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There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.
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Neoplasias de Cabeza y Cuello , Virus del Papiloma Humano , Infecciones por Papillomavirus , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidor p16 de la Quinasa Dependiente de Ciclina , ADN Viral/genética , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/epidemiología , Virus del Papiloma Humano/genética , Virus del Papiloma Humano/aislamiento & purificación , Japón/epidemiología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virologíaRESUMEN
Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK.
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Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR. Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: ⢠Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. ⢠The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: ⢠Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. ⢠Routine and semi-professional sports activities seem safe environments to promote during this pandemic.
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COVID-19 , SARS-CoV-2 , Humanos , Adolescente , Adulto Joven , Niño , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Estudios Prospectivos , CuarentenaRESUMEN
Several clinical trials are working on drug development for Duchenne and Becker muscular dystrophy (DMD and BMD) treatment, and, since the expected increase in dystrophin is relatively subtle, high-sensitivity quantification methods are necessary. There is also a need to quantify dystrophin to reach a definitive diagnosis in individuals with mild BMD, and in female carriers. We developed a method for the quantification of dystrophin in DMD and BMD patients using spectral confocal microscopy. It offers the possibility to capture the whole emission spectrum for any antibody, ensuring the selection of the emission peak and allowing the detection of fluorescent emissions of very low intensities. Fluorescence was evaluated first on manually selected regions of interest (ROIs), proving the usefulness of the methodology. Later, ROI selection was automated to make it operator-independent. The proposed methodology correctly classified patients according to their diagnosis, detected even minimal traces of dystrophin, and the results obtained automatically were statistically comparable to the manual ones. Thus, spectral imaging could be implemented to measure dystrophin expression and it could pave the way for detailed analysis of how its expression relates to the clinical course. Studies could be further expanded to better understand the expression of dystrophin-associated protein complexes (DAPCs).
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Distrofina , Distrofia Muscular de Duchenne , Humanos , Femenino , Distrofina/genética , Distrofina/metabolismo , Distrofia Muscular de Duchenne/diagnóstico por imagen , Distrofia Muscular de Duchenne/metabolismoRESUMEN
BACKGROUND: Understanding the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools. METHODS: During July 2020, we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through (1) a surveillance program in 22 summer schools of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) during 2-5 weeks; and (2) cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centers followed prevention protocols: bubble groups, handwashing, face masks, and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and the effective reproduction number in summer schools (Re*) were calculated. RESULTS: Among the >2000 repeatedly screened participants, 30 children and 9 adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median, 9 [interquartile range, 5-10] for each primary case), among which 12 new cases (4.7%) were positive for SARS-CoV-2. The Re* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9. CONCLUSIONS: The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission, supporting current recommendations for school opening.
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COVID-19 , Adulto , Niño , Humanos , Pandemias , SARS-CoV-2 , Instituciones Académicas , España/epidemiologíaRESUMEN
OBJECTIVES: Biliary atresia (BA) is still an enigmatic disease. Deeper knowledge of its pathophysiology could help develop better treatments. SOX9 regulates bile duct development, liver regeneration and fibrosis; therefore, it could be determinant in characterizing BA liver damage. Aim: To study if there is a SOX9 expression pattern in liver biopsies from BA patients. METHODS: Liver biopsies from BA patients (group BA), from age-matched infants without primary hepatic disease (group Control), and from patients with other liver conditions (group OLC) were compared. Expression of SOX9 was checked for: amount, intensity of immunoreaction, localization within ductular structures, perifibrotic epithelial cells, and lobular cells. The scores were added to create a scale from 0 to 11 that allowed group comparison. SOX9 Scale and liver survival were also looked for a correlation. RESULTS: All BA cases had a score >4, while all controls scored <4. OLC livers scored 1 to 8 (3.5â±â2.0) (Pâ<â0.001 between all groups). A cut-off at 4 had 100% sensitivity and 88.24% specificity to differentiate BA from Controls and from OLC (area under receiver operating characteristic curve: 0.9989 (95% confidence interval: 0.9964-1.000). Strong expression of SOX9 was observed mainly in the nuclei of proliferated ductules of portal spaces and fibrotic bridges. SOX9 Scale score could not be related to liver survival in this study. CONCLUSION: In BA livers, SOX9 is mainly expressed in reactive ductular epithelium, following a pattern significantly different from that seen in non-BA patients; thus, SOX9 Scale may have a role in the diagnosis of BA.
