring APD system, CSS, can be successfully applied with children for increased adherence to dialysis prescription by giving shared responsibility and may help increase the patient's quality of life. This platform is more commonly used by nurses than physicians. Its potential benefits should be evaluated in further well-designed clinical studies with larger patient groups. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: There is evidence of increased risk of hypertension, albuminuria, and development of chronic kidney disease (CKD) in long-term follow-up of survivors of Wilms tumor (WT). However, most studies were conducted in heterogeneous groups, including patients with solitary kidney. In addition, little is known about tubular dysfunction. This study aimed to investigate kidney sequelae, including CKD development, hypertension, and glomerular and tubular damage in WT survivors., Methods: This cross-sectional, single-center study included 61 patients treated for WT. Surrogates for kidney sequelae were defined as presence of at least one of the following: decrease in GFR for CKD, hypertension detected by ambulatory blood pressure monitoring, albuminuria (albumin-to-creatinine ratio [ACR] > 30 mg/g), or increase in at least one tubular biomarker (beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, kidney injury marker-1, and liver fatty acid-binding protein) in 24-h urine., Results: Median age of patients was 11.7 years, with median follow-up of 8.8 years. Thirty-eight patients (62%) had at least one surrogate for kidney sequelae. Twenty-four patients (39%) had CKD, 14 patients (23%) had albuminuria, 12 patients (21%) had hypertension, and 11 patients (18%) had tubular damage. Urine ACR was significantly higher in patients with advanced tumor stage and patients with nephrotoxic therapy than their counterparts (p < 0.05), but neither eGFR nor tubular biomarkers showed any association with tumor- or treatment-related factors., Conclusions: A considerable number of patients with WT have kidney sequelae, especially early-stage CKD with a high prevalence. Albuminuria emerges as a marker associated with tumor stages and nephrotoxic treatment. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: The phenotypic and genotypic spectrum and kidney outcome of PLCε1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLCε1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome., Methods: Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively., Results: Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors., Conclusion: PLCε1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. "A higher resolution version of the Graphical abstract is available as Supplementary information"., (© 2021. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Recessive mutations in the genes encoding the four subunits of the tRNA splicing endonuclease complex (TSEN54, TSEN34, TSEN15, and TSEN2) cause various forms of pontocerebellar hypoplasia, a disorder characterized by hypoplasia of the cerebellum and the pons, microcephaly, dysmorphisms, and other variable clinical features. Here, we report an intronic recessive founder variant in the gene TSEN2 that results in abnormal splicing of the mRNA of this gene, in six individuals from four consanguineous families affected with microcephaly, multiple craniofacial malformations, radiological abnormalities of the central nervous system, and cognitive retardation of variable severity. Remarkably, unlike patients with previously described mutations in the components of the TSEN complex, all the individuals that we report developed atypical hemolytic uremic syndrome (aHUS) with thrombotic microangiopathy, microangiopathic hemolytic anemia, thrombocytopenia, proteinuria, severe hypertension, and end-stage kidney disease (ESKD) early in life. Bulk RNA sequencing of peripheral blood cells of four affected individuals revealed abnormal tRNA transcripts, indicating an alteration of the tRNA biogenesis. Morpholino-mediated skipping of exon 10 of tsen2 in zebrafish produced phenotypes similar to human patients. Thus, we have identified a novel syndrome accompanied by aHUS suggesting the existence of a link between tRNA biology and vascular endothelium homeostasis, which we propose to name with the acronym TRACK syndrome (TSEN2 Related Atypical hemolytic uremic syndrome, Craniofacial malformations, Kidney failure)., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Objectives: The inhibition of bone destruction is one of the main goals of periodontitis treatment. The aim of this study was to investigate the protective effects of non-thermal atmospheric plasma (NTAP) on alveolar bone loss radiographically, histomorphometrically, and histologically in experimental periodontitis in rats., Materials and Methods: A total of twenty-eight rats were randomly divided into three groups: control group (CG) (n = 8), periodontitis group (PG) (n = 10), and NTAP group (NTAPG) (n = 10). In PG and NTAPG, experimental periodontitis was created with ligating. The