Implementation and Feasibility of Clinical Genome Sequencing Embedded Into the Outpatient Nephrology Care for Patients With Proteinuric Kidney Disease.

Introduction: The diagnosis and management of proteinuric kidney diseases such as focal segmental glomerulosclerosis (FSGS) are challenging. Genetics holds the promise to improve clinical decision making for these diseases; however, it is often performed too late to enable timely clinical action and it is not implemented within routine outpatient nephrology visits. Methods: We sought to test the implementation and feasibility of clinical rapid genome sequencing (GS) in guiding decision making in patients with proteinuric kidney disease in real-time and embedded in the outpatient nephrology setting. Results: We enrolled 10 children or young adults with biopsy-proven FSGS (9 cases) or minimal change disease (1 case). The mean age at enrollment was 16.2 years (range 2-30). The workflow did not require referral to external genetics clinics but was conducted entirely during the nephrology standard-of-care appointments. The total turn-around-time from enrollment to return-of-results and clinical decision averaged 21.8 days (12.4 for GS), which is well within a time frame that allows clinically relevant treatment decisions. A monogenic or APOL1-related form of kidney disease was diagnosed in 5 of 10 patients. The genetic findings resulted in a rectified diagnosis in 6 patients. Both positive and negative GS findings determined a change in pharmacological treatment. In 3 patients, the results were instrumental for transplant evaluation, donor selection, and the immunosuppressive treatment. All patients and families received genetic counseling. Conclusion: Clinical GS is feasible and can be implemented in real-time in the outpatient care to help guiding clinical management. Additional studies are needed to confirm the cost-effectiveness and broader utility of clinical GS across the phenotypic and demographic spectrum of kidney diseases.

Complicaciones quirúrgicas en pacientes pediátricos con apendicitis aguda complicada en cirugías abiertas y laparoscópicas en un centro de referencia nacional / Surgical Complications In Pediatric Patients With Complicated Acute Appendicitis In Open And Laparoscopic Surgeries In A National Referral Center

Objetivo: Determinar la incidencia y tipo de complicaciones tras una apendicetomía en pacientes con apendicitis complicada con peritonitis en relación al tipo de intervención quirúrgica y al tiempo transcurrido desde el inicio del cuadro hasta la cirugía. Métodos: Se evaluaron 157 historias clínicas de pacientes provenientes del Servicio de Cirugía Pediátrica del HNGAI y diagnosticados de apendicitis aguda complicada con peritonitis. Los pacientes estaban entre los 2 y 14 años. Se separaron en dos grupos - 81 cirugías abiertas y 76 laparoscópicas. Se evaluaron las variables de edad, sexo, tipo de cirugía, duración de la intervención quirúrgica, tiempo de hospitalización y complicaciones postoperatorias. Se utilizó el análisis de Chi cuadrado y Mann-Whitney. Resultados: Del total de historias clínicas, sólo 157 historias clínicas cumplieron con los criterios de inclusión, de las cuales, 81 apendicetomías fueron abiertas y 76 laparoscópicas. La cirugía laparoscópica fue más prolongada. Las complicaciones fueron más frecuentes en las cirugías abiertas con una incidencia de 30.8%, así como el tiempo de hospitalización prolongado de 12.7%. Conclusión: Las cirugías laparoscópicas tienen una mayor duración en comparación con las cirugías abiertas, sin embargo, las complicaciones y hospitalización prolongada se presentaron con mayor frecuencia en las cirugías abiertas. Estos datos se podrían deber a la experiencia del operador.

Objective: To determine the incidence and type of complications after an appendectomy in patients with appendicitis complicated by peritonitis in relation to the type of surgical intervention and the time elapsed from the onset of the symptoms to surgery. Methods: 157 medical records of patients from the Pediatric Surgery Service of HNGAI and diagnosed with acute appendicitis complicated with peritonitis were evaluated. The patients were between 2 and 14 years old. They were separated into two groups - 81 open surgeries and 76 laparoscopic. The variables of age, sex, type of surgery, duration of surgery, length of hospitalization and postoperative complications were evaluated. Chi square and Mann-Whitney analysis was used. Results: From the total number of medical records, only 157 medical records met the inclusion criteria, of which 81 appendectomies were open and 76 laparoscopic. Laparoscopic surgery was longer. Complications were more frequent in open surgeries with an incidence of 30.8%, as well as prolonged hospitalization time of 12.7%. Conclusion: Laparoscopic surgeries have a longer duration compared to open surgeries, however, complications and prolonged hospitalization occurred more frequently in open surgeries. This data could be due to the experience of the operator.

