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From November 2014 to May 2017, 332 patients homogeneously treated with bortezomib, lenalidomide, and dexamethasone (VRD) induction, autologous stem cell transplant, and VRD consolidation were randomly assigned to receive maintenance therapy with lenalidomide and dexamethasone (RD; 161 patients) vs RD plus ixazomib (IRD; 171 patients). RD consisted of lenalidomide 15 mg/d from days 1 to 21 plus dexamethasone 20 mg/d on days 1 to 4 and 9 to 12 at 4-week intervals, whereas in the IRD arm, oral ixazomib at a dose of 4 mg on days 1, 8, and 15 was added. Therapy for patients with negative measurable residual disease (MRD) after 24 cycles was discontinued, whereas those who tested positive for MRD remained on maintenance with RD for 36 more cycles. After a median follow-up of 69 months from the initiation of maintenance, the progression-free survival (PFS) was similar in both arms, with a 6-year PFS rate of 61.3% and 55.6% for RD and IRD, respectively (hazard ratio, 1.136; 95% confidence interval, 0.809-1.603). After 2 years of maintenance, treatment was discontinued in 163 patients with negative MRD, whereas 63 patients with positive MRD continued with RD therapy. Maintenance discontinuation in patients tested negative for MRD resulted in a low progression rate (17.2% at 4 years), even in patients with high-risk features. In summary, our results show the efficacy of RD maintenance and support the safety of maintenance therapy discontinuation in patients with negative MRD at 2 years. This trial was registered at www.clinicaltrials.gov as #NCT02406144 and at EudraCT as 2014-00055410.
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Mieloma Múltiple , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Lenalidomida/uso terapéutico , Mieloma Múltiple/terapiaRESUMEN
BACKGROUND: Tibial plateau fractures involving posteromedial (PM) and posterolateral (PL) columns are complex injuries that require an appropriate approach. The management of the PL column in these cases can be controversial, and limitations using deep posteromedial interval approaches have been referenced. In this paper, a modification of the Lobenhoffer approach, designed to optimize the access to the PL column, is described in detail. The aim of this study was to assess the feasibility of this approach in a cadaveric anatomical study. MATERIALS AND METHODS: In total, five fresh-frozen cadaveric specimens were used for detailed anatomical study surrounding the approach. Relationships with cutaneous and deep neurovascular structures were evaluated. The exposure area of the PL and PM columns using this approach was assessed. RESULTS: The cadaveric study showed safe and adequate exposure. Oblique skin and fascia incision just medial to the posterior midline was safe to protect the medial sural cutaneous nerve and the small saphenous vein. Elevation of the popliteus and tibialis posterior muscles offered safe protection of the anterior tibial artery and popliteal neurovascular bundle during retractor placement. Adequate full proximal exposure of the PM and PL columns, including the posterolateral lateral (PLL) and posterolateral central (PLC) segments, was obtained in all specimens. CONCLUSIONS: The Modified Oblique Lobenhoffer (MOL) approach can be a feasible option to access PL and PM columns in tibial plateau fractures. LEVEL OF EVIDENCE: IV.
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Cadáver , Fijación Interna de Fracturas , Fracturas de la Meseta Tibial , Humanos , Estudios de Factibilidad , Fijación Interna de Fracturas/métodos , Fracturas de la Meseta Tibial/cirugíaRESUMEN
Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with Minimal Residual Disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA/GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (CI95% 0.21-0.81; p=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (-0.04-0.14; p<0.001) when adding uHLC IP recovery. Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after one year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment.
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PURPOSE: Optical coherence tomography (OCT) software is used to classify abnormality of macular thickness by colour category based on reference data from adult series. We assessed the impact of using paediatric reference thickness values for macular thickness instead of adult reference values. METHODS: Cross-sectional study. Primary and tertiary healthcare setting. Out of 140 healthy participants aged 5 to 18 years, 126 were eligible, 83% from European origin. Following a dilated eye examination and cycloplegic refraction, participants underwent macular scanning with OCT (Topcon 3D OCT-2000). Macular thickness paediatric reference values were recorded by spherical equivalent (SE) and sex, and the specific agreement between paediatric and adult reference values below or equal to percentile 5 and above percentile 95 was estimated. The absolute interocular differences for all macular parameters were determined. RESULTS: Multivariate regression analysis confirmed statistically independent positive associations between SE and average thickness, total volume, and temporal and inferior outer quadrants (all p values ≤ 0.003). The analysis also revealed higher values in males for average thickness, central thickness, and all inner macula quadrants (all p values ≤ 0.039). The use of the adult database only detected 49% of the extreme values (≤ p5 and > p95) in our paediatric sample. The 95th percentile limits for absolute interocular differences for all macular parameters ranged from 12 to 17 µm. CONCLUSIONS: OCT-based macular reference values for paediatric SE and sex improve detection of children with abnormal macular thicknesses. Interocular differences exceeding standard references for macular parameters should be considered for further examinations.
