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Giant congenital melanocytic nevi (GCMN) can be cosmetically significant and can lead to melanoma. There is no standard pharmacologic treatment for GCMN. We present the case of an 8-year-old female with kaposiform lymphangiomatosis caused by an NRAS mutation whose nevus spilus-type GCMN improved on oral selumetinib.
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OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.
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Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.
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Metilação de DNA , Epigênese Genética , Humanos , Camundongos , Animais , Metilação de DNA/genética , Envelhecimento/genética , Longevidade/genética , Mamíferos/genéticaRESUMO
Primary systemic vasculitides, mainly of the small and medium-sized vessels, are frequently associated with peripheral neuropathies. When the disease is already known, the appearance of a neuropathy should suggest a specific injury, especially when associated with other systemic manifestations. Conversely, when neuropathy is inaugural, close collaboration between neurologists and internists is necessary to reach a diagnosis. A standardized electro-clinical investigation specifying the topography, the evolution and the mechanism of the nerve damage enables the positive diagnosis of the neuropathy. Several elements orient the etiological diagnosis and allow to eliminate the main differential diagnosis: non systemic vasculitic neuropathy. The existence of associated systemic manifestations (glomerular or vascular nephropathy, interstitial lung disease, intra-alveolar hemorrhage, ENT involvement ), biological markers (ANCA, cryoglobulinemia, rheumatoid factor), and invasive examinations allowing histological analysis (neuromuscular biopsy) are all useful tools for.
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Doenças do Sistema Nervoso Periférico , Vasculite , Humanos , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/diagnóstico , Vasculite/complicações , Vasculite/diagnóstico , Vasculite/patologia , BiópsiaRESUMO
Systemic diseases (connective disease, granulomatosis) may be associated with peripheral neuropathies. The diagnosis can be complex when the neuropathy is the presenting manifestation of the disease, requiring close collaboration between neurologists and internists. Conversely, when the systemic disease is already known, the main question remaining is its imputability in the neuropathy. Regardless of the situation, the positive diagnosis of neuropathy is based on a systematic and rigorous electro-clinical investigation, specifying the topography, the evolution and the mechanism of the nerve damage. Certain imaging examinations, such as nerve and/or plexus MRI, or other more invasive examinations (skin biopsy, neuromuscular biopsy) enable to specify the topography and the mechanism of the injury. The imputability of the neuropathy in the course of a known systemic disease is based mainly on its electro-clinical pattern, on which the alternatives diagnoses depend. In the case of an inaugural neuropathy, a set of arguments orients the diagnosis, including the underlying terrain (young subject), possible associated systemic manifestations (inflammatory arthralgias, polyadenopathy), results of first-line laboratory tests (lymphopenia, hyper-gammaglobulinemia, hypocomplementemia), autoantibodies (antinuclear, anti-native DNA, anti-SSA/B) and sometimes invasive examinations (neuromuscular biopsy).
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Doenças do Tecido Conjuntivo , Doenças do Sistema Nervoso Periférico , Humanos , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Autoanticorpos , Anticorpos Antinucleares , Doenças do Tecido Conjuntivo/complicaçõesRESUMO
Hereditary transthyretin amyloidosis (ATTRv) is a rare, lethal, autosomal dominant adult-onset genetic gain-of function (GOF) disorder provoked by mutations in the TTR gene. Until recently, therapeutic options were limited and consisted mainly in liver transplantation and TTR-stabilizers. In the last few years, ATTRv has been at the center of major therapeutic breakthroughs, including development of effective small interfering RNA (siRNA) and antisense oligonucleotide (ASO) treatments targeting liver TTR mRNA. Both siRNA (patisiran) and ASO (inotersen) treatments are now commercially available and have dramatically improved ATTRv neurological outcome. Ongoing clinical trials currently evaluate another siRNA, vutrisiran and a novel ASO formulation, eplontersen. A CRISPR-Cas9-based TTR gene editing treatment is also currently evaluated, with encouraging preliminary results. These recent therapeutic developments demonstrate the shifting paradigm of ATTRv, a previously untreatable and lethal disorder and provide a proof-of-concept for developing siRNA, ASO and CRISPR-Cas9 treatments for other GOF genetic disorders.
