RESUMEN
BACKGROUND: Despite considerable emphasis on delivering safe care, substantial patient harm occurs. Although most care occurs in the outpatient setting, knowledge of outpatient adverse events (AEs) remains limited. OBJECTIVE: To measure AEs in the outpatient setting. DESIGN: Retrospective review of the electronic health record (EHR). SETTING: 11 outpatient sites in Massachusetts in 2018. PATIENTS: 3103 patients who received outpatient care. MEASUREMENTS: Using a trigger method, nurse reviewers identified possible AEs and physicians adjudicated them, ranked severity, and assessed preventability. Generalized estimating equations were used to assess the association of having at least 1 AE with age, sex, race, and primary insurance. Variation in AE rates was analyzed across sites. RESULTS: The 3103 patients (mean age, 52 years) were more often female (59.8%), White (75.1%), English speakers (90.8%), and privately insured (70.4%) and had a mean of 4 outpatient encounters in 2018. Overall, 7.0% (95% CI, 4.6% to 9.3%) of patients had at least 1 AE (8.6 events per 100 patients annually). Adverse drug events were the most common AE (63.8%), followed by health care-associated infections (14.8%) and surgical or procedural events (14.2%). Severity was serious in 17.4% of AEs, life-threatening in 2.1%, and never fatal. Overall, 23.2% of AEs were preventable. Having at least 1 AE was less often associated with ages 18 to 44 years than with ages 65 to 84 years (standardized risk difference, -0.05 [CI, -0.09 to -0.02]) and more often associated with Black race than with Asian race (standardized risk difference, 0.09 [CI, 0.01 to 0.17]). Across study sites, 1.8% to 23.6% of patients had at least 1 AE and clinical category of AEs varied substantially. LIMITATION: Retrospective EHR review may miss AEs. CONCLUSION: Outpatient harm was relatively common and often serious. Adverse drug events were most frequent. Rates were higher among older adults. Interventions to curtail outpatient harm are urgently needed. PRIMARY FUNDING SOURCE: Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.
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Atención Ambulatoria , Registros Electrónicos de Salud , Seguridad del Paciente , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Adulto , Anciano , Massachusetts , Adolescente , Adulto JovenRESUMEN
BACKGROUND: Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted. METHODS: We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events. RESULTS: In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%). CONCLUSIONS: Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).
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Atención a la Salud , Hospitalización , Errores Médicos , Daño del Paciente , Seguridad del Paciente , Humanos , Atención a la Salud/normas , Atención a la Salud/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Hospitalización/estadística & datos numéricos , Pacientes Internos , Errores Médicos/prevención & control , Errores Médicos/estadística & datos numéricos , Seguridad del Paciente/normas , Estudios Retrospectivos , Daño del Paciente/prevención & control , Daño del Paciente/estadística & datos numéricosRESUMEN
PURPOSE: Ocular injuries pose a significant threat to performance of military functions by the U.S. service members. To estimate the burden of ocular injuries in service members, administrative health records from the Military Health System were collected and analyzed, inclusive of ocular injuries incurred during deployment, military training, or outside of duty hours. METHODS: Patient encounters which matched the predesignated ICD10 codes for ocular injury and complications were extracted and were longitudinally analyzed to categorize patients into complicated (documentation of surgical procedure performed or ocular condition requiring further treatment) or uncomplicated (documentation of injury only). Comparison of incidence rates between groups was made, and geospatial analysis of the number of patients with ocular injury was conducted. RESULTS: A total of 61,680 incidences of ocular injuries were identified from 2016 to 2019. The incidence rates for complicated and uncomplicated injuries were 21.3 and 82.3 per 10,000, respectively. The incidence rate of uncomplicated injury declined from 2016 to 2019, while that of complicated injury was relatively stable. For complicated ocular injury, the relative risk of males was 62% higher than that of females. The incidence rates of the Army and the Marines were significantly higher than those of the Air Force. California, Texas, and Virginia ranked top three in the numbers of complicated ocular injury patients. Unintentional injuries and struck were the most frequently coded intention and mechanism. CONCLUSION: Our results provide the critical information on trends of ocular injuries in relation to demographics, service branches, and occupations. Categorization of the severity of ocular injuries is important to inform health services operations analysis across the Military Health System to enhance medical readiness and improve outcomes.