kINPen 11 plasma jet was applied around the ligatured teeth in NTAPG. The samples from each group were radiographically assessed with microcomputed tomography (micro-CT); then, histological (presence of osteoclasts and inflammatory cells) and immunohistochemical (immunoreactive of OCN and ALP) findings were compared., Results: The results revealed a significant increase in alveolar bone loss in the PG compared with CG and NTAPG (p < 0.05). Inflammation, alveolar resorption, and cement damage were reduced significantly in the group treated with NTAP compared to the PG (p < 0.05). Significantly higher levels of osteoclasts were detected in the PG in comparison with both CG and NTAPG (p < 0.05). The lowest osteocalcin and ALP values were determined in PG, and the differences between PG and both groups were also significant (p < 0.05)., Conclusion: Within the limitations of the present study, we can say that NTAP may enhance the bone remodeling process by inhibiting inflammation and preventing alveolar bone destruction., Clinical Relevance: NTAP has clinical potential for accelerating and treating periodontitis with the inflammatory response modulation, osteoblast differentiation, and alveolar bone loss reduction., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Various molecular and cellular processes are involved in renal fibrosis, such as oxidative stress, inflammation, endothelial cell injury, and apoptosis. Heat shock proteins (HSPs) are implicated in the progression of chronic kidney disease (CKD). Our aim was to evaluate changes in urine and serum HSP levels over time and their relationships with the clinical parameters of CKD in children. In total, 117 children with CKD and 56 healthy children were examined. The CKD group was followed up prospectively for 24 months. Serum and urine HSP27, HSP40, HSP47, HSP60, HSP70, HSP72, and HSP90 levels and serum anti-HSP60 and anti-HSP70 levels were measured by ELISA at baseline, 12 months, and 24 months. The urine levels of all HSPs and the serum levels of HSP40, HSP47, HSP60, HSP70, anti-HSP60, and anti-HSP70 were higher at baseline in the CKD group than in the control group. Over the months, serum HSP47 and HSP60 levels steadily decreased, whereas HSP90 and anti-HSP60 levels steadily increased. Urine HSP levels were elevated in children with CKD; however, with the exception of HSP90, they decreased over time. In conclusion, our study demonstrates that CKD progression is a complicated process that involves HSPs, but they do not predict CKD progression. The protective role of HSPs against CKD may weaken over time, and HSP90 may have a detrimental effect on the disease course., (© 2021. Cell Stress Society International.)

Objectives: The aim of this randomized, controlled, three-arm parallel group, and double-blinded clinical trial was to evaluate the clinical, radiographic, and histopathological success of three different pulp-capping materials in one-stage indirect pulp treatment of primary teeth., Materials and Methods: The study included a total of 109 patients aged 5-9 years who had primary teeth with deep carious lesions and symptoms of reversible pulpitis. The teeth were divided into three groups according to the pulp-capping agents: (I) hard-setting calcium hydroxide (Dycal) (control group) (n = 36), (II) bioactive tricalcium silicate (Biodentine) (n = 37), and (III) resin-based tricalcium silicate (TheraCal LC) (n = 36). All the teeth were evaluated clinically and radiographically at 6, 12, 18, and 24 months postoperatively. A total of 23 primary mandibular second molars that were in their regular exfoliation period (24-40 months) were extracted and fixed in 10% formaldehyde solution. The specimens were evaluated histologically to assess the integrity of the odontoblastic layer, tertiary dentin formation quality of the dentin formed, severity of pulpitis, and other pulpal changes. Data were analyzed using Fisher's exact test, Pearson's chi-square test, and McNemar's test (p = 0.05)., Results: At the end of the 24-month follow-up period, the clinical and radiographic success rates for Dycal, Biodentine, and TheraCal LC were 100%, 100%, and 93.3%, respectively, and there was no significant difference among the groups (p > 0.05). However, the TheraCal LC group was statistically unsuccessful when compared to the other groups with regard to the integrity of the odontoblastic layer, severity of pulpitis, and other pulpal changes in histological examination (p < 0.05)., Conclusion: Indirect pulp capping exhibited high clinical and radiographic success rates in the treatment of primary teeth regardless of the chosen pulp-capping agent. However, histological examination indicated that the pulp status was affected by the chosen capping material especially when selecting a resin-containing material such as TheraCal LC., Clinical Relevance: Resin-free calcium silicate-based materials appear to be more favorable in the indirect pulp treatment of primary teeth, particularly in young-age groups that require long-term success.

