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Acute myeloid leukemia (AML) presents a pressing medical need in that it is largely resistant to standard chemotherapy as well as modern therapeutics, such as targeted therapy and immunotherapy, including anti-programmed cell death protein (anti-PD) therapy. We demonstrate that programmed death-1 homolog (PD-1H), an immune coinhibitory molecule, is highly expressed in blasts from the bone marrow of AML patients, while normal myeloid cell subsets and T cells express PD-1H. In studies employing syngeneic and humanized AML mouse models, overexpression of PD-1H promoted the growth of AML cells, mainly by evading T cell-mediated immune responses. Importantly, ablation of AML cell-surface PD-1H by antibody blockade or genetic knockout significantly inhibited AML progression by promoting T cell activity. In addition, the genetic deletion of PD-1H from host normal myeloid cells inhibited AML progression, and the combination of PD-1H blockade with anti-PD therapy conferred a synergistic antileukemia effect. Our findings provide the basis for PD-1H as a potential therapeutic target for treating human AML.
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Evasión Inmune , Leucemia Mieloide Aguda , Animales , Humanos , Ratones , Médula Ósea , Inmunidad Celular , Inmunoterapia , Leucemia Mieloide Aguda/tratamiento farmacológicoRESUMEN
BACKGROUND: Wearable devices may be useful for identification, quantification and characterization, and management of atrial fibrillation (AF). To date, consumer wrist-worn devices for AF detection using photoplethysmography-based algorithms perform only periodic checks when the user is stationary and are US Food and Drug Administration cleared for prediagnostic uses without intended use for clinical decision-making. There is an unmet need for medical-grade diagnostic wrist-worn devices that provide long-term, continuous AF monitoring. METHODS AND RESULTS: We evaluated the performance of a wrist-worn device with lead-I ECG and continuous photoplethysmography (Verily Study Watch) and photoplethysmography-based convolutional neural network for AF detection and burden estimation in a prospective multicenter study that enrolled 117 patients with paroxysmal AF. A 14-day continuous ECG monitor (Zio XT) served as the reference device to evaluate algorithm sensitivity and specificity for detection of AF in 15-minute intervals. A total of 91 857 intervals were contributed by 111 subjects with evaluable reference and test data (18.3 h/d median watch wear time). The watch was 96.1% sensitive (95% CI, 92.7%-98.0%) and 98.1% specific (95% CI, 97.2%-99.1%) for interval-level AF detection. Photoplethysmography-derived AF burden estimation was highly correlated with the reference device burden (R2=0.986) with a mean difference of 0.8% (95% limits of agreement, -6.6% to 8.2%). CONCLUSIONS: Continuous monitoring using a photoplethysmography-based convolutional neural network incorporated in a wrist-worn device has clinical-grade performance for AF detection and burden estimation. These findings suggest that monitoring can be performed with wrist-worn wearables for diagnosis and clinical management of AF. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04546763.
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Fibrilación Atrial , Aprendizaje Profundo , Humanos , Algoritmos , Fibrilación Atrial/diagnóstico , Electrocardiografía , Estudios Prospectivos , MuñecaRESUMEN
INTRODUCTION: Demyelinating lesions occasionally present as mass-like lesions on imaging, raising concern for malignancy. The disease course of such tumefactive demyelinating lesions (TDLs) is still being defined. METHODS: We retrospectively analyzed 21 patients with new-onset neurologic symptoms and mass-like lesions on brain magnetic resonance imaging (MRI), which resulted in biopsy-proven diagnoses of demyelination. 18 patients had a median follow-up of 52 months. The clinical, radiologic and histologic features were associated with disease course. RESULTS: An aggressive disease course (ADC) was noted in 33% of the patients and was associated with an initial largest lesion size ≥35 mm (p = 0.0007), mass effect (p = 0.01) and perilesional edema (p = 0.01) on MRI. Age 30 years and older, at presentation (p = 0.05), as well as the absence of a prior tonsillectomy (p = 0.0128) were also associated with an ADC. CONCLUSIONS: We identified several factors, including initial larger lesion size, mass effect and perilesional edema on MRI, presentation after 30 years of age and the absence of a prior tonsillectomy, that predict an ADC in patients presenting with TDLs. These predictors of disease course can help guide patient follow-up and stratification for intervention.
