The Clinical Course of Untreated Gaucher Disease in 22 Patients Over 10 Years: Hematological and Skeletal Manifestations.
Notice bibliographique
Résumé
Abstract Gaucher disease (GD) is a lysosomal storage disorder characterized by anemia and thrombocytopenia, hepatosplenomegaly, and skeletal involvement. The management of Gaucher disease was improved by the development of enzyme replacement therapy (ERT). However, the bone response to ERT is generally slower compared to other clinical manifestations. Some have recommended the early use of ERT to prevent the development of severe skeletal complications. Because we have access to over 30 untreated patients in Ontario, we questioned the extent to which the bony complications progress in severity over a long period of time. We examined retrospectively the natural history of GD and the extent of skeletal manifestations in 22 untreated type 1 GD adult patients (mean age 49 ± 3.3, range of 20–81 years). Ten patients were N370S homozygotes and twelve were compound heterozygotes. The patients were followed for a median of 9.5 years (range of 3 to 16 years). Assessments included complete blood counts (CBC); levels of angiotensin converting enzyme (ACE), ferritin, and chitotriosidase; liver and spleen volumes; and occurrences of bony complications. Dual Energy X-ray Absorptiometry (DEXA), Magnetic Resonance Imaging (MRI) of femurs, skeletal survey, and plain radiography were utilized to assess bony complications in 21 patients. Hemoglobin (Hb) concentration did not significantly change over time (mean baseline concentration of 12.8 ± 0.27 g/dL vs mean recent concentration of 12.6 ± 0.37 g/dL, p = 0.65). Mean platelet count also remained relatively stable over time (mean baseline count of 138 ± 13 × 109/L vs mean recent count of 138.5 ± 18 × 109/L, p = 0.98). Mean ferritin and ACE concentrations were elevated and were stable over time. Liver volumes decreased over time (mean baseline liver volume of 1.2 × normal (N) vs mean recent volume of 1.06 × N, p = 0.27) and 6/21 (29%) patients had moderate hepatomegaly (liver volume ≥ 1.25 × N). Spleen volumes remained stable over time (mean baseline spleen volume of 6.4 × N vs mean recent volume of 5.1 × N, p = 0.56). None of the changes was statistically significant. Three of 19 (15.8 %) patients had moderate splenomegaly (spleen volume ≥ 5 × N), 2/19 (10.5%) had severe splenomegaly (spleen volume ≥ 15 × N), and 2/22 (9%) had splenectomy. The most common skeletal manifestations were infiltration of the bone marrow in 15/21 (71%) patients followed by osteopenia in 14/21 patients (67%), and infarctions in 6/21 (29%) patients. Other bony complications included osteoporosis in 3/21 (14%), avascular necrosis (AVN) in the left knee and femur in 1/21 (5%), and osteolysis in 1/21 (5%) patients; there were no cases of fractures. Three of 21 (14%) patients developed new infarcts (2N370S homozygous patients) over time, 1/21 (5%) developed AVN, and 4/21 (19%) had an increase in the degree of osteopenia. There were no significant differences observed between the N370S homozygous and compound heterozygous patients. Although GD and its skeletal complications progress in severity in some patients, our results suggest that GD complications including bony disease may stabilize over time. Therefore, early use of ERT may not be necessary in all type 1 GD patients.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».