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Collaborative primary care has become an increasingly popular strategy to manage existing pressures on general practice. In England, the recent changes taking place in the primary care sector have included the formation of collaborative organisational models and a steady increase in practice size. The aim of this review was to summarise the available evidence on the impact of collaborative models and general practice size on patient safety and quality of care in England. We searched for quantitative and qualitative studies on the topic published between January 2010 and July 2023. The quality of articles was assessed using the Newcastle-Ottawa Scale and the Critical Appraisal Skills Programme checklist. We screened 6533 abstracts, with full-text screening performed on 76 records. A total of 29 articles were included in the review. 19 met the inclusion criteria following full-text screening, with seven identified through reverse citation searching and three through expert consultation. All studies were found to be of moderate or high quality. A predominantly positive impact on service delivery measures and patient-level outcomes was identified. Meanwhile, the evidence on the effect on pay-for-performance outcomes and hospital admissions is mixed, with continuity of care and access identified as a concern. While this review is limited to evidence from England, the findings provide insights for all health systems undergoing a transition towards collaborative primary care., (Copyright © 2023. Published by Elsevier B.V.)

Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The number of neutrophils was identified as an independent preoperative predictor of the presence of variant histology after a radical cystectomy. The overall survival of the patients with variant histology was significantly lower compared to the patients with pure urothelial carcinoma. According to our results, the presence of variant histology represents a more aggressive form of the disease. Preoperative neutrophil counts may indicate the presence of variant histology of urothelial carcinoma in patients with bladder cancer.

Background: Digital health technologies (DHTs) have become increasingly commonplace as a means of delivering primary care. While DHTs have been postulated to reduce inequalities, increase access, and strengthen health systems, how the implementation of DHTs has been realized in the sub-Saharan Africa (SSA) health care environment remains inadequately explored., Objective: This study aims to capture the multidisciplinary experiences of primary care professionals using DHTs to explore the strengths and weaknesses, as well as opportunities and threats, regarding the implementation and use of DHTs in SSA primary care settings., Methods: A combination of qualitative approaches was adopted (ie, focus groups and semistructured interviews). Participants were recruited through the African Forum for Primary Care and researchers' contact networks using convenience sampling and included if having experience with digital technologies in primary health care in SSA. Focus and interviews were conducted, respectively, in November 2021 and January-March 2022. Topic guides were used to cover relevant topics in the interviews, using the strengths, weaknesses, opportunities, and threats framework. Transcripts were compiled verbatim and systematically reviewed by 2 independent reviewers using framework analysis to identify emerging themes. The COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist was used to ensure the study met the recommended standards of qualitative data reporting., Results: A total of 33 participants participated in the study (n=13 and n=23 in the interviews and in focus groups, respectively; n=3 participants participated in both). The strengths of using DHTs ranged from improving access to care, supporting the continuity of care, and increasing care satisfaction and trust to greater collaboration, enabling safer decision-making, and hastening progress toward universal health coverage. Weaknesses included poor digital literacy, health inequalities, lack of human resources, inadequate training, lack of basic infrastructure and equipment, and poor coordination when implementing DHTs. DHTs were perceived as an opportunity to improve patient digital literacy, increase equity, promote more patient-centric design in upcoming DHTs, streamline expenditure, and provide a means to learn international best practices. Threats identified include the lack of buy-in from both patients and providers, insufficient human resources and local capacity, inadequate governmental support, overly restrictive regulations, and a lack of focus on cybersecurity and data protection., Conclusions: The research highlights the complex challenges of implementing DHTs in the SSA context as a fast-moving health delivery modality, as well as the need for multistakeholder involvement. Future research should explore the nuances of these findings across different technologies and settings in the SSA region and implications on health and health care equity, capitalizing on mixed-methods research, including the use of real-world quantitative data to understand patient health needs. The promise of digital health will only be realized when informed by studies that incorporate patient perspective at every stage of the research cycle., (©Niki O'Brien, Edmond Li, Cynthia N Chaibva, Raquel Gomez Bravo, Lana Kovacevic, Nana Kwame Ayisi-Boateng, Olivia Lounsbury, Ngnedjou Francoise F Nwabufo, Ephraim Kumi Senkyire, Alice Serafini, Eleleta Surafel Abay, Steven van de Vijver, Mercy Wanjala, Marie-Claire Wangari, Shabir Moosa, Ana Luisa Neves. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.09.2023.)

