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How do technologies animate more-than-human geographies after extinction? How can geographical scholarship evoke, or bring presence to, extinct biota? In an epoch simultaneously characterized by biotic loss at an unthinkable scale and the increased presence of representations depicting nonhuman life through mass media and digitization, we examine the epistemic, affective, and ethical possibilities of extinct animal traces to shape more-than-human geographies. We show how technological apparatuses inaugurate afterlives of extinction troubling binaries of extinct-extant and absence-presence. Specifically, we consider audio and visual remains of two taxa producing awkward and unsettling postextinction geographies: the ivory-billed woodpecker and the bucardo. Sound recordings and other historical traces continue to forge contemporary connections between human searchers and the ivory-billed woodpecker, although no sighting of the ghost bird has been universally accepted since 1944. The bucardo was declared extinct in 2000, but it was tentatively reanimated through a failed 2003 cloning project; in this milieu, visual technologies and representations conjure alternative presence and speculative futures beyond technoscientific spectacle. Through conversing our own situated, speculative, and technologically mediated relations with these taxa-and situating the technological assemblages themselves-we present some of the lively, contested, and dispersed ways technological apparatuses affect and inaugurate animated geographies after extinction.
¿Cómo animan las tecnologías a las geografías más-que-humanas después de la extinción? ¿Cómo puede la erudición geográfica evocar o darle existencia a la biota extinta? En una época que simultáneamente se caracteriza por la pérdida biótica a una escala impensable, y la creciente presencia de representaciones que muestran la vida no humana a través de los medios masivos y la digitalización, examinamos las posibilidades epistémicas, afectivas y éticas de las huellas de animales extintos para configurar las geografías más-que-humanas. Mostramos cómo los aparatos tecnológicos inauguran las posvidas de la extinción cuestionando los binarios de lo extintoexistente y de la ausenciapresencia. Específicamente, tomamos en consideración los restos sonoros y visuales de dos taxones que producen geografías postextincionales hoscas e inquietantes: el pájaro carpintero pico de marfil y el bucardo. Las grabaciones de sonidos y otros relictos históricos siguen forjando conexiones contemporáneas entre las búsquedas humanas y el pájaro carpintero pico de marfil, así desde 1944 no haya sido universalmente aceptado avistamiento alguno de esta ave fantasmal. El bucardo se declaró extinto en 2000, pero fue tentativamente revivido por medio de un fallido proyecto de clonación en 2003; en este entorno ambiental las tecnologías y representaciones visuales conjuran una presencia alternativa y unos futuros especulativos más allá del espectáculo tecnocientífico. A través de nuestras propias relaciones situadas, especulativas y tecnológicamente mediadas con aquellos taxones y situando los propios ensamblajes tecnológicos presentamos algunas de las formas vivas, controvertidas y dispersas en que los aparatos tecnológicos afectan e inauguran geografías animadas después de la extinción.
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If an apparently extinct bird calls in a forest, and there are people there to hear it-to record it, even-is it still extinct? The Ivory-billed Woodpecker was last 'officially' seen in the United States in 1944, but its extinction continues to be a subject of intense debate between conservation authorities, scientists, and grassroots activists. Tensions peaked around 2005, when scientists from the Cornell Laboratory of Ornithology announced their rediscovery of the species. However, their evidence received significant challenge from other ornithologists, and this apparent rediscovery has since been generally dismissed. In 2021, the United States Fish and Wildlife Service recommended the ivorybill be declared officially extinct. Still, many people continue to trawl the Southeastern forests in search of ivorybills. In this article, I investigate the methods, debates, and results of efforts to locate this species, with a focus on sound. In doing so, I explore the interconnected roles of sound and space in the making of extinction knowledge. Sonic search methods of listening, sounding, and translating are core ways that searchers attempt to attune to, communicate with, and establish evidence of ivorybills. Additionally, sonic search practices are critical spaces of negotiation and contestation between different searchers, between searchers and ivorybills, and between searchers and skeptics. Ultimately, this article argues that sonic geographies affect the production of extinction knowledge, and vice versa-extinction knowledge making practices produce distinct sonic geographies.
