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Children with Cerebral Palsy (CP) experience Social Cognition (SC) difficulties, which could be related to executive functioning. While motor interventions are common, there is limited knowledge about the impact of cognitive interventions on SC in this population. This study examined the relationship between SC and Executive Function (EF) skills and the effectiveness of an EF intervention that included some SC tasks for improving SC in children with CP. SC and EF domains were assessed in 60 participants with CP (30 females; 8-12 years). The relationship between SC and EF baseline scores was analyzed by bivariate correlations and contingency tables. Participants were matched by age, sex, motor ability, and intelligence quotient and randomized into intervention or control groups. The intervention group underwent a 12-week home-based computerized EF intervention. Analysis of covariance was used to examine differences in SC components between groups at post-intervention and 9 months after. Significant positive correlations were found between the SC and EF scores. The frequencies of impaired and average scores in SC were distributed similarly to the impaired and average scores in EFs. The intervention group showed significant improvements in Affect Recognition performance post-intervention, which were maintained at the follow-up assessment, with a moderate effect size. Long-term improvements in Theory of Mind were observed 9 months after. CONCLUSIONS: This study highlights the association between SC and EFs. A home-based computerized cognitive intervention program improves SC in children with CP. Including SC tasks in EF interventions may lead to positive short- and long-term effects for children with CP. CLINICAL TRIAL REGISTRATION: NCT04025749 retrospectively registered on 19 July 2019. WHAT IS KNOWN: ⢠Executive functions and social cognition are associated with social and community participation in people with cerebral palsy. ⢠A home-based computerized cognitive intervention can improve the executive functioning of children with cerebral palsy. WHAT IS NEW: ⢠Social cognition performance is related to core and higher-order executive functions. ⢠A home-based computerized executive function intervention, including social cognition tasks, has positive short- and long-term effects on social cognition skills in children with cerebral palsy.
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Paralisia Cerebral , Função Executiva , Cognição Social , Humanos , Paralisia Cerebral/psicologia , Paralisia Cerebral/reabilitação , Paralisia Cerebral/terapia , Feminino , Masculino , Criança , Resultado do Tratamento , Terapia Cognitivo-Comportamental/métodosRESUMO
BACKGROUND: Azathioprine is a widely prescribed drug for patients with chronic inflammatory diseases such as myasthenia gravis or organ transplant recipients. Azathioprine exerts immunosuppressive effects by inhibiting intracellular purine synthesis and reducing the numbers of circulating B and T lymphocytes. Case reports indicate increased risk for serious infections that can occur despite regular measurements of lymphocyte counts during azathioprine therapy. OBJECTIVE: We sought to comprehensively investigate therapy-associated patient risks and the underlying immune dysfunction of azathioprine use. METHODS: Peripheral blood leukocytes were analyzed using single-cell mass and spectral flow cytometry to detect specific effects of azathioprine use on the systemic immune signature. Therapy-associated clinical features were analyzed in 2 independent cohorts of myasthenia gravis patients. RESULTS: Azathioprine therapy selectively induced pronounced CD56dimCD16+ natural killer cell depletion and concomitant IFN-γ deficiency. Cytokine profiling revealed a specific contraction of classical TH1 cells during azathioprine treatment. We further observed an increased occurrence of reactivation of endogenous latent herpesviruses in the azathioprine-treated group versus in patients with myasthenia gravis who were not receiving immunomodulatory treatment; this increased occurrence was validated in an independent cohort. CONCLUSION: Our study highlights the risk of development of adverse events during azathioprine therapy and suggests that natural killer cell monitoring could be valuable in clinical practice.
