Orphanet Journal of Rare Diseases最新文献

{"title":"Experiences of mothers of long-term surviving patients with cerebral adrenoleukodystrophy: a qualitative study.","authors":"Yuta Koto, Nozomi Hadano, Norio Sakai","doi":"10.1186/s13023-024-03424-2","DOIUrl":"10.1186/s13023-024-03424-2","url":null,"abstract":"<p><strong>Background: </strong>Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder. Its cerebral form presents as a learning and behavioral disorder that, if untreated, leads to rapid neurological regression, disability, and death within 10 years of diagnosis. Therefore, the disease significantly impacts patients' quality of life, making quality of life assessment crucial for effective medical treatment and care. However, no disease-specific quality of life scale exists for ALD. Therefore, we conducted qualitative research to determine the experiences of patients and their families as a preliminary step toward developing one.</p><p><strong>Results: </strong>Four mothers of patients with cerebral ALD were interviewed. Based on classification using the qualitative content analysis method, the verbatim transcripts were grouped into four themes: support needs for patients, support needs for families, the impact of treatment, and challenges within support systems.</p><p><strong>Conclusions: </strong>Support for patients and family members is required after ALD is diagnosed. In addition to addressing symptoms, daily life support and caregiving burden should be considered. Furthermore, several challenges and opportunities exist for improving treatment and support systems. Therefore, combining appropriate supporters and support systems according to the progressive and hereditary characteristics of ALD is crucial.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma.","authors":"Hua Yuan, Yaxi Wang, Ning Li, Lingying Wu, Hongwen Yao","doi":"10.1186/s13023-024-03415-3","DOIUrl":"10.1186/s13023-024-03415-3","url":null,"abstract":"<p><strong>Objective: </strong>To determine the clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma (uLMS).</p><p><strong>Methods: </strong>We conducted a retrospective cohort study to evaluate the clinical characteristics and survival of women with recurrent uLMS and identify prognostic factors.</p><p><strong>Results: </strong>Overall, 71 patients with first recurrence of uLMS were included in our study. 19 patients (26.8%) received systemic therapy and 52 patients (73.2%) received secondary cytoreductive surgery (SCS). In SCS subgroup (n = 52), a complete resection with no residual disease was performed in 47 patients (90.4%). 38.5% (20/52) patients received non-reproductive organ surgeries. 10 (19.2%) patients had received thoracic surgery because of lung-only recurrence. Bowel, bladder surgery was performed in 8 (15.4%), 3 (5.8%) patients, respectively. 1 (1.9%) patient had received liver surgery. The median follow-up duration was 38.7 months (range: 2.7-317.6 months). 41 (57.7%) patients died during follow-up. 5-year OS for the entire cohort was 52.9%. Patients experienced first recurrence after initial diagnoses within 12 months (n = 24) had a worse 5-year OS than those after 12 months (n = 47) (17.0% vs. 69.1%, P < 0.001). 5-year OS for the SCS and non-SCS subgroup was 62.0% and 28.0%, respectively (P < 0.001). Multivariate analysis showed time to fist recurrence within 12 months (HR = 4.60, 95% CI: 1.49-14.4, P = 0.008) was an independent predictor of decreased 5-year OS in SCS subgroup.</p><p><strong>Conclusions: </strong>SCS is an important treatment choice for recurrent uLMS and seems to have benefited patients. Time to fist recurrence within 12 months is an independent predictor of decreased 5-year OS in SCS subgroup.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring molecular spectrum in thai patients with maple syrup urine disease: unveiling a common variant.","authors":"Panisara Lakkhana, Thipwimol Tim-Aroon, Arthaporn Khongkraparn, Saisuda Noojarern, Parith Wongkittichote, Khunton Wichajarn, Chulaluck Kuptanon, Boonchai Boonyawat, Kanya Suphapeetiporn, Karn Wejaphikul, GoHun Seo, Duangrurdee Wattanasirichaigoon","doi":"10.1186/s13023-024-03411-7","DOIUrl":"10.1186/s13023-024-03411-7","url":null,"abstract":"<p><strong>Background: </strong>Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by variants in any of the following genes: BCKDHA, BCKDHB, and DBT gene. Previous reports have highlighted a variety of common causing genes and variants among different ethnic groups affected by MSUD. This study is the first to describe the molecular characteristics, potential common variants, clinical phenotypes, and treatment outcomes of 20 Thai MSUD patients before the implementation of expanded newborn screening in Thailand.