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Multiple theoretical frameworks have been proposed to provide a more comprehensive picture of the risk factors that influence anxiety-related developmental trajectories. Nonetheless, there remains a need for an integrative model that outlines: (1) which risk factors may be most pertinent at different points in development, and (2) how parenting may maintain, exacerbate, or attenuate an affective style that is characterized by high negative emotional reactivity to unfamiliar, uncertain, and threatening situations. A developmentally informed, integrative model has the potential to guide treatment development and delivery, which is critical to reducing the public health burden associated with these disorders. This paper outlines a model integrating research on many well-established risk mechanisms for anxiety disorders, focusing on (1) the developmental progression from emotional reactivity constructs early in life to those involving higher-level cognitive processes later in youth, and (2) potential pathways by which parenting may impact the stability of youth's cognitive-affective responses to threat-relevant information across development.
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Ansiedad , Responsabilidad Parental , Humanos , Adolescente , Responsabilidad Parental/psicología , Trastornos de Ansiedad/terapia , CogniciónRESUMEN
Following a diagnosis of IgE-mediated food allergy, to secure the best outcome, the patient should receive individualized advice tailored to their specific needs, which considers the type and presentation of the food involved, level of exclusion required, risk of cross-contamination and any variance required for age, ethnicity, financial issues, and lifestyle. Issues such as food labels "may contain" statements, and variation in the threshold of reaction and impact of cofactors should also be considered. Most important is the need to ensure that the diagnosis is robust, especially given the nutritional, psychological, and socioeconomic issues that can affect an individual with a diagnosis of food allergy. Unnecessary exclusion of one or more foods that have not triggered allergic reactions, especially in individuals with allergic comorbidities, can result in severe IgE-mediated reactions on re-exposure. Given that food allergies may change over time, the diagnosis should be reviewed, to determine whether resolution is likely, or new-food triggers are reported. Regular assessment is vital, especially during childhood, to ensure reintroduction occurs at an appropriate time, thus enabling increased diversity of the diet and improvement in the quality of life. For some, an IgE-mediated food allergy may necessitate the life-long exclusion of foods, and for others, a food habitually eaten suddenly triggers an allergic reaction in adult life. People of all ages, ethnicities, and socioeconomic backgrounds deserve individual advice on the management of their food allergy to support a healthy diet and improve quality of life.
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Hipersensibilidad a los Alimentos , Calidad de Vida , Adulto , Humanos , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/terapia , Alimentos , Etnicidad , Inmunoglobulina ERESUMEN
INTRODUCTION: The role of inhaled and swallowed aeroallergens in treatment outcomes of adult patients with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of the 6-food elimination diet (SFED) in EoE. METHODS: We compared outcomes of patients with EoE who underwent SFED during vs outside of the pollen season. Consecutive adult patients with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Individual pollen sensitization and pollen count data were analyzed to define whether each patient had been assessed during or outside of the pollen season after SFED. All patients had active EoE (≥15 eosinophils/high-power field) before SFED and adhered to the diet under the supervision of a dietitian. RESULTS: Fifty-eight patients were included, 62.0% had positive SPT for birch and/or grass, whereas 37.9% had negative SPT. Overall, SFED response was 56.9% (95% confidence interval, 44.1%-68.8%). When stratifying response according to whether the assessment had been performed during or outside of the pollen season, patients sensitized to pollens showed significantly lower response to SFED during compared with outside of the pollen season (21.4% vs 77.3%; P = 0.003). In addition, during the pollen season, patients with pollen sensitization had significantly lower response to SFED compared with those without sensitization (21.4% vs 77.8%; P = 0.01). DISCUSSION: Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. The SPT for pollens may identify patients less likely to respond to the diet during the pollen season.
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Esofagitis Eosinofílica , Humanos , Adulto , Esofagitis Eosinofílica/terapia , Dieta de Eliminación , Estaciones del Año , Alimentos , PolenRESUMEN
The narrow excitation bandwidth of monochromic pulses is a sensitivity limitation for pulsed dipolar spectroscopy on Cu(II)-based measurements. In response, frequency-swept pulses with large excitation bandwidths have been adopted to probe a greater range of the EPR spectrum. However, much of the work utilizing frequency-swept pulses in Cu(II) distance measurements has been carried out on home-built spectrometers and equipment. Herein, we carry out systematic Cu(II) based distance measurements to demonstrate the capability of chirp pulses on commercial instrumentation. More importantly we delineate sensitivity considerations under acquisition schemes that are necessary for robust distance measurements using Cu(II) labels for proteins. We show that a 200 MHz sweeping bandwidth chirp pulse can improve the sensitivity of long-range distance measurements by factors of three to four. The sensitivity of short-range distances only increases slightly due to special considerations for the chirp pulse duration relative to the period length of the modulated dipolar signal. Enhancements in sensitivity also dramatically reduce measurement collection times enabling rapid collection of orientationally averaged Cu(II) distance measurements in under two hours.
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Triarylmethyl (TAM)-based labels, while still underutilized, are a powerful class of labels for pulsed-Electron Spin Resonance (ESR) distance measurements. They feature slow relaxation rates for long-lasting signals, high stability for cellular experiments, and narrow spectral features for efficient excitation of the spins. However, the typical narrow line shape limits the available distance measurements to only single-frequency experiments, such as Double Quantum Coherence (DQC) and Relaxation Induced Dipolar Modulation Enhancement (RIDME), which can be complicated to perform or hard to process. Therefore, widespread usage of TAM labels can be enhanced by the use of Double Electron-Electron Resonance (DEER) distance measurements. In this work, we developed a new spin label, 13C1-mOX063-d24, with a 13C isotope as the radical center. Due to the resolved hyperfine splitting, the spectrum is sufficiently broadened to permit DEER-based experiments at Q-band spectrometers. Additionally, this new label can be incorporated orthogonally with Cu(II)-based protein label. The orthogonal labeling scheme enables DEER distance measurement at X-band frequencies. Overall, the new trityl label allows for DEER-based distance measurements that complement existing TAM-label DQC and RIDME experiments.
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Pollen food syndrome (PFS) is a highly prevalent food allergy affecting pollen-sensitized children and adults. Sufferers experience allergic symptoms when consuming raw plant foods, due to the homology between the pollen allergens and unstable proteins in these foods. The triggers involved can vary depending on the pollen sensitization, which in turn is affected by geographical location. The British Society of Allergy and Clinical Immunology (BSACI) Standards of Care Committee (SOCC) identified a need to develop a guideline for the diagnosis and management of PFS in the United Kingdom (UK). Guidelines produced by the BSACI use either the GRADE or SIGN methodology; due to a lack of high-quality evidence these recommendations were formulated using the SIGN guidelines, which is acknowledged to be less robust than the GRADE approach. The correct diagnosis of PFS ensures the avoidance of a misdiagnosis of a primary peanut or tree nut allergy or confusion with another plant food allergy to non-specific lipid transfer proteins. The characteristic foods involved, and rapid-onset oropharyngeal symptoms, mean PFS can often be diagnosed from the clinical history alone. However, reactions involving tree nuts, peanuts and soya milk or severe/atypical reactions to fruits and vegetables may require additional diagnostic tests. Management is through the exclusion of known trigger foods, which may appear to be simple, but is highly problematic if coupled with a pre-existing food allergy or for individuals following a vegetarian/vegan diet. Immunotherapy to pollens is not an effective treatment for PFS, and although oral or sublingual immunotherapy to foods seems more promising, large, controlled studies are needed. The typically mild symptoms of PFS can lead to an erroneous perception that this condition is always easily managed, but severe reactions can occur, and anxiety about the onset of symptoms to new foods can have a profound effect on quality of life.
