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Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy
Get PDFObjective: To assess the natural history and treatment effect on survival among patients with transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) stage 1 Val30Met.
Methods: Multi-institutional, hospital-based study of patients with TTR-FAP Val30Met prospectively followed up until December 2016, grouped into untreated (n = 1,771), liver transplant (LTx)-treated (n = 957), or tafamidis-treated (n = 432) cohorts. Standardized mortality ratios, Kaplan-Meier, and Cox methods were used to estimate excess mortality, survival, and adjusted hazard ratios (HRs) for all-cause mortality.
Results: Disease-modifying treatments decreased TTR-FAP excess mortality from 10 to 4 (standardized mortality ratio 3.92, 95% confidence interval [CI] 2.64-5.59). Median overall survival of untreated and LTx-treated cohorts was 11.61 (95% CI 11.14-11.87) and 24.73 years (95% CI 22.90-27.09), respectively, and was not reached in the tafamidis-treated cohort (maximum follow-up, 10 years). Both disease-modifying treatments improved survival. Among early-onset patients (younger than 50 years of age), tafamidis reduced the mortality risk compared with untreated patients by 91% (HR 0.09, 95% CI 0.03-0.25, p < 0.001) and with LTx-treated patients by 63% (HR 0.37, 95% CI 0.14-1.00, p = 0.050). Previous tafamidis treatment did not affect mortality risk after LTx (HR 0.83, 95% CI 0.25-2.78, p = 0.763). Among late-onset patients (50 years and older), tafamidis reduced mortality risk by 82% compared with untreated patients (HR 0.18, 95% CI 0.06-0.49, p = 0.001).
Conclusion: LTx and tafamidis convey substantial survival benefits, but TTR-FAP mortality remains higher than in the general population. These results strongly reinforce the importance of timely diagnosis and earlier treatment, boosting the pursuit for an increased life expectancy.
Classification of evidence: This study provides Class III evidence that for patients with stage 1 Val30Met TTR-FAP, LTx and tafamidis increase survival.info:eu-repo/semantics/publishedVersio
International practices in the dietary management of fructose 1-6 biphosphatase deficiency
Get PDFBackground: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency.
Methods: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians.
Results: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: 16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than ≤16y were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11-16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management.
Conclusions: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency.info:eu-repo/semantics/publishedVersio
Escore CR‐POSSUM e Índice de Apgar Cirúrgico como fatores preditivos para a alocação de pacientes após cirurgia colorretal
Get PDFBackground and objectives: Surgical patients frequently require admission in high-dependency units or intensive care units. Resources are scarce and there are no universally accepted admission criteria, so patients' allocation must be optimized. The purpose of this study was to investigate the relationship between postoperative destination of patients submitted to colorectal surgery and the scores ColoRectal Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (CR-POSSUM) and Surgical Apgar Score (SAS) and, secondarily find cut-offs to aid this allocation.
Methods: A cross-sectional prospective observational study, including all adult patients undergoing colorectal surgery during a 2 years period. Data collected from the electronic clinical process and anesthesia records.
Results: A total of 358 patients were included. Median score for SAS was 8 and CR-POSSUM had a median mortality probability of 4.5%. Immediate admission on high-dependency units/intensive care units occurred in 51 patients and late admission in 18. Scores from ward and high-dependency units/intensive care units patients were statistically different (SAS: 8 vs. 7, p<0.001; CR-POSSUM: 4.4% vs. 15.9%, p<0.001). Both scores were found to be predictors of immediate postoperative destination (p<0.001). Concerning immediate high-dependency units/intensive care units admission, CR-POSSUM showed a strong association (AUC 0.78, p=0.034) with a ≥9.16 cut-off point (sensitivity: 62.5%; specificity: 75.2%), outperforming SAS (AUC 0.67, p=0.048), with a ≤7 cut-off point (sensitivity: 67.3%; specificity: 56.1%).
