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BACKGROUND: The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity. METHODS: In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared. RESULTS: Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety-two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09). CONCLUSIONS: Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.
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Anticuerpos Biespecíficos/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Inotuzumab Ozogamicina/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Biespecíficos/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Inotuzumab Ozogamicina/efectos adversos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Privación de Tratamiento/estadística & datos numéricos , Adulto JovenRESUMEN
PURPOSE: Researchers' obligations to disclose genetic incidental findings (GIFs) have been widely debated, but there has been little empirical study of the engagement of institutional review boards (IRBs) with this issue. METHODS: This article presents data from the first extensive (n = 796) national survey of IRB professionals' understanding of, experience with, and beliefs surrounding GIFs. RESULTS: Most respondents had dealt with questions about GIFs (74%), but only a minority (47%) felt prepared to address them. Although a majority believed that there is an obligation to disclose GIFs (78%), there is still not consensus about the supporting ethical principles. Respondents generally did not endorse the idea that researchers' additional time and effort (7%), and lack of resources (29%), were valid reasons for diminishing a putative obligation. Most (96%) supported a right not to know, but this view became less pronounced (63%) when framed in terms of specific case studies. CONCLUSIONS: IRBs are actively engaged with GIFs but have not yet reached consensus. Respondents were uncomfortable with arguments that could be used to limit an obligation to return GIFs. This could indicate that IRBs are providing some of the impetus for the trend toward returning GIFs, although questions remain about the relative contribution of other stakeholders.Genet Med 18 7, 705-711.
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Revelación/ética , Ética en Investigación , Investigación Genética/ética , Hallazgos Incidentales , Comités de Ética en Investigación , Humanos , Consentimiento Informado/ética , Investigadores/éticaRESUMEN
The Stanford Cancer Survivorship Program is a key initiative of Stanford Cancer Institute. The program's mission is to improve the experience and outcomes of patients and family caregivers throughout all phases of the cancer trajectory by advancing survivorship research, clinical care, and education. The four pillars of the program include clinical care delivery with a focus on primary care-survivorship collaboration and expanding specialty services, education and training of healthcare professionals, transdisciplinary patient-oriented research, and community engagement. Cross-cutting areas of expertise include the following: (a) adolescents and young adults (AYAs), (b) mental health and patient self-management, (c) integration of primary care, and (d) postgraduate medical education. The clinical care model includes embedded survivorship clinics within disease groups in outpatient clinics, novel clinics designed to address unmet needs such as sexual health for women, and primary care-based faculty-led survivorship clinics for patients undergoing active cancer care requiring co-management, those who have completed active therapy and those at high risk for cancer due to genetic risk. Educational initiatives developed to date include an online course and medical textbook for primary care clinicians, a lecture series, monthly research team meetings, and rotations for medical trainees. Patient-facing activities include webinars and a podcast series designed to promote awareness, thus expanding the provision of expert-vetted information. Ongoing research focuses on oncofertility and family building after cancer, improving communication for AYAs, changing mindsets to improve quality of life through targeted digital interventions, increasing capacity to care for cancer survivors, and strengthening collaboration with community partners. IMPLICATIONS FOR CANCER SURVIVORS: Stanford's Cancer Survivorship Program includes a robust transdisciplinary and interdisciplinary research, training and clinical platform that is committed to advancing access and improving care for people living with and beyond cancer, through innovation in design and care delivery.
