scholarly journals Computational Analysis Model Applied to Spanish Gaucher Registry Data

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2323-2323
Author(s):  
Marcio M Andrade-Campos ◽  
Laura Lopez de Frutos ◽  
Jorge J Cebolla ◽  
Blanca Medrano-Engay ◽  
Mercedes Roca-Espiau ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Bone Disease ◽  
Gaucher Disease ◽  
Computer Applications ◽  
Age At Diagnosis ◽  
Strong Impact ◽  
The Impact

Introduction Type 1 Gaucher disease (GD)(OMIM # 230800), has a pan-ethnic distribution, in Spain its prevalence is about 1/100,000. Since more than twenty years the impact of therapies in the awareness of the disease is changing the characteristics and expectations of patients. The Spanish Gaucher disease Registry (SGDR) is working since 1993 and compiled demographic, clinical, genetic, analytical and imaging data about 360 type 1 GD Spanish patients. The application of new high computing capacity and powerful network analysis to analyze the registered data could provide a visualization tool and allows to extract knowledge from complex and very numerous relationships. The objective of this analysis is to discover useful ideas and new correlations to predict the risk of developing late complications and to extract knowledge of complex and very numerous relationships. Patients & Methods From 416 patients included in the SGDR we have selected 358 with more than 70% of data and follow-up. GD type 2 patients have been excluded. The variables included in the database at diagnosis: demographic data and the clinical, analytical and imaging information at diagnostic and during the treatment follow-up as well as comorbidities. With Kampal Data Solutions, a spin-off company of the University of Zaragoza dedicated to the development of computer applications and advanced data analytics, this company has experience in the homogenization of information and in the elaboration of classic and advanced statistics projects, as well as in the visualization of said information complex network techniques and the relationship between variables and model designs.Variables:Birthdate, age at diagnosis, gender, death date, severity category of disease (mild, moderate, severe), concomitant diseases, Parkinson disease in relatives, liver volume, spleen volume, spleen removal, bone disease, S-MRI, DEXA, chitotriosidase, CCL18/PARC, lyso Gb1, B12 vitamin level, iron concentration, ferritin, cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, AST, ALT, GGT, acid phosphatase, bilirubin, hemoglobin concentration, Hsc, WBC count, platelets count, serum gammaglobulin fraction, IgG, IgA, IgM, GBA activity, GBAgenotype, CHIT1genotype, age to start therapy, type of therapy (ERT, SRT), new bone crisis or joint replacement, development of malignancies or Parkinson disease. Results: The 358 subjects were mostly GD1 (340 vs 18 GD3), 18% were splenectomized and 39% have advanced bone disease and bone complications. Most of the patients have a complex heterozygous genotype (81% vs 19% homozygous). 47% of patients were diagnosed before 2,000 and 10% die before this study. Most of them are receiving ERT (54%). About comorbidities, 4% of patients developed MGUS or Parkinson disease and 6% malignant neoplasias. The main results have founded a significant correlation between skeletal complications and impaired and spleen removal (p=0.0005); this fact confirm previous reports. In this study a low IgA serum level shows a significant correlation with severe bone disease(p=0.0000), and with the incidence of new bone crisis during long term ERT. A IgG increase was related to the development of neoplasia. There were two more important factors that we have found; the age at diagnosis and the age to start therapy. Comments: Registries are key resources to help increasing timely and accurate diagnosis, improving patient's management, tailoring treatments, facilitating clinical trials, supporting healthcare planning and speeding up research. This is the very first attempt to establish a correlation network among different biomarkers and clinical characteristics in a national base cohort. As has been hypothesized seems that the impairment of immune system has a strong impact in long term complications, in our study the humoral immunity dysfunction pops up as an important factor. Despite of our short cohort, the quality of data is accurate and can reflect the own Spanish Gaucher disease characteristics. Currently we are working in the design of algorithms to help to predict patient outcomes. Disclosures No relevant conflicts of interest to declare.