Aim: The aim of this study was to assess whether BMI, severity of knee osteoarthritis, age and gender have any influence on the final clinical results of bone marrow aspirate concentrate injection. Method: A total of 111 study participants with painful knee osteoarthritis and different characteristics concerning before mentioned factors underwent bone marrow aspirate concentrate (BMAC) therapy and were followed up for 1 year. Result: Significant pain and functional improvement were observed in all participant groups. Participants' age and BMI did not influence the clinical outcome, but there was an influence of OA severity, especially among older patients. Conclusion: This study shows that BMAC therapy is effective. Younger patients with milder OA changes could be better candidates for long-lasting and more efficient BMAC therapy. Clinical Trial Registration: NCT03825133 (ClinicalTrials.gov).

The calcium-sensing receptor (CaSR) plays a crucial role in maintaining the balance of calcium in the body. Altered signaling through the CaSR has been linked to the development of various tumors, such as colorectal and breast tumors. This retrospective study enrolled 79 patients who underwent surgical removal of invasive breast carcinoma of no special type (NST) to explore the expression of the CaSR in breast cancer. The patients were categorized based on age, tumor size, hormone receptor status, HER2 status, Ki-67 proliferation index, tumor grade, and TNM staging. Immunohistochemistry was conducted on core needle biopsy samples to assess CaSR expression. The results revealed a positive correlation between CaSR expression and tumor size, regardless of the tumor surrogate subtype ( p = 0.001). The expression of ER exhibited a negative correlation with CaSR expression ( p = 0.033). In contrast, a positive correlation was observed between CaSR expression and the presence of HER2 receptors ( p = 0.002). Increased CaSR expression was significantly associated with lymph node involvement and the presence of distant metastasis ( p = 0.001 and p = 0.038, respectively). CaSR values were significantly higher in the patients with increased Ki-67 ( p = 0.042). Collectively, higher CaSR expression in breast cancer could suggest a poor prognosis and treatment outcome regardless of the breast cancer subtype.

At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients' attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients' sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. Furthermore, we found significantly higher vaccination rates in patients who had consulted with doctors involved in their treatment, particularly with urologists. A significant association was observed between COVID-19 vaccination and doctor's advice, family member influence, and personal beliefs toward the vaccination. Our study showed multiple associations of patients' sociodemographic characteristics with vaccination rates. Furthermore, consultation with doctors who are particularly involved in oncology treatment and advice received from them were associated with significantly higher vaccination rates among uro-oncology patients.

In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed statistically significant inverse correlations for LMR, PNI, and GNRI with the tumor stage. SIRI was identified as an independent predictor of the presence of LVI. dNLR was identified as an independent predictor of positive surgical margins. GNRI was identified as an independent predictor of the presence of metastases in the lymph nodes. We noticed the predictive value of SIRI, dNLR, and GNRI in the pathology of bladder cancer patients.

This study aimed to evaluate the performance of multiparametric breast magnetic resonance imaging (mpMRI) for predicting response to neoadjuvant chemotherapy (NAC) in patients with luminal B subtype breast cancer. The prospective study included thirty-five patients treated with NAC for both early and locally advanced breast cancer of the luminal B subtype at the University Hospital Centre Zagreb between January 2015 and December 2018. All patients underwent breast mpMRI before and after two cycles of NAC. Evaluation of mpMRI examinations included analysis of both morphological (shape, margins, and pattern of enhancement) and kinetic characteristics (initial signal increase and post-initial behavior of the time-signal intensity curve), which were additionally interpreted with a Göttingen score (GS). Histopathological analysis of surgical specimens included grading the tumor response based on the residual cancer burden (RCB) grading system and revealed 29 NAC responders (RCB-0 (pCR), I, II) and 6 NAC non-responders (RCB-III). Changes in GS were compared with RCB classes. A lack of GS decrease after the second cycle of NAC is associated with RCB class and non-responders to NAC.