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Atresia Biliar , Atresia Biliar/diagnóstico , Biopsia , Epitelio/metabolismo , Humanos , Lactante , Hígado/patología , Factor de Transcripción SOX9/metabolismoRESUMEN
AIM: To study neurotransmitter status in children with early epileptic and developmental and epileptic encephalopathy (DEE) and to explore the clinical response to dopaminergic and serotoninergic therapies in a group of patients. METHOD: Two hundred and five patients (111 males [54.1.%] and 94 females [45.9%], mean age 10 months at the onset of epilepsy [SD 1 year 1 month], range 0-3 year) with epileptic encephalopathy/DEE were recruited, including those with West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, myoclonic encephalopathy in non-progressive disorders, infantile spasms, Doose syndrome, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and those unclassified. Cerebrospinal fluid (CSF) neurotransmitter studies and patients' medical records were reviewed. Additionally, we present clinical data of 10 patients with low CSF neurotransmitter levels who received dopaminergic/serotoninergic treatments. RESULTS: Abnormal neurotransmitter values were identified in 68 (33%) patients. 5-Hydroxyindoleacetic acid (5-HIAA) deficit was the most prevalent alteration (91%). Low CSF 5-HIAA levels were significantly higher in 1- to 3-year-old children. A negative significant correlation was found between 5-HIAA levels and epilepsy duration before CSF study (Spearman's ρ=-0.191, p=0.007). Abnormalities in deep grey matter were associated with low levels of CSF homovanillic acid and 5-HIAA. Ten patients with low CSF neurotransmitter levels received dopamine and/or serotonin therapies. Six of them showed initial decrease of seizure frequency and severity and maintained improvement in some neurodevelopmental skills. INTERPRETATION: A considerable number of patients showed neurotransmitter abnormalities. Age at seizure onset and duration of epilepsy before CSF study were the principal factors related to neurotransmitter depletion. Early monoamine supplementation would seem advisable as a neuroprotective strategy. WHAT THIS PAPER ADDS: 5-Hydroxyindoleacetic acid homeostasis is especially vulnerable in patients with epileptic encephalopathy/developmental and epileptic encephalopathy. Age of seizure onset and duration of epilepsy are determinants of neurotransmitter depletion.
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Epilepsias Mioclónicas , Epilepsia , Espasmos Infantiles , Preescolar , Electroencefalografía , Epilepsia/terapia , Femenino , Humanos , Ácido Hidroxiindolacético/uso terapéutico , Lactante , Masculino , Neurotransmisores , Convulsiones , Espasmos Infantiles/tratamiento farmacológicoRESUMEN
BACKGROUND: Susceptibility of children and adults to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and persistence of antibody response to the virus after infection resolution remain poorly understood, despite their significant public health implications. METHODS: A prospective cross-sectional seroprevalence study with volunteer families that included at least 1 first-reported adult case positive by SARS-CoV-2 by polymerase chain reaction (PCR) and at least 1 child aged <15 years living in the same household under strict home confinement was conducted in the metropolitan Barcelona Health Region, Spain, during the pandemic period 28 April 2020-3 June 2020. All household members were tested at home using a rapid SARS-CoV-2 antibody assay with finger prick-obtained capillary blood. RESULTS: A total of 381 family households including 381 first-reported PCR-positive adult cases and 1084 contacts (672 children, 412 adults) were enrolled. SARS-CoV-2 seroprevalence rates were 17.6% (118 of 672) in children and 18.7% (77 of 335) in adult contacts (Pâ =â .64). Among first-reported cases, seropositivity rates varied from 84.0% in adults previously hospitalized and tested within 6 weeks since the first positive PCR result to 31.5% in those not hospitalized and tested after that lag time (Pâ <â .001). Nearly all (99.9%) positive children were asymptomatic or had mild symptoms. CONCLUSIONS: Children appear to have similar probability as adults to become infected by SARS-CoV-2 in quarantined family households but remain largely asymptomatic. Adult antibody protection against SARS-CoV-2 seems to be weak beyond 6 weeks post-infection confirmation, especially in cases that have experienced mild disease.