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Herpesviridae , Miastenia Gravis , Humanos , Azatioprina/efeitos adversos , Células Matadoras Naturais , Interferon gama/farmacologia , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/induzido quimicamenteRESUMO
Children with cerebral palsy (CP) often show executive function (EF) impairments that are key to quality of life. The aim of this study was to assess whether a home-based computerized intervention program improves executive functions (EFs) compared to usual care. Sixty participants (30 females) with CP (8-12 years old) were paired by age, sex, motor ability, and intelligence quotient score and then randomized to intervention and waitlist control groups. The intervention group received a 12-week home-based computerized EF intervention (5 days/week, 30 min/day, total dose 30 h). Core and higher-order EFs were assessed before, immediately after, and 9 months after completing the intervention. The intervention group performed better than the waitlist control group in the three core EFs (immediately and 9 months after the intervention): inhibitory control (F = 7.58, p = 0.13 and F = 7.85, p = 0.12), working memory (F = 8.34, p = 0.14 and F = 7.55, p = 0.13), and cognitive flexibility (F = 4.87, p = 0.09 and F = 4.19, p = 0.08). No differences were found between the groups in higher-order EFs or EF manifestations in daily life. CONCLUSIONS: A home-based computerized EF intervention improved core EFs in children with CP, but further research is needed to identify strategies that allow the transfer of these improvements to everyday life. TRIAL REGISTRATION: NCT04025749 retrospectively registered on 19 July 2019. WHAT IS KNOWN: ⢠One in two children with cerebral palsy has an intellectual impairment. Visual perception and executive functions are the most reported specific cognitive deficits. ⢠The majority of interventions for cerebral palsy focus on motor impairments, but only a few randomized controlled trials have explored the effect of interventions on executive functions. WHAT IS NEW: ⢠A home-based computerized cognitive intervention can improve the core executive functions of children with cerebral palsy. ⢠Short- and long-term effects on core executive functions have been found.
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Paralisia Cerebral , Transtornos Cognitivos , Disfunção Cognitiva , Criança , Feminino , Humanos , Paralisia Cerebral/terapia , Função Executiva , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , MasculinoRESUMO
INTRODUCTION: Distal cholangiocarcinoma is a malignant epithelial neoplasia that affects the extrahepatic bile ducts, below the cystic duct. No relevant relationship between perioperative factors and worse long-term outcome has been proved. OBJECTIVE: To analyze the risk factors for mortality and long-term recurrence of distal cholangiocarcinoma in resected patients. MATERIALS AND METHODS: A single-center prospective database of patients operated on for distal cholangiocarcinoma between 1990 and 2021 was analyzed in order to investigate mortality and recurrence factors. RESULTS: One hundred and thirteen patients have undergone surgery, with mean actuarial survival of 100.2 (76-124) months after resection. The bivariate study did not show differences between patients depending on age or preoperative variables studied. When multivariate analysis was performed, the presence of affected adenopathy was a risk factor for long-term mortality. The presence of affected lymph nodes, tumor recurrence, and biliary fistula during the postoperative period implied worse actuarial survival when comparing the Kaplan-Meier curves. CONCLUSIONS: The presence of affected lymph nodes influence the prognosis of the disease. The occurrence of biliary fistula during postoperative cholangiocarcinoma distal could aggravate long-term outcomes, a finding that should be reaffirmed in future studies.
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INTRODUCTION/AIMS: Very few studies analyzing the pattern of muscle involvement in magnetic resonance imaging (MRI) of patients with McArdle disease have been reported to date. We aimed to examine the pattern of muscle fat replacement in patients with McArdle disease. METHODS: We performed a retrospective study including all patients with genetically confirmed McArdle disease followed in our center from January 2010 to March 2021. Clinical data were collected from the medical record. Whole-body MRI was performed as part of the diagnostic evaluation. The distribution of muscle fat replacement and its severity were analyzed. RESULTS: Nine patients were included. Median age at onset was 7 y (range, 5-58) and median age at the time when MRI was performed was 57.3 y (range, 37.2-72.8). At physical examination, four patients had permanent weakness: in three the weakness was limited to paraspinal muscles, whereas in one the weakness involved the paraspinal and proximal upper limb muscles. Muscle MRI showed abnormalities in six of the seven studied patients. In all of them, fat replacement of paravertebral muscles was found. Other muscles frequently affected were the tongue in three, subscapularis in three, and long head of biceps femoris and semimembranosus in two. DISCUSSION: Our findings suggest that paraspinal muscle involvement is common in McArdle disease and support the need to include this disease in the differential diagnosis of the causes of paraspinal muscle weakness. Involvement of the tongue and subscapularis are also frequent in McArdle disease.