In addition to traditionally assessed abuse, neglect, and household dysfunction, adverse childhood experiences (ACEs) include adversities like racial discrimination, community violence, and bullying. Prior research established associations between the original ACEs and substance use, but few used Latent Class Analysis (LCA) to examine patterns of ACEs. Examining patterns of ACEs may yield additional insights beyond cumulative risk studies focusing only on the number of different ACEs experiences. Therefore, we identified associations between latent classes of ACEs and cannabis use. Studies on ACES rarely examine cannabis use outcomes, which is important as cannabis remains one of the most commonly used substances and is associated with negative effects on health. Yet it is still unclear how ACEs influence cannabis use. Participants were adults in Illinois (n = 712) recruited through Qualtrics' online quota-sampling method. They completed measures of 14 ACEs, past 30-day and lifetime cannabis use, medical cannabis use (DFACQ) and probable cannabis use disorders (CUDIT-R-SF). Latent class analyses were performed using ACEs. We identified four classes, labeled: Low Adversity, Interpersonal Harm, Interpersonal Abuse and Harm , and High Adversity . The largest effect sizes (p<.05) were observed for those in the High Adversity class, who had elevated risks for lifetime (OR =6.2), 30-day (OR = 5.05), and medicinal cannabis use (OR = 17.9) relative to those in the Low Adversity class. Those in the Interpersonal Abuse and Harm and Interpersonal Harm classes also had increased odds (p<.05) for lifetime (OR =2.44/OR=2.82), 30-day (OR = 4.88/OR= 2.53), and medicinal cannabis use (OR = 2.59/OR =1.67(ns)) relative to those in the Low Adversity class. However, no class with elevated ACEs had higher odds for CUD relative to the Low Adversity class. Additional research could further disentangle these findings using extensive measures of CUD. Additionally, as participants in the High Adversity class had higher odds of medicinal cannabis use, future research could carefully study their consumption patterns., Competing Interests: We have no known conflict of interest to disclose., (© 2023 Authors et al.)

Background and Objectives: Oxidative stress induced by increased reactive oxygen species (ROS) production plays an important role in carcinogenesis. The entire urinary tract is continuously exposed to numerous potentially mutagenic environmental agents which generate ROS during their biotransformation. In first line defense against free radicals, antioxidant enzymes superoxide dismutase (SOD2) and glutathione peroxidase (GPX1) both have essential roles. Altered enzyme activity and decreased ability of neutralizing free oxygen radicals as a consequence of genetic polymorphisms in genes encoding these two enzymes are well described so far. This study aimed to investigate the association of GPX1 (rs1050450) and SOD2 (rs4880) genetic variants with the urothelial bladder cancer (UBC) risk independently and in combination with smoking. Furthermore, we aimed to determine whether the UBC stage and pathological grade were influenced by GPX1 and SOD2 polymorphisms. Material and Methods: The study population included 330 patients with UBC (mean age 65 ± 10.3 years) and 227 respective controls (mean age 63.4 ± 7.9 years). Single nucleotide polymorphism (SNP) of GPX1 (rs1050450) was analyzed using the PCR-RFLP, while SOD2 (rs4880) SNP was analyzed using the q-PCR method. Results: Our results showed that UBC risk was significantly increased among carriers of at least one variant SOD2 Val allele compared to the SOD2 Ala16Ala homozygotes (OR = 1.55, p = 0.03). Moreover, this risk was even more pronounced in smokers with at least one variant SOD2 Val allele, since they have even 7.5 fold higher UBC risk (OR = 7.5, p < 0.001). Considering GPX1 polymorphism, we have not found an association with UBC risk. However, GPX1 genotypes distribution differed significantly according to the tumor stage (p ˂ 0.049) and pathohistological grade (p ˂ 0.018). Conclusion: We found that SOD2 genetic polymorphism is associated with the risk of UBC development independently and in combination with cigarette smoking. Furthermore, we showed that GPX1 genetic polymorphism is associated with the aggressiveness of the disease.