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Mácula Lútea , Tomografía de Coherencia Óptica , Adulto , Biometría , Niño , Estudios Transversales , Humanos , Masculino , Valores de Referencia , Refracción OcularRESUMEN
In this work, we report the room-temperature synthesis of pure calcium tungstate (CaWO4) and copper-doped calcium tungstate solid solution (Ca0.99Cu0.01WO4) by using a sonochemistry method. These materials were structurally characterized by X-ray diffraction (XRD) and Raman spectroscopy. The obtained XRD patterns were submitted to a Rietveld refinement showing, in both materials, a tetragonal phase with space group and point group of I41/a and C4h6, respectively. Microscopy images of both materials, obtained by field emission scanning electron microscopy, showed spherical agglomerated structures composed by spherical nanoparticles, while calcium and tungstate elements were identified by energy-dispersive X-ray spectroscopy for pure calcium tungstate and copper, calcium, and tungstate for Ca0.99Cu0.01WO4 solid solution. The decrease of optical band gap (Egap) from 4.0 eV (CaWO4) to 3.45 eV (Ca0.99Cu0.01WO4) confirmed the substitution of calcium atoms for copper atoms in the clusters [CaO8]. Maximum photoluminescence (PL) emission was shifted from 522 nm in the pure CaWO4 to 475 nm in the Ca0.99Cu0.01WO4 solid solution. Consequently, there was an increase of PL emissions intensity in the blue and green regions of the visible spectrum, due to electronic transitions between the orbitals O 2p, Cu 3d, and W 5d.
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AIM: The aim is to study access to intrathecal baclofen (ITB) for children with cerebral palsy (CP) in Europe, as an indicator of access to advanced care. METHODS: Surveys were sent to CP registers, clinical networks, and pump manufacturers. Enquiries were made about ITB treatment in children born in 1990 to 2005 by sex, CP type, level of gross motor function classification system (GMFCS) and age at the start of treatment. Access to ITB was related to the country's gross domestic product (GDP) and % GDP spent on health. RESULTS: In 2011 population-based data from Sweden, Norway, England, Portugal, Slovenia, and Denmark showed that 114 (3.4%) of 3,398 children with CP were treated with ITB, varying from 0.4 to 4.7% between centers. The majority of the children were at GMFCS levels IV-V and had bilateral spastic CP. In Sweden, dyskinetic CP was the most commonly treated subtype. Boys were more often treated with ITB than girls (p = 0.014). ITB was reported to be available for children with CP in 25 of 43 countries. Access to ITB was associated with a higher GDP and %GDP spent on health (p < 0.01). Updated information from 2019 showed remaining differences between countries in ITB treatment and sex difference in treated children was maintained. CONCLUSION: There is a significant difference in access to ITB for children with CP across Europe. More boys than girls are treated. Access to ITB for children with CP is associated with GDP and percent of GDP spent on health in the country.
