Current management issues of immediate postoperative care in pediatric kidney transplantation

The number of pediatric kidney transplants has been increasing in many centers worldwide, as the procedure provides long-lasting and favorable outcomes; however, few papers have addressed the immediate postoperative care of this unique population. Herein, we describe the management of these patients in the early postoperative phase. After the surgical procedure, children should ideally be managed in a pediatric intensive care unit, and special attention should be given to fluid balance, electrolyte disturbances and blood pressure control. Antibiotic and antiviral prophylaxes are usually performed and are based on the recipient and donor characteristics. Thrombotic prophylaxis is recommended for children at high risk for thrombosis, although consensus on the optimum therapy is lacking. Image exams are essential for good graft control, and Doppler ultrasound must be routinely performed on the first operative day and promptly repeated if there is any suspicion of kidney dysfunction. Abdominal drains can be helpful for surveillance in patients with increased risk of surgical complications, such as urinary fistula or bleeding, but are not routinely required. The immunosuppressive regimen starts before or at the time of kidney transplantation and is usually based on induction with monoclonal or polyclonal antibodies, depending on the immunological risk, and maintenance with a calcineurin inhibitor (tacrolimus or ciclosporin), an anti-proliferative agent (mycophenolate or azathioprine) and steroids

Phylogenetic And Molecular Variability Studies Reveal A New Genetic Clade Of Citrus Leprosis Virus C

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Citrus leprosis virus C (CiLV-C) causes a severe disease affecting citrus orchards in the Western hemisphere. This study reveals the molecular variability of the virus by analyzing four genomic regions (p29, p15, MP and RNA2-intergenic region) distributed over its two RNAs. Nucleotide diversity (pi) values were relatively low but statistically different over the analyzed genes and subpopulations, indicating their distinct evolutionary history. Values of pi(p29) and pi(MP) were higher than those of pi(p15) and pi(RNA2-IR), whereas pi(MP) was increased due to novel discovered isolates phylogenetically clustered in a divergent clade that we called SJP. Isolate BR_SP_SJP_01 RNA1 and RNA2 sequences, clade SJP, showed an identity of 85.6% and 88.4%, respectively, with those corresponding to CiLV-C, the type member of the genus Cilevirus, and its RNA2 5'-proximal region was revealed as a minor donor in a putative inter-clade recombination event. In addition to citrus, BR_SP_SJP_01 naturally infects the weed Commelina benghalensis and is efficiently transmitted by Brevipalpus yothersi mites. Our data demonstrated that negative selection was the major force operating in the evaluated viral coding regions and defined amino acids putatively relevant for the biological function of cilevirus proteins. This work provides molecular tools and sets up a framework for further epidemiological studies.86Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [375843/2012-4, 481771/2013-1, 401564/2012-6]Fundacao de Apoio a Pesquisa no Estado de Sao Paulo [2012/18771-0, 2012/20667-7, 2014/08458-9]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Unveiling the fate of adhering bacteria to antimicrobial surfaces: expression of resistance-associated genes and macrophage-mediated phagocytosis

Since most antibacterial coatings reported to fight biomaterial-associated infections (BAI) fail in completely preventing bacterial colonization, it is crucial to know the impact of that small fraction of adhered bacteria in BAI recrudescence. This study aims to understand the fate of Staphylococcus aureus able to adhere to an antimicrobial coating previously developed, in terms of potential development of bacterial resistance and their macrophage-mediated phagocytosis. Antimicrobial coating comprised the co-immobilization of Palm peptide and DNase I onto polydimethylsiloxane. Expression of genes associated to resistance and virulence mechanisms showed that cells in contact with antimicrobial surfaces for a long period of 30 days, exhibit genes equally or less expressed, as compared to cells recovered from control surfaces. Recovered cells also exhibit the same susceptibility patterns, which strengthens the evidence of no resistance development. Remarkably, cells adhered to modified surfaces shows a reduced metabolic activity upon vancomycin treatment unlike the cells found on control surfaces, which can be identified as a clinical opportunity for prophylactically administration after implant surgery. Furthermore, results highlight that functionalization of PDMS with Palm and DNase I should not compromise the action of host immune cells. The overall results reinforce the potential of this antimicrobial strategy to fight BAI.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01 0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. The authors also acknowledge the support by FCT and the European Community fund FEDER, through Program COMPETE, under the scope of the Project AntiPep PTDC/SAUSAP/113196/2009 (FCOMP-01-0124-FEDER-016012) and the PhD Grant of Diana Alves (SFRH/BD/78063/2011) and Andreia Magalhães (SFRH/BD/132165/2017). A special thanks to Doctor Agostinho Carvalho and Doctor Cristina Amorim from Life and Health Sciences Research Institute (ICVS), University of Minho for kindly providing the monocyte cell line used in this study. Doctor Nuno Cerca, from CEB, Centre of Biological Engineering, University of Minho, is also acknowledged for his important contribution on the interpretation of gene expression results.info:eu-repo/semantics/publishedVersio

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Critical analysis of chronic peritoneal dialysis prescription in pediatric patients.