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COVID-19 , SARS-CoV-2 , Adulto , Niño , Estudios Transversales , Humanos , Estudios Prospectivos , Estudios Seroepidemiológicos , España/epidemiologíaRESUMEN
BACKGROUND: Umbilical cord blood (UCB) donation is becoming inefficient and we recently proposed the estimated fetal weight percentile (EFWp) ≥60th as a predictor for a prenatal selection of donors. The aim of this study is to prospectively validate this and to identify new potential prenatal predictive parameters. STUDY DESIGN AND METHODS: Prospective cohort study of low-risk pregnancies undergoing third trimester ultrasound, whose UCB was collected at delivery (2016-2018) and compared with a historical cohort (2013-2016, N = 869). Several ultrasound parameters (EFWp, amniotic fluid, Doppler evaluation, placental thickness) were assessed ultrasound and perinatal data were collected. The association with standard of high quality of UCB was assessed by logistic regression analysis. RESULTS: Among 297 cases, 161 (54%) were selected according to the EFWp ≥60th for UCB units' collection. Cellular criteria for banking was achieved in 27 cases (16.8%), with an average increase of 1.7 times compared to the historical cohort (9.8%, P = .009). Selecting donors according to the 60th EFWp resulted in a higher probability of collecting clinical suitable UCB (P = .025). Among prenatal and perinatal parameters, EFWp, amniotic fluid, umbilical vein (UV) velocity, newborn weight and percentile and placental weight were significantly associated with a higher cellular content. At logistic regression analysis, significant contributors of UCB collection, were EFWp at 37-38 weeks ultrasound (OR 1.04; 95% CI: 1-1.08; P = .042) and UV velocity (OR 1.14; 95% CI: 1-1.29; P = .037). CONCLUSION: The evaluation of the EFWp equal or above 60 and the increased UV velocity can result in higher efficiency of public UCB donation programs.
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Donantes de Sangre/estadística & datos numéricos , Selección de Donante/métodos , Sangre Fetal/trasplante , Peso Fetal/fisiología , Adulto , Donantes de Sangre/provisión & distribución , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Humanos , Recién Nacido , Modelos Logísticos , Placenta/irrigación sanguínea , Embarazo , Tercer Trimestre del Embarazo , Atención Prenatal/normas , Estudios Prospectivos , Ultrasonografía/métodos , Ultrasonografía Doppler en Color/métodos , Venas Umbilicales/diagnóstico por imagenRESUMEN
In recent years, several studies have examined the possible relationship between periodontal disease in pregnant women and preterm birth. One of the difficulties facing these studies is the heterogeneity of the clinical criteria used to define periodontitis. The aim of this cross-sectional study was to determine the degree of association between maternal periodontitis and preterm birth according to different consensus definitions of periodontal disease. In a study of 146 mothers (60 with preterm births and 86 with term deliveries) at the Sant Joan de Déu Maternal and Children's Hospital in Barcelona, a periodontal examination was carried out within 2 days of birth and the presence of periodontal disease was evaluated using the main clinical classifications published in the literature. The prevalence of periodontitis ranged from 25.4 to 52.1%, depending on the criteria used for its definition. Using the most restrictive criteria, pregnant women with periodontitis had a higher risk of preterm birth (OR: 7.49; p < 0.001) and premature rupture of membranes (OR: 2.49; p = 0.017). Premature infants born to mothers with periodontitis presented a tendency toward low weight, adjusted for gestational age (OR: 3.32; p = 0.065). Our findings suggest that the association between periodontitis and preterm birth is influenced by the definitions of periodontitis used.
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Periodontitis , Nacimiento Prematuro , Niño , Estudios Transversales , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Periodontitis/complicaciones , Periodontitis/diagnóstico , Periodontitis/epidemiología , Embarazo , Nacimiento Prematuro/epidemiologíaRESUMEN
Facial emotion recognition is considered the foundation of effective social functioning, but it has been found impaired in several clinical populations. How- ever, there are few validated tests to measure the ability. To the best of our knowledge, there is no validated measure in a Spanish population. We translated and validated Baron Cohen’s Face Test in a general Spanish population.