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Hipersensibilidad a los Alimentos , Rinitis Alérgica Estacional , Adulto , Alérgenos , Arachis , Niño , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/terapia , Frutas , Humanos , Polen , Calidad de Vida , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/terapia , Pruebas Cutáneas , Síndrome , Reino Unido/epidemiologíaRESUMEN
Recent advances in site-directed Cu2+ labeling of proteins and nucleic acids have added an attractive new methodology to measure the structure-function relationship in biomolecules. Despite the promise, accessing the higher sensitivity of Q-band Double Electron Electron Resonance (DEER) has been challenging for Cu2+ labels designed for proteins. Q-band DEER experiments on this label typically require many measurements at different magnetic fields, since the pulses can excite only a few orientations at a given magnetic field. Herein, we analyze such orientational effects through simulations and show that three DEER measurements, at strategically selected magnetic fields, are generally sufficient to acquire an orientational-averaged DEER time trace for this spin label at Q-band. The modeling results are experimentally verified on Cu2+ labeled human glutathione S-transferase (hGSTA1-1). The DEER distance distribution measured at the Q-band shows good agreement with the distance distribution sampled by molecular dynamics (MD) simulations and X-band experiments. The concordance of MD sampled distances and experimentally measured distances adds growing evidence that MD simulations can accurately predict distances for the Cu2+ labels, which remains a key bottleneck for the commonly used nitroxide label. In all, this minimal collection scheme reduces data collection time by as much as six-fold and is generally applicable to many octahedrally coordinated Cu2+ systems. Furthermore, the concepts presented here may be applied to other metals and pulsed EPR experiments.
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Simulación de Dinámica Molecular , Proteínas , Espectroscopía de Resonancia por Spin del Electrón/métodos , Humanos , Marcadores de SpinRESUMEN
BACKGROUND: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
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Esofagitis Eosinofílica , Gastroenterología , Adulto , Niño , Consenso , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/terapia , Humanos , Calidad de Vida , Sociedades MédicasRESUMEN
In recent years considerable variations in conditioning protocols for allogeneic hematopoietic cell transplantation (allo-HCT) protocols have been introduced for higher efficacy, lower toxicity, and better outcomes. To overcome the limitations of the classical definition of reduced intensity and myeloablative conditioning, a transplantation conditioning intensity (TCI) score had been developed. In this study, we compared outcome after two frequently used single alkylator-based conditioning protocols from the intermediate TCI score category, fludarabine/melphalan 140 mg/m2 (FluMel) and fludarabine/treosulfan 42 g/m2 (FluTreo) for patients with acute myeloid leukemia (AML) in complete remission (CR). This retrospective analysis from the registry of the Acute Leukemia Working Party (ALWP) of the European Society of Bone Marrow Transplantation (EBMT) database included 1427 adult patients (median age 58.2 years) receiving either Flu/Mel (n = 1005) or Flu/Treo (n = 422). Both groups showed similar 3-year overall survival (OS) (54% vs 51.2%, p value 0.49) for patients conditioned with FluMel and FluTreo, respectively. However, patients treated with FluMel showed a reduced 3-year relapse incidence (32.4% vs. 40.4%, p value < 0.001) and slightly increased non-relapse mortality (NRM) (25.7% vs. 20.2%, p value = 0.06) compared to patients treated with FluTreo. Our data may serve as a basis for further studies examining the role of additional agents/ intensifications in conditioning prior to allo-HCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Enfermedad Aguda , Adulto , Trasplante de Médula Ósea/efectos adversos , Busulfano/análogos & derivados , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Melfalán , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Vidarabina/farmacología , Vidarabina/uso terapéuticoRESUMEN
Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front-line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real-world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available.