The incidence of kidney stones in children is increasing. Approximately two-thirds of pediatric cases have a predisposing cause. Children with recurrent kidney stones have an increased higher risk of developing chronic kidney. A complete metabolic workup should be performed. Ultrasound examination is the initial imaging modality recommended for all children with suspected nephrolithiasis. A general dietary recommendation includes high fluid consumption, dietary salt restriction, and increased intake of vegetables and fruits. Depending on size and location of the stone, surgical intervention may be necessary. Multidisciplinary management is key to successful treatment and prevention., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: In this study we aimed to screen for the presence of biomarkers that are downregulated in children with nephrolithiasis (RS) compared to healthy controls (HC) using a proteomic approach. We hypothesized that RS and HC would display unique inhibitory protein profiles that could be used for comparative pathway analysis., Methods: This is a prospective, controlled, pilot study of pooled urine from RS (N = 30, 24 females, mean age 12.95 ± 4.03 years) versus age- and gender-matched HC, using liquid chromatography-mass spectrometry. The criteria for protein selection were: (1) patient/control abundance ratio of < 0.5; and (2) ≤ 0.05 p-value for the Fisher's Exact Test. Results were confirmed by ELISA testing in individual samples., Results: 67 proteins were downregulated in RS group, and 17 of those were significantly different compared to controls. Of those seventeen proteins, five (two actins, annexin A5, keratin 6B, and serpin B4) were completely absent in the urine of stone patients but were found in controls. The remaining twelve proteins were significantly less abundant in the patient's urine compared to healthy controls. Protein-protein interaction modeling of significant proteins identified syndecan-1 as the key node, a protein associated with adhesion pathways. ELISA analysis by subgroups showed statistically significant difference in the urinary excretion of osteopontin (5.1 ± 3.22 ng/mg creatinine vs 14.1 ± 9.5 ng/mg creatinine, p = 0.046) between stone patients with hypocitraturia and controls. Urinary osteopontin concentration was positively correlated with urinary citrate excretion (r = 0.417, p = 0.03)., Conclusions: Children with RS have a different urinary inhibitory polypeptide profile compared to HC. Decreased urinary excretion of these proteins indicates their potential inhibitory role in renal stone formation, especially of the adhesion phase. Lower concentration of urinary osteopontin in children with nephrolithiasis and hypocitraturia suggests its potential involvement in the pathogenesis of this disease. Further characterization of these proteins in a larger sample is imperative., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Nipple discharge is one of the most common symptoms related to the breast, but it is a presenting feature of breast cancer in 5%-12% of women., Aims: The purpose of this study was to determine the diagnostic performance of digital breast tomosynthesis (DBT) in the evaluation of patients with nipple discharge and to compare it with mammography (MMG), ultrasound (US), and magnetic resonance imaging (MRI)., Methods and Results: This retrospective study included 53 patients with nipple discharge. All patients underwent DBT, and results were compared to MMG, breast US, and MRI. Radiological findings for each method were categorized according to BI-RADS classification: categories 1-2 were considered negative and categories 3-5 positive. If a tissue specimen was obtained, the final diagnosis was established based on the results of histopathological analysis; otherwise, a clinical follow-up was required for at least 2 years to confirm benign radiological findings. Measures of diagnostic accuracy of DBT, MMG, US, and MRI were calculated and compared., Results: Final histopathological analysis revealed six malignant breast lesions, all of which were detected in patients with pathologic nipple discharge. DBT and MRI exhibited high sensitivity (100%) and high negative predictive value (100%) for the detection of breast cancer in patients with nipple discharge. DBT showed higher specificity compared to MRI (82.9% vs. 61.9%). Sensitivity and specificity of MMG were 83.3% and 76.6%, respectively. Breast US was determined to have a sensitivity of 66.7% and specificity of 57.5%., Conclusion: DBT exhibited higher specificity than MRI at the same level of sensitivity and negative predictive value. Therefore, the use of DBT should be considered as an alternative to MRI in the assessment of patients with nipple discharge., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

We aimed to determine diagnostic accuracy of CT-guided bone lesion biopsy for the confirmation of bone metastases in patients with breast cancer and assessment of hormone receptor status in metastatic tissue. A total of 56 female patients with breast cancer that underwent CT-guided biopsy of suspected bone metastasis were enrolled in this retrospective study. Three different techniques were employed to obtain samples from various sites of skeleton. Collectively, 11 true negative and 3 false negative findings were revealed. The sensitivity of CT-guided biopsy for diagnosing bone metastases was 93.6%, specificity was 100% and accuracy was 94.8%. Discordance in progesterone receptor status and complete concordance in estrogen receptor status was observed. Based on our single-center experience, bone metastasis biopsy should be routinely performed in patients with breast cancer and suspicious bone lesions, due to the impact on further treatment.