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Baclofeno/uso terapéutico , Parálisis Cerebral/tratamiento farmacológico , Producto Interno Bruto/estadística & datos numéricos , Gastos en Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Relajantes Musculares Centrales/uso terapéutico , Adolescente , Baclofeno/administración & dosificación , Niño , Preescolar , Europa (Continente) , Femenino , Encuestas de Atención de la Salud , Humanos , Inyecciones Espinales , Masculino , Relajantes Musculares Centrales/administración & dosificaciónRESUMEN
BACKGROUND: Assessment of interobserver reproducibility and interocular symmetry using optical coherence tomography (OCT)-based measurements of the macular ganglion cell complex (GCC) in healthy children facilitates interpretation of OCT data. We assessed the interobserver reproducibility and interocular symmetry of GCC and evaluated candidate determinants. METHODS: This was a cross-sectional study performed in a primary and tertiary health-care setting. A total of 126 healthy participants aged 5 to 18 years were eligible. GCC scans were performed by 4 operators using the Topcon 3D OCT-2000 device. Intraclass correlation coefficients (ICCs) were used to estimate reproducibility and symmetry. Cut-off points for symmetry were defined as the 95th percentile of the absolute interocular difference for 6 GCC parameters. Percentile distributions of interocular difference were generated based on age and difference in absolute interocular spherical equivalent (SE). RESULTS: The reproducibility ICC ranged from 0.96 to 0.98 for all 6 GCC parameters. Cut-off points for interocular symmetry of the superior and inferior quadrants and total macular retinal nerve fibre layer thickness (mRNFL) and macular ganglion cell layer-inner plexiform layer thickness were 3.5, 4.5, 3.0, 3.0, 2.5, and 2.5 µm respectively. A positive association was observed between the absolute interocular difference of SE and superior and total mRNFL symmetry values (p = 0.047 and p = 0.040, respectively). CONCLUSIONS: OCT measurements of GCC in healthy children show excellent reproducibility. Interocular differences in SE should be assessed when mRNFL differences exceed the 95% cut-off. These findings can contribute to establish reference values for interocular symmetry in paediatric GCC parameters.
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Mácula Lútea/citología , Células Ganglionares de la Retina/citología , Tomografía de Coherencia Óptica/métodos , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Fibras Nerviosas , Variaciones Dependientes del Observador , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
AIM: To assess, at national level, the implementation of eight principles for infant- and family-centred developmental care (IFCDC) in neonatal units. A European expert group established eight 'Principles of care' in 2018 that define neurodevelopmental and family-centred care. METHODS: The implementation of each principle was assessed by a survey sent to level-III Spanish units. A principle was considered to be implemented if all answers to the principle-associated questions were positive. RESULTS: The response rate was 84.5% (65/77). No unit had implemented eight principles. Principle 1 (free parental access) was implemented in 21.5% of the centres; Principle 2 (psychological support) 40%; Principle 3 (pain management) 7.7%; Principle 4 (environmental influences) 29%; Principle 5 (postural support) 84.6%; Principle 6 (kangaroo-care) 67.7%; Principle 7 (breastfeeding) 23% and Principle 8 (sleep protection) in 46%. In units attending ≥50 very low birth weight (VLBW) infants, four or more principles had been implemented in 31% vs 13% <50 VLBW neonates (odds ratio 3.0 CI 95% 0.9-10.1, P .07). CONCLUSION: The principle with the highest implementation was related to newborn body positioning. Pain management was the principle with lowest implementation. More principles for IFCDC tend to be implemented in units providing care for a higher number of VLBW infants.
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Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Lactancia Materna , Niño , Femenino , Humanos , Cuidado del Lactante , Recién Nacido , PadresRESUMEN
IMPORTANCE: Optical coherence tomography software classifies abnormality of macular ganglion cell-inner plexiform layer thickness and macular retinal nerve fibre layer thickness based on adult series. BACKGROUND: We assessed the impact of using paediatric reference macular ganglion cell complex values instead of adult reference values. DESIGN: Cross-sectional study. Primary and tertiary health-care setting. PARTICIPANTS: Out of 140 healthy participants aged 5 to 18 years, 90% were eligible. METHODS: Following a dilated eye examination and cycloplegic refraction, participants underwent optical coherence tomography ganglion cell scans (Topcon 3D OCT-2000; Topcon Corporation, Tokyo, Japan). Right eye measurements for superior, inferior, and total layer thickness and spherical equivalent were reported, together with age, sex and origin. MAIN OUTCOME MEASURES: Paediatric reference values by age and spherical equivalent were produced, and the specific agreement between paediatric and adult ganglion cell complex reference values below or equal to percentile 5 was estimated. RESULTS: The multivariate analysis confirmed a positive association between spherical equivalent and macular ganglion cell-inner plexiform layer thickness, and between age and macular retinal nerve fibre layer (five out of six regression coefficients P values were ≤ 0.03). Specific agreement was 25% for ganglion cell-inner plexiform layer thickness and > 80% for macular retinal nerve fibre layer. Adult-based software identified low ganglion cell values in one in seven children compared to paediatric reference values (0.8% vs 5.5%, P = 0.031). CONCLUSIONS AND RELEVANCE: The availability of optical coherence tomography ganglion cell complex reference values for paediatric age and spherical equivalent groups can be used to improve detection of children with low cell layer thickness.