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Encéfalo , Esclerosis Múltiple , Adulto , Biopsia , Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , Humanos , Imagen por Resonancia Magnética , Pronóstico , Estudios RetrospectivosRESUMEN
The importance of safe, effective, and cost-effective prescribing habits can hardly be overstated in the current pay-for-value environment. The prescribing process taught in most medical curricula focuses primarily on accurate medical indications. While this may be of utmost importance from the clinician's perspective, it falls short of addressing the other key elements of highly effective prescribing. These other elements are often paramount in the minds of patients. A patient-centric framework that associates and incorporates the necessary components of optimal prescribing is overdue. Building this framework into medical curricula will foster increased teamwork among providers and enhance shared decision making between patients and clinicians. In addition to establishing accurate medical indications, prescribing teams need to assure every prescribed medication is desired, effective, affordable, and safe for patients who receive them. Prescription writing is an honorable prerogative, and doing so safely, effectively, and cost-effectively requires both teamwork and technology. Highly effective prescribing teams can implement the IDEAS (Indicated, Desired, Effective, Affordable, Safe) framework through appropriate and deliberate delegation. By empowering members of the care team to support and educate patients, this framework will allow physicians to focus on ensuring appropriate indications and real-world effectiveness. This novel IDEAS framework serves as an important mental model for medical trainees and reinforces sound prescribing habits among seasoned clinicians. High-touch and high-tech partnerships have the potential to maximize the triple aim (i.e., improving the patient's experience of care, improving the health of populations, and reducing the per capita cost of health care). In an era when costs overwhelm quality, providing a fiduciary framework to instill responsibility for optimal prescribing, especially among young physician-leaders, is invaluable.
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Curriculum , Quimioterapia/métodos , Educación Médica , Costos y Análisis de Costo , Sistemas de Apoyo a Decisiones Clínicas , Quimioterapia/economía , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Cumplimiento de la MedicaciónRESUMEN
Pregnancy results in substantial hemodynamic and prothrombotic changes that form the foundation for downstream vascular complications, both during pregnancy and in the postpartum period. In addition, several important risk factors, including older patient age, diabetes, and smoking, can increase the risk for vascular-related pregnancy complications. Because radiologists often play an important role in evaluation of the pregnant patient, understanding the pathophysiology of vascular-related complications in pregnancy and their imaging appearances is essential for diagnostic accuracy. The authors review relevant normal physiologic changes of pregnancy, pathophysiologic changes, and imaging features of vascular conditions that can manifest in conjunction with pregnancy. Particular attention is given to pertinent imaging information that radiologists should provide to referring clinicians to optimally affect the management of pregnant patients as well as women in the peripartum and postpartum stages. Among the complications discussed are preeclampsia; hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome; spontaneous coronary artery dissection; placental abruption; amniotic fluid embolism and acute pulmonary embolism; dural venous sinus thrombosis; ovarian vein thrombophlebitis; vasa previa; uterine arteriovenous malformations; heritable aortopathies; and hereditary hemorrhagic telangiectasia. To help radiologists avoid the use of unnecessary ionizing radiation in pregnancy, imaging examination selection and optimization are also reviewed. Radiologists should be familiar with the physiologic changes of pregnancy, radiation risks during gestation, and pregnancy-related vascular complications to improve imaging examination selection, diagnosis, and clinical management. ©RSNA, 2017.
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Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo/fisiopatologíaAsunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Hepatitis B Crónica/complicaciones , Trasplante de Hígado/efectos adversos , Trastornos Linfoproliferativos/patología , Complicaciones Posoperatorias/patología , Anciano , Humanos , Trastornos Linfoproliferativos/etiología , Imagen por Resonancia Magnética , Masculino , Plasmacitoma/patologíaAsunto(s)
Neoplasias del Íleon/diagnóstico por imagen , Mesenterio/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoma Mieloide/diagnóstico por imagen , Adulto , Biomarcadores de Tumor/análisis , Quimioterapia Adyuvante , Diagnóstico Diferencial , Procedimientos Quirúrgicos del Sistema Digestivo , Femenino , Humanos , Neoplasias del Íleon/química , Neoplasias del Íleon/terapia , Mesenterio/química , Mesenterio/cirugía , Valor Predictivo de las Pruebas , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/terapia , Resultado del TratamientoRESUMEN
RATIONALE AND OBJECTIVES: Ongoing concerns over the rising cost of health care are driving large-scale changes in the way that health care is practiced and reimbursed in the United States. MATERIALS AND METHODS: To effectively implement and thrive within this new health care delivery environment, academic medical institutions will need to modify financial and business models and adapt institutional cultures. In this article, we review the expected features of the new health care environment from the perspective of academic radiology departments. CONCLUSIONS: Our review will include background on accountable care organizations, identify challenges associated with the new managed care model, and outline key strategies-including expanding the use of existing information technology infrastructure, promoting continued medical innovation, balancing academic research with clinical care, and exploring new roles for radiologists in efficient patient management-that will ensure continued success for academic radiology.
