Osteoporosis en alcoholismo crónico : un problema infravalorado. Incidencia y complicaciones de las fracturas en el paciente alcohólico

Main goal. To estimate the incidence of pathologic fractures and associated complications in patients in follow-up for moderate to severe chronic alcoholism by the Unidad de Conductas Adictivas (UCA) of our health area. To highlight the importance of recognizing osteoporosis in patients with chronic alcoholism in order to establish strategies for prevention of both primary and secondary fractures. Material and methods. Retrospective analysis of patients in follow-up for chronic alcoholism by the UCA between 2014 and 2018 that required assessment by the Orthopedics Unit for fractures during that period, excluding fractures in the context of politraumatism. In addition, the complications derived from these fractures were collected and it was determined whether bone densitometry (BMD) was indicated following the main osteoporosis guidelines. Results. The incidence rate of fractures due to low-energy trauma in the selected population during the follow-up period was 7.2 for every 1,000 patients / year. 41% of the 44 study patients suffered new fractures during this period. 33% of the patients with fractures that required surgical treatment suffered major complications. 100% of the patients fulfilled criteria for BMD after the first traumatic event, despite only 20% of them being ultimately performed. Conclusions. The prevalence of fractures and associated complications in alcoholic patients is significantly higher than in the general population. It is necessary to stress the importance of both primary and secondary prevention of pathologic fractures in alcoholic patients, and if they occur, osteosynthesis techniques adapted to an osteoporotic bone should be applied

Dietary curcumin promotes gilthead seabream larvae digestive capacity and modulates oxidative status

The larval stage is highly prone to stress due to the ontogenetic and metabolic alterations occurring in fish. Curcumin inclusion in diets has been shown to improve growth by modulating oxidative status, immune response, and/or feed digestibility in several fish species. The aim of the present work was to assess if dietary curcumin could promote marine fish larvae digestive maturation and improve robustness. Gilthead seabream larvae were fed a diet supplemented with curcumin at dose of 0 (CTRL), 1.5 (LOW), or 3.0 g/Kg feed for 27 days. From 4 to 24 days after hatching (DAH), no differences were observed in growth performance. At the end of the experiment (31 DAH) LOW larvae had a better condition factor than CTRL fish. Moreover, HIGH larvae showed higher trypsin and chymotrypsin activity when compared to CTRL fish. LOW and HIGH larvae were able to maintain the mitochondrial reactive oxygen species production during development, in contrast to CTRL larvae. In conclusion, curcumin supplementation seems to promote larvae digestive capacity and modulate the oxidative status during ontogeny. Furthermore, the present results provide new insights on the impacts of dietary antioxidants on marine larvae development and a possible improvement of robustness in the short and long term.ALG-01-0145-FEDER-029151info:eu-repo/semantics/publishedVersio

Protocol for the phase 2 EDELIFE trial investigating the efficacy and safety of intra-amniotic ER004 administration to male subjects with X-linked hypohidrotic ectodermal dysplasia

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene

Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Background: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). Results: Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT. Conclusions: The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams

Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience

Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time

Deep Molecular Characterization of Milder Spinal Muscular Atrophy Patients Carrying the c.859G&gt;C Variant in SMN2

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype-phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype-phenotype correlations and improve prognostic outcomes

Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease

Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symptoms, and disease progression are heterogeneous, and patients may present with many different manifestations to a wide range of specialists. Expertise in diagnosing and managing MPS II varies widely between countries, and substantial delays between disease onset and diagnosis can occur. In recent years, disease-specific treatments such as enzyme replacement therapy and stem cell transplantation have helped to address the underlying enzyme deficiency in patients with MPS II. However, the multisystem nature of this disorder and the irreversibility of some manifestations mean that most patients require substantial medical support from many different specialists, even if they are receiving treatment. This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies. Take-home message. Expertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan-European recommendations for the diagnosis and management of this life-limiting disease