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Traducciones , Humanos , EspañaRESUMEN
OBJECTIVE: Phosphomannomutase deficiency (PMM2 congenital disorder of glycosylation [PMM2-CDG]) causes cerebellar syndrome and strokelike episodes (SLEs). SLEs are also described in patients with gain-of-function mutations in the CaV2.1 channel, for which acetazolamide therapy is suggested. Impairment in N-glycosylation of CaV2.1 promotes gain-of-function effects and may participate in cerebellar syndrome in PMM2-CDG. AZATAX was designed to establish whether acetazolamide is safe and improves cerebellar syndrome in PMM2-CDG. METHODS: A clinical trial included PMM2-CDG patients, with a 6-month first-phase single acetazolamide therapy group, followed by a randomized 5-week withdrawal phase. Safety was assessed. The primary outcome measure was improvement in the International Cooperative Ataxia Rating Scale (ICARS). Other measures were the Nijmegen Pediatric CDG Rating Scale (NPCRS), a syllable repetition test (PATA test), and cognitive scores. RESULTS: Twenty-four patients (mean age = 12.3 ± 4.5 years) were included, showing no serious adverse events. Thirteen patients required dose adjustment due to low bicarbonate or asthenia. There were improvements on ICARS (34.9 ± 23.2 vs 40.7 ± 24.8, effect size = 1.48, 95% confidence interval [CI] = 4.0-7.6, p < 0.001), detected at 6 weeks in 18 patients among the 20 responders, on NPCRS (95% CI = 0.3-1.6, p = 0.013) and on the PATA test (95% CI = 0.5-3.0, p = 0.006). Acetazolamide improved prothrombin time, factor X, and antithrombin. Clinical severity, epilepsy, and lipodystrophy predicted greater response. The randomized withdrawal phase showed ICARS worsening in the withdrawal group (effect size = 1.46, 95% CI = 2.65-7.52, p = 0.001). INTERPRETATION: AZATAX is the first clinical trial of PMM2-CDG. Acetazolamide is well tolerated and effective for motor cerebellar syndrome. Its ability to prevent SLEs and its long-term effects on kidney function should be addressed in future studies. Ann Neurol 2019;85:740-751.
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Acetazolamida/uso terapéutico , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/tratamiento farmacológico , Trastornos Congénitos de Glicosilación/diagnóstico , Trastornos Congénitos de Glicosilación/tratamiento farmacológico , Fosfotransferasas (Fosfomutasas)/deficiencia , Acetazolamida/farmacología , Adolescente , Inhibidores de Anhidrasa Carbónica/farmacología , Enfermedades Cerebelosas/genética , Niño , Preescolar , Trastornos Congénitos de Glicosilación/genética , Femenino , Glicosilación/efectos de los fármacos , Humanos , Masculino , Fosfotransferasas (Fosfomutasas)/genética , Método Simple Ciego , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To delineate the epileptic phenotype of LAMA2-related muscular dystrophy (MD) and correlate it with the neuroradiological and muscle biopsy findings, as well as the functional motor phenotype. METHODS: Clinical, electrophysiological, neuroradiological, and histopathological data of 25 patients with diagnosis of LAMA2-related MD were analyzed. RESULTS: Epilepsy occurred in 36% of patients with LAMA2-related MD. Mean age at first seizure was 8 years. The most common presenting seizure type was focal-onset seizures with or without impaired awareness. Visual aura and autonomic signs, including vomiting, were frequently reported. Despite a certain degree of variability, bilateral occipital or temporo-occipital epileptiform abnormalities were by far the most commonly observed. Refractory epilepsy was found in 75% of these patients. Epilepsy in LAMA2-related MD was significantly more prevalent in those patients in whom the cortical malformations were more extensive. In contrast, the occurrence of epilepsy was not found to be associated with the patients' motor ability, the size of their white matter abnormalities, or the amount of residual merosin expressed on muscle. SIGNIFICANCE: The epileptic phenotype of LAMA2-related MD is characterized by focal seizures with prominent visual and autonomic features associated with EEG abnormalities that predominate in the posterior quadrants. A consistent correlation between epileptic phenotype and neuroimaging was identified, suggesting that the extension of the polymicrogyria may serve as a predictor of epilepsy occurrence.