Long-term follow-up of 103 untreated adult patients with type 1 Gaucher disease

2019 ◽  
Vol 126 (2) ◽  
pp. S49
Author(s):  
Tama Dinur ◽  
Ari Zimran ◽  
Michal Becker Cohen ◽  
David Arkadir ◽  
Claudia Cozma ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Adult Patients ◽  
Long Term Follow Up ◽  
Type 1 Gaucher Disease

scholarly journals Long Term Follow-Up of 103 Untreated Adult Patients with Type 1 Gaucher Disease

2019 ◽  
Vol 8 (10) ◽  
pp. 1662 ◽  
Author(s):  
Dinur ◽  
Zimran ◽  
Becker-Cohen ◽  
Arkadir ◽  
Cozma ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Substrate Reduction Therapy ◽  
Type I ◽  
Specific Therapy ◽  
Substrate Reduction ◽  
Long Term Follow Up ◽  
Disease Specific

The introduction of disease-specific therapy for patients with type I Gaucher disease (GD1) was a revolution in the management of patients, but not without cost. Thus, the management of mildly affected patients is still debated. We herein report a long-term follow-up (median (range) of 20 (5–58) years) of 103 GD1 patients who have never received enzymatic or substrate reduction therapy. The median (range) platelet count and hemoglobin levels in last assessment of all but six patients who refused therapy (although recommended and approved) were 152 (56–408) × 103/mL and 13.1 (7.6–16.8) g/dL, respectively. Most patients had mild hepatosplenomegaly. Nine patients were splenectomized. No patient developed clinical bone disease. The median (range) lyso-Gb1 levels at last visit was 108.5 (8.1–711) ng/mL; lowest for patients with R496H/other and highest for patients refusing therapy. This rather large cohort with long follow-up confirms that mildly affected patients may remain stable for many years without GD-specific therapy. The challenge for the future, when newborn screening may detect all patients, is to be able to predict which of the early diagnosed patients is at risk for disease-related complications and therefore for early treatment, and who may remain asymptomatic or minimally affected with no need for disease-specific therapy.

Tyrosinemia Type I

2016 ◽  
Author(s):  
David Cassiman ◽  
Wouter Meersseman
Keyword(s):  
Bone Disease ◽  
Type I ◽  
Long Term Effects ◽  
Liver Malignancy ◽  
Tyrosinemia Type I ◽  
Plasma Tyrosine ◽  
Rare Metabolic Disorder

Tyrosinemia type 1 (HT-1) is a rare metabolic disorder affecting degradation pathways of the amino acid tyrosine. HT-1 presents with liver, kidney and/or bone disease and can cause acute porphyria attacks. Biochemical diagnosis is made by measuring raised plasma tyrosine and detection of succinylacetone in urine. Long-term management with diet and nitisinone leads to excellent short term results, but since long term effects are largely unknown, life-long treatment and follow-up for liver malignancy, bone disease and kidney disease seem necessary. HT-1 is treatable by liver transplantation.

Maintenance Efficacy of Low Dose Imiglucerase for Gaucher Disease

2020 ◽  
Author(s):  
Zhengqing Qiu ◽  
Baohui Zhang ◽  
Yuhang Song ◽  
Hongbing Zhang ◽  
Yuting Wu
Keyword(s):  
Gaucher Disease ◽  
Low Dose ◽  
Standard Dose ◽  
Mineral Density ◽  
Recommended Treatment ◽  
Type 3 ◽  
Term Maintenance