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Doença de Depósito de Glicogênio Tipo V , Músculos Paraespinais , Adulto , Doença de Depósito de Glicogênio Tipo V/diagnóstico por imagem , Doença de Depósito de Glicogênio Tipo V/patologia , Humanos , Imageamento por Ressonância Magnética , Debilidade Muscular/etiologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Músculos Paraespinais/diagnóstico por imagem , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: Mild cognitive impairment (MCI), as a stage in the cognitive continuum between normal ageing and dementia, is mainly characterized by memory impairment. The aims of this study were to examine CANTAB measures of temporal changes of visual memory in MCI and to evaluate the usefulness of the baseline scores for predicting changes in cognitive status. METHODS: The study included 201 participants aged over 50 years with subjective cognitive complaints. Visual memory was assessed with four CANTAB tests [paired associates learning (PAL), delayed matching to sample (DMS), pattern recognition memory (PRM) and spatial span (SSP)] administered at baseline and on two further occasions, with a follow-up interval of 18-24 months. Participants were divided into three groups according to the change in their cognitive status: participants with subjective cognitive complaints who remained stable, MCI participants who remained stable (MCI-Stable) and MCI participants whose cognitive deterioration continued (MCI-Worsened). Linear mixed models were used to model longitudinal changes, with evaluation time as a fixed variable, and multinomial regression models were used to predict changes in cognitive status. RESULTS: Isolated significant effects were obtained for age and group with all CANTAB tests used. Interactions between evaluation time and group were identified in the PAL and DMS tests, indicating different temporal patterns depending on the changes in cognitive status. Regression models also indicated that CANTAB scores were good predictors of changes in cognitive status. CONCLUSIONS: Decline in visual memory measured by PAL and DMS tests can successfully distinguish different types of MCI, and considered together PAL, DMS, PRM and SSP can predict changes in cognitive status.
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Disfunção Cognitiva/diagnóstico , Transtornos da Memória/diagnóstico , Testes Neuropsicológicos/estatística & dados numéricos , Idoso , Envelhecimento/fisiologia , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos/fisiologiaRESUMO
OBJECTIVE: To identify CT-acquisition parameters accounting for radiomics variability and to develop a post-acquisition CT-image correction method to reduce variability and improve radiomics classification in both phantom and clinical applications. METHODS: CT-acquisition protocols were prospectively tested in a phantom. The multi-centric retrospective clinical study included CT scans of patients with colorectal/renal cancer liver metastases. Ninety-three radiomics features of first order and texture were extracted. Intraclass correlation coefficients (ICCs) between CT-acquisition protocols were evaluated to define sources of variability. Voxel size, ComBat, and singular value decomposition (SVD) compensation methods were explored for reducing the radiomics variability. The number of robust features was compared before and after correction using two-proportion z test. The radiomics classification accuracy (K-means purity) was assessed before and after ComBat- and SVD-based correction. RESULTS: Fifty-three acquisition protocols in 13 tissue densities were analyzed. Ninety-seven liver metastases from 43 patients with CT from two vendors were included. Pixel size, reconstruction slice spacing, convolution kernel, and acquisition slice thickness are relevant sources of radiomics variability with a percentage of robust features lower than 80%. Resampling to isometric voxels increased the number of robust features when images were acquired with different pixel sizes (p < 0.05). SVD-based for thickness correction and ComBat correction for thickness and combined thickness-kernel increased the number of reproducible features (p < 0.05). ComBat showed the highest improvement of radiomics-based classification in both the phantom and clinical applications (K-means purity 65.98 vs 73.20). CONCLUSION: CT-image post-acquisition processing and radiomics normalization by means of batch effect correction allow for standardization of large-scale data analysis and improve the classification accuracy. KEY POINTS: ⢠The voxel size (accounting for the pixel size and slice spacing), slice thickness, and convolution kernel are relevant sources of CT-radiomics variability. ⢠Voxel size resampling increased the mean percentage of robust CT-radiomics features from 59.50 to 89.25% when comparing CT scans acquired with different pixel sizes and from 71.62 to 82.58% when the scans were acquired with different slice spacings. ⢠ComBat batch effect correction reduced the CT-radiomics variability secondary to the slice thickness and convolution kernel, improving the capacity of CT-radiomics to differentiate tissues (in the phantom application) and the primary tumor type from liver metastases (in the clinical application).