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Centros Médicos Académicos/métodos , Atención a la Salud/métodos , Radiología/métodos , Centros Médicos Académicos/economía , Organizaciones Responsables por la Atención/economía , Organizaciones Responsables por la Atención/métodos , Atención a la Salud/economía , Costos de la Atención en Salud , Humanos , Patient Protection and Affordable Care Act/economía , Radiología/economía , Estados UnidosRESUMEN
OBJECT: Over a 16-year period, 570 patients presenting with acute aneurysmal subarachnoid hemorrhage were successfully treated using endosaccular coil embolization within 30 days of hemorrhage by a single surgeon. Patients were followed to assess the stability of aneurysm occlusion and its longer-term efficacy in protecting against rebleeding. METHODS: Patients were followed for 6 to 191 months (mean 73.7 months, median 67 months) by clinical review, angiography performed at 6 and 24 months posttreatment, and questionnaires sent via the postal service every 5 years. Late rebleeding was defined as > 30 days after treatment. RESULTS: Stable angiographic occlusion was evident in 74.5% of small, 72.2% of large, and 60% of giant aneurysms. Recurrent filling was found in 119 (26.3%) of 452 aneurysms. Rebleeding was diagnosed in 9 patients (6 treated aneurysms) and occurred between 2 and 114 months posttreatment. It was due to aneurysm recurrence in 6 patients, rupture of a coincidental untreated aneurysm in 2 patients, and rupture of a de novo aneurysm in 1 patient. Rebleeding occurred in 3 (2.5%) of 119 unstable aneurysms and in 3 (0.9%) of 333 stable aneurysms, as seen on initial follow-up angiography studies. Annual rebleeding rates ranged from 0.2% to 0.6% for all causes and from 0.2% to 0.4% for rebleeding of treated aneurysms. No rebleeding was recorded after the first decade, with 138 patients having more than 10 years of follow-up. CONCLUSIONS: Periodic follow-up with angiographic studies after coil embolization is recommended to identify aneurysm recurrence and patients at a high risk of late rebleeding in the medium term. More frequent follow-up is recommended for patients harboring coincidental unruptured aneurysms.
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Aneurisma Roto/cirugía , Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma Intracraneal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma Roto/patología , Angiografía Cerebral , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Intracraneal/patología , Masculino , Persona de Mediana Edad , Selección de Paciente , Recurrencia , Reoperación , Hemorragia Subaracnoidea/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Authors are required to describe in their manuscripts ethical approval from an appropriate committee and how consent was obtained from participants when research involves human participants. OBJECTIVE: To assess the reporting of these protections for several study designs in general medical journals. DESIGN: A consecutive series of research papers published in the Annals of Internal Medicine, BMJ, JAMA, Lancet and The New England Journal of Medicine between February and May 2003 were reviewed for the reporting of ethical approval and patient consent. Ethical approval, name of approving committee, type of consent, data source and whether the study used data collected as part of a study reported elsewhere were recorded. Differences in failure to report approval and consent by study design, journal and vulnerable study population were evaluated using multivariable logistic regression. RESULTS: Ethical approval and consent were not mentioned in 31% and 47% of manuscripts, respectively. 88 (27%) papers failed to report both approval and consent. Failure to mention ethical approval or consent was significantly more likely in all study designs (except case-control and qualitative studies) than in randomised controlled trials (RCTs). Failure to mention approval was most common in the BMJ and was significantly more likely than in The New England Journal of Medicine. Failure to mention consent was most common in the BMJ and was significantly more likely than in all other journals. No significant differences in approval or consent were found when comparing studies of vulnerable and non-vulnerable participants. CONCLUSION: The reporting of ethical approval and consent in RCTs has improved, but journals are less good at reporting this information for other study designs. Journals should publish this information for all research on human participants.
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Comités de Ética en Investigación , Ética en Investigación , Experimentación Humana/ética , Consentimiento Informado , Políticas Editoriales , Adhesión a Directriz , Humanos , Publicaciones Periódicas como Asunto , Proyectos de Investigación , Estudios RetrospectivosRESUMEN
Prevalence studies generally find nosocomial urinary tract infections to be the most common type of nosocomial infection, accounting for between 21% and 45% of all HAIs. The main risk factor appears to be the presence of a urinary catheter, with an estimated 80% of these infections being associated with their use. This paper describes a model which quantifies the extent of the burden of these infections in terms of the number of patients affected and the costs incurred by the hospital sector; and identifies the potential benefits of the routine use of silver alloy coated catheters, as a means of reducing the incidence of this type of infection. An illustrative model of the annual costs and benefits associated with the routine use of this intervention in adult, non-day case patients admitted to the medical and surgical specialties of NHS hospitals throughout England is presented. The results suggest that a 14.6% reduction in the incidence of urinary tract infections in catheterized medical patients, and a 11.4% reduction in catheterized surgical patients, would cover the cost of the intervention. Any further reduction in incidence would result in net positive benefits.