Abstract Background Imiglucerase is the recommended treatment for Gaucher disease (GD), a hereditary metabolic disease. In high risk adults and all children, the minimum recommended dose for long-term maintenance is 30 U/kg/2 weeks. However, the extremely high cost of this enzyme largely hinders its clinical use. The minimal maintenance dose of imiglucerase has thus been a subject of debate. We aimed to analyze the long-term maintenance outcomes of imiglucerase at dosage < 20 U/kg/2 weeks after standard dose. Methods Seventeen patients with GD type 1 or GD type 3 were enrolled for analysis. We evaluated maintenance efficacy of imiglucerase on hemoglobin, platelet, visceral volumes and bone conditions during the 7-year follow-up. Results Parameters on hemoglobin, platelet, liver, and spleen volumes of all patients were stabilized or improved. Seven out of 14 patients showed bone mineral density improvement. Three out of 16 patients showed worse bone pain; 6 out of 15 patients showed worse Erlenmeyer flask; 6 out of 15 patients showed worse bone infarction; 1 out of 16 patients showed worse marrow infiltration and 3 out of 15 patients showed worse osteonecrosis. Conclusions Imiglucerase less than 20 U/kg/2 weeks is enough to maintain blood and visceral parameters, but is not sufficient to stabilize skeletal conditions.

scholarly journals OUTCOME AND TOXICITY PATTERNS IN CHILDREN AND ADOLESCENTS WITH NON-HODGKIN LYMPHOMA: A SINGLE INSTITUTION EXPERIENCE

2018 ◽  
Vol 10 (1) ◽  
pp. e2018020 ◽  
Author(s):  
Paola Angelini ◽  
Laura Rodriguez ◽  
Mohammed Zolaly ◽  
Ahmed Naqvi ◽  
Sheila Weitzman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Hodgkin Lymphoma ◽  
Survival Rates ◽  
Age At Diagnosis ◽  
Single Institution ◽  
Non Hodgkin Lymphoma ◽  
Sick Children ◽  
The Impact

Background: The incidence and biology of non-Hodgkin lymphoma (NHL) vary according to age. Some data suggest that the impact of age in pediatric and adolescent NHL patients depends on the histological subtype. Objectives: We aimed to analyze the impact of age at diagnosis on clinical characteristics and treatment-related toxicity in children and adolescents with NHL.Methods: Retrospective review of medical records of children and adolescents diagnosed with NHL at the Hospital for Sick children, Toronto, between January 1995 and December 2008.Results: 164 children were diagnosed with NHL during the study period, with a median age at diagnosis of 10 years. With a median follow-up of 6.2 years, 5-year OS in patients aged <15 and 15-18 years was 89± 2% vs 82% ± 6%, respectively (P = 0.30), and 5-year EFS was 84% ± 3% vs. 77% ± 7%  (P= 0.37). In Burkitts lymphoma (BL) and lymphoblastic lymphoma (LL) there was a trend towards better outcomes in children compared to adolescents, with EFS of  91% ± 4% vs. 75% ± 15%, respectively in BL (P= 0.17),  and 82% ± 7% vs. 51.4% ± 2% respectively in LL (P= 0.16). Late effects occurred in 21 patients (12.8%).Conclusions: Children with NHL aged < 15 years tend to have better survival rates and less long-term toxicity than adolescents aged 15-18 years.

Momelotinib Therapy for Myelofibrosis: Impact on Long-Term Survival and Genotype Correlations

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4062-4062
Author(s):  
Ayalew Tefferi ◽  
Ramy Abdelrahman ◽  
Christy Finke ◽  
Terra L. Lasho ◽  
Kebede H. Begna ◽  
...  
Keyword(s):  
Median Survival ◽  
Mayo Clinic ◽  
Study Entry ◽  
Control Group ◽  
Term Survival ◽  
Mutational Status ◽  
The Impact