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Neuropatias Amiloides Familiares , Adulto , Humanos , Neuropatias Amiloides Familiares/terapia , Neuropatias Amiloides Familiares/tratamento farmacológico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Fígado , Mutação , Pré-Albumina/genética , Pré-Albumina/uso terapêuticoRESUMO
Lymphoproliferative syndromes (multiple myeloma, Waldenström's disease, chronic lymphocytic leukemia, lymphomas) may be associated with peripheral neuropathies. The mechanism can be dysimmune, associated or not with monoclonal gammopathies; paraneoplastic; infiltrative; or more commonly, iatrogenic or due to vitamin deficiency. The diagnosis can be complex, especially when the neuropathy is the presenting manifestation, requiring a close cooperation between internists and neurologists. The positive diagnosis of the neuropathy is based on a systematic electro-clinical investigation, which specifies the topography and the mechanism of the nerve damage, sometimes reinforced by imaging examinations, in particular, nerve and/or plexus MRI. The imputability of the neuropathy to a lymphoproliferative syndrome is based on a set of arguments including the clinical context (B signs, tumour syndrome), first-line laboratory tests (hemogram, protein electrophoresis, viral serologies, complement), auto-antibodies discussed according to the neuropathy (anti-MAG, anti-gangliosides) and sometimes more invasive examinations (bone marrow or neuro-muscular biopsies).
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Paraproteinemias , Doenças do Sistema Nervoso Periférico , Autoanticorpos , Humanos , Glicoproteína Associada a Mielina , SíndromeRESUMO
PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.
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Ataxia Telangiectasia , Melanoma , Proteínas Mutadas de Ataxia Telangiectasia/genética , Austrália , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Melanoma/genéticaRESUMO
BACKGROUND: FMS-like tyrosine kinase 3 (FLT3) is the most frequent mutation in AML. With two FLT3 inhibitors recently approved by the FDA (midostaurin and gilteritinib), there is a need to evaluate these targeted agents. PURPOSE: To assess the clinical effectiveness of FLT3 inhibitors in AML patients. METHODS: Standard systematic review methods were utilised. Searches were conducted to July 2020 for completed and in-progress randomised controlled trials of FLT3 inhibitors in AML. A fixed-effect meta-analysis was undertaken. RESULTS: Eight completed trials involving 2656 patients and assessing five different FLT3 inhibitors (sorafenib, lestaurtinib, midostaurin, gilteritinib and quizartinib) were included. The pooled results were as follows (FLT3 inhibitor/control): overall survival hazard ratio (HR) = 0.83 (95% confidence interval [CI] 0.75 to 0.92, p = 0.0005), event-free survival HR = 0.85 (95% CI 0.77 to 0.94, p = 0.002), relapse-free survival HR = 0.76 (95% CI 0.64 to 0.90, p = 0.001), complete remission relative risk (RR) = 1.11 (95% CI 1.00 to 1.22. p = 0.05) and 60-day mortality RR = 1.04 (95% CI 0.77 to 1.40, p = 0.79). Relative risk of grade 3 and above vascular, dermatological, respiratory and hepatobiliary adverse events were found to be statistically significantly higher in the FLT3 inhibitor group compared to control, but the actual numbers of events were relatively small. Nineteen ongoing trials are still in progress, only one of which specifically targets older patients with AML. CONCLUSIONS: There is evidence to support the use of FLT3 inhibitors in patients with AML, but more data is needed to verify the optimum use of the drugs regarding type of inhibitor, disease stage and patient characteristics, not only in relation to disease control, but adverse events and quality of life. There are a large number of ongoing trials; therefore, the results of this review are not a fait accompli; thus, is it recommended that the review be updated in a couple of years' time. Given the challenges in extracting the complete data set required to assess clinical effectiveness, it is highly recommended that ongoing and future trials improve transparency and consistency of reporting of all trial outcomes, particularly disease control and adverse events, to enable a global clinical effectiveness assessment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017055581.
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Leucemia Mieloide Aguda , Tirosina Quinase 3 Semelhante a fms , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva Local de Neoplasia , Qualidade de Vida , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
INTRODUCTION: Cervical spinal sarcoidosis can mimic compressive cervical myelopathy leading to potentially harmful surgical procedures before the diagnosis can be made. METHODS: Retrospective description of 3 patients and review of the literature. RESULTS: Twenty-seven patients (16 men/11 women), median age 58 years [range 29-74] were described. Neurosurgical procedures consisted of laminectomy (n=10), laminoplasty (n=15) and anterior discectomy (n=2). Immediately after surgery, 17 patients (63%) worsened or remained disabled. Among the 10 patients who improved, 9 worsened secondarily. The analysis of preoperative MRI showed T2 hypersignal lesions and contrast enhancement in all patients. Neurological symptoms were inaugural in 25/27 patients, and systemic involvement of the sarcoidosis was found after surgery in 15/27 patients. After surgery, all patients received corticosteroids, along with immunosuppressive therapy in 8 cases/27. After a follow-up of 24 [16-72] months; 13 patients were stabilized or worsened, 7 were partially improved. Three died of other cause. Only 5 recovered without sequelae. CONCLUSION: In patients with compressive cervical myelopathy, leptomeningeal contrast enhancement, a T2-weighted hypersignal exceeding the compression level on MRI, and the presence of extraneurological symptoms should point to inflammatory disease. These rare manifestations may be the first symptoms of sarcoidosis and should be recognized to avoid harmful surgical procedures and to provide appropriate medical treatment.