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Aleaciones/economía , Aleaciones/normas , Catéteres de Permanencia/economía , Catéteres de Permanencia/normas , Materiales Biocompatibles Revestidos/economía , Materiales Biocompatibles Revestidos/normas , Costo de Enfermedad , Infección Hospitalaria/economía , Infección Hospitalaria/prevención & control , Costos de Hospital/estadística & datos numéricos , Modelos Econométricos , Plata/economía , Plata/normas , Cateterismo Urinario/efectos adversos , Cateterismo Urinario/instrumentación , Infecciones Urinarias/economía , Infecciones Urinarias/prevención & control , Adulto , Análisis Costo-Beneficio , Infección Hospitalaria/epidemiología , Infección Hospitalaria/etiología , Inglaterra/epidemiología , Humanos , Incidencia , Control de Infecciones/economía , Control de Infecciones/métodos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Admisión del Paciente/economía , Admisión del Paciente/estadística & datos numéricos , Prevalencia , Factores de Riesgo , Sensibilidad y Especificidad , Medicina Estatal , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiologíaRESUMEN
Between April 1994 and May 1995 4000 adult patients admitted to selected specialties of a district general hospital were recruited to this study. Hospital-acquired infections presenting during the in-patient stay were identified using previously validated methods of surveillance, and information on daily resource use by both infected and uninfected patients was recorded and estimates of their cost derived. Linear regression modelling techniques were used to estimate how much of the observed variation in resource use and costs could be explained by the presence of an infection. Complete in-patient data sets were obtained for 3980 patients. Of these, 309 patients (7.8%; 95% CI; 7.0, 8.6) presented with one or more hospital-acquired infections during the in-patient period. Infected patients, on average, incurred hospital costs 2.9 (regression model estimate: 2.8; 95% CI; 2.6, 3.0) times higher than uninfected patients, equivalent to an additional pound3154 (regression model estimate pound2917). Both the incidence and the economic impact varied with site of infection and with admission specialty. Estimates of the burden of hospital-acquired infections occurring in adult patients admitted to similar specialties at NHS hospitals in England were derived from the results of this study. An estimated 320 994 (95% CI; 288 071, 353 916) patients per annum acquire one or more infections which present during the in-patient period, and these infections cost the hospital sector an estimated 930.62 million pounds (95% CI; 780.26 pounds; 1080.97 million pounds) per annum. The results presented represent the gross economic benefits that might accrue if these infections are prevented. Further research is required to establish the net benefits of prevention.
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Costo de Enfermedad , Infección Hospitalaria/economía , Infección Hospitalaria/epidemiología , Costos de Hospital/estadística & datos numéricos , Hospitales de Distrito/economía , Hospitales Generales/economía , Adolescente , Adulto , Anciano , Economía Médica , Inglaterra/epidemiología , Femenino , Hospitales de Distrito/estadística & datos numéricos , Hospitales Generales/estadística & datos numéricos , Humanos , Incidencia , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Medicina/estadística & datos numéricos , Persona de Mediana Edad , Vigilancia de la Población , Análisis de Regresión , EspecializaciónRESUMEN
Adult inpatients in common specialties who developed hospital acquired infection (HAI) remained in hospital 2.5 times longer, incurred hospital costs almost three times higher, and incurred higher general practitioner, district nurse, and hospital costs a
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STUDY OBJECTIVE: To establish the degree of validity of data on time to pregnancy, derived retrospectively using a short questionnaire. DESIGN: Information from the questionnaire was compared with data that had been collected concurrently from the same individuals. SETTING AND PARTICIPANTS: Questionnaires were mailed to 1647 women who continue to be followed up by the Oxford Family Planning Association contraceptive study, and a further 424 were approached for personal interview. Response rates were 91% and 79% respectively. MAIN RESULTS: Matching was successful in 91% of pregnancies. Median recall time was 14 years (interquartile range, 11-16 years). At the group level, remarkably good agreement was found between the two sources of information, presented as cumulative percentage distributions of live births. The findings were at least as good with longer recall (> 14 years) as with shorter recall. Digit performance was present to a limited degree. At the individual level, some misclassification was evident, which has implications for statistical power. For detection of clinical infertility (no conception within 12 months), the sensitivity was in the range 67%-91%, and the specificity was 92%-96%. Variations with format, duration of recall, age at delivery, year of birth, parity, social class, smoking habit, last contraceptive method, and outcome (live birth or not) were generally small, and were not statistically significant. CONCLUSIONS: Time to pregnancy is a sensitive way of assessing reproductive function in either sex. Valid data at a group level can be derived retrospectively, with a long duration of recall, using a short questionnaire.