| 1. |
- Hakkarainen, M, et al.
(author)
-
The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia
- 2023
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:23, s. 2853-2866
-
Journal article (peer-reviewed)abstract
- Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
|
|
| 2. |
- Hakkarainen, M, et al.
(author)
-
The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia
- 2023
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:23, s. 2853-2866
-
Journal article (peer-reviewed)abstract
- Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
|
|
| 3. |
- Biskup, E, et al.
(author)
-
Awareness of sex and gender dimensions among physicians: the European federation of internal medicine assessment of gender differences in Europe (EFIM-IMAGINE) survey
- 2022
-
In: Internal and emergency medicine. - : Springer Science and Business Media LLC. - 1970-9366 .- 1828-0447. ; 17:5, s. 1395-1404
-
Journal article (peer-reviewed)abstract
- Sociocultural gender is a complex construct encompassing different aspects of individuals’ life, whereas sex refers to biological factors. These terms are often misused, although they impact differently on individuals’ health. Recognizing the role of sex and gender on health status is fundamental in the pursuit of a personalized medicine. Aim of the current study was to investigate the awareness in approaching clinical and research questions on the impact of sex and gender on health among European internists. Clinicians affiliated with the European Federation of Internal Medicine from 33 countries participated to the study on a voluntary basis between January 1st, 2018 and July 31st, 2019. Internists’ awareness and knowledge on sex and gender issues in clinical medicine were measured by an online anonymized 7-item survey. A total of 1323 European internists responded to the survey of which 57% were women, mostly young or middle-aged (78%), and practicing in public general medicine services (74.5%). The majority (79%) recognized that sex and gender are not interchangeable terms, though a wide discrepancy exists on what clinicians think sex and gender concepts incorporate. Biological sex and sociocultural gender were recognized as determinants of health mainly in cardiovascular and autoimmune/rheumatic diseases. Up to 80% of respondents acknowledged the low participation of female individuals in trials and more than 60% the lack of sex-specific clinical guidelines. Internists also express the willingness of getting more knowledge on the impact of sex and gender in cerebrovascular/cognitive and inflammatory bowel diseases. Biological sex and sociocultural gender are factors influencing health and disease. Although awareness and knowledge remain suboptimal across European internists, most acknowledge the underrepresentation of female subjects in trials, the lack of sex-specific guidelines and the need of being more informed on sex and gender-based differences in diseases.
|
|