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Sarcoidose/diagnóstico , Sarcoidose/cirurgia , Compressão da Medula Espinal/diagnóstico , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/cirurgia , Adulto , Idoso , Vértebras Cervicais , Diagnóstico Diferencial , Progressão da Doença , Discotomia/efeitos adversos , Feminino , Humanos , Laminectomia/efeitos adversos , Laminoplastia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Prognóstico , Estudos Retrospectivos , Sarcoidose/epidemiologia , Compressão da Medula Espinal/epidemiologia , Compressão da Medula Espinal/cirurgia , Doenças da Medula Espinal/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Germline mutations in telomere-related genes such as POT1 and TERT predispose individuals to familial melanoma. OBJECTIVES: To evaluate the prevalence of germline mutations in POT1 and TERT in a large cohort of Spanish melanoma-prone families (at least two affected first- or second-degree relatives). METHODS: Overall, 228 CDKN2A wild-type melanoma-prone families were included in the study. Screening of POT1 was performed in one affected person from each family and TERT was sequenced in one affected patient from 202 families (26 families were excluded owing to DNA exhaustion/degradation). TERT promoter sequencing was extended to an additional 30 families with CDKN2A mutation and 70 patients with sporadic multiple primary melanoma (MPM) with a family history of other cancers. RESULTS: We identified four families with potentially pathogenic POT1 germline mutations: a missense variant c.233T>C (p.Ile78Thr); a nonsense variant c.1030G>T (p.Glu344*); and two other variants, c.255G>A (r.125_255del) and c.1792G>A (r.1791_1792insAGTA, p.Asp598Serfs*22), which we confirmed disrupted POT1 mRNA splicing. A TERT promoter variant of unknown significance (c.-125C>A) was detected in a patient with MPM, but no germline mutations were detected in TERT promoter in cases of familial melanoma. CONCLUSIONS: Overall, 1·7% of our CDKN2A/CDK4-wild type Spanish melanoma-prone families carry probably damaging mutations in POT1. The frequency of TERT promoter germline mutations in families with melanoma in our population is extremely rare.
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Predisposição Genética para Doença , Melanoma/genética , Regiões Promotoras Genéticas/genética , Neoplasias Cutâneas/genética , Telomerase/genética , Proteínas de Ligação a Telômeros/genética , Adulto , Idoso , Códon sem Sentido , Estudos de Coortes , Inibidor p16 de Quinase Dependente de Ciclina/genética , Análise Mutacional de DNA , Feminino , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Masculino , Anamnese , Melanoma/epidemiologia , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Linhagem , Complexo Shelterina , Neoplasias Cutâneas/epidemiologia , Espanha/epidemiologia , Melanoma Maligno CutâneoRESUMO
BACKGROUND AND PURPOSE: The aim is to describe an uncommon phenotype of hereditary ATTR neuropathy with upper limb onset. METHODS: The French TTR Familial Amyloid Polyneuropathy database was used for a retrospective evaluation of 32 consecutive patients with upper limb onset of the neuropathy (study group) and they were compared to 31 Portuguese early-onset patients and 99 late-onset patients without upper limb onset. RESULTS: Initial upper limb symptoms were mostly sensory. Lower limb symptoms began 2.3 ± 3 years after upper limb symptoms. Twenty-four (75%) patients were initially misdiagnosed, with 15 different diagnoses. More patients in the study group had a Neuropathy Impairment Score upper limb/lower limb ratio > 1 compared to the late-onset patient group. The study group had significantly more pronounced axonal loss in the median and ulnar motor nerves and the ulnar sensory and sural nerves. On radial nerve biopsies (n = 11), epineurial vessels were abnormal in six cases, including amyloid deposits in vessel walls (3/11), with vessel occlusion in two cases. CONCLUSION: Upper limb onset of hereditary ATTR neuropathy is not rare in non-endemic areas. It is important to propose early TTR sequencing of patients with idiopathic upper limb neuropathies, as specific management and treatment are required.