Background: Following therapeutic mammoplasty (TM), the contralateral breast may require a later balancing procedure to optimize shape and symmetry. The alternative is to offer patients simultaneous TM with immediate contralateral symmetrization via a dual-surgeon approach, with the goal of reducing costs and minimizing the number of subsequent hospital appointments in an era of COVID-19 surges. The aim of this cost-consequence analysis is to characterize the cost-benefit of immediate bilateral symmetrization dual-operator mammoplasty versus staged unilateral single operator for breast cancer surgery., Method: A prospective single-centre observational study was conducted at an academic teaching centre for breast cancer surgery in the UK. Pseudonymized data for clinicopathological variables and procedural care information, including the type of initial breast-conserving surgery and subsequent reoperation(s), were extracted from the electronic patient record. Financial data were retrieved using the Patient-Level Information and Costing Systems., Results: Between April 2014 and March 2020, 232 women received either immediate bilateral (n = 44), staged unilateral (n = 57) for breast cancer, or unilateral mammoplasty alone (n = 131). The median (interquartile range (i.q.r.)) additional cost of unilateral mammoplasty with staged versus immediate bilateral mammoplasty was €5500 (€4330 to €6570) per patient (P < 0.001), which represents a total supplementary financial burden of €313 462 to the study institution. There was no significant difference between groups in age, Charlson comorbidity index, operating minutes, time to adjuvant radiotherapy in months, or duration of hospital stay., Conclusion: Synchronous dual-surgeon immediate bilateral TM can deliver safe immediate symmetrization and is financially beneficial, without delay to receipt of adjuvant therapy, or additional postoperative morbidity., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Objective: To screen for the presence of biomarkers involved in tubular injury and kidney damage in children with urolithiasis (RS), and to validate these proteins by ELISA., Methods: Prospective-controlled pilot study of children with urolithiasis and their age- and gender-matched controls (HC). Initial screening test was done by quantitative proteomic comparison of pooled urine from RS versus HC, using liquid chromatography-mass spectrometry. Proteins of interest were selected using the following criteria: (1) ≥5 spectral counts; (2) ≥2-fold difference in spectral counts; and (3) ≤.05 P value for the Fisher's Exact Test. Validation was performed by ELISA testing. Statistical analysis was performed by Student t-test and Mann-Whitney U test., Results: Proteomic analysis identified 3 proteins of interest, Cystatin C (CYTC), neutrophil gelatinase-associated lipocalin (NGAL) and lysozyme C that were significantly over-represented in RS group versus HC. ELISA analysis revealed significantly increased urinary levels of CYTC and NGAL, and nearly significantly increased urinary levels of lysozyme C in RS group (N = 24) compared to controls (N = 13). Subgroup analysis showed significantly higher urinary levels of CYTC in both hypercalciuria (N = 14) and hypocitraturia (N = 10) versus HC (P <.05)., Conclusion: Children with urolithiasis showed significant increase in urinary CYTC and NGAL irrespective of their normal serum creatinine. These biomarkers indicate tubular injury and early kidney damage and represent valid tools for early screening when traditional tests are normal., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We investigated the inhibitory effect of bisphosphonates (BPs) on the crystallization of calcium oxalate monohydrate (COM), calcium phosphate (CaP), and magnesium ammonium phosphate (MAP) in synthetic urine, aiming to see 1) which specific BPs work best on a particular type of crystal and 2) what is the lowest concentration of BPs that inhibits crystal formation., Materials and Methods: Crystals from synthetic urine were exposed to different concentrations of BPs. Urinary turbidity was used as a marker of crystallization and was measured by spectrophotometry by use of a validated method in our laboratory. The percent inhibitory activity (IA) was calculated by using the formula: ( a - b )/ a ×100, where a is baseline maximal turbidity and b is maximal turbidity with various concentrations of medication. Potassium citrate and magnesium citrate were used as positive controls., Results: At the lowest dose of 0.001 mg/mL, risedronate induced the highest IA of 37% on CaP, whereas ibandronate had the strongest IA on COM (24%). To initiate the inhibition of MAP crystallization, risedronate required a two-fold higher concentration (0.002 mg/mL) to reach 30% IA, whereas etidronate required a four-fold higher concentration (0.004 mg/mL) to reach 42% IA., Conclusions: BPs are good inhibitors of crystallization in synthetic urine, with risedronate and ibandronate being the most potent. At a low clinically acceptable dose, their highest inhibitory action was on CaP and COM crystals. Higher doses were needed to prevent MAP crystallization. Further investigation of the use of BPs in kidney stone prevention is warranted., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (© The Korean Urological Association, 2020.)

Background: Enuresis is an extremely common condition, which, although somatically benign, poses long-term psychosocial risks if untreated. There are still many misconceptions regarding the proper management of these children., Aim: A cross-professional team of experts affiliated with the International Children's Continence Society (ICCS) undertook to update the previous guidelines for the evaluation and treatment of children with enuresis., Methods: The document used the globally accepted ICCS terminology. Evidence-based literature served as the basis, but in areas lacking in primary evidence, expert consensus was used. Before submission, a full draft was made available to all ICCS members for additional comments., Results: The enuretic child does, in the absence of certain warning signs (i.e., voiding difficulties, excessive thirst), not need blood tests, radiology or urodynamic assessment. Active therapy is recommended from the age of 6 years. The most important comorbid conditions to take into account are psychiatric disorders, constipation, urinary tract infections and snoring or sleep apneas. Constipation and daytime incontinence, if present, should be treated. In nonmonosymptomatic enuresis, it is recommended that basic advice regarding voiding and drinking habits be provided. In monosymptomatic enuresis, or if the above strategy did not make the child dry, the first-line treatment modalities are desmopressin or the enuresis alarm. If both these therapies fail alone or in combination, anticholinergic treatment is a possible next step. If the child is unresponsive to initial therapy, antidepressant treatment may be considered by the expert. Children with concomitant sleep disordered breathing may become dry if the airway obstruction is removed., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of the study was to assess the differences in the concentration and function of urinary proteins between patients with cystine stones (CYS) and healthy controls (HC). We postulated that CYS and HC groups would demonstrate different proteomic profiles., Methods: A pilot study was performed comparing urinary proteomes of 10 patients with CYS and 10 age- and gender-matched HC, using liquid chromatography-mass spectrometry. Proteins which met the selection criteria (i) ≥ 2 unique peptide identifications; (ii) ≥ twofold difference in protein abundance; and (iii) ≤ 0.05 p value for the Fisher's Exact Test were analyzed using Gene Ontology classifications., Results: Of the 2097 proteins identified by proteomic analysis, 398 proteins were significantly different between CYS and HC. Of those, 191 were involved in transport processes and 61 in inflammatory responses. The majority were vesicle-mediated transport proteins (78.5%), and 1/3 of them were down-regulated; of those, 12 proteins were involved in endosomal transport (including 6 charged multivesicular body proteins (CHMP) and 3 vacuolar sorting-associated proteins) and 9 in transmembrane transport. Myosin-2 and two actin-related proteins were significantly up-regulated in the vesicle-mediated transport group., Conclusion: We provide proteomic evidence of impaired endocytosis, dysregulation of actin and myosin cytoskeleton, and inflammation in CYS. Endosomal transport proteins were down-regulated mainly through defective CHMP. These findings may contribute to further understanding of the pathogenesis of CYS, potentially affecting its management.

Purpose: To study (1) the differences in the relative abundance of urinary proteins between children with kidney stones (RS) and hypercalciuria, hypocitraturia, normal metabolic work-up, and healthy controls (HC); (2) the association of these proteins with various diseases., Methods: Quantitative proteomic comparison of pooled urine from RS (N = 30, 24 females, mean age 12.95 ± 4.03 years) versus age- and gender-matched HC, using mass spectrometry. Relative protein abundance was estimated using spectral counting. Proteins of interest were selected using the following criteria: (1) ≥ 5 spectral counts; (2) ≥ twofold difference in spectral counts; and (3) ≤ 0.05 p value for the Fisher's Exact Test., Results: Of the 1813 proteins identified, 229 met the above criteria, with 162 proteins up-regulated in the RS group and 67 up-regulated in HC. The largest group of proteins (30 out of 229) was found to be associated with cardiovascular disease (CVD). Of those, 16 were involved in coagulation, fibrinolysis, and adhesion, 10 in inflammation, 5 in lipid transport and metabolism, and 4 in oxidative stress. All except two were exclusively found in children with hypercalciuria and hypocitraturia, and were not seen in children with normal metabolic work-up., Conclusion: Using a proteomic approach, we found a significant association between hypercalciuric and hypocitraturic nephrolithiasis and CVD in children. The shared risk factors among both diseases are endothelial dysfunction and atherosclerosis caused by abnormal coagulation, adhesion, disturbance of lipid transport and metabolism, oxidative stress and inflammation. Further understanding of the pathophysiological link between nephrolithiasis and CVD is necessary for developing new therapeutic targets.