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Supervivientes de Cáncer , Neoplasias , Adolescente , Adulto Joven , Humanos , Femenino , Calidad de Vida/psicología , Atención a la Salud , Supervivencia , Cuidadores , Neoplasias/terapiaAsunto(s)
Pruebas Genéticas/ética , Diagnóstico Prenatal/ética , Diagnóstico Precoz , Intervención Educativa Precoz , Femenino , Feto , Genoma Humano , Humanos , Padres , EmbarazoRESUMEN
BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a malignant vascular neoplasm representing â¼1% of sarcomas. Due to its rarity, its clinical course is not well characterized and optimal treatment remains unknown. MATERIALS AND METHODS: This was a retrospective review of patients with EHE treated at Stanford University between 1998 and 2020. Demographic characteristics, pathology results, treatment modalities, and clinical outcomes were collected from the electronic medical records. RESULTS: A total of 58 patients had a mean age of 50.6 years and a slight female predominance (52%). Primary disease sites were liver (33%), soft tissue (29%), lung (14%), bone (9%), and mediastinum (9%). A majority (55%) had advanced or metastatic disease. Median overall survival (OS) was 16.9 years, with OS 89% at 1 year, 68% at 5 years, and 64% at 10 years. The longest median OS was associated with soft tissue sites and shortest with lung and mediastinal disease (P=0.03). The localized disease had improved median OS compared with metastatic disease (P=0.02). There was no OS difference between tumors >3 cm and those equal or smaller (P=0.85). Surgery was a common treatment (71%), while radiation and ablation were sometimes used (28% and 9%, respectively). The median time to initiating therapy of any kind was 68 days. The median time to systemic therapy was 114 days. CONCLUSIONS: We report on the clinical characteristics and outcomes of patients with EHE at a large academic center. Treatment options included surgical excision, liver transplant, ablation, radiation, and systemic therapy. A subset of patients had indolent disease not requiring treatment upfront.
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Hemangioendotelioma Epitelioide/mortalidad , Hemangioendotelioma Epitelioide/terapia , Antineoplásicos/uso terapéutico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Femenino , Hemangioendotelioma Epitelioide/patología , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Resultado del TratamientoRESUMEN
Much of the time, care teams react to complications instead of preventing them. A doctor calls on the medical system to take responsibility.
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Paro Cardíaco/complicaciones , Potencial Evento Adverso , Medicina Preventiva , Femenino , Paro Cardíaco/terapia , Humanos , Masculino , Respiración ArtificialRESUMEN
Despite improved rates of remission and cure in newly diagnosed adult acute lymphoblastic leukemia (ALL), the prognosis for patients with relapsed or refractory disease remains poor and the 5-year overall survival rate after relapse is under 10%. A recent paradigm shift has focused on the promise of targeted immunotherapy rather than standard chemotherapy, as ALL blast cells express a variety of antigens, and monoclonal antibodies may be developed to identify and destroy the leukemic cells. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. CD22 expression is detected on leukemic blasts in over 90% of patients with ALL. Based on promising results from preclinical studies, inotuzumab ozogamicin was tested in Phase 1/2 and Phase 3 clinical trials and it demonstrated improved complete remission rates, progression-free survival and overall survival in relapsed or refractory adult ALL compared to standard therapy. Ongoing studies are evaluating the value of inotuzumab ozogamicin when given in combination with chemotherapy as part of upfront treatment. This review discusses the drug's biochemical properties and mechanism of action, preclinical research outcomes, clinical trial results, adverse events and toxicities, drug approval and ongoing investigations.
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Aminoglicósidos/uso terapéutico , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adulto , Humanos , Inotuzumab OzogamicinaRESUMEN
A 61-year-old woman with newly diagnosed anaplastic thyroid cancer and known metastases to the brain, lungs, and adrenal glands complained of groin muscle pain. F-FDG PET/CT was performed to assess for extent of disease and showed extensive hypermetabolic lesions throughout the skeletal musculature concerning for metastatic disease. As this would be a very rare presentation for anaplastic thyroid carcinoma, a biopsy of the left gluteal muscle was conducted. Pathology demonstrated anaplastic thyroid carcinoma, metastatic to skeletal muscle.