Introdução: Diálise peritoneal (DP) é modalidade de terapia renal substitutiva útil em crianças em estágio final de doença renal. O estado nutricional e o crescimento são considerados como marcadores prognósticos na adequação em diálise pediátrica, que dependem da sua prescrição, do controle da volemia e pressão arterial e do manejo dos distúrbios metabólicos e eletrolíticos. Objetivo: Descrever a prescrição da DP e parâmetros de adequação dos pacientes seguidos na Unidade de Nefrologia Pediátrica do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP; analisar os resultados hemodinâmicos e antropométricos iniciais e finais; comparar os parâmetros observados na adequação da DP com aqueles sugeridos pela literatura em DP Crônica pediátrica. Métodos: Análise retrospectiva baseada na avaliação de prontuário durante o período entre janeiro de 1998 e maio de 2005, incluindo pacientes em DP por mais de 6 meses. Dados antropométricos, pressão arterial sistêmica, volume de infusão, pressão intra-abdominal (PIA), Teste do Equilíbrio Peritoneal (PET) e Kt/V semanal de uréia e mudanças de prescrição dialítica peritoneal foram analisadas. Resultados: foram analisados dados de 30 pacientes pediátricos, 17/30 (56,7%) sexo masculino. Uropatia foi a etiologia de doença renal crônica em 66,7% dos pacientes. A membrana peritoneal foi caracterizada como alto transportador em 5/18 pacientes, médio/alto transportador em 9/18 pacientes, médio/baixo transportador em 1/18 pacientes e baixo transportador em 3/18 pacientes. O Kt/V de uréia semanal foi > 2,1 em todos os pacientes em que este índice foi coletado. Pressão arterial sistêmica acima do p95 foi observada em 5/30 pacientes. Quatro dos cinco pacientes com hipertensão arterial apresentavam glomerulopatia como etiologia de doença renal crônica. O índice de massa corpórea e o índice de peso para estatura iniciais e finais foram preservados na maioria dos pacientes. Conclusão: Manejo clínico ótimo parece ser mais importante para adequação de DP pediátrica que índices de adequação baseados em estimativa de remoção de pequenos solutos.I ntroduction: Peritoneal dialysis (PD) is an useful modality of renal replacement therapy in pediatric end-stage renal disease. Growth and nutritional state are considered outcome markers of adequacy in pediatric dialysis, which depends on the dialysis prescription, volume and blood pressure control and management of metabolic and electrolyte disorders. Objective: To describe the PD prescription and adequacy parameters of patients followed by the Pediatric Nephrology Unit of \"Instituto da Criança\" of \"Hospital das Clínicas\" of University of São Paulo; to analyze initial and final anthropometric and hemodynamic results; to compare the observed PD adequacy parameters with those suggested by the pediatric chronic PD literature. Methods: Retrospective analysis based on patients\' files evaluation covering the period between January 1998 and May 2005 and including patients on PD for more than 6 months. Data on anthropometry, systemic blood pressure, infusion volume, intraperitoneal pressure (IPP), peritoneal equilibration test (PET), weekly Kt/V urea and changes in peritoneal dialysis prescription were analyzed. Results: Data from 30 pediatric patients were analyzed, 17/30 (56,7%) boys. Uropathy was the etiology of chronic renal disease in 66,7% patients. The infusion volume was > 1000 ml/m2 in 9 patients. The peritoneal membrane was characterized as a high transporter in 5/18 patients, high/average transporter in 9/18 patients, low/average transporter in 1/18 patients and low transporter in 3/18 patients. The weekly Kt/V urea was >2,1 in all patients for whom this parameter was collected. Systemic blood pressure was above p95 in 5/30 despite antihypertensive medication. Four of 5 patients with high blood pressure had chronic renal failure related to glomerulopathy. The initial and final body mass index and weight to height index were preserved in most of the patients. Conclusion: Optimal clinical management seems to be more important for pediatric PD adequacy than adequacy indexes based on estimation of small solute removal

Molecular genetic pathogenesis of steroid-resistant nephrotic syndrome, congenital nephrotic syndrome and focal segmental glomerulosclerosis: reality and contributions from the analysis of a Brazilian pediatric population