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Neuropatias Amiloides Familiares , Extremidade Superior , Idoso , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/epidemiologia , Neuropatias Amiloides Familiares/patologia , Neuropatias Amiloides Familiares/fisiopatologia , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.
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Alelos , Mutação , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/genética , Triptofano-tRNA Ligase/genética , Adolescente , Idade de Início , Biópsia , Análise Mutacional de DNA , Fibroblastos/metabolismo , Estudos de Associação Genética , Genótipo , Humanos , Levodopa/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Transtornos Parkinsonianos/tratamento farmacológico , Fenótipo , Polimorfismo de Nucleotídeo Único , Medicina de PrecisãoRESUMO
Congenital lipomatous overgrowth with vascular, epidermal, and skeletal (CLOVES) anomalies and Klippel-Trenaunay (KTS) syndromes are caused by somatic gain-of-function mutations in PIK3CA, encoding a catalytic subunit of phosphoinositide 3-kinase. Affected tissue is needed to find mutations, as mutant alleles are not detectable in blood. Because some patients with CLOVES develop Wilms tumor, we tested urine as a source of DNA for mutation detection. We extracted DNA from the urine of 17 and 24 individuals with CLOVES and KTS, respectively, and screened 5 common PIK3CA mutation hotspots using droplet digital polymerase chain reaction. Six of 17 CLOVES participants (35%) had mutant PIK3CA alleles in urine. Among 8 individuals in whom a mutation had been previously identified in affected tissue, 4 had the same mutant allele in the urine. One study participant with CLOVES had been treated for Wilms tumor. We detected the same PIK3CA mutation in her affected tissue, urine, and tumor, indicating Wilms tumors probably arise from PIK3CA mutant cells in patients with CLOVES. No urine sample from a participant with KTS had detectable PIK3CA mutations. We suggest that urine, which has the advantage of being collected non-invasively, is useful when searching for mutations in individuals with CLOVES syndrome.
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Classe I de Fosfatidilinositol 3-Quinases/genética , Síndrome de Klippel-Trenaunay-Weber/genética , Lipoma/genética , Anormalidades Musculoesqueléticas/genética , Nevo/genética , Malformações Vasculares/genética , Tumor de Wilms/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , DNA/genética , DNA/urina , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Síndrome de Klippel-Trenaunay-Weber/patologia , Síndrome de Klippel-Trenaunay-Weber/urina , Lipoma/patologia , Lipoma/urina , Masculino , Pessoa de Meia-Idade , Anormalidades Musculoesqueléticas/patologia , Anormalidades Musculoesqueléticas/urina , Mutação , Nevo/patologia , Nevo/urina , Fenótipo , Malformações Vasculares/patologia , Malformações Vasculares/urina , Tumor de Wilms/patologia , Tumor de Wilms/urinaRESUMO
BACKGROUND: Newborn infant skin changes after birth but studies have focused on the epidermal barrier. Dermal properties are relevant for care, but literature on postnatal changes is sparse. We further characterized skin maturational changes in lightness, color and response to biomechanical stress. METHODS: Normal skin sites from subsets of participants in a trial on the progression and stage of infantile hemangiomas were retrospectively examined. Standardized photographs were analyzed as L*, a*, and b* images. Biomechanics were measured with the Cutometer® . RESULTS: Color changed significantly with increasing age. Skin was darker and redder at 2.0 vs. 5.4, 8.5 and 12.8 months. Yellow color increased, with higher values at 12.8 vs. 2.0, 3.5 and 5.4 months. Chest tissue was consistently more elastic than arm and face sites, with significantly higher elasticity for the youngest and oldest age groups. Biological elasticity, elastic recovery, and total recovery were significantly greater for the oldest subjects. Viscoelasticity and elastic deformation were lower at 5.5 vs. 8.8 and 17.6 months. Arm viscoelastic creep was highest at 2.8 months. CONCLUSION: Skin maturation continues into year two. Increasing elasticity and decreasing viscoelasticity may reflect increased collagen structure/function. The findings have implications for prevention of skin injury associated with mechanical forces.