Prevalence of Cardiovascular Disease Risk Factors in Childhood Glomerular Diseases.

Background Cardiovascular disease is a major cause of morbidity and mortality in children with chronic kidney disease. We sought to determine the prevalence of cardiovascular risk factors in children with glomerular disease and to describe current practice patterns regarding risk factor identification and management. Methods and Results Seven-hundred sixty-one children aged 0 to 17 years with any of 4 biopsy-confirmed primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy/vasculitis) were enrolled at a median of 16 months from glomerular disease diagnosis in the multicenter prospective Cure Glomerulonephropathy Network study. Prevalence of traditional (hypertension, hypercholesterolemia, and obesity) and novel (proteinuria, prematurity, and passive smoke exposure) cardiovascular risk factors were determined at enrollment and compared across glomerular disease subtypes. Frequency of screening for dyslipidemia and prescribing of lipid-lowering or antihypertensive medications were compared across glomerular disease subtype, steroid exposure, and remission status groups. Compared with the general population, all traditional risk factors were more frequent: among those screened, 21% had hypertension, 51% were overweight or obese, and 71% had dyslipidemia. Children who were not in remission at enrollment were more likely to have hypertension and hypercholesterolemia. Fourteen percent of hypertensive children were not receiving antihypertensives. Only 49% underwent screening for dyslipidemia and only 9% of those with confirmed dyslipidemia received lipid-lowering medications. Conclusions Children with primary glomerular diseases exhibit a high frequency of modifiable cardiovascular risk factors, particularly untreated dyslipidemia. Lipid panels should be routinely measured to better define the burden of dyslipidemia in this population. Current approaches to screening for and treating cardiovascular risk factors are not uniform, highlighting a need for evidence-based, disease-specific guidelines.

The effect of transfer to adult transplant care on kidney function and immunosuppressant drug level variability in pediatric kidney transplant recipients.

Adolescent age at time of transplant has been recognized as a risk factor for renal allograft loss. Increased risk for graft failure may persist from adolescence to young adulthood. Transfer of care is hypothesized as a risk factor for non-adherence and graft loss. We explored whether kidney allograft function declined at an accelerated rate after transfer of care to adult transplant centers and whether coefficient of variation of tacrolimus (CV TAC) trough levels predicted allograft loss. Single-center, retrospective chart review was performed for pediatric kidney transplant recipients who received transplants between 1999 and 2011. Change in eGFR pre- and post-transfer was performed via a linear mixed-effects model. CV TAC was calculated in transplant recipients with TAC data pre- and post-transfer. t test was performed to determine the difference between means of CV TAC in subjects with and without allograft loss following transfer of care. Of the 138 subjects who transferred to adult care, 47 subjects with data pre- and post-transfer demonstrated a decrease in the rate of eGFR decline post-transfer from 8.0 mL/min/1.73 m2 per year to 2.1 mL/min/1.73 m2 per year, an ~80% decrease in eGFR decline post-transfer (P = 0.01). Twenty-four subjects had CV TAC data pre- and post-transfer of care. Pretransfer CV TAC for subjects with allograft loss post-transfer was significantly higher than in subjects without allograft loss (49% vs 26%, P < 0.05). Transfer of care was not independently associated with acceleration in eGFR decline. CV TAC may aid in identifying patients at risk for allograft loss post-transfer.

Monitoring nonadherence and acute rejection with variation in blood immunosuppressant levels in pediatric renal transplantation.

BACKGROUND: Acute rejection associated with medication nonadherence is a major cause of allograft loss in pediatric kidney transplant patients. There is currently no reliable method to detect medication nonadherence and prevent allograft rejection. METHODS: In 46 pediatric patients who underwent renal transplantation between 2002 and 2003, the variation of serum drug levels was studied as a potential objective tool to monitor medication nonadherence. Tacrolimus (TAC) and mycophenolic acid (MPA) trough levels were measured from 1 to 12 months posttransplant, and standard deviation (SD) and percent coefficient of variation (CV%) were calculated. Because SD increased as mean trough levels rose, CV% (CV%=SD/mean multiplied by 100%) was used to eliminate this confounding effect. RESULTS: Ten of 46 patients had biopsy-proven rejection. The median TAC CV% was 53.4% in patients with biopsy-proven rejection, which was significantly higher than 30% in those without rejection (P=0.005). Median MPA CV% was 51.9% in patients without rejection and 45.1% in patients with rejection (P=NS). High TAC CV% correlated with increased risk for rejection, whereas MPA CV% did not. CONCLUSION: The TAC CV% seems to be a useful and superior marker, compared with SD alone, for assessing medication nonadherence and the possibility of allograft rejection in pediatric renal transplantation.

