Surgical management of pediatric vesicoureteral reflux: A comparative study between endoscopic, laparoscopic, and open surgery

Our retrospective study compared the results of three surgical procedures for correction of pediatric vesicoureteral reflux (VUR): open Cohen, laparoscopic Lich-Gregoir reimplantation (LEVUR), and endoscopic subureteric injection (STING) procedure. METHODS: We analyzed 90 patients (50 girls, 40 boys, average age 4.86 years) operated in two centers of pediatric surgery for VUR. Exclusion criteria were Grade 1 VUR, Grade 5 VUR with megaureters requiring ureteral tapering, secondary VUR, and patients already operated for VUR. Thirty patients underwent Cohen, 30 LEVUR, and 30 STING procedure. Follow-up included renal ultrasonography and voiding cystourethrography 6 months postoperatively. The statistical analysis was performed using χ(2) Pearson and Fisher tests. RESULTS: Operative time was shorter using STING either for unilateral or bilateral correction (P = .001). Hospitalization was statistically shorter using STING and LEVUR compared to Cohen (P = .001). The pain scores were worse after Cohen (P = .001). Analgesic requirements were higher after Cohen (P = .001). Reflux persistence was higher after STING (10 cases versus 5 Cohen and 4 LEVUR). Cohen presented more complications compared to LEVUR and STING (P = .001). Intraoperative costs were higher for STING procedure (P = .001), while hospitalization costs were significantly higher for Cohen procedure (P = .001). CONCLUSIONS: In children affected by VUR, open Cohen and LEVUR reported a higher success rate than STING procedure. However, Cohen procedure had a very long and painful hospital stay, more complications, more analgesic requirements compared to STING and LEVUR. Comparing the three techniques, it seems that LEVUR presents a high success rate similar to the Cohen procedure, but in addition, it presents the same advantages of STING procedure with no postoperative pain and a lower postoperative morbidity

Laparoscopic transposition of lower pole crossing vessels (vascular hitch) in children with pelviureteric junction obstruction

Abstract BACKGROUND: Congenital hydronephrosis due to intrinsic or extrinsic uretero-pelvic-junction (UPJ) obstruction (UPJO) is a common problem in childhood UPJO may be caused by intrinsic disorganization or by extrinsic compression from crossing vessels (CV); extrinsic causes usually present symptomatically in older children. This report the large Italian experience in the treatment of children with extrinsic-UPJO by CV. METHODS: We analyzed the data of 51 children (17 girls and 34 boys, median age 10, 7 years) affected by extrinsic-UPJO were treated in three Italian institutions with laparoscopic transposition of CV (Hellström Vascular Hitch modified by Chapman).The intraoperative diuretic-test was performed in all patients before and after the vessels transpositions confirming the extrinsic-UPJO. We included in the study only patients with suspicion of vascular extrinsic obstruction of the UPJ. Symptoms at presentation were recurrent abdominal/flank pain and haematuria. All patients presented intermittent ultrasound (US) detection of hydronephrosis (range, 18-100 mm). Preoperative diagnostic studies included: US/doppler scan, MAG3-renogram, functional-magnetic-resonance-urography (fMRU). RESULTS: Median operative time was 108 minutes; median hospital stay: 3, 4 days. Unique complications: a small abdominal wall hematoma and higher junction-translocation without obstruction. During follow-up (range, 12-96 months) all patients reported resolution of their symptoms, a decrease in the hydronephrosis grade and improved drainage on diuretic renogram. CONCLUSIONS: We believe that Vascular Hitch is less technically demanding than laparoscopic pyeloplasty, resulting in a lower complication rate and a significantly reduced hospitalization. The results of our study allow us to conclude that laparoscopic VH may be a safe, feasible, and attractive alternative to treat obstructed hydronephrosis due to CV presenting a useful alternative to AHDP in the management of symptomatic children where CV are deemed the sole aetiology. We recommend careful patient selection based on preoperative clinical and radiologic findings that are diagnostic of extrinsic-UPJO, combined with intraoperative-DT to confirm the appropriate selection of corrective procedure

Retroperitoneal and laparoscopic heminephrectomy in duplex kidney in infants and children