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Fibras Nerviosas , Retina/anatomía & histología , Células Ganglionares de la Retina/citología , Neuronas Retinianas/citología , Adolescente , Antropometría , Niño , Preescolar , Estudios Transversales , Bases de Datos Factuales , Femenino , Humanos , Masculino , Valores de Referencia , Refracción Ocular , Tomografía de Coherencia ÓpticaRESUMEN
AIM: To develop and evaluate a classification system for magnetic resonance imaging (MRI) findings of children with cerebral palsy (CP) that can be used in CP registers. METHOD: The classification system was based on pathogenic patterns occurring in different periods of brain development. The MRI classification system (MRICS) consists of five main groups: maldevelopments, predominant white matter injury, predominant grey matter injury, miscellaneous, and normal findings. A detailed manual for the descriptions of these patterns was developed, including test cases (www.scpenetwork.eu/en/my-scpe/rtm/neuroimaging/cp-neuroimaging/). A literature review was performed and MRICS was compared with other classification systems. An exercise was carried out to check applicability and interrater reliability. Professionals working with children with CP or in CP registers were invited to participate in the exercise and chose to classify either 18 MRIs or MRI reports of children with CP. RESULTS: Classification systems in the literature were compatible with MRICS and harmonization possible. Interrater reliability was found to be good overall (k=0.69; 0.54-0.82) among the 41 participants and very good (k=0.81; 0.74-0.92) using the classification based on imaging reports. INTERPRETATION: Surveillance of Cerebral Palsy in Europe (SCPE) proposes the MRICS as a reliable tool. Together with its manual it is simple to apply for CP registers.
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Encéfalo/diagnóstico por imagen , Parálisis Cerebral/clasificación , Parálisis Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Parálisis Cerebral/fisiopatología , Niño , Preescolar , Bases de Datos Bibliográficas/estadística & datos numéricos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Sistema de Registros , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
AIM: To monitor the trends in prevalence of cerebral palsy (CP) by birthweight in Europe, 1980 to 2003. METHOD: Data were collated from 20 population-based registers contributing to the Surveillance of Cerebral Palsy in Europe database. Trend analyses were conducted in four birthweight groups: <1000g (extremely low birthweight [ELBW]); 1000 to 1499g (very low birthweight [VLBW]); 1500 to 2499g (moderately low birthweight [MLBW]); and >2499g (normal birthweight [NBW]). RESULTS: The overall prevalence of CP decreased from 1.90 to 1.77 per 1000 live births, p<0.001, with a mean annual fall of 0.7% (95% confidence interval [CI] -0.3% to -1.0%). Prevalence in NBW children showed a non-significant trend from 1.17 to 0.89 per 1000 live births (p=0.22). Prevalence in MLBW children decreased from 8.5 to 6.2 per 1000 live births (p<0.001), but not linearly. Prevalence in VLBW children also declined from 70.9 to 35.9 per 1000 live births (p<0.001) with a mean annual fall of 3.4% (95% CI -2.4% to -4.3%). Prevalence in ELBW children remained stable, at a mean rate of 42.4 per 1000 live births. INTERPRETATION: The decline in prevalence of CP in children of VLBW continues, and confirms that previously reported. For the first time, there is also a significant decline among those of MLBW, resulting in a significant overall decrease in the prevalence of CP.