</p><p><strong>Results: </strong>A cross-sectional, multicenter study was conducted, including twenty Thai MSUD patients from 1997 to 2023. Most of the patients presented with classic neonatal onset (95%). The mortality rate was 20%, while global developmental delay was observed in 40% of the patients. Variants in the BCKDHB gene were detected in 85% (17/20) of the patients, while the BCKDHA gene accounted for 15% (3/20). The study identified the 11-kb deletion involving 5'UTR, exon 1, and intron 1 in the BCKDHB gene, from a position of g.80102385 to g.80113453 (NC_000006.12), accounting for 50% of all variants (20/40 alleles) in Thai MSUD patients. All patients with the 11-kb deletion in BCKDHB presented with the classic type. The gap-PCR for this common deletion was established in the study.</p><p><strong>Conclusion: </strong>This study is the first to describe the clinical and molecular spectrum of Thai MSUD patients before the implementation of expanded NBS. The 11-kb deletion involving exon 1 in the BCKDHB emerges as the most common variant among Thai individuals with MSUD. Furthermore, the gap-PCR test for detecting the 11-kb exon 1 deletion status holds the potential for integration into stepwise molecular analysis following positive expanded newborn screening.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis using next-generation sequencing and multiplex ligation probe amplification in Chinese aniridia patients.","authors":"Li Wang, Qingdan Xu, Wentao Wang, Xinghuai Sun, Yuhong Chen","doi":"10.1186/s13023-024-03388-3","DOIUrl":"10.1186/s13023-024-03388-3","url":null,"abstract":"<p><strong>Background: </strong>Congenital aniridia is a rare pan-ocular disease characterized by complete irideremia, partial iridocoloboma. The progressive nature of aniridia is frequently accompanied by secondary ocular complications such as glaucoma and aniridia-associated keratopathy, which can lead to severely impaired vision or blindness. The genetic basis of aniridia has been the subject of numerous studies, leading to the development of innovative therapeutic options based on PAX6 nonsense mutations. Specific knowledge of the genetics of aniridia has become increasingly important. To report the clinical features, elucidate the genetic etiology, and reveal the mutational spectrum of congenital aniridia in the Chinese population, sixty patients with congenital aniridia from 51 families were recruited. Candidate genes associated with developmental eye diseases were identified and analyzed using panel-based next-generation sequencing (NGS), and mutations were confirmed through polymerase chain reaction and Sanger sequencing. Multiplex ligation probe amplification (MLPA) of PAX6 and FOXC1 was performed to detect copy number variations in the patients without intragenic mutations.</p><p><strong>Results: </strong>Clinical examination revealed complete iris hypoplasia in 58 patients and partial iris hypoplasia in two patients. Additionally, two patients were diagnosed with Wilms' tumor-aniridia-genital anomalies-retardation syndrome and nephroblastoma. By combining panel-based NGS and MLPA, 43 intragenic mutations or deletions of PAX6, FOXC1, and BCOR were identified in 59 patients, including 33 point mutations (76.7%) in 43 patients and 10 deletions (23.3%) in 16 patients. The total detection rate was 98.3%. Phenotypic variation was observed between and within families.</p><p><strong>Conclusions: </strong>Variations in PAX6 and its adjacent regions were the predominant causes of aniridia in China. In addition to intragenic point mutations in PAX6, deletion of PAX6 or its adjacent genes is a common cause of congenital aniridia. Furthermore, FOXC1 is an important gene associated with congenital aniridia. The combination of panel-based NGS and MLPA significantly enhanced the detection rate of gene mutations in patients with congenital aniridia.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of clinical trials and guidelines for children and youth with mucopolysaccharidosis: outcome selection and measurement.","authors":"Alison H Howie, Kylie Tingley, Michal Inbar-Feigenberg, John J Mitchell, Kim Angel, Jenifer Gentle, Maureen Smith, Martin Offringa, Nancy J Butcher, Philippe M Campeau, Pranesh Chakraborty, Alicia Chan, Dean Fergusson, Eva Mamak, Peyton McClelland, Saadet Mercimek-Andrews, Aizeddin Mhanni, Zeinab Moazin, Cheryl Rockman-Greenberg, C Anthony Rupar, Becky Skidmore, Sylvia Stockler, Kednapa Thavorn, Alexandra Wyatt, Beth K Potter","doi":"10.1186/s13023-024-03364-x","DOIUrl":"10.1186/s13023-024-03364-x","url":null,"abstract":"<p><strong>Background: </strong>To inform the development of a core outcome set (COS) for children and youth with mucopolysaccharidoses (MPS), we aimed to identify all outcomes and associated outcome measurement instruments that are reported in recent clinical trials and recommended as measurements in clinical management guidelines.