Abstract BACKGROUND: Two main techniques are adopted to perform partial nephrectomy in children: laparoscopy and retroperitoneoscopy. The aim of this paper is to review the larger multicentric experience recently published by our group to review indications, techniques and results of both approaches. METHODS: Data of 102 patients underwent partial nephrectomy in a 5-year period using minimally invasive surgery (MIS) procedures were analyzed. Fifty-two children underwent laparoscopic partial nephrectomy (LPN), and 50 children underwent retroperitoneoscopic partial nephrectomy (RPN). Median age at surgery was 4.2 years. Statistical analysis was performed using χ2 test and Student's t-test. RESULTS: The overall complications rate was significantly higher after RPN (15/50, 30%) than after LPN (10/52, 19%) (χ2 =0.05). In LPN group, complications [4 urinomas, 2 symptomatic refluxing distal ureteral stump (RDUS) and 4 urinary leakages] were conservatively managed. In RPN group, complications (6 urinomas, 8 RDUS, 1 opening of remaining calyxes) required a re-operation in 2 patients. In both groups no conversion to open surgery was reported. Operative time (LPN: 166.2 min vs. RPN: 255 min; P<0.001) and hospitalization (LPN: 3.5 days vs. RPN: 4.1 days; P<0.001) were significantly shorter in LPN group. No postoperative loss of renal function was reported in both groups. CONCLUSIONS: MIS now represents the gold standard technique to perform partial nephrectomy in children with duplex kidney. Our results demonstrate that RPN remains a technically demanding procedure with a significantly higher complications and re-operation rate compared to LPN. In addition, length of surgery and hospitalization were significantly shorter after LPN compared to RPN. LPN seems to be a faster, safer and technically easier procedure to perform in children compared to RPN due to a larger operative space and the possibility to perform a complete ureterectomy in refluxing systems

A genome search for primary vesicoureteral reflux shows further evidence for genetic heterogeneity

Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p < 0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL = 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL = 2.01, p = 0.01). We identified a genomic area on 3q22.2-23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2-34.3 (D1S228-D1S255, max. NPL = 1.70, p = 0.03), after additional fine typing. Furthermore, on chromosome 22q11.22-12.3, patients from a single family showed excess allele sharing (NPL = 3.35, p = 0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder

Kinetics of cytomegalovirus and Epstein-Barr virus DNA in whole blood and plasma of kidney transplant recipients: Implications on management strategies

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management

Osservazioni

di Calogero Piro. Convertire la realtà che ci circonda in immagini, è stata fin dai primordi dell’essere umano un’atavica necessità. Ancora oggi nella nostra cultura visiva è tutto basato sull’utilizzo dell’immagine per conoscere la realtà che ci circonda. Con la scoperta della fotografia, la riflessione intorno alla natura si fa sempre più interessante. Il ruolo della macchina fotografica in questo progetto per raccontare l’ambiente, la struttura, gli oggetti, i segni, i colori e le atmosfere che caratterizzano il centro del CNR di capo Granitola ha trovato prepotentemente in questi giovani allievi della cattedra di fotografia dell’Accademia di Belle Arti di Palermo, diretta dal Professore Sandro Scalia, momenti di grande professionalità, realizzando un grande reportage con tutti gli aspetti essenziali della struttura e delle articolazioni primarie del linguaggio fotografico. Questa esperienza extradidattica difficile ed impegnativa non soltanto per la necessità del confronto col “nuovo” in termini organizzativi, ma anche per la necessità di descrivere attraverso la fotografia il tema della Biodiversità, è stato affrontato brillantemente. Mettendo in primo piano, siti naturali, siti storici come: Mozia e Selinunte, i laboratori del centro di ricerche, la Flora e la Fauna, sono riusciti a raggiungere con acuta osservazione ottimi risultati visibili in questo catalogo, e con la tangibile riprova di cosa possa e debba essere una educazione estetica assolutamente “libera” da condizionamenti, viatico ineludibile perché l’espressione artistica, sotto qualunque forma, sia artefice dei grandi processi di vera maturazione culturale, si avverte in questi giovani artisti la purezza e la consapevolezza dei propri messaggi ancora privi, e speriamo sempre, di qualunque tipo di inquinamento tendenzioso

How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?

Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG.The authors’ lab is funded by the Wellcome Trust (093008/Z10/Z) and the Medical Research Council (MR/L008246/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.ppat.100525

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases