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Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.
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BACKGROUND: Abdominal sarcomas are a heterogeneous group of rare soft tissue tumors and can be localized intraperitoneally or retroperitoneally. A pretherapeutic differentiated subtyping is essential for planning an individual, multimodal treatment concept in an interdisciplinary team of experts. OBJECTIVE: The central aspects of histology acquisition, imaging diagnostics and (molecular) pathological subtyping of abdominal soft tissue sarcomas are described in detail. MATERIAL AND METHODS: Imaging and pathological diagnostics are depicted based on the German S3 guidelines on adult soft tissue sarcomas, a current literature search and personal experiences at the Sarcoma Center at the National Center for Tumor Diseases in Dresden (NCT/UCC). RESULTS: Preoperative imaging and (molecular) pathological subtyping of abdominal soft tissue sarcomas place high demands on surgeons, radiologists and pathologists. Genome analyses of sarcomas have the potential to identify points of attack for individualized treatment options. The limitations of resectability can only be assessed by experienced sarcoma surgeons at specialized centers. CONCLUSION: The treatment of abdominal soft tissue sarcomas at an experienced center is associated with a better prognosis. Even at the first suspicion of an abdominal sarcoma, a referral to an experienced center should be made in order to guarantee optimal expertise in diagnostics and treatment.
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Sarcoma , Neoplasias de los Tejidos Blandos , Adulto , Terapia Combinada , Humanos , Pronóstico , Derivación y Consulta , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugíaRESUMEN
Aim of this study was to investigate frequency, incidence and risk factors of liver cysts in the general population in a longitudinal survey. Cyst frequency was investigated in 607 adult volunteers (288 women, 319 men, mean age 55 years) using strong T2-weighted magnetic resonance imaging. Risk factors were investigated for occurrence, frequency and size of cystic lesions at baseline. Incidence and physiological growing of the lesions were observed in a 5-years follow-up. At baseline, 431 volunteers had 1,479 cysts (71.0%). The mean number of cysts per person was 3.4 ± 9.0. The mean size of cysts was 13.1 ± 11.7 mm. Women had a higher number of cysts than men (p = 0.026). Older and male volunteers demonstrated a higher cyst frequency (p = 0.002 and p = 0.025). Per one-year increase in age the chance for a liver cyst increased by 2%. Four-hundred seventeen volunteers had cysts in the follow-up, in 24.6% new lesions had occurred. Lesion size significantly increased in follow-up (p < 0.001). Age and male sex were associated with the occurrence of at least one liver cyst. Women had a higher average number of cysts. Cystic lesion progression is a physiological phenomenon in the long-term follow-up.
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Quistes/epidemiología , Neoplasias Hepáticas/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores , Quistes/diagnóstico por imagen , Quistes/patología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Hallazgos Incidentales , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Factores de Riesgo , Adulto JovenRESUMEN
AIM: To define reference values for the transverse relaxation rate (R2∗) in iron storage organs and to investigate the role of human haemochromatosis protein (HFE) genotype on iron storage. MATERIALS AND METHODS: Whole-body magnetic resonance imaging (MRI) including a five-echo gradient-echo sequence was performed in 483 volunteers (269 men, mean age 59.3 ± 12.2 years) without clinical evidence of an iron storage disease at 1.5 T. R2∗ values were assessed for liver, spleen, pancreas, heart, bones, and brain parenchyma. The HFE genotype was determined regarding the single nucleotide polymorphisms (SNPs) rs74315324, rs1799945, rs41303501, rs1800562, rs1800730. R2∗ values were compared among participants without and with at least one mutation. R2∗ reference values were defined using volunteers without any mutation. RESULTS: Three hundred and one participants had no mutations in any HFE SNP, 182 had at least one mutation. HFE gene mutations were distributed as (heterozygous/homozygous) rs1799945:132/9, rs1800562:33/1, and rs1800730:11/0. Mean R2∗ values ± SD (per second) in the group without mutation were: liver: 33.4 ± 12.7, spleen: 24.1 ± 13.8, pancreas: 27.2 ± 6.6, heart: 32.7 ± 11.8, bone: 69.3 ± 21.0, brain parenchyma: 13.9 ± 1.2. No significant difference in R2∗ values were found between participants with and without the HFE gene mutation for any examined iron storage organ (pliver=0.09, pspleen=0.36, ppancreas = 0.08, pheart = 0.36, pbone = 0.98, pbrain=0.74). CONCLUSION: Reference values of R2∗ in iron storage organs are feasible to support the diagnosis of iron storage diseases. Non-specific mutations in HFE SNPs appear not to affect the phenotype of tissue iron accumulation.
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Proteína de la Hemocromatosis/genética , Hemocromatosis/diagnóstico , Hierro/metabolismo , Imagen por Resonancia Magnética/métodos , Polimorfismo de Nucleótido Simple/genética , Imagen de Cuerpo Entero/métodos , Estudios de Cohortes , Femenino , Genotipo , Alemania , Hemocromatosis/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the eccrine sweat glands. Due to the lack of effective therapies, metastasis is associated with a high mortality rate. OBJECTIVES: To investigate the drivers of EPC progression. METHODS: We carried out genomic and transcriptomic profiling of metastatic EPC (mEPC), validation of the observed alterations in an EPC patient-derived cell line, confirmation of relevant observations in a large patient cohort of 30 tumour tissues, and successful treatment of a patient with mEPC under the identified treatment regimens. RESULTS: mEPC was characterized by a high tumour mutational burden (TMB) with an ultraviolet signature, widespread copy number alterations and gene expression changes that affected cancer-relevant cellular processes such as cell cycle regulation and proliferation, including a pathogenic TP53 (tumour protein 53) mutation, a copy number deletion in the CDKN2A (cyclin dependent kinase inhibitor 2A) region and a CTNND1/PAK1 [catenin delta 1/p21 (RAC1) activated kinase 1] gene fusion. The overexpression of EGFR (epidermal growth factor receptor), PAK1 and MAP2K1 (mitogen-activated protein kinase kinase 1; also known as MEK1) genes translated into strong protein expression and respective pathway activation in the tumour tissue. Furthermore, a patient-derived cell line was sensitive to EGFR and MEK inhibition, confirming the functional relevance of the pathway activation. Immunohistochemistry analyses in a large patient cohort showed the relevance of the observed changes to the pathogenesis of EPC. Our results indicate that mEPC should respond to immune or kinase inhibitor therapy. Indeed, the advanced disease of our index patient was controlled by EGFR-directed therapy and immune checkpoint inhibition for more than 2 years. CONCLUSIONS: Molecular profiling demonstrated high TMB and EGFR/MAPK pathway activation to be novel therapeutic targets in mEPC.
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Porocarcinoma Ecrino , Receptores ErbB , Sistema de Señalización de MAP Quinasas , Neoplasias de las Glándulas Sudoríparas , Porocarcinoma Ecrino/genética , Receptores ErbB/genética , Humanos , Terapia Molecular Dirigida , Mutación , Neoplasias de las Glándulas Sudoríparas/tratamiento farmacológico , Neoplasias de las Glándulas Sudoríparas/genéticaAsunto(s)
COVID-19 , Inhibidores de Puntos de Control Inmunológico , Humanos , Inmunoterapia , SARS-CoV-2RESUMEN
In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.
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Biomarcadores de Tumor/análisis , Síndromes Mielodisplásicos/clasificación , Síndromes Mielodisplásicos/diagnóstico , Neoplasias Primarias Secundarias/clasificación , Neoplasias Primarias Secundarias/diagnóstico , Medición de Riesgo/métodos , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Neoplasias Primarias Secundarias/terapia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Evidence for the association of atrial fibrillation (AF) present on the ECG and cardiovascular outcomes in AF patients is limited. OBJECTIVE: To investigate the prognostic significance of AF on a single surface ECG for cardiovascular outcomes in AF patients. METHODS: A total of 3642 AF patients were prospectively enrolled. Main exclusion criteria were rhythms other than sinus rhythm (SR) or AF. The primary end-point was a composite of all-cause death and hospitalizations for congestive heart failure (CHF). Secondary end-points were all-cause death, CHF hospitalizations, cardiovascular death, myocardial infarction, any stroke and stroke subtypes. Associations were assessed with multivariable Cox proportional hazards models. RESULTS: Mean age was 71 years, 28% were female, and mean follow-up was 3.4 years. Patients with SR on the ECG at study enrolment (56%) were younger (69 vs. 74 years, P < 0.0001), had more often paroxysmal AF (73 vs. 18%, P < 0.0001) and fewer comorbidities. The incidence of the primary end-point was 1.8 and 3.1 per 100 person-years in patients with SR and AF, respectively. The multivariable-adjusted hazard ratio was 1.4 (95% confidence intervals 1.1; 1.7; P = 0.001) for patients with AF on the ECG compared to patients with SR. The hazard ratios (95% confidence intervals) were 1.4 (1.1; 1.8; P = 0.006) for all-cause death, 1.5 (1.2; 1.9; P = 0.001) for CHF and 1.6 (1.1; 2.2; P = 0.006) for cardiovascular death. None of the other associations were statistically significant. CONCLUSIONS: The presence of AF in a single office ECG had significant prognostic implications with regard to mortality and CHF hospitalizations in patients with AF. These patients present a high-risk group and might benefit from intensified treatment.
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Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Electrocardiografía , Anciano , Fibrilación Atrial/mortalidad , Causas de Muerte , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Visita a Consultorio Médico , Pronóstico , Estudios Prospectivos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidadRESUMEN
The current coronavirus disease of 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions can provide fine-grained resolution of the mechanisms behind the virus biology and the human organism response. We present a curated dataset of physical molecular interactions focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family that has been manually extracted by International Molecular Exchange (IMEx) Consortium curators. Currently, the dataset comprises over 4400 binarized interactions extracted from 151 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (https://www.ebi.ac.uk/intact) and will be continuously updated as research on COVID-19 progresses.
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Betacoronavirus , Coronaviridae , Infecciones por Coronavirus , Interacciones Huésped-Patógeno , Pandemias , Neumonía Viral , Mapas de Interacción de Proteínas , COVID-19 , Humanos , Especificidad de Órganos , Proteómica , SARS-CoV-2 , Proteínas ViralesRESUMEN
BACKGROUND: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. METHODS: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. RESULTS: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. CONCLUSION: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.
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Complicaciones Posoperatorias/diagnóstico , Mallas Quirúrgicas/efectos adversos , Adherencias Tisulares/diagnóstico , Consenso , Técnica Delphi , Femenino , Humanos , MasculinoRESUMEN
In a previous study, we showed that access to willow fodder decreased somatic cell counts (SCC) in the milk of local Mamber goats grazing in brushland at the end of lactation. To test whether the consumption of willow affects the cells of the immune system, Alpine crossbred dairy goats grazing in the same environment were either offered free access to freshly cut willow fodder (W, n = 24) or not (C, n = 24) for 2 weeks. The willow fodder contained 7.5 g/kg DM of salicin. The other major secondary compounds were catechin, myricitrin, hyperin and chlorogenic acid (2.2, 2.6, 1.0 and 0.75 g/kg DM, respectively). Udder health status was determined before the experiment, and each of the two groups included five (W) or six (C) goats defined as infected, as established by microbial cfu in milk, and 19 (W) or 18 (C) non-infected goats. Goats ingested, on average, 600 g of DM from willow (25% of food intake), resulting in minor changes in dietary quality compared to the controls, as established by faecal near-IR spectrometry. Throughout the 2 weeks of experiment, differences between groups in dietary CP contents were minor and affected neither by infection nor by access to willow; the dietary percentage of neutral detergent fibre (NDF) decreased in C and increased in W; dietary acid detergent fibre (ADF) increased; and the dietary tannin contents decreased for both treatments. However, milking performance and milk quality attributes in both W and C goats were similar. Initial SCC and milk neutrophil (cluster of differentiation (CD)18+ and porcine granulocyte (PG)68) cell counts were higher in infected than in non-infected goats; counts decreased significantly in W but not in C uninfected goats. The percentage of CD8+ T-cells increased in all C goats, while in the W group, a significant increase was found only for infected goats. The consumption of willow mitigated an increase in CD8+ in blood and triggered an increase in CD8+ in milk, suggesting an immune-regulatory effect independent of udder status. To our knowledge, this is the first report of a direct nutraceutical effect of fodder ingestion on the immune status of goats.
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Leche , Salix , Alimentación Animal , Animales , Femenino , Cabras , Lactancia , PorcinosRESUMEN
The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions enables studying fine-grained resolution of the mechanisms behind the virus biology and the human organism response. Here we present a curated dataset of physical molecular interactions, manually extracted by IMEx Consortium curators focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family. Currently, the dataset comprises over 2,200 binarized interactions extracted from 86 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website ( www.ebi.ac.uk/intact ), and will be continuously updated as research on COVID-19 progresses.
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OBJECTIVE: The gold standard for diagnosing anti-NMDAR encephalitis is demonstration of the antibody in CSF. Clinical diagnostic criteria have been proposed for when this is not available in a timely manner which is evaluated, in this study, for a psychiatric population. METHODS: This study retrospectively assessed the proposed criteria in patients presenting to psychiatric services for the first time with known anti-NMDAR antibody status. Antibody-positive cases were derived from the literature (conception to December 2019) and a state-wide (Queensland, Australia) cohort. Antibody-negative cases were derived from a service-wide (Metro South, Queensland, Australia) cohort of psychiatric cases which underwent antibody testing for routine organic screening. Sensitivity and specificity were calculated at 1 week following admission and the point of discharge. RESULTS: The proposed criteria were applied to 641 cases (500 antibody-positive and 141 antibody-negative), demonstrating a sensitivity which increased from around 19% after 1 week to 49% by the point of discharge. Specificity was 100% at both time points. The mean average time to become positive using the proposed criteria was 19.5 days compared to 34.9 days for return of antibody testing. CONCLUSIONS: High specificity of the proposed criteria, seen in this study, suggests that cases which are positive can be considered for expedited commencement of treatment. However, if clinical suspicion is high despite criteria being negative, it is essential to test CSF for anti-NMDAR antibody.
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Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Femenino , Humanos , Masculino , Servicios de Salud Mental , Queensland , Receptores de N-Metil-D-Aspartato/inmunología , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Even though endometriosis presents one of the most common gynaecological diseases, the pathogenesis is insufficiently studied. Besides immunologic, inflammatory or oxidative processes, recent studies also suggest an influence of nutrition on disease onset and progression. Because data about the actual nutrient intake of endometriosis patients are scarce, we aimed to examine the actual nutrient intake and potential influencing factors in these women. A total of 156 women with endometriosis (EM) and 52 age-matched controls were included in this retrospective case-control study. All women filled in a validated food frequency questionnaire to acquire the nutrient intake of the past 12 months and a disease-related questionnaire for the determination of disease status, clinical symptoms and comorbidities. Patients with endometriosis suffered significantly more from diet-related comorbidities like food intolerances (25.6% versus 7.7%; P = 0.009) and allergies (57% versus 31%; P < 0.001) compared to controls. Also gastrointestinal symptoms, including constipation, flatulence, pyrosis, diarrhea or frequent defecation, were higher in the EM group (77% versus 29%; P < 0.001). The nutrient intake of patients with endometriosis differed significantly compared to controls with a significantly lower ingestion of organic acids (P = 0.006), maltose (P = 0.0.16), glycogen (P = 0.035), tetradecenoic acid (P = 0.041), methionine (P = 0.046), lysine (P = 0.048), threonine (P = 0.046) and histidine (P = 0.049). The total intake of animal proteins was significantly lower in the EM group compared to the controls (P = 0.047). EM patients showed a decreased intake of vitamin C (P = 0.031), vitamin B12 (P = 0.008) and magnesium (P = 0.043) compared to controls. This study confirms a high association of endometriosis and gastrointestinal disorders accompanied by an altered nutrient intake. A dietary intervention by a professional nutritionist may help to reduce disease burden in the affected women.
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Endometriosis/etiología , Ingestión de Energía/fisiología , Enfermedades Gastrointestinales/etiología , Adulto , Estudios de Casos y Controles , Dieta , Femenino , Humanos , Prevalencia , Estudios Retrospectivos , Encuestas y Cuestionarios , Vitaminas/administración & dosificaciónRESUMEN
BACKGROUND AND PURPOSE: Antibodies to glycine receptors (GlyR-Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other clinical presentations. Our aim was to assess the clinical associations of all patients identified with GlyR-Abs in Queensland, Australia, between April 2014 and May 2017 and to compare these to cases reported in the literature. METHODS: A literature review identified the clinical features of all published GlyR-Ab-positive cases through online databases. A case series was undertaken via collection of clinical information from all patients diagnosed or known to immunology, pathology or neurological services in Queensland during the study period of 3 years. RESULTS: In all, 187 GlyR-Ab-positive cases were identified in the literature. The majority (47.6%) had PERM, 22.4% had epilepsy, but the remaining 30% included mixed phenotypes consisting of cerebellar ataxia, movement disorders, demyelination and encephalitis/cognitive dysfunction. By contrast, in our series of 14 cases, eight had clinical presentations consistent with seizures and epilepsy and only three cases had classical features of PERM. There was one case each of global fatiguable weakness with sustained clonus, laryngeal dystonia and movement disorder with hemiballismus and tics. The rate of response to immune therapy was similar in all groups. CONCLUSION: Antibodies to glycine receptors are linked to a spectrum of neurological disease. The results of the literature review and our case series suggest a greater relationship between GlyR-Abs and epilepsy than previously reported.
