Feasibility and Safety of Implanting InterStimtm Device in Conjunction with Other Neuromodulator Devices, Case Report

Maryam Aleissa,1,2 Ernesto Drelichman,1 Jasneet Singh Bhullar1 1Department of Surgery, Ascension Providence Hospital-Michigan State University College of Human Medicine, Southfield, MI, USA; 2College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaCorrespondence: Jasneet Singh Bhullar, Program Director of Colorectal Surgery Fellowship, Clinical Assistant Professor WSUCOM/MSUCHM, Department of Surgery, Ascension Providence Hospital-Michigan State University/College of Human Medicine, Southfield, MI, USA, Email [email protected]: Sacral nerve stimulation (SNS) has emerged as a viable option in patients with fecal incontinence who do not respond to conservative care. Technology has significantly progressed over the years. The current InterStimTM device is compatible with MRI, lasts for many years, and is performed using a minimally invasive technique, using mild sedation and local anesthesia. The precise mechanism of action remains unknown, and there is increasing interest in expanding the indications for the management of digestive diseases. There is now an increasing interest in brain neuromodulator devices, which may enable physicians to visit a larger number of patients simultaneously.Case Presentation: We present a case report of a patient with fecal incontinence (FI) who failed to respond to conservative management. The patient also had an occipital device for cluster headaches. The FI symptoms improved significantly with InterStimTM and there was no interaction with another device.Discussion: InterStimTM may be safely integrated with other neuromodulators. Additional research is required to determine the safety and benefit of InterStimTM implantation with other neuromodulators devices.Keywords: neuromodulators, fecal incontinence, sacral nerve stimulato

Enfermedad de Gaucher en Argentina: un informe del Registro Internacional de Gaucher y del Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher

La Enfermedad de Gaucher por su baja frecuencia está incluida dentro de las enfermedades huérfanas. En 1991 comenzó el ingreso de pacientes en el Registro Internacional de Gaucher. En 1992 se incorporaron los primeros dos pacientes de Latinoamérica. En 2006 se creó el Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher siendo sus objetivos principales el entendimiento de la prevalencia, presentación, manejo y tratamiento de la Enfermedad de Gaucher en Argentina. Hasta el 1 de febrero del 2013 ingresaron al Registro Internacional 5.986 pacientes provenientes de 60 países, de los cuales 133 (2.22%) fueron argentinos. El análisis de esta publicación fue realizado sobre 133 pacientes con Enfermedad de Gaucher. Esta es la primera publicación del Grupo Argentino de Diagnóstico y Tratamiento en base a los datos del Registro Internacional. La casuística argentina mostró un predominio femenino y la forma clínica más frecuente fue el tipo 1 (97.7%, n=128). El genotipo fue identificado en 57 pacientes (42.9%), siendo el más frecuente el N370S/ otro alelo (82.5%). Entre los pacientes con datos reportados, los síntomas basales predominantes, previos al inicio del tratamiento con Imiglucerasa que predominaron fueron la esplenomegalia (100%, n=13) y la hepatomegalia (88.9%, n=8) y como citopenias más frecuentes, la trombocitopenia (64.2%, n=34) y la anemia (45.9%, n=28). La infiltración de la médula ósea como un marcador específico de enfermedad ósea se encontró en el 50% de los pacientes. En total, el 85.7% de los pacientes argentinos reciben terapia de reemplazo enzimático con Imiglucerasa, lográndose las metas terapéuticas, en la mayoría de los casos, en la última evaluación. Las metas terapéuticas más frecuentemente alcanzadas resultaron: el control de las manifestaciones óseas (dolor óseo y crisis ósea, 81.9% y 99% respectivamente) y la normalización de la hemoglobina (86.5%). La terapia de reemplazo enzimática con Imiglucerasa, a largo plazo en la población argentina demostró ser una herramienta eficaz para mejorar los parámetros clínicos y bioquímicos de la Enfermedad de Gaucher tipo1.Fil: Drelichman, G.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Fernández Escobar, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Basack, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Kohan, R.. Registro Argentino de Gaucher; ArgentinaFil: Watman, N.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Bolesina, M.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Elena, G.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Veber, S. E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Dragosky, M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Oncología Marie Curie; ArgentinaFil: Annetta, I.. Gobierno de la Ciudad de Buenos Aires. Hospital de Oncología Marie Curie; ArgentinaFil: Feliu, A.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sciuccati, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Cuello, María Fernanda. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fynn, Alcira. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Dodelson de Kremer, Raquel. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Angaroni, Celia Juana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Giner Ayala, Alicia. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Del Valle Oller, Ana María. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guelbert, Norberto Bernardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Delgado, María Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Becerra, Adriana Berónica. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Oliveri, María Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larroudé, M.. Centro Médico TIEMPO; ArgentinaFil: Masllorens, F.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Nacional “Prof. Dr. A. Posadas"; ArgentinaFil: Szlago, M.. Fundación para el eEstudio de las Enfermedades Neurometabólicas; Argentina. Laboratorio de Neuroquímica “Dr. N. A. Chamoles”; ArgentinaFil: Schenone, A.. Laboratorio de Neuroquímica “Dr. N. A. Chamoles”; Argentina. Fundación para el eEstudio de las Enfermedades Neurometabólicas; Argentin

Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy

In the phase 3 trial of eliglustat in patients with Gaucher disease type 1 already stabilized with enzyme therapy (ENCORE), at one year, eliglustat was non-inferior to imiglucerase enzyme therapy in maintaining stable platelet counts, hemoglobin concentrations, and spleen and liver volumes. After this primary analysis period, patients entered a long-term extension phase in which all received eliglustat. Duration on eliglustat ranged from 2 to 5 years, depending on timing of enrollment (which spanned 2 years), treatment group to which patients were randomized, and whether they lived in the United States when commercial eliglustat became available. Here we report long-term safety and efficacy of eliglustat for 157 patients who received eliglustat in the ENCORE trial; data are available for 46 patients who received eliglustat for 4 years. Mean hemoglobin concentration, platelet count, and spleen and liver volumes remained stable for up to 4 years. Year to year, all four measures remained collectively stable (composite endpoint relative to baseline values) in ≥85% of patients, as well as individually in ≥92%. Mean bone mineral density Z-scores (lumbar spine and femur) remained stable and were maintained in the healthy reference range throughout. Eliglustat was well-tolerated over 4 years; 4 (2.5%) patients withdrew due to adverse events that were considered related to the study drug. No new or long-term safety concerns were identified. Clinical stability assessed by composite and individual measures was maintained in adults with Gaucher disease type 1 treated with eliglustat who remained in the ENCORE trial for up to 4 years.The ENCORE trial was funded and conducted by Sanofi Genzyme

War, Taxes and Borders: How Beer Created Belgium

The present-day border between Belgium and the Netherlands traces back to the separation of the Low Countries after the Dutch Revolt (1566-1648) against Spanish rule. The capacity to finance war expenditures played a central role in the outcome of this conflict. Excise taxes on beer consumption were the single largest income source in Holland, the leading province of the Dutch Republic. Beer taxes thus played a crucial role in financing the Dutch Revolt which led to the separation of the Low Countries and, eventually, the creation of Belgium

GROWTH AND DEVELOPMENT OF PAEDIATRIC PATIENTS WITH BETA-THALASSAEMIA TREATED WITH DEFERASIROX FOR UP TO 5 YEARS

WOS: 000496828404088

Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: Efficacy and safety during 5 years' follow-up

PubMedID: 21628399Patients with ß-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ? 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ? 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ? 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ? 4 years'exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with ß- thalassemia suggests treatment for ? 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials-.gov as #NCT00171210. © 2011 by The American Society of Hematology

Risk sharing with the monarch : contingent debt and excusable defaults in the age of Philip II, 1556–1598

Contingent sovereign debt can create important welfare gains. Nonetheless, there is almost no issuance today. Using hand-collected archival data, we examine the first known case of large-scale use of state-contingent sovereign debt in history. Philip II of Spain entered into hundreds of contracts whose value and due date depended on verifiable, exogenous events such as the arrival of silver fleets. We show that this allowed for effective risk sharing between the king and his bankers. The existence of state-contingent debt also sheds light on the nature of defaults—they were simply contingencies over which Crown and bankers had not contracted previously

Leucemia linfoblástica aguda pediátrica, evaluación de enfermedad mínima residual

Minimal residual disease (MRD) has proven to be an independent predictor for risk of relapse, allowing the adequacy of treatment according to risk groups.Between June 2010 and May 2019, 137 patients were evaluated with diagnosis of acute lymphoblastic leukemia treated using the ALLIC BFM-GATLA 2010 protocol. Evaluation at day 15 was used as indicator to stratify risk groups.The cut-off used for MRD on day 15 was 0.1%. Although MRD > 0.1% (87 patients, 63%) was associated with risk and relapse, neither overall survival (OS) nor disease-free survival (DFS) has shown a significance correlation. Moreover, MRD at day 33 > 0.05% (20 patients) was highly associated with risk, relapse, OS and DFS. OS at month 24 for MRD day 33 negative/day 72 negative was 88%, MRD at day 33 positive/at day 72 negative was 71% and MRD at day 33 positive/at day 72 positive was 40% (p= 0.001).DFS at month 24 for MRD at day 33 negative/at day 72 negative was 89%, MRD at day 33 positive/at day 72 negative was 61% and MRD at day 33 positive/at day 72 positive was 40% (p= 0.0001).The MRD at day 33 with 0.05% or higher was the only that shows association with relapse (p 0.02),hazard risk 4,1 (IC 95 1.72-10.055) which suggests that MRD day 33 positive increases 4 times the risk of relapse.La enfermedad mínima residual (EMR) demostró ser un factor pronóstico independiente de riesgo de recaída, permitiendo la adecuación del tratamiento según grupos de riesgo(1). Entre junio de 2010 y mayo de 2019 se evaluaron 137 pacientes (p) pediátricos con diagnóstico de novo de leucemia linfoblástica aguda (LLA), tratados de acuerdo al protocolo ALLIC BFM-GATLA 2010, incluyendo la EMR al día 15 para estratificar grupos de riesgo. El punto de corte utilizado para definir EMR al día 15 positiva fue 0.1 %. La EMR al día 15 > 0.1% (87 p, 63%) se asoció con recaídas, no así con SLE y SG. La EMR al día 33 > 0,05 (20 p) se asoció significativamente con riesgo, recaída, SG y SLE. La SG a 24 meses de pacientes EMR al día 33 (-)/al día 72 (-) fue 88%, EMR al día 33 (+)/al día 72 (-) 71% y EMR al día 33 (+)/al día 72 (+) 40% (p= 0.001). La SLE a 24 meses fue 89%, 61% y 40% (p= 0.000) para los mismos grupos de pacientes. La EMR al día 33 ≥ 0.05 fue la única variable independiente asociada a recaída (p= 0,02), hazard risk (HR) 4.1 (IC 95 1.72-10.055), lo que muestra que tener EMR + al día 33 aumenta 4 veces el riesgo de recaída