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Distrofias Musculares/congénito , Adolescente , Edad de Inicio , Anticonvulsivantes/uso terapéutico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Niño , Preescolar , Electroencefalografía , Electromiografía , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Distrofias Musculares/diagnóstico por imagen , Distrofias Musculares/tratamiento farmacológico , Distrofias Musculares/fisiopatología , Neuroimagen , Fenotipo , Adulto JovenRESUMEN
We assessed the utility of raloxifene (60 mg/day) as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 24-week, double-blind, randomized, placebo-controlled study. Patients were recruited from the inpatient and outpatient services of Parc Sanitari Sant Joan de Déu, Hospital Universitari Institut Pere Mata, and Corporació Sanitària Parc Taulí. Seventy eight postmenopausal women with schizophrenia were randomized to either adjunctive raloxifene or placebo. Sixty-eight began the clinical trial (37 women on raloxifene adjunct) and 31 on placebo adjunct. The outcome measures were: memory, attention and executive function. Assessment was conducted at baseline and at week 24. Between groups homogeneity was tested with the Student's t test for continuous variables and/or the Mann-Whitney U test for ordinal variables and the χ2 test or Fisher's exact test for categorical variables. The differences between the two groups in neuropsychological test scores were compared using the Student's t test. The sample was homogenous with respect to age, formal education, illness duration and previous pharmacological treatment. The addition of raloxifene to antipsychotic treatment as usual showed no differences in cognitive function. The daily use of 60 mg raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia has no appreciable effect.ClinicalTrials.gov Identifier: NCT01573637.
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Antipsicóticos/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Posmenopausia/efectos de los fármacos , Clorhidrato de Raloxifeno/farmacología , Esquizofrenia/tratamiento farmacológico , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Anciano , Antipsicóticos/administración & dosificación , Atención/efectos de los fármacos , Disfunción Cognitiva/etiología , Método Doble Ciego , Quimioterapia Combinada , Función Ejecutiva/efectos de los fármacos , Función Ejecutiva/fisiología , Femenino , Humanos , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Clorhidrato de Raloxifeno/administración & dosificación , Esquizofrenia/complicaciones , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Resultado del TratamientoRESUMEN
INTRODUCTION: Phosphomannomutase-2 deficiency (PMM2-CDG) is associated with a recognisable facial pattern. There are no early severity predictors for this disorder and no phenotype-genotype correlation. We performed a detailed dysmorphology evaluation to describe facial gestalt and its changes over time, to train digital recognition facial analysis tools and to identify early severity predictors. METHODS: Paediatric PMM2-CDG patients were evaluated and compared with controls. A computer-assisted recognition tool was trained. Through the evaluation of dysmorphic features (DFs), a simple categorisation was created and correlated with clinical and neurological scores, and neuroimaging. RESULTS: Dysmorphology analysis of 31 patients (4-19 years of age) identified eight major DFs (strabismus, upslanted eyes, long fingers, lipodystrophy, wide mouth, inverted nipples, long philtrum and joint laxity) with predictive value using receiver operating characteristic (ROC) curveanalysis (p<0.001). Dysmorphology categorisation using lipodystrophy and inverted nipples was employed to divide patients into three groups that are correlated with global clinical and neurological scores, and neuroimaging (p=0.005, 0.003 and 0.002, respectively). After Face2Gene training, PMM2-CDG patients were correctly identified at different ages. CONCLUSIONS: PMM2-CDG patients' DFs are consistent and inform about clinical severity when no clear phenotype-genotype correlation is known. We propose a classification of DFs into major and minor with diagnostic risk implications. At present, Face2Gene is useful to suggest PMM2-CDG. Regarding the prognostic value of DFs, we elaborated a simple severity dysmorphology categorisation with predictive value, and we identified five major DFs associated with clinical severity. Both dysmorphology and digital analysis may help physicians to diagnose PMM2-CDG sooner.