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Lesiones Oculares , Personal Militar , Masculino , Femenino , Humanos , Estados Unidos/epidemiología , Incidencia , Lesiones Oculares/epidemiología , Lesiones Oculares/cirugía , Texas , VirginiaRESUMEN
INTRODUCTION: Optic neuritis (ON), an acute inflammation of the optic nerve resulting in eye pain and temporary vision loss, is one of the leading causes of vision-related hospital bed days in the U.S. Military and may be a harbinger of multiple sclerosis (MS). We developed a case identification algorithm to estimate incidence rates of ON and the conversion rate to MS based on a retrospective assessment of medical records of service members (SMs) of the U.S. Armed Force. MATERIALS AND METHODS: Electronic medical records (EMRs) from 2006 to 2018 in the Defense Medical Surveillance System were screened using the case identification algorithms for ON and MS diagnosis. The incidences rates of ON were calculated. The rates of conversion to MS was modeled using the Kaplan-Meier survival analysis. RESULTS: The overall incidence rate of ON was 8.1 per 100,000 from 2006 to 2018. Females had a rate (16.9 per 100,000) three times higher than males. Most (68%) of subsequent diagnoses of MS were made within 1 year after diagnosis of ON. The overall 5-year risk of progression to MS was 15% (11%-16% for 95% CI). The risk of conversion to MS in females was significantly higher than in males. CONCLUSIONS: We developed an efficient tool to explore the EMR database to estimate the burden of ON in the U.S. Military and the MS conversion based on a dynamic cohort. The estimated conversion rates to MS feeds into inform retention and fitness-for-duty policy in these SMs.
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Personal Militar , Esclerosis Múltiple , Neuritis Óptica , Masculino , Femenino , Humanos , Incidencia , Estudios Retrospectivos , Esclerosis Múltiple/epidemiología , Neuritis Óptica/epidemiología , Neuritis Óptica/etiologíaRESUMEN
BACKGROUND: Twenty-five years after the seminal work of the Harvard Medical Practice Study, the numbers and specific types of health care measures of harm have evolved and expanded. Using the World Café method to derive expert consensus, we sought to generate a contemporary list of triggers and adverse event measures that could be used for chart review to determine the current incidence of inpatient and outpatient adverse events. METHODS: We held a modified World Café event in March 2018, during which content experts were divided into 10 tables by clinical domain. After a focused discussion of a prepopulated list of literature-based triggers and measures relevant to that domain, they were asked to rate each measure on clinical importance and suitability for chart review and electronic extraction (very low, low, medium, high, very high). RESULTS: Seventy-one experts from 9 diverse institutions attended (primary acceptance rate, 72%). Of 525 total triggers and measures, 67% of 391 measures and 46% of 134 triggers were deemed to have high or very high clinical importance. For those triggers and measures with high or very high clinical importance, 218 overall were deemed to be highly amenable to chart review and 198 overall were deemed to be suitable for electronic surveillance. CONCLUSIONS: The World Café method effectively prioritized measures/triggers of high clinical importance including those that can be used in chart review, which is considered the gold standard. A future goal is to validate these measures using electronic surveillance mechanisms to decrease the need for chart review.
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Pacientes Internos , Consenso , Humanos , IncidenciaAsunto(s)
Enfermedades de la Córnea/epidemiología , Personal Militar/estadística & datos numéricos , Enfermedades Profesionales/epidemiología , Adulto , Córnea/patología , Enfermedades de la Córnea/patología , Dilatación Patológica/epidemiología , Femenino , Humanos , Incidencia , Masculino , Enfermedades Profesionales/patología , Prevalencia , Estados Unidos/epidemiología , Adulto JovenAsunto(s)
Oftalmología/organización & administración , United States Department of Defense , United States Department of Veterans Affairs , Oftalmopatías/terapia , Lesiones Oculares/terapia , Humanos , Estados Unidos , United States Department of Defense/organización & administración , United States Department of Veterans Affairs/organización & administraciónRESUMEN
The current report used an ocular and vision disease classification system and several healthcare burden measures to quantify the impacts of various ocular and vision-related illnesses and injuries among active component service members of the U.S. Armed Forces during 2018. More service members received care for refractive error and related disorders than any other ocular and vision-related major category; this category accounted for slightly more than one-half (51.1%) of all ocular and vision-related medical encounters. Conjunctival disorders accounted for the next highest percentage of total medical encounters (13.3%) followed by corneal disorders (7.5%). The 3 specific ocular and vision-related conditions that accounted for the most medical encounters (i.e., myopia, astigmatism, and acute conjunctivitis) accounted for almost one-half (47.7%) of all ocular and vision-related medical encounters overall. In general, the conditions that accounted for the most medical encounters were predominantly refractive error and related disorders and conjunctival disorders. More active component service members received medical care for myopia than for any other specific condition. Optic nerve conditions and visual discomfort/disturbances accounted for more than onequarter (30.1%) of all ocular and vision-related hospital bed days.