Brote de diarrea debida a intoxicación por alimentos en una empresa X: San José, Costa Rica, del 8 al 9 de julio 2003 / Outbreak of diarrhea due to food poisoning at a company for San José, Costa Rica, from 8 to 9 July 2003

El 9 de julio del 2003, se informó al Ministerio de Salud, la existencia de un brote de diarrea en una empresa X, en San José. Se investigó el brote, con el objetivo de verificar su mangnitud, determinar factores de riesgo y mecanismo de transmisión, también recomendar medidas de prevención y control, a las autoridades de salud. Se revisaron 40 expedientes clínicos de pacientes atendidos por diarrea, en el consultorio de la empresa. Se definió como caso a todo funcionario, que presentó más de 2 deposiciones semilíquidas, y que consumió alimentos del comedor de la empresa, el 8 julio del 2003. Se tomaron corpocultivos, muestras de alimentos consumidos, y se enviaron a un laboratorio privado para el análisis. Se realizó un estudio de cohorte retrospectivo, y se aplicó un cuestionario. Se calcularon los riesgos relativos, RR, con intervalos de confianza del 95 por ciento, las tasas de ataque y porcentajes para los alimentos servidos. El 100 por ciento de los casos presentaron diarrea, sin fiebre. A los coprocultivos y a las muestras de alimentos, no se les buscó Clostridium perfringens. Las muestras de agua no reportaron contaminación fecal. El alimento sospechoso: cerdo con piña, presentó un RR igual 1,94; IC: 95 por ciento, 1, 26-2,96. El período de incubación y la descripción de la enfermedad coincidieron con una intoxicación por Clostridium perfringens, por lo que, se asoció el brote al alimento sospechoso. Como en la empresa X se desconocían los procedimientos a seguir ante un brote de diarrea, causado por alimentos, se recomendó a los encargados de epidemiología del Área Rectora de Salud, capacitar en el abordaje de las intoxicaciones causadas por alimentos; a las empresas bajo su responsabilidad, que cuentan con establecimientos de alimentación.

On July the 9th., 2003, an outbreak in company X was notified to the Ministry of Public Health in San José. This outbreak was investigated with thepurposes of verifying its magnitude, determining risk factors, and mechanisms of transmission as well asrecommending prevention and control measures to the Local Health authorities. Forty clinical chartsbelonging to diarrhea patients seen at the company´s infirmary, were reviewed. The case definition was anyworker with more than 2 semi-liquid bowel movements and who ate in the worker´s dining room on the 8th.of July, 2003. Stool and food cultures were taken and sent for analysis to a private lab. A retrospective cohort study was carried out and a questionnaire wasadministered to the employees. Relative Risks (with 95% confidence intervals) as well as attack rates and percentages were calculated for the foodstuffs served. All cases showed diarrhea but without fever. Clostridium perfringens was not searched in either thestool or the food cultures. Water samples didn´t report fecal contamination. The likely source of contamination, namely pineapple pork, showed a relative risk of 1.94 with a confidence interval between 1.26 and 2.96. The incubation period as well as the clinical characteristics of the illness were consistent with an intoxication dueto Clostridium perfringens. Since the employees were unaware of the procedures to be followed duringa foodborne outbreak, training was offered to the Local Health Area which in turn, educated the companies under its supervision regarding protocols to be followed during any future similar problems.

Estudio fitoquímico de erythroxylum havanence jacq: (erythroxylaceae) / Phytochemical study of erythroxylum havanense jacq: (erythroxylaceae)

Se realizó el estudio fitoquímico de Erythroxylum havanense jacq.(Erythroxylaceae), de donde se obtuvo el éster metílico de la anhidroecgonina como alcaloide mayoritario, el cual fue caracterizado espectroscópicamente