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Trastornos Congénitos de Glicosilación/diagnóstico , Trastornos Congénitos de Glicosilación/genética , Facies , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Fenotipo , Fosfotransferasas (Fosfomutasas)/deficiencia , Adolescente , Niño , Preescolar , Femenino , Pruebas Genéticas , Humanos , Masculino , Fosfotransferasas (Fosfomutasas)/genética , Curva ROC , España , Adulto JovenRESUMEN
PURPOSE: To study the relationship between symptoms of anal incontinence (AI) and the anatomy and functionality of the levator ani muscle in women with a history of obstetric anal sphincter injury (OASI). METHODS: This is a cohort study including patients with OASI from 2013 to 2016. Patients were assessed by a physical examination, endoanal ultrasound using Starck Scale, perineometry and 4D transperineal ultrasound. AI in all patients was measured with the Wexner scale. Correlation between variables has been analyzed in these patients. RESULTS: 72 patients were analyzed: 28 with a IIIA degree tear, 26 with a IIIB, 13 with a IIIC and 5 with a IV. 38 patients showed a residual anal sphincter (AS) defect on endoanal ultrasound with an average Starck score of 6.5 ± 3.7. 21 patients expressed AI, with an average Wexner score of 4.1 ± 2.4. In 27 (37.5%) patients, a levator ani avulsion was observed: 17 unilateral and 10 bilateral. Patients with a levator ani defect had weaker pelvic floor muscle (PFM) function. These differences were statistically significant with perineometry (p = 0.01 and p = 0.03) but not for the Oxford test (p = 0.08). Patients with a residual AS defect as well as an injury to the levator ani muscle expressed greater AI symptomatology than patients with residual sphincter injury who maintain the integrity of the levator ani: Wexner 4.9 0.9 vs 3.3 1 (p = 0.02). CONCLUSIONS: The PFM has correlation with AI symptom development in patients with a history of OASI. Therefore, we suggest a key role of anatomical and functional assessments of the levator ani muscle in these patients.
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Canal Anal/lesiones , Enfermedades del Ano/etiología , Dolor/etiología , Diafragma Pélvico/fisiopatología , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , Factores de RiesgoRESUMEN
BACKGROUND: The need for high-cellular-content cord blood units (CBUs) for allogenic transplantation is evident to improve clinical outcomes. In our environment and with current donation programs, very few collected units meet suggested clinical thresholds, making collection programs highly inefficient. To increase the clinical conversion rate, we have assessed factors influencing the cellular content of the cord blood collection and established the estimated fetal weight percentile (EFWp) as a tool to predict which deliveries will obtain higher cellular counts. STUDY DESIGN AND METHODS: We conducted a retrospective analysis of 11,349 collected CBUs. An analysis of diagnostic efficiency (receiver operating characteristic [ROC] curve) was performed to establish the cutoffs of several obstetric and perinatal variables from which we would obtain more than 1500 × 106 total nucleated cells and 4 × 106 CD34 cells. We then calculated the optimal EFWp cutoff to increase efficiency. RESULTS: In the univariate analysis, factors positively and significantly associated were a greater neonatal and placental weight and longer weeks of gestation. In the multivariate analysis only neonatal and placental weight remain significant (p < 0.001). The ROC curve analysis showed that the optimal EFWp cutoff is 60, which has the maximum area under the curve. Applying this, donations meeting clinical cellular numbers will increase more than 30% with respect to not using any threshold. CONCLUSION: The EFWp predicts the quality of the collected CBUs and can be used to make a prenatal selection of the donors, therefore increasing the efficiency of umbilical cord blood collection programs.