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Peso al Nacer , Parálisis Cerebral/epidemiología , Recién Nacido de Bajo Peso , Sistema de Registros/estadística & datos numéricos , Europa (Continente) , Humanos , PrevalenciaRESUMEN
AIM: Children with cerebral palsy (CP) often experience communication difficulties. We aimed to identify a classification system for communication of children with CP suitable for epidemiological surveillance. METHOD: Systems to classify the communication of children with CP were identified. The Communication Function Classification System (CFCS), Functional Communication Classification System (FCCS), and Viking Speech Scale (VSS) were chosen for further investigation and translated. They were administered to 155 children aged 4 to 13 years with CP (across all motor severity levels) from eight European countries. Children's parents/carers, speech therapists, and other health professionals applied the systems through direct observation. Other professionals applied them from case notes only. The systems were assessed for agreement, stability, ease, and feasibility of application. RESULTS: Test-retest stability was moderate-to-high for VSS (k=0.66-0.88), CFCS (k=uncomputed-0.91), and FCCS (k=0.52-0.91). Overall interrater agreement was fair to very good for every classification system. VSS achieved the best agreement between parents/carers and speech therapists. VSS was considered the easiest instrument to apply. INTERPRETATION: Because of its ease of use by a range of healthcare professionals, the VSS should be considered for CP registers which intend to survey speech intelligibility. For a wider assessment of communication, the CFCS or FCC should be considered.
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Parálisis Cerebral/fisiopatología , Trastornos de la Comunicación/clasificación , Monitoreo Epidemiológico , Pruebas Neuropsicológicas/normas , Psicometría/instrumentación , Adolescente , Parálisis Cerebral/complicaciones , Niño , Preescolar , Trastornos de la Comunicación/etiología , Femenino , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Little is known about the healthcare process for patients with prostate cancer, mainly because hospital-based data are not routinely published. The main objective of this study was to determine the clinical characteristics of prostate cancer patients, the, diagnostic process and the factors that might influence intervals from consultation to diagnosis and from diagnosis to treatment. METHODS: We conducted a multicentre, cohort study in seven hospitals in Spain. Patients' characteristics and diagnostic and therapeutic variables were obtained from hospital records and patients' structured interviews from October 2010 to September 2011. We used a multilevel logistic regression model to examine the association between patient care intervals and various variables influencing these intervals (age, BMI, educational level, ECOG, first specialist consultation, tumour stage, PSA, Gleason score, and presence of symptoms) and calculated the odds ratio (OR) and the interquartile range (IQR). To estimate the random inter-hospital variability, we used the median odds ratio (MOR). RESULTS: 470 patients with prostate cancer were included. Mean age was 67.8 (SD: 7.6) years and 75.4% were physically active. Tumour size was classified as T1 in 41.0% and as T2 in 40% of patients, their median Gleason score was 6.0 (IQR:1.0), and 36.1% had low risk cancer according to the D'Amico classification. The median interval between first consultation and diagnosis was 89 days (IQR:123.5) with no statistically significant variability between centres. Presence of symptoms was associated with a significantly longer interval between first consultation and diagnosis than no symptoms (OR:1.93, 95%CI 1.29-2.89). The median time between diagnosis and first treatment (therapeutic interval) was 75.0 days (IQR:78.0) and significant variability between centres was found (MOR:2.16, 95%CI 1.45-4.87). This interval was shorter in patients with a high PSA value (p = 0.012) and a high Gleason score (p = 0.026). CONCLUSIONS: Most incident prostate cancer patients in Spain are diagnosed at an early stage of an adenocarcinoma. The period to complete the diagnostic process is approximately three months whereas the therapeutic intervals vary among centres and are shorter for patients with a worse prognosis. The presence of prostatic symptoms, PSA level, and Gleason score influence all the clinical intervals differently.
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Vías Clínicas/estadística & datos numéricos , Detección Precoz del Cáncer/estadística & datos numéricos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Tiempo de Tratamiento/estadística & datos numéricos , Distribución por Edad , Anciano , Estudios de Cohortes , Escolaridad , Empleo/estadística & datos numéricos , Humanos , Masculino , Prevalencia , Neoplasias de la Próstata/epidemiología , España/epidemiologíaRESUMEN
OBJECTIVE: To describe the demographic and clinical profiles of a cohort of environmentally representative severe traumatic brain injury (TBI) cases collected for the past 25 years and to analyse the changes that occurred by dividing the analysis period into 3 equal time periods. MATERIAL AND METHODS: This was an observational cohort study of consecutive adult patients (>14 years of age) with severe closed TBI (Glasgow Coma Scale score [GCS]≤8) who were admitted during the first 48h after injury to the 12 de Octubre hospital from 1987 to 2012. The most relevant epidemiological and clinical variables reported in the literature were defined and compared in 3 equal time periods (1987-1995, 1996-2004 and 2005-2014). RESULTS: There was a 13% reduction in the frequency of severe TBI from the first to the last time period. An increase in the mean age from 35 to 43 years was observed, whereas the frequency of severe TBI according to sex remained approximately the same during the last decades of life. A distinct change was observed in the injury mechanism; traffic accidents decreased from 76% to 55%, particularly those involving 4-wheeled vehicles. However, falls increased significantly, especially in older women, and contusion and subdural haematoma were the most frequent structural injuries. Motor scores could not be reliably assessed for the last time period because of early intubation and sedative drug use. CONCLUSIONS: TBI epidemiology in Western countries has changed. This trend was also observed in our environment as an increase in mean age, which reflected the increase in falls among elderly patients.