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Fluorodesoxiglucosa F18 , Neoplasias de los Músculos/diagnóstico por imagen , Neoplasias de los Músculos/secundario , Músculo Esquelético/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/patología , Femenino , Humanos , Persona de Mediana Edad , Músculo Esquelético/patologíaRESUMEN
PURPOSE: Adolescent and young adult (AYA) patients with cancer face significant challenges with regard to fatigue, reduced physical activity, and social isolation, which may negatively impact quality of life. This study investigated whether the use of digital wearable technology (Fitbits, along with synced iPads) can affect health-related quality of life (HRQOL) in AYA aged patients with cancer. MATERIALS AND METHODS: This was a prospective cohort study that offered Fitbits and iPads to all AYA patients aged 15 to 29 at an academic medical center at the time of cancer diagnosis. Patients completed the Short Form Health Survey developed by RAND (RAND-36) assessing eight dimensions of HRQOL on entering the study and at the time of their 6-month follow-up or the end of treatment, whichever occurred first. At the time of follow-up, patients also completed a questionnaire that assessed user experience, including frequency of wearable device use, enjoyment, challenges, and participation, in online communities. RESULTS: Thirty-three patients participated in the study. Most patients reported enjoying the digital technology and using the devices to track multiple aspects of their health (85%). Most also reported a subjective increase in physical activity (79%). After the intervention, participants demonstrated significant improvements across all eight dimensions of HRQOL measured by the RAND-36 (p < 0.00 to 0.01). CONCLUSION: Distributing wearable technology at the time of diagnosis may provide an avenue for improving HRQOL in adolescents and young adults with cancer.
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Neoplasias/terapia , Calidad de Vida/psicología , Dispositivos Electrónicos Vestibles/normas , Adolescente , Adulto , Femenino , Humanos , Masculino , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The current Iraq and Afghanistan conflicts have seen the highest survival rates in US service members ever, despite staggering numbers of traumatic brain injury and limb loss cases. The improvement in survival can be attributed at least in part to advances in far-forward, rapid medical treatment, including the administration of hypertonic saline solutions and decompressive craniectomies to manage elevated intracranial pressure. After evacuation to military hospitals in the continental United States, service members who have had limb loss face extensive rehabilitation. The growing amputee population has led to a burgeoning interest in the treatment of phantom limb pain and in the development of advanced prostheses.
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OBJECTIVE: To review current literature on neurology telemedicine and to discuss its application to patient care, neurology practice, military medicine, and current federal policy. METHODS: Review of practice models and published literature on primary studies of the efficacy of neurology telemedicine. RESULTS: Teleneurology is of greatest benefit to populations with restricted access to general and subspecialty neurologic care in rural areas, those with limited mobility, and those deployed by the military. Through the use of real-time audio-visual interaction, imaging, and store-and-forward systems, a greater proportion of neurologists are able to meet the demand for specialty care in underserved communities, decrease the response time for acute stroke assessment, and expand the collaboration between primary care physicians, neurologists, and other disciplines. The American Stroke Association has developed a defined policy on teleneurology, and the American Academy of Neurology and federal health care policy are beginning to follow suit. CONCLUSIONS: Teleneurology is an effective tool for the rapid evaluation of patients in remote locations requiring neurologic care. These underserved locations include geographically isolated rural areas as well as urban cores with insufficient available neurology specialists. With this technology, neurologists will be better able to meet the burgeoning demand for access to neurologic care in an era of declining availability. An increase in physician awareness and support at the federal and state level is necessary to facilitate expansion of telemedicine into further areas of neurology.
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Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/terapia , Neurología , Telemedicina , Humanos , Consulta RemotaRESUMEN
OBJECTIVE: This study evaluated usage of the Army Knowledge Online (AKO) Telemedicine Consultation Program for neurology and traumatic brain injury (TBI) cases in remote overseas areas with limited access to subspecialists. We performed a descriptive analysis of quantity of consults, response times, sites where consults originated, military branches that benefitted, anatomic locations of problems, and diagnoses. METHODS: This was a retrospective analysis that searched electronic databases for neurology consults from October 2006 to December 2010 and TBI consults from March 2008 to December 2010. RESULTS: A total of 508 consults were received for neurology, and 131 consults involved TBI. For the most part, quantity of consults increased over the years. Meanwhile, response times decreased, with a mean response time of 8 hours, 14 minutes for neurology consults and 2 hours, 44 minutes for TBI consults. Most neurology consults originated in Iraq (67.59%) followed by Afghanistan (16.84%), whereas TBI consults mainly originated from Afghanistan (40.87%) followed by Iraq (33.91%). The most common consultant diagnoses were headaches, including migraines (52.1%), for neurology cases and mild TBI/concussion (52.3%) for TBI cases. In the majority of cases, consultants recommended in-theater management. After receipt of consultant's recommendation, 84 known neurology evacuations were facilitated, and 3 known neurology evacuations were prevented. CONCLUSIONS: E-mail-based neurology and TBI subspecialty teleconsultation is a viable method for overseas providers in remote locations to receive expert recommendations for a range of neurologic conditions. These recommendations can facilitate medically necessary patient evacuations or prevent evacuations for which on-site care is preferable.