Background: Acute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN., Patients, Design and Setting: We collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate., Results: Thirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/min/1.73 m 2 3-6 months later (p<0.001). After 3-6 months, eGFR normalised in 41% of patients (eGFR ≥90 mL/min/1.73 m 2 ), with only 3% having severe or end-stage impairment of renal function (<30 mL/min/1.73 m 2 ). 80% of patients received corticosteroid therapy. Median eGFR after 3-6 months did not differ between steroid-treated and steroid-untreated patients. Other immunosuppressants were used in 18% (n=31) of patients, 21 of whom received mycophenolate mofetil., Conclusions: Despite different aetiologies, acute paediatric TIN had a favourable outcome overall with 88% of patients showing no or mild impairment of eGFR after 3-6 months. Prospective randomised controlled trials are needed to evaluate the efficacy of glucocorticoid treatment in paediatric patients with acute TIN., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Congenital anomalies of the kidney and urinary tract (CAKUT) is the leading cause of end-stage kidney disease in children. Until now, more than 50 monogenic causes for CAKUT have been described, all of which only explain 10% to 20% of all patients with CAKUT, suggesting the presence of additional genes that cause CAKUT when mutated. Herein, we report two siblings of a consanguineous family with CAKUT, both of which rapidly progressed to chronic kidney disease in early childhood. Whole-exome sequencing followed by homozygosity mapping identified a homozygous variation in HOXA11. We therefore showed for the first time an association between a homozygous HOXA11 variation with CAKUT in humans, expanding the genetic spectrum of the disease., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: The aim of the study is to identify the effect of salt intake and diabetes itself on blood pressure (BP) profile and microalbuminuria in children with type one diabetes mellitus (T1DM). Our hypothesis is that higher amount of salt consumption and/or hyperglycemia may impair blood pressure pattern in children with T1DM., Methods: This cross-sectional study included 84 children and adolescents with T1DM (62% females, age 13.9 ± 3.2 years, disease duration 7.3 ± 3.1 years, 43% poorly controlled diabetes) and 54 aged- and sex-matched healthy children with an adequately collected 24-h urine samples. Urine sodium, creatinine, and microalbumin were measured and salt intake was assessed on the basis of sodium excretion in 24-h urine. Blood pressure profile of the children with T1DM was evaluated with 24-h ambulatory blood pressure monitoring., Results: Compared to the children with well-controlled diabetes, children with poorly controlled diabetes had significantly higher standard deviation scores (SDS) of nighttime systolic BP (0.22 ± 1.28 vs - 0.87 ± 0.76, p = 0.003) and lower dipping in diastole (13.4 ± 5.9 vs 18.4 ± 8.1, p = 0.046). Among T1DM group, children with the highest quartile of salt intake had higher nighttime systolic and diastolic BP-SDS (0.53 ± 1.25 vs - 0.55 ± 0.73, p = 0.002 and 0.89 ± 1.19 vs 0.25 ± 0.63, p = 0.038, respectively) and lower dipping in systole compared to their counterparts (7.7 ± 5.0 vs 11.5 ± 6.1, p = 0.040). High averaged HbA1c was independently associated with higher both daytime and nighttime systolic BP-SDS (p = 0.010, p < 0.001) and nighttime diastolic BP-SDS (p = 0.001), and lower diastolic dipping (p = 0.001). High salt intake was independently associated with higher nighttime systolic BP-SDS (p = 0.002) and lower systolic dipping (p = 0.019). A 24-h MAP-SDS was the only independent risk factor for microalbuminuria (p = 0.035)., Conclusion: Beside poor diabetic control, high salt consumption appears to be an important modifiable risk factor for impaired BP pattern, which contributes to the development of diabetic kidney disease in children with T1DM.

Introduction: The aim of the present in vitro study was to evaluate the cytotoxicity of different sealers including GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex on L929 murine fibroblasts., Methods and Materials: Samples of GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex were fabricated in Teflon disks of 5 mm diameter and 3 mm thickness. L929 fibroblasts were exposed to the extracts of these materials for 3, 24, 72 and 168 h at 37 ° C with 5% CO 2 . Cell viability was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The data were analysed by ANOVA., Results: GuttaFlow Bioseal was nontoxic at all experimental time points ( P >0.05), whereas MTA Fillapex and AH-Plus were toxic ( P <0.001). At 7 days, there were more viable cells in the GuttaFlow 2 group than in the control group, and MTA Fillapex was more cytotoxic than AH-Plus. There were more apoptotic cells in the MTA Fillapex and AH-Plus groups than in the other groups at 3 h ( P <0.001)., Conclusion: GuttaFlow sealers are less cytotoxic than MTA Fillapex and AH-Plus. At all experimental time points, there was no significant difference in the cell viability between the GuttaFlow Bioseal group and the control group., Competing Interests: ‘None declared’.

Background: The purpose of this study was to report the management and outcomes of ten patients with chronic Achilles tendon rupture treated with a turndown gastrocnemius-soleus fascial flap wrapped with a surgical mesh (Hyalonect)., Methods: Ten men with neglected Achilles tendon rupture were treated with a centrally based turndown gastrocnemius fascial flap wrapped with Hyalonect. Hyalonect is a knitted mesh composed of HYAFF, a benzyl ester of hyaluronic acid. The Achilles tendon ruptures were diagnosed more than 1 month after injury. The mean patient age was 41 years. All of the patients had weakness of active plantarflexion. The mean preoperative American Orthopaedic Foot and Ankle Society score was 64.8., Results: The functional outcome was excellent. The mean American Orthopaedic Foot and Ankle Society score was 97.8 at the latest follow-up. There were significant differences between the preoperative and postoperative scores. Ankle range of motion was similar in both ankles. Neither rerupture nor major complication, particularly of wound healing, was observed., Conclusions: For patients with chronic Achilles tendon rupture with a rupture gap of at least 5 cm, surgical repair using a single turndown fascial flap covered with Hyalonect achieved excellent outcomes.