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Leucemia Mieloide Aguda , Adulto , Consenso , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapiaRESUMEN
BACKGROUND: Myriad parenting behaviors have been linked to the development of internalizing disorders in children. Intrusive parenting, characterized by autonomy-limiting behaviors that hold the parent's agenda above that of the child, may uniquely contribute to the development of child internalizing symptoms. The current study investigates bidirectional effects between maternal intrusiveness and internalizing symptomology from infancy to middle childhood. METHODS: Participants were a community sample of 218 infant-mother dyads assessed at 7 time points (5 and 10 months; 2, 3, 4, 6, and 9 years). Maternal intrusiveness was behaviorally coded at all timepoints; mothers completed the CBCL for their child at ages 3, 4, 6, and 9 years. The empirically derived Internalizing subscale was used to assess child internalizing symptoms. RESULTS: About 1/3 to ½ of mothers displayed maternal intrusiveness across infancy and childhood, with the exception of ages 2-3 years, when an increase in the number of mothers displaying intrusiveness was observed. A cross-lagged panel model showed that intrusiveness and internalizing symptoms were concurrently related at 3 years, but this relationship disappeared when we controlled for maternal education. There was no evidence of prospective relationships between our constructs. CONCLUSIONS: Mothers in a community-based sample may increase intrusiveness in the toddler and early preschool years as children strive for more autonomy. Intrusiveness may play more of a maintenance role in child internalizing symptoms, and associations between maternal intrusiveness and child internalizing symptomatology may be weaker than hypothesized, varying by maternal education. Suggestions for assessing intrusive parenting in future studies are discussed.
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Relaciones Madre-Hijo , Responsabilidad Parental , Niño , Preescolar , Femenino , Humanos , Lactante , Estudios Longitudinales , Madres , Estudios ProspectivosAsunto(s)
Médula Ósea , Hematología , Mieloma Múltiple , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Aloinjertos/trasplante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia/métodos , Médula Ósea/patología , Ensayos Clínicos como Asunto , Análisis Citogenético/normas , Diagnóstico por Imagen/normas , Diagnóstico por Imagen/tendencias , Detección Precoz del Cáncer/normas , Electroforesis/métodos , Hematología/organización & administración , Cadenas alfa de Inmunoglobulina/inmunología , Inmunoterapia/métodos , Inmunoterapia Adoptiva/métodos , Hibridación Fluorescente in Situ/normas , Mieloma Múltiple/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Estadificación de Neoplasias/normas , Selección de Paciente/ética , Guías de Práctica Clínica como Asunto , Pronóstico , Inhibidores de Proteasoma/uso terapéutico , Reino Unido/epidemiologíaRESUMEN
Care of long-term survivors of allogeneic transplant is known to be variable despite international guidelines and accreditation standards. In 2014 a survey of UK NHS-based adult transplant centres identified significant barriers to delivery of long-term follow-up services. In 2019, we repeated the survey to assess changes over a 5-year period when health service policies had mandated JACIE accreditation incorporating standards for long-term care. Improvements were seen in the number of centres having a dedicated long-term follow-up clinic for allogeneic transplant recipients (52% versus 33%) and a standard operating procedure (88% versus 69%). Inclusion of psychological support in standard operating procedures remained low at both time points (32% versus 28%). There was ongoing variation in practice regarding vaccination programmes, access to cancer screening, and audit processes between centres. Perceived barriers to implementation of comprehensive long-term follow-up clinics were similar in 2019; mainly resourcing clinical staff and psychological support. Whilst the survey reflects the changing practice of transplant centres, best explained by increasing recognition of late effects and survivorship by clinicians, health service policy and JACIE accreditation standards, further developments are warranted to address unmet healthcare needs of long-term HSCT survivors, especially access to psychological support, cancer screening and vaccinations.
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Trasplante de Células Madre Hematopoyéticas , Supervivencia , Acreditación , Adulto , Aloinjertos , Servicios de Salud , Humanos , Políticas , Medicina Estatal , Reino UnidoRESUMEN
Structural chromosomal changes including copy number aberrations (CNAs) are a major feature of multiple myeloma (MM), however their evolution in context of modern biological therapy is not well characterized. To investigate acquisition of CNAs and their prognostic relevance in context of first-line therapy, we profiled tumor diagnosis-relapse pairs from 178 NCRI Myeloma XI (ISRCTN49407852) trial patients using digital multiplex ligation-dependent probe amplification. CNA profiles acquired at relapse differed substantially between MM subtypes: hyperdiploid (HRD) tumors evolved predominantly in branching pattern vs. linear pattern in t(4;14) vs. stable pattern in t(11;14). CNA acquisition also differed between subtypes based on CCND expression, with a marked enrichment of acquired del(17p) in CCND2 over CCND1 tumors. Acquired CNAs were not influenced by high-dose melphalan or lenalidomide maintenance randomization. A branching evolution pattern was significantly associated with inferior overall survival (OS; hazard ratio (HR) 2.61, P = 0.0048). As an individual lesion, acquisition of gain(1q) at relapse was associated with shorter OS, independent of other risk markers or time of relapse (HR = 2.00; P = 0.021). There is an increasing need for rational therapy sequencing in MM. Our data supports the value of repeat molecular profiling to characterize disease evolution and inform management of MM relapse.