Abstract Background: In a previously published phase-1/2 study, momelotinib (a JAK 1/2 inhibitor) induced 53% anemia, 39% spleen and >50% constitutional symptoms response rates in patients with myelofibrosis (MF) (Pardanani A, et al. Leukemia. 2013;27:1322). The particular study included 100 patients from the Mayo Clinic who experienced 43% spleen and 44% anemia response rates (Pardanani et al. Leukemia. 2015;29:741); CALR and ASXL1 mutations independently predicted spleen but not anemia response. In the current study, we examined the impact of momelotinib therapy on DIPSS-plus- and molecular risk-adjusted survival. Methods: The current study represents sponsor-independent analysis of long-term survival among 100 consecutive Mayo Clinic patients who received momelotinib therapy as part of a larger (n =166) phase-1/2 study (NCT00935987). Safety and efficacy data from NCT00935987, as well as protocol design and drug dosing and schedule, have already been formally reported and not reiterated here (Pardanani A, et al. Leukemia. 2013;27:1322; Pardanani A, et al. Leukemia. 2015;29:741; Abdelrahman RA, et al. BJH. 2015;169:77). All statistical analyses considered clinical and laboratory parameters obtained at the time of entry to study. Survival analysis was considered from the date of study entry to date of death or last contact. Cox proportional hazard regression model was used for multivariable analysis of survival. Samples from time of study entry were used for mutation screening. Driver mutations were classified into two prognostically-relevant groups: CALR type 1/type 1-like (favorable) vs all others including CALR type 2/type 2-like, JAK2, MPL and triple-negative (unfavorable). Results: 100 patients with MF (median age 66 years; 58% males) were treated at the Mayo Clinic between 11/20/09 and 11/10/10; 64 patients had primary MF, 22 post-polycythemia vera MF and 14 post-essential thrombocythemia MF. Baseline data: DIPSS-plus risk distribution was 63% high, 36% intermediate-2 and 1% intermediate-1 (JCO 2011;29:392); for the purposes of the current analysis, the single patient with intermediate-1 risk disease was included in the intermediate-2 category. 54 (54%) patients displayed abnormal karyotype. 73 (73%) patients harbored JAK2, 16 (16%) CALR, 7 MPL and 4 "triple-negative". Among the 16 CALR -mutated cases, 13 were classified as "type 1/type 1-like". 94 patients were screened for ASXL1 mutations; 41 (44%) were mutated. Follow-up data was updated in July 2015, providing a minimum follow-up of over 4.5 years since the last patient registration on the protocol. At a median follow-up of 3.2 years, 67 (67%) deaths and 13 (13%) leukemic transformations were documented. Median survival from the time of study entry was 3.2 years and was affected by driver mutation prognostic groups (median survival "not reached" for "favorable" vs 3 years for "unfavorable"; p=0.01), ASXL1 mutational status (median survival 3.9 years in unmutated vs 2.5 years in mutated; p=0.02) and DIPSS-plus risk stratification (median survival 2.6 years in high-risk vs 4 years in intermediate-2 risk; p=0.07). In order to assess the impact of momelotinib on long-term outcome, we compared survival of the study cohort (n =100) with that of 442 consecutive Mayo Clinic patients with high or intermediate-2 risk primary MF (median age 67 years; 66% males). There was no significant difference between this control group of PMF patients versus the momelotinib patient cohort in distribution of age (p=0.56), sex (p=0.12), JAK2/CALR/MPL mutational status (p=0.41) or ASXL1 mutational status (p=0.9); however, the momelotinib cohort had a higher fraction of patients with DIPSS-plus high-risk disease (63% vs 47%; p=0.004). Overall survival was similar between the momelotinib cohort and the control group of PMF patients who were not treated with momelotinib (Figure 1; p=0.99); the difference in survival remained not significant during multivariable analysis that included risk stratification by DIPSS-plus (p=0.32), "favorable" vs "unfavorable" driver mutational status (p=0.78) or ASXL1 mutational status (Figure 2; p=0.61). Conclusions: In the current long-term study, we could not demonstrate a survival impact from momelotinib therapy in myelofibrosis. Although adjusted for clinical and molecular risk status, our study is retrospective and cannot be relied upon to discount marginal survival effect. Disclosures Al-Kali: Novartis: Research Funding. Pardanani:Stemline: Research Funding.

