Assessing the test-retest reliability and smallest detectable change of the Haemophilia Activities List.

INTRODUCTION: The Haemophilia Activities List (HAL) is a preferred instrument to measure self-reported limitations in activities in persons with haemophilia (PWH). Information on reliability and interpretability of HAL scores is lacking. AIM: To examine the test-retest reliability and smallest detectable change (SDC) of the HAL in adult PWH. METHODS: Fifty adult (≥18 years) persons with mild to severe haemophilia completed the HAL (42 items, 7 domains, optimum 100) at baseline (T0) and 3-4 weeks later (T1). The intraclass correlation coefficient (ICC) and SDC were calculated for sum and component scores. RESULTS: Fifty persons with haemophilia were included (median age 49 years; 92% haemophilia A; 70% severe haemophilia). The median (interquartile ranges) HAL sum score was 77 (62 to 99) at T0 and 81 (64 to 98) at T1. Reliability was good with ICCs for sum and component scores >0.9. The SDC for the sum score was 10.2, for the upper extremity component score 9.2, for the basic lower extremity component score 16.7 and for the complex lower extremity component score 13.4. CONCLUSION: The HAL has a good reliability for the sum and component scores. Score changes of the normalized sum HAL score greater than the SDC 10.2 indicate that the change was not a result of measurement error.

Metastatic Patterns of Duodenopancreatic Neuroendocrine Tumors in Patients With Multiple Endocrine Neoplasia Type 1.

Patients with multiple endocrine neoplasia 1 syndrome (MEN1) often develop multifocal duodenopancreatic neuroendocrine tumors (dpNETs). Nonfunctional pancreatic neuroendocrine tumors (PanNETs) and duodenal gastrinomas are the most frequent origins of metastasis. Current guidelines recommend surgery based on tumor functionality, size ≥2 cm, grade or presence of lymph node metastases. However, in case of multiple primary tumors it is often unknown which specific tumor metastasized. This study aims to unravel the relationship between primary dpNETs and metastases in patients with MEN1 by studying endocrine differentiation. First, it was shown that expression of the endocrine differentiation markers ARX and PDX1 was concordant in 18 unifocal sporadic neuroendocrine tumors (NETs) and matched metastases. Thereafter, ARX, PDX1, Ki67 and gastrin expression, and the presence of alternative lengthening of telomeres were determined in 137 microscopic and macroscopic dpNETs and 36 matched metastases in 10 patients with MEN1. ARX and PDX1 H-score clustering was performed to infer relatedness. For patients with multiple metastases, similar intrametastases transcription factor expression suggests that most metastases (29/32) originated from a single NET of origin, while few patients may have multiple metastatic primary NETs. In 6 patients with MEN1 and hypergastrinemia, periduodenopancreatic lymph node metastases expressed gastrin, and clustered with minute duodenal gastrinomas, not with larger PanNETs. PanNET metastases often clustered with high grade or alternative lengthening of telomeres-positive primary tumors. In conclusion, for patients with MEN1-related hypergastrinemia and PanNETs, a duodenal origin of periduodenopancreatic lymph node metastases should be considered, even when current conventional and functional imaging studies do not reveal duodenal tumors preoperatively.