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Autoanticuerpos , Rigidez Muscular/inmunología , Mioclonía/inmunología , Receptores de Glicina/inmunología , Adolescente , Adulto , Anciano , Australia , Niño , Preescolar , Encefalitis/inmunología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/inmunología , Fenotipo , Adulto JovenAsunto(s)
Crisis Blástica/patología , Médula Ósea/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Biopsia , Femenino , Pruebas Genéticas , Humanos , Inmunofenotipificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes. RESULTS: The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal. CONCLUSIONS: PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and download.
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Mapas de Interacción de Proteínas , Proteoma/metabolismo , Proteómica , Bases de Datos de Proteínas , Humanos , Mutación/genética , Biología de SistemasRESUMEN
INTRODUCTION: Periacetabular osteotomy (PAO) is an effective procedure in treatment of symptomatic hip dysplasia. To achieve a good outcome a strict patient selection has to be applied. The aim of this study was to evaluate the influence of patient age at surgery on clinical outcome. METHODS: In a prospective study 86 patients (106 hips) underwent clinical and radiographic follow-up at a mean time of 5 years (2.5-8.5â¯years) after PAO. Patient-related outcome measurements (PROMs: EQ-5D, WOMAC, OHS, GTO) were applied preoperatively as well as postoperatively and the deformity correction as well as development of osteoarthritis were evaluated. In order to analyze the influence of patient age at surgery on clinical outcome, we subdivided the patient cohort into four different age groups (<20â¯years, 20-29â¯years, 30-39â¯years, >40â¯years). RESULTS: Of the patients 90% were very satisfied or satisfied with the results 5 years after surgery, and in all age groups PROMs significantly increased. Even though preoperative as well as postoperative algofunction declined in cohorts with increasing age, the overall benefit as measured in WOMAC and EQ-5D scores was equal in all age groups. Increasing age is associated with a progression in osteoarthritis as well as a higher conversion rate to total arthroplasty. DISCUSSION: Age is an important influencing factor on the long-term outcome after PAO. A certain age as cut off for indications could not be identified in this study. Even patients in the age groups 30-39 years and >â¯40 years showed PROM improvement and satisfaction with outcome at medium-term follow-up. The expected success rate has to be discussed preoperatively with the patient; however, as a higher conversion rate to hip arthroplasty as well as progressive osteoarthritis is associated with higher age, not only patient age alone but also morphological characteristics of the hip joint have to be taken into consideration.
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Acetábulo/cirugía , Luxación de la Cadera/cirugía , Osteotomía/métodos , Acetábulo/diagnóstico por imagen , Adolescente , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Luxación de la Cadera/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Columna Vertebral/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: The purpose of this study was to compare the results of immediate and delayed percutaneous sacroiliac screws surgery for unstable pelvic fractures, regarding technical results and complication rate. DESIGN: Retrospective study. SETTING: The study was conducted at the Soroka University Medical center, Beer Sheva, Israel, which is a level 1 trauma Center. PATIENTS: 108 patients with unstable pelvic injuries were operated by the orthopedic department at the Soroka University Medical Center between the years 1999-2010. A retrospective analysis found 50 patients with immediate surgery and 58 patients with delayed surgery. Preoperative and postoperative imaging were analyzed and data was collected regarding complications. INTERVENTION: All patients were operated on by using the same technique-percutaneous fixation of sacroiliac joint with cannulated screws. MAIN OUTCOME MEASUREMENTS: The study's primary outcome measure was the safety and quality of the early operation in comparison with the late operation. RESULTS: A total of 156 sacroiliac screws were inserted. No differences were found between the immediate and delayed treatment groups regarding technical outcome measures (P value = 0.44) and complication rate (P value = 0.42). CONCLUSIONS: The current study demonstrated that immediate percutaneous sacroiliac screw insertion for unstable pelvic fractures produced equally good technical results, in comparison with the conventional delayed operation, without additional complications.