Centre Hospitalier de Luxembourg

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder. It primarily involves cutaneous, neurological and skeletal systems, with vascular involvement being relatively uncommon. Among the reported vascular manifestations, stenoses, aneurysms, and arteriovenous fistulas (AVFs) are infrequent but potentially serious complications. Their manifestation with cerebral steal syndrome is of even lower prevalence. We report a case of a 52-year-old female with known NF1 who presented with progressive headache, transient episodes of right-sided weakness and speech problems. Total selective digital subtractive cerebral angiography revealed AVF of the left occipital region, primarily supplied by a large longitudinal defect in the V4 segment of the left vertebral artery, with additional feeders from the left occipital and ascending cervical arteries. A vertebrobasilar "steal" phenomenon was observed, with retrograde filling of the basilar circulation via the carotid system. Given the progressive symptoms and hemodynamic compromise, the patient underwent endovascular embolization using balloon catheters, detachable coils and Onyx 18 liquid embolic agent. The procedure was uneventful, with successful devascularization of the AVF and improved perfusion to the surrounding tissue. Post procedural recovery was favorable, with disappearing of existed symptoms. AVFs are rare in patients with NF1, and their pathogenesis is not fully understood. Steal syndrome occurs when high flow vascular malformations divert blood from surrounding brain parenchyma, leading to ischemic symptoms. Our case contributes to the limited literature on NF1-associated AVF and supports early neurovascular imaging in symptomatic individuals. Awareness of this rare vascular complication in NF1 is crucial for timely diagnosis and management.

Cardiac arrest (CA) is a leading cause of mortality and neurological disability. Prediction of post-CA outcomes is challenging. Epitranscriptomic (RNA) modifications are emerging as potential biomarkers due to their regulatory roles in RNA metabolism and disease progression. However, their relevance in CA remains unexplored. This study aimed to investigate the association between N1-methyladenosine (m¹A) RNA modification and outcome after CA. Total RNA was extracted from whole blood samples of 211 patients collected 48 h after return of spontaneous circulation (ROSC). M¹A and adenosine (A) blood levels were quantified using liquid chromatography coupled to mass spectrometry (LC-MS), and the ratio m¹A/A was calculated. Neurological outcome assessed using the cerebral performance category (CPC) score and survival at 6 months were used as end-points. Patients with moderate to severe neurological outcome or death within 6 months after CA (CPC 2–5) exhibited elevated m¹A/A ratio compared to survivors without neurological sequelae (CPC 1) (p = 0.03). In multivariable logistic regression, higher m1A/A levels were associated with an increased risk of moderate to severe neurological outcome or death at 6 months compared to survivors without neurological sequelae (odds ratio [95% confidence interval] 1.50 [1.04–2.19]), after adjustment for age, time between CA and return of spontaneous circulation, lactate and neuron-specific enolase levels. In Kaplan-Meier survival analysis, patients with elevated m¹A/A levels showed a lower probability of survival at 6 months (p = 0.003). This study provides the first evidence that m1A RNA methylation, reflected by the m1A/A ratio, is associated with neurological outcome and death at 6 months after CA. Although these findings require validation, they raise the possibility that m¹A RNA methylation could help to improve prognostication after CA.

Background/Objectives: University faculty in health sciences are an underexplored population despite facing significant emotional, occupational, and organizational demands due to their dual role as educators and health professionals. These demands may increase vulnerability to perceived stress, burnout, and reduced professional quality of life. Although previous research has primarily focused on stress and burnout, evidence integrating occupational balance and personal resources, such as sense of coherence, from an occupational health perspective remains limited. This study aimed to examine perceived stress, professional quality of life, occupational balance, and satisfaction with meaningful occupations among health sciences faculty in Spain, and to analyze their associations with individual, occupational, and organizational factors within an occupation-centered and salutogenic framework. Methods: A cross-sectional observational study following STROBE guidelines was conducted with 253 health sciences faculty members from Spanish universities. Data were collected through an anonymous online questionnaire including validated instruments (PSS-10, OBQ-E, ProQoL, SOC-13) and items on occupational satisfaction and perceived institutional support. Descriptive statistics, t tests, one-way ANOVA, and Pearson correlation analyses were performed. Results: Participants reported moderate levels of perceived stress and occupational balance, high overall professional quality of life satisfaction, and moderate levels of compassion fatigue. Higher perceived stress scores were observed among women and younger faculty members. Occupational balance, burnout, and satisfaction measures showed significant differences according to age and years of teaching experience. Perceived institutional support differed across organizational domains, academic positions, and types of institution. Conclusions: Health sciences faculty in Spain experience notable psychosocial demands affecting stress, occupational balance, and professional quality of life. Occupational balance and sense of coherence emerged as relevant constructs associated with lower perceived stress and burnout and higher professional satisfaction. By integrating these occupation-centered and salutogenic resources, the study extends existing research beyond traditional stress-burnout models and contributes to a more comprehensive understanding of professional well-being among health sciences faculty.