</p><p><strong>Methods: </strong>To identify English-language clinical trials and guidelines pertaining to MPS published between 2011 and mid-2021, we applied a comprehensive peer-reviewed search strategy to relevant databases and registers on May 16, 2021. Two reviewers independently screened retrieved citations and then full-text articles to determine eligibility for inclusion. From articles meeting inclusion criteria, we extracted details of the study design, population, intervention, and comparator, along with verbatim outcomes and associated outcome measurement instruments. Outcomes were organized into domains within five a priori core areas: life impact, pathophysiological manifestations, growth and development, resource use, and death. We conducted descriptive analyses at the study level, grouping articles arising from the same study.</p><p><strong>Results: </strong>From 2593 unique citations, 73 articles from 61 unique studies were included in the review, pertaining to all MPS subtypes except for exceptionally rare subtypes. Eighty-four unique outcomes were reported across the studies, 33 (39%) of which were reported by three or fewer studies. Most outcomes (55; 65%) were in the pathophysiological manifestations core area, followed by life impact (17; 20%) and growth and development (10; 12%); one outcome each pertained to resource use and death. The most frequently reported outcomes were general adverse events (45; 74%), immune-related adverse events (39; 64%), and urinary glycosaminoglycans (38; 62%). Substantial variability existed in the reporting of outcome measurement instruments. Some differences in outcome reporting were observed by MPS subtype and publication year.</p><p><strong>Discussion: </strong>Outcomes reported in clinical trials and guidelines for MPS in children and youth vary considerably and largely focus on pathophysiological manifestations. A COS is needed to standardize the selection and measurement of meaningful outcomes across future studies. We will present the outcomes identified in this review to knowledge users as part of a consensus process to select the most critical outcomes for inclusion in the COS. Trial Registration The protocol for this study was registered in PROSPERO (CRD42021267531) and in the COMET Database.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncertainties in evaluating the health-related quality of life and disease burden of people with rare diseases and their caregivers in NICE HST submissions.","authors":"Alissa Looby, Amy Dymond, William Green, Hannah Wentzel, Kinga Malottki","doi":"10.1186/s13023-024-03382-9","DOIUrl":"https://doi.org/10.1186/s13023-024-03382-9","url":null,"abstract":"<p><strong>Background and aims: </strong>The NICE Highly Specialised Technology (HST) programme evaluates interventions for very rare conditions within the UK. This review aimed to analyse previous NICE HST appraisals and determine commonly used methods to overcome uncertainties relating to health-related quality of life (HRQoL) and disease burden for people with rare diseases and their caregivers. The review also aimed to identify areas where further methodological development is required.</p><p><strong>Approach and results: </strong>A targeted review of all previous NICE HST appraisals published by the 28th February 2022, in which at least one committee meeting had taken place, was conducted. A total of 24 appraisals were included (17 fully completed and seven ongoing). Data were extracted by one reviewer. The evidence review group (ERG) and committee comments were compared against the NICE reference case and synthesised to identify the following methodological uncertainties that occurred most commonly: using alternatives to the EuroQol-5 Dimension (EQ-5D), sourcing HRQoL data from single-arm studies, measuring caregiver disutilities and estimating disease burden.</p><p><strong>Conclusions: </strong>This review has highlighted the need for new methodology to reflect the impact of the diseases on people with rare diseases and their families. The review identified the following methodological requirements: alternative approaches that should be used when EQ-5D is not appropriate, methods to evaluate paediatric HRQoL and methods to quantify disease burden. This review also highlights the need to establish clear recommendations on the estimation of utilities across different rare diseases.