Age and time course of long-term motor and nonmotor complications in Parkinson disease

Neurology ◽  
2018 ◽  
Vol 92 (2) ◽  
pp. e148-e160 ◽  
Author(s):  
Stéphane Prange ◽  
Teodor Danaila ◽  
Chloé Laurencin ◽  
Catherine Caire ◽  
Elise Metereau ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Impulse Control ◽  
Time Course ◽  
Disease Duration ◽  
Freezing Of Gait ◽  
Impulse Control Disorders ◽  
Motor Fluctuations ◽  
Age At Diagnosis

ObjectiveTo determine the time course of hazard for motor and nonmotor milestones of Parkinson disease (PD) in the long term and to investigate whether risk scales nonlinearly with time is instrumental in identifying changes in pathological processes and evaluating disease-modifying therapies in PD.MethodsOutpatients with PD at the Lyon University Movement Disorders Center were evaluated for 7 clinical milestones in this retrospective cohort study, encompassing 4 domains of PD progression: (1) motor (motor fluctuations, dyskinesias); (2) axial (postural instability and falls, freezing of gait); (3) neuropsychiatric (impulse control disorders, hallucinations); and (4) cognitive (dementia) complications. For each complication, we estimated the outcome-specific hazard using parsimonious smooth parametric Poisson regression models allowing for nonlinear scaling over disease duration, age at diagnosis, current age, and their interaction.ResultsA total of 1,232 patients with PD experienced 1,527 disease-related complications in up to 12 years of follow-up. Specific to each complication, hazard rates increased dramatically starting from diagnosis and were highest for motor fluctuations and lowest for dementia up to 6 years after diagnosis in patients aged 65 years at diagnosis. Nonlinear patterns indicated dramatic changes in the course of PD after 5 years and predicted more severe axial prognosis after 70 years and for motor fluctuations, dyskinesias, and impulse control disorders before 60 years at diagnosis.ConclusionTime course of motor and nonmotor milestones in PD is determined by disease duration and age at diagnosis in nonlinear patterns and their interaction. This indicates disease- and age-specific thresholds across the multiple neurodegenerative processes accumulating in PD at different paces.

A form of Autoimmune Diabetes in Adults Named LADA – An Update on Essential Features and Controversies

2019 ◽  
Vol 15 (3) ◽  
pp. 172-173 ◽  
Author(s):  
Valdemar Grill ◽  
Bjørn O. Åsvold
Keyword(s):  
Genetic Background ◽  
Clinical Utility ◽  
Autoimmune Diabetes ◽  
Classical Type ◽  
Phenotypic Characteristics ◽  
Latent Autoimmune Diabetes ◽  
The Impact

Latent Autoimmune Diabetes in the Adult, LADA has been investigated less than “classical” type 1 and type 2 diabetes and the criteria for and the relevance of a LADA diagnosis has been challenged. Despite the absence of a genetic background that is exclusive to LADA, this form of diabetes displays phenotypic characteristics that distinguish it from other forms of diabetes. LADA is heterogeneous in terms of the impact of autoimmunity and lifestyle factors, something that poses problems as to therapy and follow-up perhaps particularly in those with marginal positivity. Yet, there appears to be clear clinical utility in classifying individuals as LADA.

scholarly journals A Follow-Up Study of a European IgG4-Related Disease Cohort Treated with Rituximab

2021 ◽  
Vol 10 (6) ◽  
pp. 1329
Author(s):  
Johanna Backhus ◽  
Christian Neumann ◽  
Lukas Perkhofer ◽  
Lucas A Schulte ◽  
Benjamin Mayer ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Activity ◽  
Inflammatory Disorder ◽  
International Consensus ◽  
Steroid Pulse ◽  
Related Disease ◽  
Igg4 Related Disease

Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. Methods: We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. Results: Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. Conclusion: RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6–9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy.

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