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Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: The purpose of the study was to obtain a pediatric reference database for optic disc parameters and interocular symmetry. To ascertain factors that modify these parameters (age, spherical equivalent [SE], and sex). METHODS: This was a cross-sectional study. 90 patients aged 5-17 years fulfilled all the inclusion criteria. After a full examination including cycloplegic refraction, all patients underwent optical coherence tomography (OCT) of the papilla using the three-dimensional (3D) scan protocol of the Topcon 3D 2000 OCT device. We provide reference values for optic disc parameters in the pediatric population. We also retrieved interocular symmetry reference values for these parameters. RESULTS: The multivariate regression analysis did not reveal variations in any of the optic disc parameters associated with age, sex, or SE (all P ≥ 0.126). The 95th percentile limit for absolute interocular differences for the cup-to-disc area ratio was 0.24. The multivariate regression analysis revealed the absence of a correlation between asymmetry of the optic disc parameters and age, sex, and the interocular difference in SE (all P ≥ 0.105). CONCLUSION: Pediatric reference databases for optic disc parameters and ranges of normality for interocular symmetry provide key diagnostic support in diseases that affect the optic nerve.
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CLINICAL RELEVANCE: The detection of abnormal values of peripapillary nerve fibre layer (pRNFL) thickness measured with optical coherence tomography (OCT) is important for detecting optic nerve disease in children. BACKGROUND: To evaluate the level of agreement between the adult reference database supplied with an OCT device and the present paediatric study database for the measurement of pRNFL thickness in children. This study also aimed to provide reference values for pRNFL thickness according to the spherical equivalent in the paediatric population. METHODS: This was a cross-sectional study. One hundred and twenty-six healthy children were included, who had undergone a full ophthalmological examination including cycloplegic refraction and examination of pRNFL thickness using the Topcon 3D OCT 2000 device (Topcon Corporation, Tokyo, Japan). Values equal to or below the fifth percentile (≤p5) and above the 95th percentile (>p95) were considered abnormal. Observed agreement and specific agreement were investigated between OCT measurements classified with paediatric and adult reference values for normality. RESULTS: Values ≤ p5 in the adult database were recorded for 2 of the 30 values (6.6%) of the pRNFL values by quadrants ≤p5 in the paediatric database and 17 of the 88 (19.3%) values by sectors ≤p5. For values >p95 in the adult database, 88% by quadrants and 72% by sectors would have been classified as being within the normal range using the paediatric database. CONCLUSION: The use of adult reference values currently available in OCT devices can lead to classification errors concerning the normal range of pRNFL thickness in a large proportion of paediatric patients. The use of normative paediatric databases, such as the one discussed in this study, should be taken into consideration.
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INTRODUCTION: In light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their use while minimising the risk of delayed diagnosis of intracranial lesions (ICLs). Identifying children at higher risk of poor outcomes would enable them to be better monitored. The use of the blood-based brain biomarkers glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) could help clinicians in this decision. The overall aim of this study is to provide new knowledge regarding GFAP and UCH-L1 in order to improve TBI management in the paediatric population. METHODS AND ANALYSIS: We will conduct a European, prospective, multicentre study, the BRAINI-2 paediatric study, in 20 centres in France, Spain and Switzerland with an inclusion period of 30 months for a total of 2880 children and adolescents included. To assess the performance of GFAP and UCH-L1 used separately and in combination to predict ICLs on CT scans (primary objective), 630 children less than 18 years of age with mild TBI, defined by a Glasgow Coma Scale score of 13-15 and with a CT scan will be recruited. To evaluate the potential of GFAP and UCH-L1 in predicting the prognosis after TBI (secondary objective), a further 1720 children with mild TBI but no CT scan as well as 130 children with moderate or severe TBI will be recruited. Finally, to establish age-specific reference values for GFAP and UCH-L1 (secondary objective), we will include 400 children and adolescents with no history of TBI. ETHICS AND DISSEMINATION: This study has received ethics approval in all participating countries. Results from our study will be disseminated in international peer-reviewed journals. All procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT05413499.