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychological conditions of caregivers of adult subjects with Prader-Willi syndrome.","authors":"Anna Guerrini Usubini, Adele Bondesan, Diana Caroli, Francesca Frigerio, Graziano Grugni, Gianluca Castelnuovo, Alessandro Sartorio","doi":"10.1186/s13023-024-03385-6","DOIUrl":"https://doi.org/10.1186/s13023-024-03385-6","url":null,"abstract":"<p><strong>Background: </strong>Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder. Individuals with PWS face a range of cognitive, behavioral, and emotional challenges that require comprehensive and lifelong care, posing significant demands on their caregivers. The study is not only aimed to assess the psychological conditions of caregivers of adult subjects with PWS focusing on psychological distress and coping, but also to shed light on a crucial yet often overlooked aspect of healthcare. This study aims to compare the psychological well-being of individuals with PWS and their caregivers, providing valuable insights that can potentially improve the quality of care for these individuals. The sample recruited at the Division of Auxology, IRCCS Istituto Auxologico Italiano, was composed of 30 adult subjects with PWS (11 men and 19 women; mean age ± SD: 36.4 ± 10.31 years; mean Body Mass Index (BMI): 35.7 ± 8.92: kg/m2) and their caregivers (10 men and 20 women). To assess the psychological condition of caregivers, the Italian-validated versions of the Depression Anxiety and Stress Scale (DASS-21) and the Coping Orientation to the Problems Experiences (COPE) were used, while to assess the psychological well-being of individuals with PWS and their caregivers, the Italian validated version of the Psychological General Well-Being Index (PGWBI) was used.</p><p><strong>Results: </strong>Depression (p < 0.001), Stress (p = 0.050), and Total score (p = 0.009) of DASS 21 were higher in the caregivers of subjects with PWS than in the general population. PGWBI scores of caregivers were significantly lower than in individuals with PWS in Positive Well-being (p < 0.001), General Health (p = 0.006), Vitality (p = 0.004), and the total score (p = 0.006). The depression subscale of PGWBI was higher in caregivers than in subjects with PWS. Correlations between the subscales of COPE and the total score of PGWBI in caregivers revealed that the Avoidance subscale of COPE had a negative significant correlation with the total score of PGWBI (p = 0.003).</p><p><strong>Conclusions: </strong>Our results highlighted several critical insights into the profound emotional and psychological challenges faced by the caregivers of individuals with PWS.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a value assessment framework for orphan medicinal products in China.","authors":"Handong Chen, Yuliang Xiang, Xian Tang, Ming Hu","doi":"10.1186/s13023-024-03393-6","DOIUrl":"10.1186/s13023-024-03393-6","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to establish a suitable value assessment framework for orphan medicinal products in China based on the multi-criteria decision analysis (MCDA) method.</p><p><strong>Methods: </strong>First, a draft framework of the MCDA criteria was built based on a systematic literature evaluation and the EVIDEM framework tools. Second, stakeholder groups were formed and expert opinions were collected through the brainstorming and expert consultation methods. Third, from the perspective of stakeholders, the five-point weighting method and a two-step percentile distribution method were employed to weigh the quantitative criteria in the framework for orphan drug value evaluation. Meanwhile, from the public perspective, a survey was conducted on a sample of 71 people to obtain the scoring scale of the framework for orphan drugs through a two-step percentile distribution method. Finally, based on the synthetization and comparison of all evidence and methods, we developed the framework criteria and scoring scale for the orphan medicinal products.</p><p><strong>Results: </strong>Combined with the stakeholder selection and suggestions in the stakeholder workshop, the framework criteria for the evaluation were constructed based on China's national conditions, which included 11 quantitative and 8 qualitative criteria. The two-step percentile distribution method was selected as the weighting method.</p><p><strong>Conclusions: </strong>MCDA is feasible for the value assessment of orphan drugs in China and can be used as a supplementary tool for drug access decisions in medical insurance. It is suggested to further improve the value assessment framework of orphan medicinal products, scientifically evaluate the MCDA framework weighting method, explore a framework system suitable for China's national conditions.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like receptors ligand immunomodulators for the treatment congenital diaphragmatic hernia.","authors":"Mayte Vallejo-Cremades, Javier Merino, Rita Carmona, Laura Córdoba, Beatriz Salvador, Leopoldo Martínez, Juan Antonio Tovar, Miguel Ángel Llamas, Ramón Muñoz-Chápuli, Manuel Fresno","doi":"10.1186/s13023-024-03384-7","DOIUrl":"https://doi.org/10.1186/s13023-024-03384-7","url":null,"abstract":"<p><strong>Background: </strong>Congenital diaphragmatic hernia (CDH) is a rare disease that affects the development of the diaphragm, leading to abnormal lung development. Unfortunately, there is no established therapy for CDH. Retinoic acid pathways are implicated in the ethology of CDH and macrophages are known to play a role in repairing organ damage.