Introduction: There is ongoing debate about whether nocturnal enuresis (NE) is affected by the presence of attention deficit hyperactivity disorder (ADHD) in children. Clarifying this relationship could categorize them as a separate entity, potentially requiring a different management from enuretic children without ADHD., Aims: To study whether (1) children with ADHD exhibited greater severity of enuresis and associated voiding symptoms compared with children without ADHD, (2) whether there was a difference in enuretic response to treatment between children with/without ADHD, (3) whether previously prescribed medication for ADHD affected severity of enuresis or voiding symptoms, and response to treatment., Methods: Data on all consecutive children seen with primary NE and ADHD and age- and gender-matched children with NE without ADHD over the course of 2 years were extracted from our database. Controls were identified using a random number generator to choose patients within each age/gender group. Changes in Dysfunctional Voiding Scoring System (DVSS) and Bristol scores were assessed before and after treatment for NE using repeated measures ANOVAs. Number of weekly wet nights was compared between the groups before and after the treatment of enuresis. Children with more than a 50% decrease in number of wet nights per week were categorized as responding to treatment., Results: Compared with controls, ADHD children (N = 95) had significantly more severe voiding symptoms, NE and constipation (Table). No significant differences were found between children on ADHD medication (63.2%) and those who were not on ADHD medication (36.8%) on any of the demographic and pre-treatment clinical parameters. Similar enuretic response rates to behavioral modification alone were seen in both study (13.5%) and control (12.8%) groups (p = 0.73). Response to pharmacological treatment was seen in nine patients with ADHD (42.9%) and in six (20.7%) controls, with pharmacological intervention being significantly more effective than behavioral modification for patients with ADHD (p = 0.012). Additionally, no difference was found between ADHD patients on and off ADHD medication in terms of response to enuresis treatment., Conclusion: In children with primary NE, the presence of ADHD was associated with more severe NE, voiding symptoms and constipation. The severity of voiding symptoms and/or NE was unrelated to the use of stimulant medication. The response to behavioral modification was comparable in both groups. However, patients with ADHD were significantly more responsive to medication for NE compared with behavioral modification, indicating a possible benefit for earlier pharmacological treatment for enuresis in this population subgroup., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Specific factors associated with the risk of developing pediatric urinary stone disease remain unclear, especially those that may be associated with recurrent stone disease., Objective: We compared the results of 24-h urine collections in children with a solitary stone episode to those with multiple stone episodes to determine if there is a difference that may be associated with multiple stone formation in children., Study Design: A multi-institutional retrospective analysis was completed to assess 24-h urinary metabolic profiles in children with urolithiasis aged 2-18 years old. Differences in mean urine collections between the two groups were assessed using chi-square tests to test the associations among gender, stone type, and multiple stone status, as well as multivariate analyses using general linear models., Results: We analyzed 142 solitary stone patients and 136 multiple stone patients from four centers were included. Multiple stone patients were older than solitary stone patients (mean 13.4 ± 3.6 years vs. 12 ± 3.9 years, p = 0.002). Females were more likely to have multiple stones (58% vs. 39%, p = 0.002). BMI was not associated with multiple stones (p = 0.8467). Multiple stone formers had lower urine volumes, although this did not reach statistical significance when compared with solitary stone formation (20.4 mL/kg/day ± 11.5 vs. 22.9 ± 13.0, p = 0.0880). Higher values for super-saturation of calcium oxalate were associated with multiple stone disease in univariate (p = 0.0485) and multivariate analysis (p = 0.0469) (Figure). Centers located in the Southeast of the United States saw a higher proportion of children with multiple stones (Tennessee 62.7%, Virginia 44.4%, Oregon 31.6%, Michigan 27.3%, p < 0.0001)., Discussion: In a large multi-institutional retrospective analysis we found that multiple stone disease was associated with higher super-saturations of calcium oxalate. Many urinary parameters changed with patient age, highlighting that the values should be interpreted with respect to patient age. The inability to comment on follow-up because of the nature of our dataset is a limitation of this study., Conclusion: Multiple stone disease in children is associated with higher super-saturation calcium oxalate, while lower urinary volume may also be associated with multiple stones; however, further study is required. Early metabolic evaluation may help risk stratify children likely to form multiple stones., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters., Methods: Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples., Results: Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005)., Conclusions: We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.