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Lesiones Encefálicas/diagnóstico , Medicina Militar/métodos , Telemedicina/métodos , Adolescente , Adulto , Lesiones Encefálicas/terapia , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Neurología , Evaluación de Programas y Proyectos de Salud , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Studies of copy number variation (CNV) have characterized loci and molecular pathways in a range of neuropsychiatric conditions. We analyzed rare CNVs in Tourette syndrome (TS) to identify novel risk regions and relevant pathways, to evaluate burden of structural variation in cases versus controls, and to assess overlap of identified variations with those in other neuropsychiatric syndromes. METHODS: We conducted a case-control study of 460 individuals with TS, including 148 parent-child trios and 1131 controls. CNV analysis was undertaken using 370 K to 1 M probe arrays, and genotyping data were used to match cases and controls for ancestry. CNVs present in < 1% of the population were evaluated. RESULTS: While there was no significant increase in the number of de novo or transmitted rare CNVs in cases versus controls, pathway analysis using multiple algorithms showed enrichment of genes within histamine receptor (subtypes 1 and 2) signaling pathways (p = 5.8 × 10(-4) - 1.6 × 10(-2)), as well as axon guidance, cell adhesion, nervous system development, and synaptic structure and function processes. Genes mapping within rare CNVs in TS showed significant overlap with those previously identified in autism spectrum disorders but not intellectual disability or schizophrenia. Three large, likely pathogenic, de novo events were identified, including one disrupting multiple gamma-aminobutyric acid receptor genes. CONCLUSIONS: We identify further evidence supporting recent findings regarding the involvement of histaminergic and gamma-aminobutyric acidergic mechanisms in the etiology of TS and show an overlap of rare CNVs in TS and autism spectrum disorders.
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Trastorno Autístico/genética , Variaciones en el Número de Copia de ADN/genética , Receptores de GABA/genética , Receptores Histamínicos H1/genética , Receptores Histamínicos H2/genética , Síndrome de Tourette/genética , Adulto , Estudios de Casos y Controles , Niño , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Discapacidad Intelectual , Esquizofrenia/genética , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: After amputation, the sensorimotor cortex reorganizes, and these alterations might influence motor functions of the remaining extremities. OBJECTIVE: The authors examined how amputation of the dominant or nondominant upper or lower extremity alters deftness in the intact limbs. METHODS: The participants were 32 unilateral upper- or lower-extremity amputees and 6 controls. Upper-extremity deftness was tested by coin rotation (finger deftness) and pegboard (arm, hand, and finger deftness) tasks. RESULTS: Following right-upper- or right-lower-extremity amputation, the left hand's finger movements were defter than the left-hand fingers of controls. In contrast, with left-upper- or left-lower-extremity amputation, the right hand's finger performance was the same as that of the controls. CONCLUSIONS: Although this improvement might be related to increased use (practice), the finding that right-lower-extremity amputation also improved the left hand's finger deftness suggests an alternative mechanism. Perhaps in right-handed persons the left motor cortex inhibits the right side of the body more than the right motor cortex inhibits the left side, and the physiological changes induced by right-sided amputation reduced this inhibition.
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Amputación Quirúrgica , Dedos/fisiología , Extremidad Inferior/fisiología , Destreza Motora/fisiología , Adulto , Análisis de Varianza , Lateralidad Funcional/fisiología , Mano/fisiología , Humanos , Masculino , Corteza Somatosensorial/fisiología , Extremidad Superior/fisiologíaRESUMEN
We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 × 10(-7)). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.