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Variaciones en el Número de Copia de ADN/genética , Mieloma Múltiple/genética , Ciclina D1/genética , Variaciones en el Número de Copia de ADN/efectos de los fármacos , Humanos , Lenalidomida/farmacología , Melfalán/farmacología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Proteínas del Tejido Nervioso/genética , Pronóstico , RecurrenciaRESUMEN
PURPOSE: Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS: Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS: A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment (P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment (P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION: Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.
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Mieloma Múltiple/terapia , Recurrencia Local de Neoplasia/terapia , Trasplante de Células Madre , Adulto , Anciano , Toma de Decisiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor , Medición de Resultados Informados por el Paciente , Calidad de Vida , Inducción de Remisión , Reproducibilidad de los Resultados , Proyectos de Investigación , Terapia Recuperativa , Encuestas y Cuestionarios , Trasplante Autólogo , Resultado del TratamientoRESUMEN
A 17-year-old man with no significant past medical history presented with a 2-week history of worsening jaundice, lethargy, anorexia and progressive right upper quadrant abdominal pain. There were no stigmata of chronic liver disease. Initial investigations were suggestive of cholangitis with large intrahepatic and extrahepatic bile duct strictures but otherwise normal hepatic and splenic appearances. A percutaneous transhepatic cholangiogram with the positioning of drains was performed to alleviate the obstructive jaundice. Within 2 weeks of the first presentation, full blood count revealed a significantly raised white blood count and a subsequent peripheral blood smear and bone marrow were consistent with a diagnosis of acute myeloid leukaemia. Chemotherapy was started after partial improvement of his obstructive jaundice. Complete morphological and cytogenetic remission was obtained 4 weeks after the first cycle of chemotherapy (half dose of daunorubicin and full dose of cytarabine, treated off trial) on control bone marrow. The patient remains in remission.
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Conductos Biliares Extrahepáticos/patología , Colangitis/etiología , Leucemia Mieloide Aguda/complicaciones , Adolescente , Antibióticos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Conductos Biliares Extrahepáticos/diagnóstico por imagen , Colangiografía/métodos , Colangitis/diagnóstico , Colestasis/etiología , Constricción Patológica , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Daunorrubicina/administración & dosificación , Daunorrubicina/uso terapéutico , Quimioterapia/métodos , Humanos , Ictericia Obstructiva/etiología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Masculino , Resultado del TratamientoRESUMEN
Eosinophilic oesophagitis (EoE) is a chronic disease associated with significant morbidity that can result in permanent fibrosis and stricture formation. Given the complexity, a multidisciplinary approach is recommended to manage these patients. In the majority of children with EoE not responsive to proton-pump inhibitor (PPI), inflammation is driven by sensitivity to foods and treatment with an elimination diet can be effective. Foods most commonly identified to trigger EoE in children are milk and wheat, but egg, soy, meats and grains can also be triggers. Foods can be eliminated using a step-down or step-up approach. If the goal is to achieve quick remission, elemental diet or six food elimination diets are the most effective. A step-up approach starting from a 1-2 food elimination diet and increasing the number of foods based on a personalized dietary approach is recommended if the goal is to achieve remission using the least number of endoscopies and with increased acceptability to the patient. Children with EoE on elimination diets require frequent monitoring of growth and nutrition, as well as screening for symptoms of EoE, allergy and mindfulness regarding psychosocial impact of chronic disease on the family and child. Current research focused on tools to select patients who mostly will benefit from dietary treatment, identify relevant food allergens, obtain oesophageal tissue non-invasively and induce tolerance will greatly improve the treatment of EoE.