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Análise de Dados , Processamento de Imagem Assistida por Computador , Humanos , Imagens de Fantasmas , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
"Hemosuccus pancreaticus" (HP), "wirsungorrhagia" or "pseudohemobilia" is a rare cause of upper gastrointestinal bleeding consisting of blood loss along the duct of Wirsung with exteriorization through the ampulla of Vater. Due to its rarity, the literature on HP is limited to retrospective studies, case reports, and case series.
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Ampola Hepatopancreática , Neoplasias Intraductais Pancreáticas , Ampola Hepatopancreática/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Humanos , Ductos Pancreáticos/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: Cerebral palsy (CP) is frequently associated with specific cognitive impairments, such as executive dysfunction which are related to participation and quality of life (QOL). The proposed study will examine whether a computerized executive function (EF) training programme could provide superior benefits for executive functioning, participation, QOL and brain plasticity, as compared to usual care. METHODS: A single-blind randomized controlled trial (RCT) design will be performed. Thirty children with CP aged 8 to 12 years will participate in a home-based computerized multi-modal executive training programme (12 weeks, 5 days a week, 30 min a day training, total dose = 30 h). Thirty children with CP matched by age, sex, motor and intelligence quotient (IQ) will compose the waitlist group. Cognitive, behavioural, emotional, participation and QOL measures will be obtained at three time points: before, immediately after and 9 months after completing the training. Additionally, structural and functional (resting state) magnetic resonance images (MRI) will be obtained in a subsample of 15 children from each group. Outcomes between groups will be compared following standard principles for RCTs. DISCUSSION: The study will test whether the cognitive training programme exerts a positive effect not only on neuropsychological and daily functioning of children with CP but also on other measures such as participation and QOL. We will also use brain MRI to test brain functional and structural changes after the intervention. If this on-line and home-based training programme proves effective, it could be a cost-effective intervention with short- and long-term effects on EF, participation or QOL in CP. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04025749. Registered 19 July 2019. Retrospectively registered.
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Paralisia Cerebral , Disfunção Cognitiva , Encéfalo , Criança , Função Executiva , Humanos , Imageamento por Ressonância Magnética , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. MATERIAL AND METHODS: A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher's exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. RESULTS: RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). CONCLUSION: RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD.
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Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Idoso , Colecistectomia , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Valor Preditivo dos Testes , Prognóstico , Reoperação , Estudos Retrospectivos , Medição de Risco , Taxa de SobrevidaRESUMO
Animals fight over resources such as mating partners, territory, food or shelter and repeated contests lead to stable social hierarchies in different phyla. The group dynamics of hierarchy formation are not characterized in the Norway lobster (Nephrops norvegicus). Lobsters spend most of the day in burrows and forage outside of them according to a diel (i.e. 24â h-based) activity rhythm. Here, we use a linear and generalized mixed model approach to analyse, in seven groups of four male lobsters, the formation of dominance hierarchies and rank-related changes in burrowing behaviour. We show that hierarchies emerge within 1-3â days and increase in steepness over a period of 5â days, while rank changes and number of fights gradually decrease over a 5-day period. The rank position determined by open area fights predicts the outcome of fights over burrows, the time spent in burrows, and the locomotor activity levels. Dominant lobsters are more likely to evict subordinate lobsters from their burrows and are more successful in defending their own burrows. They spend more time in burrows and display lower levels of locomotor activity outside the burrow. Lobsters do not change their diel activity rhythms as a result of a change in rank, and all tested individuals showed higher activity at night and dusk compared with dawn and daytime. We discuss how behavioural changes in burrowing behaviour could lead to rank-related benefits such as reduced exposure to predators and energy savings.