Conclusions: Both CR-POSSUM and SAS were associated with the clinical decision to admit a patient to the high-dependency units/intensive care units immediately after surgery. CR-POSSUM alone showed a better discriminative capacity.Justificativa e objetivos
Os pacientes cirúrgicos com frequência precisam de internação em unidade de alta dependência ou unidade de terapia intensiva. Os recursos são escassos e não há critérios de admissão universalmente aceitos; portanto, a alocação dos pacientes precisa ser aprimorada. O objetivo primário deste estudo foi investigar a relação entre o destino dos pacientes após cirurgia colorretal e o Índice de Apgar Cirúrgico (IAC) e o escore CR‐POSSUM – do inglês ColoRectal Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity – e, secundariamente, descobrir pontos de corte para auxiliar essa alocação.
Métodos
Estudo prospectivo de observação transversal, incluiu todos os pacientes adultos submetidos à cirurgia colorretal durante um período de dois anos. Os dados foram coletados do prontuário clínico eletrônico e dos registros de anestesia.
Resultados
Foram incluídos 358 pacientes. A mediana para o IAC foi 8 e para a probabilidade de mortalidade no CR‐POSSUM, 4,5%. A admissão imediata em unidade de alta dependência/unidade de terapia intensiva ocorreu em 51 pacientes e a admissão tardia em 18. Os escores dos pacientes na enfermaria e na unidade de alta dependência/unidade de terapia intensiva foram estatisticamente diferentes (tempo de internação: 8 vs. 7, p < 0,001; CR‐POSSUM: 4,4% vs. 15,9%, p < 0,001). Os dois escores foram preditivos do destino imediato pós‐cirurgia (p < 0,001). Em relação à admissão imediata em UAD/UTI, CR‐POSSUM mostrou uma forte associação (ASC 0,78; p = 0,034) com um ponto de corte ≥ 9,16 (sensibilidade: 62,5%; especificidade: 75,2%), superou o IAC (ASC 0,67, p = 0,048), com ponto de corte ≤ 7 (sensibilidade: 67,3%; especificidade: 56,1%).
Conclusões
Tanto o CR‐POSSUM quanto o IAC foram associados à decisão clínica de admitir um paciente em unidade de alta dependência/unidade de terapia intensiva imediatamente após a cirurgia. CR‐POSSUM isolado mostrou uma capacidade discriminativa melhor.info:eu-repo/semantics/publishedVersio
Exploring the clinical features of narcolepsy type 1 versus narcolepsy type 2 from European Narcolepsy Network database with machine learning
Get PDFNarcolepsy is a rare life-long disease that exists in two forms, narcolepsy type-1 (NT1) or type-2 (NT2), but only NT1 is accepted as clearly defined entity. Both types of narcolepsies belong to the group of central hypersomnias (CH), a spectrum of poorly defined diseases with excessive daytime sleepiness as a core feature. Due to the considerable overlap of symptoms and the rarity of the diseases, it is difficult to identify distinct phenotypes of CH. Machine learning (ML) can help to identify phenotypes as it learns to recognize clinical features invisible for humans. Here we apply ML to data from the huge European Narcolepsy Network (EU-NN) that contains hundreds of mixed features of narcolepsy making it difficult to analyze with classical statistics. Stochastic gradient boosting, a supervised learning model with built-in feature selection, results in high performances in testing set. While cataplexy features are recognized as the most influential predictors, machine find additional features, e.g. mean rapid-eye-movement sleep latency of multiple sleep latency test contributes to classify NT1 and NT2 as confirmed by classical statistical analysis. Our results suggest ML can identify features of CH on machine scale from complex databases, thus providing 'ideas' and promising candidates for future diagnostic classifications.The EU-NN database is financed by the EU-NN. The EU-NN has received financial support from UCB Pharma Brussels for developing the EU-NN database.info:eu-repo/semantics/publishedVersio
eHealth and mHealth in prostate cancer detection and active surveillance