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Biomarcadores , Lesiones Traumáticas del Encéfalo , Proteína Ácida Fibrilar de la Glía , Tomografía Computarizada por Rayos X , Ubiquitina Tiolesterasa , Humanos , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Ubiquitina Tiolesterasa/sangre , Niño , Biomarcadores/sangre , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Proteína Ácida Fibrilar de la Glía/sangre , Adolescente , Preescolar , Europa (Continente) , Femenino , Masculino , Lactante , Estudios Multicéntricos como Asunto , Valor Predictivo de las PruebasRESUMEN
A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.
RESUMEN
The CD3ε cytoplasmic tail contains a conserved proline-rich sequence (PRS) that influences TCR-CD3 expression and signaling. Although the PRS can bind the SH3.1 domain of the cytosolic adapter Nck, whether the PRS is constitutively available for Nck binding or instead represents a cryptic motif that is exposed via conformational change upon TCR-CD3 engagement (CD3Δc) is currently unresolved. Furthermore, the extent to which a cis-acting CD3ε basic amino acid-rich stretch (BRS), with its unique phosphoinositide-binding capability, might impact PRS accessibility is not clear. In this study, we found that freshly harvested primary thymocytes expressed low to moderate basal levels of Nck-accessible PRS ("open-CD3"), although most TCR-CD3 complexes were inaccessible to Nck ("closed-CD3"). Ag presentation in vivo induced open-CD3, accounting for half of the basal level found in thymocytes from MHC(+) mice. Additional stimulation with either anti-CD3 Abs or peptide-MHC ligands further elevated open-CD3 above basal levels, consistent with a model wherein antigenic engagement induces maximum PRS exposure. We also found that the open-CD3 conformation induced by APCs outlasted the time of ligand occupancy, marking receptors that had been engaged. Finally, CD3ε BRS-phosphoinositide interactions played no role in either adoption of the initial closed-CD3 conformation or induction of open-CD3 by Ab stimulation. Thus, a basal level of open-CD3 is succeeded by a higher, induced level upon TCR-CD3 engagement, involving CD3Δc and prolonged accessibility of the CD3ε PRS to Nck.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Complejo CD3/metabolismo , Prolina/metabolismo , Secuencias de Aminoácidos/inmunología , Animales , Complejo CD3/genética , Complejo CD3/inmunología , Línea Celular Tumoral , Epítopos de Linfocito T/fisiología , Hibridomas , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/metabolismo , Prolina/inmunología , Complejo Receptor-CD3 del Antígeno de Linfocito T/genética , Complejo Receptor-CD3 del Antígeno de Linfocito T/inmunología , Complejo Receptor-CD3 del Antígeno de Linfocito T/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
Metabolic diseases such as obesity and diabetes mellitus seem to have an influence on reoperation and long-term functional outcomes after arthroscopic repair of chronic rotator cuff tears. High prevalence of these pathologies can be found in the Canary Islands. A retrospective cohort study was carried out, in which 80 patients undergoing shoulder arthroscopic surgery for the repair of chronic rotator cuff tears were included, with a minimum follow up of 5 years, to study the occurrence of complications, reoperation, and functional outcomes. Functionality after surgery improved in 75% of patients with diabetes and remained the same or worsened in 25% (OR = 1.444). In the group of non-diabetic patients, 83.9% had improved function after surgery while it remained the same or worsened in 16.1% (OR = 0.830). Functionality after surgery improved in 76.6% of obese patients and remained the same or worsened in 23.4% (OR = 1.324). In the non-obese group, 87.9% had improved function after surgery, while it remained the same or worsened in 12.1% (OR = 0.598). Despite not obtaining statistically significant differences, the analysis of the results obtained suggests that obesity and diabetes could act by decreasing the subjective improvement in functionality after surgery, and, in the case of obesity, also increase the risk of reoperation.