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Comportamento Animal , Nephropidae/fisiologia , Animais , Ritmo Circadiano , Comportamento Competitivo , Hierarquia Social , MasculinoRESUMO
INTRODUCTION: A borderline resectable group (APBR) has recently been defined in adenocarcinoma of the pancreas. The objective of the study is to evaluate the results in the surgical treatment after neoadjuvancy of the APBR. METHOD: Between 2010 and 2014, we included patients with APBR in a neoadjuvant and surgery protocol, staged by multidetector computed tomography (MDCT). Treatment with chemotherapy was based on gemcitabine and oxaliplatin. Subsequently, MDCT was performed to rule out progression, and 5-FU infusion and concomitant radiotherapy were given. MDCT and resection were performed in absence of progression. A descriptive statistical study was performed, dividing the series into: surgery group (GR group) and progression group (PROG group). RESULTS: We indicated neoadjuvant treatment to 22 patients, 11 of them were operated, 9 pancreatoduodenectomies, and 2 distal pancreatectomies. Of the 11 patients, 7 required some type of vascular resection; 5 venous resections, one arterial and one both. No postoperative mortality was recorded, 7 (63%) had any complications, and 4 were reoperated. The median postoperative stay was 17 (7-75) days. The pathological study showed complete response (ypT0) in 27%, and free microscopic margins (R0) in 63%. At study clossure, all patients had died, with a median actuarial survival of 13 months (9,6-16,3). The median actuarial survival of the GR group was higher than the PROG group (25 vs. 9 months; p < 0.0001). CONCLUSION: The neoadjuvant treatment of APBR allows us to select a group of patients in whom resection achieves a longer survival to the group in which progression is observed. Post-adjuvant pancreatic resection requires vascular resection in most cases.
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Adenocarcinoma/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias PancreáticasRESUMO
The ultimatum game is commonly used to explore fairness in adults in bargaining situations. Although the changes in responses that occur during development have been investigated in children, the results have been mixed. Whereas some studies show that proposers offer more when they grow older, others indicate the opposite. Moreover, these studies are outcome-based and leave intentions out of the scene, although intentions play a relevant role in daily life. The mini-ultimatum game offers the opportunity to test both outcomes and intentions, but one major obstacle for accurately pinpointing developmental transitions in strategic behavior and inequity aversion so far has been the multiple confounds that have plagued previous studies, including different methods, small sample sizes, and reduced age differences. We administered an anonymous direct-method one-shot mini-ultimatum game to 478 6- and 10-year-old children. Strategic behavior was present at 10 years of age; older participants matched more accurately what responders would accept than younger participants. However, this was true only for older girls. No sex differences were detected in younger children. No age group seemed to consider the proposer's intentions given that the rejections of the default option were not significant across conditions. Both disadvantageous and advantageous inequity aversions were present in 6-year-olds. However, older children exhibited significantly more disadvantageous inequity aversion than younger children. This contrast made the pattern of rejection of 6-year-olds look more similar to the pattern of rejection found in adults. No sex differences were found in responders' behavior.
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Envelhecimento/psicologia , Comportamento Infantil/psicologia , Comportamento de Escolha , Intenção , Caracteres Sexuais , Adulto , Afeto/fisiologia , Criança , Feminino , Jogos Experimentais , Humanos , Masculino , Comportamento SocialRESUMO
INTRODUCTION: To decide treatment of hepatic cysts diagnosis between simple hepatic cyst (SHC) and cystic mucinous neoplasm (CMN). Radiological features are not patognomonic. Some studies have suggested the utility of intracystic tumor markers. METHODS: Retrospective analysis of our prospective database including patients treated due to symptomatic SHC from 2003 to 2021. The aim of the study was to evaluate the results of treatment of symptomatic SHC and the usefulness of the determination of intracystic "carcinoembryonic antigen" (CEA) and "carbohydrate antigen" CA 19.9. RESULTS: 50 patients diagnosed and treated for symptomatic SHC were included. In 15 patients the first treatment was percutaneous drainage. In 35 patients the first treatment was laparoscopic fenestration. Four patients were diagnosed of premalignant or malignant liver cystic lesions (MCN, IPMN, lymphoma B); three of them required surgery after initial fenestration and pathological diagnosis. Median CEA and CA 19-9 were 196 µg/L and 227.321 U/mL respectively. Patients with malignant or premalignant pathology did not have higher levels of intracystic tumor markers. Positive predictive value was 0% for both markers, and negative predictive value was 89% and 91% respectively. CONCLUSION: Values of intracystic tumor markers CEA and CA 19-9 do not allow distinguishing simple cysts from cystic liver neoplasms. The most effective treatment for symptomatic simple liver cysts is surgical fenestration. The pathological analysis of the wall of the cysts enables the correct diagnosis, allowing to indicate a surgical reintervention in cases of hepatic cyst neoplasia.