Get PDFeHealth and mobile health (mHealth) offer patients, healthcare providers, researchers, and policy makers new potential to improve wellness, practice prevention and reduce suffering from diseases. While the eHealth market is growing to an expected US $26 billion, its potential in the field of Urology is still underused. Research has shown that currently only 176 apps (of the 300,000 medical apps available) were found in the Apple App Store and Google Play Store, of which 20 were prostate cancer related. Three good examples of eHealth/mHealth applications are the Rotterdam Prostate Cancer Risk Calculator (RPCRC) website and app, the Prostate cancer Research International Active Surveillance (PRIAS) website and the Follow MyPSA app for men on active surveillance for prostate cancer: they are tools with a clear vision that offer true added value in daily clinical practice and which positively influence healthcare beyond borders. To increase the uptake of eHealth applications in the coming years, it is important to involve professionals in their design and development, and to guarantee the safety and privacy of its users and their data.info:eu-repo/semantics/publishedVersio
Seemingly Harmless Differentiated Thyroid Carcinoma Presenting as Bone Metastasis
Get PDFThyroid carcinoma is the most common endocrine neoplasia. Differentiated thyroid carcinomas (DTCs) represent the majority of cases, which usually follow an indolent clinical course with low mortality rates. The authors describe two cases of well DTC without classic histological poor prognosis features, presenting as extensive and unresectable osteolytic bone metastases. DTCs are considered harmless tumours, due to their benign and silent behaviour. The authors want to underline the importance of clinical awareness during follow-up in cases of DTC, which can be aggressive in presentation and behaviour. Timely identification and diagnosis of these tumours are essential for prompt treatment initiation and improvement of overall survival.info:eu-repo/semantics/publishedVersio
Acne Vulgaris in Adults
Get PDFIntrodução: A acne vulgar é uma doença inflamatória crónica da unidade pilossebácea, de etiologia multifatorial. Trata-se de uma das doenças dermatológicas mais comuns. Afeta mais de 85% dos adolescentes, especialmente do género masculino. Apesar de infrequente na idade adulta, dados epidemiológicos recentes mostram uma prevalência crescente, cerca de 40%, predominantemente no género feminino, com impacto negativo na qualidade de vida. A acne do adulto ou acne tardia é uma entidade que está presente após os 25 anos de idade. Classifica-se como acne de início tardio e acne persistente. O tipo persistente é o mais comum, representando 70% a 80% dos casos, e caracteriza-se pela persistência da acne da adolescência, enquanto que a acne de início tardio é definida pela manifestação inaugural após os 25 anos de idade, com uma prevalência de cerca de 20% a 30%.
Objetivo: Revisão bibliográfica da literatura científica atual, especialmente focada na fisiopatologia da acne tardia, fatores desencadeantes e agravantes, bem como nas particularidades da sua abordagem terapêutica.
Metodologia: Foi utilizada a base de dados MEDLINE-PubMed e foram revistos artigos originais e de revisão bibliográfica publicados entre 2001 e 2017.
Discussão: A acne pode ser uma manifestação clínica de doença sistémica, frequentemente endocrinológica, como síndrome do ovário poliquístico, hiperplasia suprarrenal, e tumores secretores virilizantes. É importante considerar estas etiologias, especialmente na mulher e na presença de outros sinais de hiperandrogenismo. Vários estudos apontam outros fatores desencadeantes ou agravantes, nomeadamente fatores genéticos, stress, tabagismo, exposição à radiação ultravioleta, obesidade, dieta hiperglicémica, fármacos, cosméticos, e colonização por estirpes resistentes de Propionibacterium acnes.
Conclusão: Na maioria dos casos, a acne do adulto localiza-se na face, tem uma gravidade clínica ligeira a moderada e cursa com níveis hormonais normais. A localização exclusiva no terço inferior da face associa-se mais frequentemente a outros sinais de hiperandrogenismo e a patologia endocrinológica, bem como a um predomínio de lesões inflamatórias. A acne tardia é descrita como potencialmente refratária à terapêutica convencional, sendo muito recidivante. Assim, constitui um desafio terapêutico, que obriga a uma abordagem individualizada.info:eu-repo/semantics/publishedVersio
Distonia temprana poco frecuente (DYT16) en una niña portuguesa
Get PDFDistonia temprana poco frecuente (DYT16) en una niña portuguesa.info:eu-repo/semantics/publishedVersio
Síndrome de Leigh: a propósito de um caso clínico com mutação no DNA mitocondrial
Get PDFObjective:
Leigh syndrome is a neurodegenerative disorder with an incidence of 1:40,000 live births. It presents wide clinical, biochemical, and genetic heterogeneity, but with homogenous neuropatoradiological alterations. There is no specific treatment, and the prognosis is reserved. This case report aimed familiarize health professionals with the disease.