</p><p><strong>Methods: </strong>We have analyzed the effect of several Toll like receptor (TLR) ligands in the nitrofen-induced CDH model in pregnant rats widely used to study this disease and in the G2-GATA4^Cre;Wt1^fl/fl CDH genetic mice model. Morphometric and histological studies were carried out. Immune cell infiltration was assayed by immunochemistry and immunofluorescence and retinoic pathway gene expression analyzed in vivo and in vitro in macrophages.</p><p><strong>Results: </strong>We found that administering a single dose of atypical TLR2/4 ligands (CS1 or CS2), 3 days after nitrofen, cured diaphragmatic hernia in 73% of the fetuses and repaired the lesion with complete diaphragm closure being on the other hand nontoxic for the mothers or pups. Moreover, these immunomodulators also improved pulmonary hypoplasia and alveolar maturation and vessel hypertrophy, enhancing pulmonary maturity of fetuses. We also found that CS1 treatment rescued the CDH phenotype in the G2-GATA4^Cre;Wt1^fl/fl CDH genetic mice model. Only 1 out of 11 mutant embryos showed CDH after CS1 administration, whereas CDH prevalence was 70% in untreated mutant embryos. Mechanistically, CS1 stimulated the infiltration of repairing M2 macrophages (CD206⁺ and Arg1⁺) into the damaged diaphragm and reduced T cell infiltration. Additionally, those TLR ligands induced retinol pathway genes, including RBP1, RALDH2, RARα, and RARβ, in the affected lungs and the diaphragm and in macrophages in vitro.</p><p><strong>Conclusions: </strong>Our research has shown that TLR ligand immunomodulators that influence anti-inflammatory macrophage activation can be effective in treating CDH, being nontoxic for the mothers or pups suggesting that those TLR ligands are a promising solution for CDH leading to orphan drug designation for CS1. The immune system of the fetus would be responsible for repairing the damage and closure of the hernia in the diaphragm and enhanced proper lung development after CS1 treatment.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of life and unmet needs in patients with fabry disease: a qualitative study.","authors":"Montserrat Morales, Jordi Cruz, Eduardo Brignani, Laura Acuña, Esther Lázaro, Cristina Soria","doi":"10.1186/s13023-024-03412-6","DOIUrl":"https://doi.org/10.1186/s13023-024-03412-6","url":null,"abstract":"<p><strong>Background: </strong>Patients with Fabry disease (FD) consider their quality of life to be significantly affected. The majority of studies evaluate the quality of life using quantitative measures and standardised scales that offer relevant information about experience with the disease in multiple aspects. The main objective of the research was to examine in depth the quality of life and unmet needs of patients diagnosed with FD in relation to their disease and treatment. A qualitative and transversal study was carried out in two stages: (a) nine semi-structured qualitative interviews with patients and one representative of the patient association, conducted individually by phone; (b) a focus group was set up with three patients diagnosed with FD and one relative. A deductive, thematic analysis approach was used for data coding and analysis.</p><p><strong>Results: </strong>The analysis of the interviews revealed various relevant themes: experience with the disease, impact on daily activities, experience of the family and work environment, experience related to treatment and healthcare professionals, and unmet support needs. Diagnosis has a significant impact on both those suffering from the disease and on the family environment. The symptoms and evolution of the disease are highly variable among the patients interviewed and depend on the years diagnosed as well as the time taken to receive the diagnosis. The families of the interviewees have to go through an adjustment process in light of the significant psychological impact brought about by the disease. Patients show various unmet needs. The need mentioned most is to have more information, support, and understanding from people around them and society, improving empathy and raising awareness about the difficulties faced by people with FD while giving the disease visibility. A lack of social understanding is highlighted as one of the main challenges, as this does not only affect the emotional management of the disease but also has repercussions on working life and social relationships.</p><p><strong>Conclusions: </strong>It seems necessary to define possible strategies that help to improve the quality of life of patients and their experience with the disease. Some recommendations obtained from the study include: facilitate access to mental health professionals for patients and their families; improve training for specialists and coordination among them; and carry out actions to raise awareness of the disease that are aimed at the general public, the patients themselves, and the people around them.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}