Síndrome nefrótica (SN) é a segunda causa mais frequente de doença renal estágio terminal (DRET) na faixa etária pediátrica. Atualmente até 30% dos casos de SN congênita (SNC) e SN córtico-resistente (SNCR) nessa faixa etária se associam a causas mendelianas, entretanto as casuísticas até então analisadas apresentam pouca representação de pacientes provenientes do Hemisfério Sul. Nesse cenário, 101 pacientes de 98 famílias com SNC, SNCR e/ou glomeruloesclerose segmentar e focal (FSGS), seguidos prioritariamente no Instituto da Criança e do Adolescente do Hospital das Clínicas da Faculdade de Medicina da USP, foram submetidos a avaliação genético-molecular por meio da análise de um painel de 62 genes associados a SN ou de sequenciamento de exoma completo, bem como por meio de análise genética para avaliação de ancestralidade. Também avaliamos seus dados clínicos e laboratoriais, correlacionando-os com os achados genético-moleculares. Utilizamos os critérios do ACMG para classificar a patogenicidade das variantes, e posteriormente análises de mecânica molecular in silico para ampliar e fortalecer a avaliação das variantes de significado incerto. Nessa casuística, a idade de manifestação da SN foi de 2,9 anos, ocorrendo no primeiro ano de vida em 13,8% dos casos, e o tempo de seguimento de 5,7 anos. A taxa de consanguinidade parental autodeclarada foi de 5,9% e de história familiar de doença renal de 13,9%. Pacientes que atingiram remissão completa de SN após uso de corticosteroide ou inibidor de calcineurina, assim como os que apresentaram lesões histológicas mínimas (LHM), não evoluíram para DRET, desfecho atingido por outros 44 pacientes (43,6%). Oito pacientes apresentaram genótipo de alto risco (GAR) de APOL1, grupo que manifestou SN mais tardiamente e apresentou mais frequentemente glomerulopatia colapsante. Não observamos, entretanto, associação de GAR de APOL1 com a raça autodeclarada não branca ou com ancestralidade genética global africana. Causas mendelianas foram encontradas em 13 famílias (13,3%), frequência similar às de populações equivalentes com baixas taxas de consanguinidade, e incluíram variantes nos genes NPHS1, NPHS2, WT1, PLCE1, COQ2, CUBN e COL4A5. Duas das nove variantes causativas novas identificadas se posicionam em regiões genômicas de ancestralidade nativo-americana. Pacientes com causas mendelianas ou com GAR de APOL1 progrediram mais rapidamente para DRET que aqueles sem achados genéticos identificados, assim como pacientes autodeclarados não brancos. Pacientes com maior porcentagem de ancestralidade não europeia apresentaram a mesma tendência. Análise por regressão logística de Cox revelou que idade de manifestação de SN menor que 1 ano ou maior ou igual a 9 anos, raça autodeclarada não branca e histologia renal que não LHM se associaram a risco aumentado para atingir DRET, independentemente de GAR de APOL1 ou de causas mendelianas. Recidiva.de SN foi observada em 9/29 pacientes (31%) submetidos a transplante renal, mas não em quatro pacientes com causas mendelianas e outros quatro com GAR de APOL1. Nossos resultados ampliam a caracterização genética molecular e clínica da SNC, SNCR e GESF em idade pediátrica, bem como o entendimento de sua patogêneseNephrotic Syndrome (NS) is the second leading cause of end-stage kidney disease (ESKD) in the pediatric age range. Currently, up to 30% of congenital NS (CNS) and steroid-resistant NS (SNCR) cases in this age range are associated with Mendelian causes, however the previously analyzed cohorts display low representation of patients from the Southern Hemisphere. In this scenario, 101 patients from 98 families with CNS, SNCR and/or focal segmental glomerulosclerosis (FSGS) followed primarily at the Instituto da Criança e do Adolescente do Hospital das Clínicas da Faculdade de Medicina da USP underwent genetic molecular evaluation through analysis of a panel including 62 genes associated with NS or whole-exome sequencing, as well as genetic analysis to evaluate ancestry. We also analyzed their clinical and laboratorial data and correlated them with the molecular genetic findings. ACMG criteria were used to classify the pathogenicity of the variants, followed by in silico molecular mechanics analysis to broaden and strengthen the assessment of variants of uncertain significance. In this cohort, the age of NS onset was 2.9 years, occurring in the first year of life in 13.8% of the cases, and the follow-up time was 5.7 years. The rate of self-reported parental consanguinity was 5.9% and of family history of kidney disease 13.9%. Patients who achieved complete remission of NS after using corticosteroids or calcineurin inhibitor, as well as those who presented minimal change disease (MCD), did not progress to ESKD, outcome reached by another 44 patients (43.6%). Eight patients harbored an APOL1 high-risk genotype (HRG), a group of patients that displayed later NS onset and presented more often collapsing glomerulopathy. However, we did not observe association of APOL1 HRG with self-declared non-White race and with African global genetic ancestry. Mendelian causes were found in 13 families (13,3%), a frequency similar to the ones detected in equivalent populations with low inbreeding rates, and included variants in the NPHS1, NPHS2, WT1, PLCE1, COQ2, CUBN and COL4A5 genes. Two of the nine novel identified causative variants are located in genomic regions of Native American ancestry. Patients with Mendelian causes or with APOL1 HRG progressed more rapidly do ESKD than those with no identified genetic findings, as well as self-declared non-White patients. Patients with higher percentage of non-European ancestry showed the same trend. Cox logistic regression analysis revealed that age of NS onset below 1 year or equal or above 9 years of age, self-declared non-White race, and non-MCD renal histology were associated with increased risk of reaching ESKD regardless of APOL1 HRG or Mendelian causes. NS recurrence was observed in 9/29 patients (31%) who underwent kidney transplantation, but not in four patients with Mendelian causes nor in another four with APOL1 HRG. Our results extend the molecular and clinical genetic characterization of CNS, SRNS and FSGS in pediatric age, as well as the understanding of its pathogenesi