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Cistos , Hepatopatias , Neoplasias Hepáticas , Humanos , Antígeno Carcinoembrionário/análise , Biomarcadores Tumorais , Estudos Retrospectivos , Cistos/diagnóstico , Cistos/cirurgia , Antígeno CA-19-9/análise , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgiaRESUMO
INTRODUCTION: Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLM) and its indication and results have varied in the last 30 years. METHODS: All patients operated on for CRLM in our centre from 1990 to 2021 were prospectively collected, establishing 3 subgroups based on the year of the first surgery: group A 1990-1999, group B 2000-2010, group C 2011-2021. Clinical characteristics and the results of survival, recurrence and prognostic factors were compared. RESULTS: 1736 hepatectomies were included (Group A n = 208; Group B n = 770; Group C n = 758). Patients in group C had better survival at 5 and 10 years (A 40.5%/28.2%; B 45.9%/32.2%; C 51.6%/33.1%, p = 0.013), although there were no differences between groups in overall recurrence at 5 and 10 years (A 73%/75.7%; B 67.6%/69.2%, and C 63.9%/66%, p = 0.524), nor in liver recurrence (A 46.4%/48.2%; B 45.8%/48.2%; and C 44.4%/48.4%, p = 0.899). An improvement was observed in median survival after recurrence, being 19 months, 23 months, and 31 months (groups A, B and C respectively). Prognostic factors of long-term survival changed over the 3 study periods. The only ones that remained relevant in the last decade were the presence of >4 liver metastasis, extrahepatic disease at the time of hepatectomy, and intraoperative blood transfusion. CONCLUSIONS: Survival after surgery for CRLM has improved significantly, although this cannot be explained by a reduction in overall and hepatic recurrence, but rather by an improvement in post-recurrence survival. Involvement of the resection margin has lost prognostic value in the last decade.
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Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Hepatectomia/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Fatores de Tempo , Estudos Prospectivos , Taxa de Sobrevida , Prognóstico , Adulto , Idoso de 80 Anos ou maisRESUMO
Serological tests are important to detect autoantibodies (autoAbs) in patients with autoimmune neuropathies (AN) and myasthenia gravis (MG) as they are biomarkers for diagnosis, stratification, treatment selection, and monitoring. However, tests to detect autoAbs frequently lack proper standardization and results differ across diagnostic laboratories. We compared results for tests routinely performed in Spanish diagnostic laboratories to detect AN and MG autoAbs. In the Spanish Society of Immunology Autoimmunity Group national workshop, serum samples from 13 patients with AN or MG were tested for anti-ganglioside, anti-myelin-associated glycoprotein (MAG), anti-nicotinic acetylcholine receptor (AChR), and anti-muscle-specific kinase (MuSK) autoAbs using reference methods and were distributed for analysis to 27 participating laboratories using their routine methods. Overserved were inter-laboratory variability and worryingly low sensitivity, especially for anti-ganglioside immunoglobulin G and anti-MAG autoAb detection. This pilot study reflects autoAbs detection state of the art in AN and MG testing in leading diagnostic laboratories in Spain, highlighting the need for standardization prior to clinical use.