Introduction: Since the first description of Turner syndrome (TS), both genotypic spectrum and phenotypic presentation have evolved. This study aimed to examine trends in this evolution over the past three decades and provides an overview of current genetic and clinical features in a large nationwide multicenter cohort of girls with TS. Methods: We analyzed data from growth hormone (GH)-treated girls with TS included in BELGROW, the national GH registry of the BELux Society for Pediatric Endocrinology and Diabetology, between 1985 and 2022. Karyotype, age at diagnosis, and phenotype were studied in 716 girls. Two periods were compared: 1991–2002 (group 1, n = 250) and 2003–2017 (group 2, n = 270). Results: The annual number of girls with TS starting GH remained stable (mean n = 19/year). In the entire cohort, monosomy 45,X was the most frequent karyotype (44%), followed by structural anomalies of the X chromosome (27%), 45,X/46,XX mosaicism (13%), triple X mosaicism (4%), 45,X/46,XY or complex Y anomalies (6%), and others (6%). The proportion of 45,X decreased between the two periods (46%–38%, p < 0.05). Overall, median age at diagnosis was 6.4 years with 7.6% of girls diagnosed prenatally, 24% before age 1, 49% in childhood, and 19% after 12 years. Prenatal diagnoses increased from 2.5% (group 1) to 15% (group 2) (p < 0.001). Girls with a 45,X karyotype were diagnosed earlier than girls with other genotypes (median 2.2 vs. 8 years, p < 0.001). Skeletal (73%), neurosensory (60%), and cardiac (29%) systems were most affected. Skeletal and cardiac malformations were more frequent in girls with a 45,X karyotype (p < 0.05 and p < 0.01, respectively). Conclusion: Genotype distribution and timing of TS diagnosis have significantly changed since 1991, while the annual number of girls starting GH therapy has remained stable. A 45,X karyotype is associated with earlier diagnosis and more comorbidities.

This study evaluates mobility in patients with multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and Parkinson’s disease (PD) by integrating clinical assessments, instrumented gait analysis (IGA) in the hospital, and 1 week of physical activity monitoring (PAM) at home, using wearable sensors. Clinical scores provide a broad measure of disease severity but lack precision in quantifying gait impairments. IGA offers objective gait metrics under standardized conditions, identifying deficits in stride dynamics and postural control. However, these controlled assessments do not reflect real-world mobility. PAM addresses this gap by continuously tracking movement patterns and physical activity during daily-life, offering insights into how patients walk beyond clinical settings. The combination of IGA and PAM provides a more comprehensive understanding of mobility limitations, particularly in MSA and PSP, where gait and balance impairments differ from PD. This dual approach enhances patient assessment, supports personalized disease management, and improves clinical decision-making. Trial registration: ClinicalTrials.gov, NCT04608604, date of registration: 19/10/2020, first patient enrollment: 01/02/2021.

The INS c.16 C > T (insulin p.Arg6Cys, R6C) variant was reported to cause autosomal dominant monogenic diabetes, yet its pathogenicity has been questioned. R6C preproinsulin exhibits impaired translocation into the endoplasmic reticulum (ER). We explored R6C pathogenicity using integrative clinical, genetic, and functional approaches.Homozygous INS R6C individuals presented early-onset insulin-treated diabetes, whereas heterozygous carriers showed variable or absent glycemic phenotypes. Population-level analysis revealed no significant enrichment of diabetes among heterozygotes. Heterozygous R6C patient’s induced pluripotent stem cell (iPSC)-derived pancreatic β cells exhibited minimal defects, while homozygous R6C β cells displayed preproinsulin accumulation and reduced insulin content and secretion. In vivo, homozygous R6C β cell transplants recapitulated insulin deficiency and responded poorly to GLP-1 receptor agonist. Homozygous R6C β cells had a gene signature of attenuated translation, translocation and ER related pathways.Our findings establish R6C as a recessive loss-of-function mutation, prompting a clinical reassessment of heterozygous R6C carriers. This study highlights the power of population genetic databases, patients’ iPSC-based modeling and multi-modal variant classification frameworks for dissecting the consequences of genetic variants in monogenic diabetes.