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Envelhecimento da Pele/fisiologia , Fenômenos Fisiológicos da Pele , Fenômenos Biomecânicos , Elasticidade/fisiologia , Feminino , Hemangioma/fisiopatologia , Humanos , Lactente , Masculino , Fotografação , Estudos Retrospectivos , Pele/crescimento & desenvolvimento , Neoplasias Cutâneas/fisiopatologia , Pigmentação da Pele/fisiologia , Estresse Mecânico , ViscosidadeRESUMO
Transthyretin familial amyloid polyneuropathy (FAP) is a rare disease with autosomal transmission due to point mutation of the transthyretin (TTR) gene. It is the most disabling hereditary neuropathy affecting sensory, motor and autonomic nerves, and is irreversible and fatal within 7 to 12 years of onset in the absence of therapy. Diagnosis is usually delayed for 1-5 years because the onset is usually insidious, and a positive family history is lacking in 50% of late-onset cases. Penetrance is variable, and depends of the age of the carrier and age of onset in family members. Two treatments are available: liver transplantation, to suppress the main source of systemic production of mutant TTR; and TTR tetramer stabilizer drugs, to avoid the release of highly amyloidogenic monomers and oligomers. These therapies are able to stop or slow the progression of the disease in its early stages. Genetic counseling is crucial to detect carriers at risk of developing the disease. The European network for TTR-FAP recommends careful baseline assessment by questionnaire, clinical examination and neurophysiological tests, and periodic consultations to detect the onset of disease in time to start anti-amyloid therapy after biopsy findings of amyloid deposition. A therapeutic educational program is important for improving patients' awareness. Patients are considered symptomatic and ill when they themselves perceive symptoms or changes, including changes from baseline measurements on neurophysiological tests, followed by findings of amyloid deposition on biopsy. The most sensitive biopsies are from the labial salivary gland and skin.
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Neuropatias Amiloides Familiares/terapia , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/fisiopatologia , Humanos , Pré-Albumina/genética , Pré-Albumina/metabolismoAssuntos
Hemangioendotelioma , Síndrome de Kasabach-Merritt , Humanos , Linfedema , Sarcoma de KaposiRESUMO
BACKGROUND: Infantile hemangiomas (IHs) are benign vascular neoplasms with rapid capillary proliferation shortly after birth and slow involution with diminishing capillary proliferative activity, fibrosis, and fatty replacement over 7-10 years. METHODS: Hemangiomas and contralateral control sites in 88 subjects were measured using a suction device, 6-mm probe and 200 mbar negative pressure. Mechanical properties were assessed vs. controls and effects of body site, depth, clinical stage, histology diagnosis, and time. RESULTS: Biological elasticity, overall elasticity, net elasticity, total recovery, and elastic recovery were lower for IH vs. controls (P < 0.001). IH total deformation, elastic deformation, viscoelastic creep, and residual deformation were higher than controls (P < 0.001). Involuting IHs had lower viscoelasticity than proliferating and stable lesions (P < 0.001) and lower viscoelastic creep than stable IHs (P = 0.04). IH viscoelasticity was higher at 2.3 than 12.9, 23.7, and 61.0 months and at 4.9 and 8.1 than 61.0 months. IH elastic recovery varied by body site with larger differences vs. control for abdomen and leg. Elastic recovery differences from control were smaller at younger vs. older ages. CONCLUSIONS: Measurement of biomechanical properties may be useful to characterize IH progression and treatment response in clinical settings.
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Envelhecimento , Hemangioma/patologia , Hemangioma/fisiopatologia , Envelhecimento da Pele/patologia , Pele/patologia , Pele/fisiopatologia , Criança , Pré-Escolar , Módulo de Elasticidade , Feminino , Dureza , Humanos , Lactente , Masculino , Modelos Biológicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , ViscosidadeRESUMO
We report the case of a 62-year-old man hospitalized in May 2015 for symptomatic heart failure. His medical history included two liver transplantations. The first liver transplantation was performed in 1999 for a mixed alcoholic and hepatitis C-related cirrhosis and the patient received the liver of another patient with Val30Met transthyretin amyloidosis using the domino technique. In 2008, he complained of neuropathic pains and an iatrogenic-acquired transthyretin amyloidosis was diagnosed. On cardiac evaluation, amyloidosis was suspected. In March 2010, a second liver transplantation was performed with a deceased donor without complication. In May 2015, a first episode of symptomatic heart failure occurred and cardiac amyloidosis was investigated by a multimodality evaluation. Electrocardiogram, cardiac biomarkers, echocardiography, and cardiac MRI were in favor of the diagnosis of amyloidosis, whereas 99m Tc-dicarboxypropane diphosphonate scintigraphy was not. Endomyocardial biopsy finally confirmed the positive diagnosis of iatrogenic-acquired cardiac amyloidosis. This case is, to the best of our knowledge, the first to report biopsy-proven cardiac amyloidosis induced by domino liver transplantation and progressing heart failure in spite of retransplantation. The diagnostic modalities are discussed. This case should alert physicians to the cardiac risk in domino liver transplanted patients.
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BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.