Current management issues of immediate postoperative care in pediatric kidney transplantation

The number of pediatric kidney transplants has been increasing in many centers worldwide, as the procedure provides long-lasting and favorable outcomes; however, few papers have addressed the immediate postoperative care of this unique population. Herein, we describe the management of these patients in the early postoperative phase. After the surgical procedure, children should ideally be managed in a pediatric intensive care unit, and special attention should be given to fluid balance, electrolyte disturbances and blood pressure control. Antibiotic and antiviral prophylaxes are usually performed and are based on the recipient and donor characteristics. Thrombotic prophylaxis is recommended for children at high risk for thrombosis, although consensus on the optimum therapy is lacking. Image exams are essential for good graft control, and Doppler ultrasound must be routinely performed on the first operative day and promptly repeated if there is any suspicion of kidney dysfunction. Abdominal drains can be helpful for surveillance in patients with increased risk of surgical complications, such as urinary fistula or bleeding, but are not routinely required. The immunosuppressive regimen starts before or at the time of kidney transplantation and is usually based on induction with monoclonal or polyclonal antibodies, depending on the immunological risk, and maintenance with a calcineurin inhibitor (tacrolimus or ciclosporin), an anti-proliferative agent (mycophenolate or azathioprine) and steroids

Patterns of Internet and smartphone use by parents of children with chronic kidney disease.

BackgroundSmartphones have become a part of universal technology by combining mobile and handheld functions, enabling expanded access to health information sources available on the Internet. The purpose of this study was to describe the pattern of smartphones and Internet use to search for health information by parents of children with chronic kidney disease (CKD).MethodsIn a cross-sectional study, a questionnaire was applied to 111 parents of patients in a Brazilian pediatric nephrology center. Descriptive assessments were performed on Internet use patterns, and associative analyses were made of the influence of the smartphone use pattern on the search for health information.ResultsOf the 111 participants, 91% (101/111) accessed the Internet, 88% (89/101) searched for health information, and 90% (80/89) searched for CKD information. Smartphones were the most commonly used devices to access the Internet. There was no significant difference between age groups, schooling levels, places of residence and smartphone use to search information about CKD. Physicians continue to be primary sources of information (87%, 88/101), but now they share space with the Internet, which surpassed traditional sources such as books and other health professionals. There seems to be some discomfort on the part of the parents in admitting their research habit to the physician, considering that 65% (52/80) said they did not discuss the fact that they had looked for information on the Internet with their doctor. Obtaining more information about the disease and gaining knowledge regarding its complications were the main reasons that led to performing a search on the Internet, whose results were considered useful by 93% (74/80).ConclusionParents of children with CKD have been using the Internet largely through smartphones to research about CKD, irrespective of age, schooling and place of residence. Given its wide use, the Internet can be an important vehicle for health education and contribute to providing the support needed by parents and patients to cope with the disease

Flow-through peritoneal dialysis in neonatal enema-induced hyperphosphatemia

Fleet enemas are hypertonic solutions with an osmotic action and a high concentration of phosphate. When retained in the human body they have a great toxic potential, causing severe hydro-electrolyte disorders in children, especially in newborns. We report the case of a previously healthy 8-day-old newborn who needed neonatal intensive care treatment after the inadvertent administration of an osmotically active hypertonic phosphate enema. Taking into account that phosphate removal by peritoneal dialysis (PD) strongly depends on total dialysate turnover, we chose continuous flow PD (CFPD) as the treatment option, with a successful outcome. Clinical experience with this dialytic modality is limited to a few case reports in pediatric and adult patients. To the best of our knowledge, we report here the first description of CFPD in the setting of acute phosphate nephropathy in the neonatal period. The modality of PD described here has potential as an alternative management option as it is a highly efficient, methodologically simple, and low-cost method without any need for sophisticated equipment. Physicians and parents should be aware of the adverse effects of a hypertonic phosphate enema and should never use these medications in infants and newborns