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Autoanticorpos , Miastenia Gravis , Humanos , Miastenia Gravis/diagnóstico , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Autoanticorpos/sangue , Projetos Piloto , Espanha , Masculino , Feminino , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/sangue , Pessoa de Meia-Idade , Receptores Colinérgicos/imunologia , Adulto , IdosoRESUMO
BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38ß MAPK) for the treatment of facioscapulohumeral muscular dystrophy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4-driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. FINDINGS: Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45·7 (SD 12·5) years. Least squares mean changes from baseline in DUX4-driven gene expression did not differ significantly between the losmapimod (0·83 [SE 0·61]) and placebo (0·40 [0·65]) groups (difference 0·43 [SE 0·56; 95% CI -1·04 to 1·89]; p=0·56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drug-related) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. INTERPRETATION: Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy. FUNDING: Fulcrum Therapeutics.
Assuntos
Distrofia Muscular Facioescapuloumeral , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ciclopropanos/efeitos adversos , Ciclopropanos/uso terapêutico , Método Duplo-Cego , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Resultado do TratamentoRESUMO
Pompe disease is a rare genetic disorder with an estimated prevalence of 1:60.000. The two main phenotypes are Infantile Onset Pompe Disease (IOPD) and Late Onset Pompe Disease (LOPD). There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment. We created a registry to collect all these data from patients with Pompe in Spain. Here, we report the data of the 122 patients registered including nine IOPD and 113 LOPD patients. There was a high variability in how the diagnosis was obtained and how the follow-up was performed among different centres. Seven IOPD patients were still alive being all treated with enzymatic replacement therapy (ERT) at last visit. Ninety four of the 113 LOPD patients had muscle weakness of which 81 were receiving ERT. We observed a progressive decline in the results of muscle function tests during follow-up. Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient's journey and clinical characteristics of patients in Spain. Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country.
Assuntos
Doença de Depósito de Glicogênio Tipo II , Humanos , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/terapia , alfa-Glucosidases/genética , Fenótipo , Sistema de Registros , Terapia de Reposição de Enzimas/métodosRESUMO
The aim of this study was to describe the relationship between low-income Chilean adolescent maternal playfulness and mothers' non-intrusiveness in their children's development and to analyze whether a mother's non-intrusiveness mediates the relationship between maternal playfulness and children's development. The Parental Playfulness Scale and the Subscale of Intrusiveness from the Early Head Start Research and Evaluation Project were used to assess maternal playfulness and mothers' non-intrusiveness respectively. Ages and Stages Questionnaire 3rd Edition (ASQ-3) was applied to measure the children's communication, gross and fine motor skills, problem-solving and personal-social development. The sample consisted of 79 mother-child dyads with children aged 10-24 months (M = 15.5, SD = 4.2) and their mothers aged 15-21 years old (M = 19.1, SD = 1.7). A bivariate analysis showed that maternal playfulness was significantly associated with communication, fine motor, problem-solving and personal-social development. Moreover, higher levels of communication, fine motor skills and problem-solving development were observed in the children of less intrusive mothers. Maternal playfulness had a significant effect on children's development of language, problem-solving and personal-social skills when their mothers showed less intrusiveness during interaction. These findings contribute to the understanding of the interaction between adolescent mothers and their children. Active play and less intrusiveness can enhance child development.
RESUMO
The lack of economic resources has a negative effect on the maternal role of younger mothers. In Chile, the majority of adolescent pregnancies occur in socially and economically vulnerable contexts. The current study aimed to examine the relationship between demographic variables within the family context and parenting behaviors among Chilean adolescent mothers (including affection, responsiveness, encouragement, and teaching). These factors were correlated with communication, problem-solving abilities, and personal-social development in typically developing infants. The study included a sample of 79 Chilean adolescent mother-child dyads with children aged 10 to 24 months. Communication, problem-solving, and personal-social development were assessed using the Ages and Stages Questionnaire-3, along with a demographic information questionnaire. The parenting behaviors mentioned above were observed using the Spanish version of Parenting Interactions with Children: Checklist of Observations Linked to Outcomes. The findings indicated that mothers in employment and those who had not dropped out of school had children with better problem-solving skills. Additionally, children residing with their fathers and female children performed better in communication, problem-solving, and personal-social development. Maternal responsiveness was associated with communication and problem-solving, while maternal encouragement was linked to improved problem-solving skills. Maternal teaching was connected to communication, problem-solving, and personal-social development. The study emphasized the significance of parenting and sociodemographic factors among adolescent mothers and their influence on their children's development.