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Almacenamiento de Sangre/métodos , Recolección de Muestras de Sangre/métodos , Sangre Fetal/citología , Peso Fetal , Donantes de Sangre , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Estudios RetrospectivosRESUMEN
Phosphomannomutase deficiency (PMM2-CDG) causes a cerebellar syndrome that has been evaluated using the International Cooperative Ataxia Rating Scale (ICARS). However, no particular dysarthria tests have been used. Speech ICARS subscore subjectively assesses fluency and clarity of speech with two items. Repetition of syllables, traditionally used for characterization of ataxic speech, was validated in early-onset ataxia conditions. We assess the validity of the PATA test (SCA Functional Index [SCAFI]) in PMM2-CDG patients.PATA rates from 20 patients were compared with a control population were and correlated with ICARS and neuroimaging.There was a difference between the PATA rate in patients and controls. PATA rate increased with age in controls. In patients, the improvement of PATA rate with age was not significant. In patients, the PATA rate was negatively correlated with the total ICARS score and the Speech ICARS subscore. Regarding neuroimaging, midsaggital vermis relative diameter was positively correlated with PATA results. These last differences were also significant when the results are corrected by age.PATA rate provides an easy measure for a quantitative assessment of dysarthria that may help clinicians to monitor patients' evolution in a regular consultation. It could also be used in PMM2-CDG clinical trials implementing ICARS speech subscore information.
Asunto(s)
Enfermedades Cerebelosas/diagnóstico , Trastornos Congénitos de Glicosilación/complicaciones , Disartria/diagnóstico , Fosfotransferasas (Fosfomutasas)/deficiencia , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Factores de Edad , Enfermedades Cerebelosas/etiología , Niño , Disartria/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Estudios Prospectivos , Adulto JovenRESUMEN
AIM: Gamma-aminobutyric acid (GABA) is a major modulator in brain maturation and its role in many different neurodevelopmental disorders has been widely reported. Although the involvement of GABA in different disorders has been related to its regulatory function as an inhibitory neurotransmitter in the mature brain, co-transmitter, and signalling molecule, little is known about its role as a clinical biomarker in neuropaediatric disorders. The aim of this study is to report the cerebrospinal fluid (CSF) free-GABA concentrations in a large cohort of patients (n=85) with different neurological disorders. METHOD: GABA was measured in the CSF of neuropaediatric patients using capillary electrophoresis with laser-induced fluorescence detection. Other neurotransmitters (amino acids and monoamines) were also analysed. RESULTS: GABA concentrations in CSF were abnormal, with a greater frequency (44%) than monoamines (20%) in neuropaediatric patients compared with our reference values. Although we included a few patients with inborn errors of metabolism, GABA levels in CSF were more frequently abnormal in metabolic disorders than in other nosological groups. INTERPRETATION: Our work suggests further research into brain GABAergic status in neuropaediatric disorders, which could also lead to new therapeutic strategies. WHAT THIS PAPER ADDS: Homeostasis of GABA seems more vulnerable than that of monoamines in the developing brain. The highest GABA levels are found in the primary GABA neurotransmitter disorder SSADH deficiency. GABA alterations are not specific for any clinical or neuroimaging presentation.
Asunto(s)
Epilepsia/líquido cefalorraquídeo , Discapacidad Intelectual/líquido cefalorraquídeo , Errores Innatos del Metabolismo/líquido cefalorraquídeo , Enfermedades Mitocondriales/líquido cefalorraquídeo , Trastornos del Movimiento/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Ácido gamma-Aminobutírico/líquido cefalorraquídeo , Adolescente , Adulto , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Adulto JovenRESUMEN
Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in CACNA1A (encoding CaV2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the hypothesis of abnormal CaV2.1 function due to aberrant N-glycosylation as a potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell patch-clamp, N-glycosylation blockade and mutagenesis. Nine SLE were identified. Neuroimages showed no signs of stroke. Comparison of characteristics between SLE positive versus negative patients' group showed no differences. Acute and chronic phenotypes of patients with PMM2-CDG or CACNA1A channelopathies show similarities. Hypoglycosylation of both CaV2.1 subunits (α1A and α2α) induced gain-of-function effects on channel gating that mirrored those reported for pathogenic CACNA1A mutations linked to FHM and ataxia. Unoccupied N-glycosylation site N283 at α1A contributes to a gain-of-function by lessening CaV2.1 inactivation. Hypoglycosylation of the α2δ subunit also participates in the gain-of-function effect by promoting voltage-dependent opening of the CaV2.1 channel. CaV2.1 hypoglycosylation may cause ataxia and SLEs in PMM2-CDG patients. Aberrant CaV2.1 N-glycosylation as a novel pathomechanism in PMM2-CDG opens new therapeutic possibilities.