Case Description:
A 16-month-hold girl who was followed in outpatient clinic due to axial hypotonia and delayed psychomotor development. Karyotype, auditory evoked potentials and ophthalmologic evaluation were normal. Evidence of hyperlactacidemia and hypocitrullinemia was detected in the patient. After performing brain magnetic resonance under anesthesia, hypotonia got worse, and the patient was hospitalized after an episode of cyanosis and apnea. The electroencephalogram showed no epileptiform activity. Neuroimaging revealed bilateral lenticular hyperintensity, especially in the putamen and in the left globus pallidus regions. Molecular analysis revealed an 8993T>G (MT-ATP6) mutation in the mitochondrial DNA.
Comments:
Between 10 and 30% of individuals with Leigh syndrome have mitochondrial DNA mutations. The decompensation after anesthetic intercurrences is typically associated with neurological deterioration and, in this case, increased the diagnosis suspicion. It is important to alert for similar cases and to reduce invasive diagnostic tests if the diagnosis is suspected.Objetivo:
A síndrome de Leigh é uma doença neurodegenerativa com incidência de 1:40.000 nados-vivos. Apresenta ampla heterogeneidade clínica, bioquímica e genética, mas com alterações neuropatorradiológicas homogêneas. Não existe tratamento específico, e o prognóstico é reservado. O objetivo deste estudo foi familiarizar os profissionais de saúde com a doença.
Descrição do caso:
Menina de 16 meses, com hipotonia axial e atraso do desenvolvimento psicomotor. Dos exames realizados: cariótipo, potenciais auditivos evocados e avaliação oftalmológica normais; presença de hiperlactacidemia e hipocitrulinemia. Após a realização de ressonância magnética cerebral sob anestesia, observou-se agravamento da hipotonia com necessidade de internação por episódios de cianose/apneia. O eletroencefalograma não mostrou atividade epileptiforme. A neuroimagem revelou hipersinal lenticular bilateral com lesão do putâmen e do globo pálido esquerdo. Encontrou-se a mutação 8993T>G (MT-ATP6) no DNA mitocondrial.
Comentários:
De 10 a 30% dos doentes com síndrome de Leigh apresentam mutações do DNA mitocondrial. A descompensação com agravamento neurológico após intervenção anestésica está descrita e, nesse caso, apoiou o diagnóstico. Importante alertar para casos semelhantes, com diminuição de exames invasivos para diagnóstico.info:eu-repo/semantics/publishedVersio
Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
Get PDFUnverricht-Lundborg disease (ULD) is a common form of progressive myoclonic epilepsy caused by mutations in the cystatin B gene (CSTB) that encodes an inhibitor of several lysosomal cathepsins. Presently, only pharmacological treatment and psychosocial support are available for ULD patients. To overcome the pathogenic effect of the ULD splicing mutation c.66G>A (exon 1), we investigated whether an antisense oligonucleotide therapeutic strategy could correct the defect in patient cells. A specific locked nucleic acid (LNA) antisense oligonucleotide was designed to block a cryptic 5'ss in intron 1. Overall, this approach allowed the restoration of the normal splicing pattern. Furthermore, the recovery was both sequence and dose-specific. In general, this work provides a proof of principle on the correction of a CSTB gene defect causing ULD through a mutation-specific antisense therapy. It adds evidence to the feasibility of this approach, joining the many studies that are paving the way for translating antisense technology into the clinical practice. The insights detailed herein make mutation-based therapy a clear candidate for personalized treatment of ULD patients, encouraging similar investigations into other genetic diseases.This work was funded by FCT (Fundação para a Ciência e a Tecnologia—MCTES, Portugal) project PTDC/BBB-BMD/6301/2014. Liliana Matos was grant recipient from FCT under the same project.info:eu-repo/semantics/publishedVersio