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Costo de Enfermedad , Oftalmopatías/epidemiología , Personal Militar/estadística & datos numéricos , Trastornos de la Visión/epidemiología , Lesiones Oculares/epidemiología , Humanos , Estados Unidos/epidemiologíaRESUMEN
This analysis describes the incidence of visual dysfunctions following a diagnosis of traumatic brain injury (TBI) among active component service members. The visual dysfunctions were divided into 9 major categories. A comparison group of service members with no history of TBI was used to determine relative incidence rates. The most commonly diagnosed visual dysfunctions were subjective visual disturbances, convergence insufficiency (CI), visual field loss, and accommodative dysfunction (AD). Service members with mild or moderate/severe TBI had significantly higher incidences of AD and CI compared to service members with no TBI. Results of survival analysis showed that service members with mild or moderate/severe TBI had lower probabilities of remaining without the visual dysfunction outcome at almost every week of follow-up in the first year after TBI diagnosis compared to those with no TBI. The findings of this report suggest opportunities to improve both documentation and access to care for service members with these conditions.
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Lesiones Traumáticas del Encéfalo/complicaciones , Personal Militar/estadística & datos numéricos , Trastornos de la Visión/epidemiología , Adulto , Lesiones Traumáticas del Encéfalo/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiología , Trastornos de la Visión/etiología , Adulto JovenRESUMEN
During 2001-2018, there were approximately 1.38 million incident diagnoses of myopia, 1.21 million incident diagnoses of astigmatism, and 492,000 incident diagnoses of hyperopia among active component service members (crude overall incidence rates of 7.8, 6.6, and 2.2 diagnoses per 100 personyears, respectively). Incidence rates of all 3 conditions were higher among women compared to men. Service members in the Marine Corps, enlisted personnel, and those working in other/unknown military occupations had higher overall rates of incident myopia diagnoses compared to their respective counterparts. Incidence rates of astigmatism diagnoses were similar across all services and among both enlisted personnel and officers. Overall rates of hyperopia diagnoses were similar across all race/ethnicity groups and service branches and among both enlisted personnel and officers. However, across occupational groups, overall rates of hyperopia and astigmatism diagnoses were highest among service members working in healthcare occupations. Future analyses should focus on the specific effects of military refractive surgery programs on the readiness of service members.
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Personal Militar/estadística & datos numéricos , Errores de Refracción/epidemiología , Adolescente , Adulto , Astigmatismo/epidemiología , Femenino , Humanos , Hiperopía/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Miopía/epidemiología , Prevalencia , Grupos Raciales/estadística & datos numéricos , Factores de Riesgo , Factores Sexuales , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Central serous chorioretinopathy (CSCR) is a condition that affects central visual function. It can produce blurred and/or distorted vision that can impact the performance of military duties. CSCR can recur in susceptible individuals. Incident cases of CSCR among active component service members were found to average 18.3 per 100,000 person-years (p-yrs) during 2001-2018. Incidence rates increased during the surveillance period by 60.7% and were more common with increasing age. Overall rates of incident CSCR diagnoses were highest among Air Force (20.7 per 100,000 p-yrs) and Navy members (19.9 per 100,000 p-yrs) and lowest among Marine Corps members (12.5 per 100,000 p-yrs). Pilot/air crew occupational groups had rates almost twice that of other groups. Annual recurrence rates increased 71.4% over the course of the 18-year period.
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Coriorretinopatía Serosa Central/epidemiología , Personal Militar/estadística & datos numéricos , Adulto , Factores de Edad , Femenino , Humanos , Incidencia , Masculino , Recurrencia , Factores de Riesgo , Factores Sexuales , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Exertional heat illness (EHI) risk is a serious concern among athletes, laborers, and warfighters. US Governing organizations have established various activity modification guidelines (AMGs) and other risk mitigation plans to help ensure the health and safety of their workers. The extent of metabolic heat production and heat gain that ensue from their work are the core reasons for EHI in the aforementioned population. Therefore, the major focus of AMGs in all settings is to modulate the work intensity and duration with additional modification in adjustable extrinsic risk factors (e.g., clothing, equipment) and intrinsic risk factors (e.g., heat acclimatization, fitness, hydration status). Future studies should continue to integrate more physiological (e.g., valid body fluid balance, internal body temperature) and biometeorological factors (e.g., cumulative heat stress) to the existing heat risk assessment models to reduce the assumptions and limitations in them. Future interagency collaboration to advance heat mitigation plans among physically active population is desired to maximize the existing resources and data to facilitate advancement in AMGs for environmental heat.
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Ejercicio Físico , Trastornos de Estrés por Calor/prevención & control , Calor , Aclimatación , Atletas , Guías como Asunto , Humanos , Personal Militar , Salud Laboral , Estados UnidosRESUMEN
BACKGROUND: The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. METHODS: A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively. RESULTS: A total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4-9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near-complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow-up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues. CONCLUSIONS: Children with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas.
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Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/genética , Fibrosarcoma/patología , Humanos , Lactante , Recién Nacido , Masculino , Terapia Neoadyuvante , Proteínas de Fusión Oncogénica/genética , Receptor trkA/genética , Sarcoma/genética , Sarcoma/patología , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Resultado del TratamientoAsunto(s)
Servicios Médicos de Urgencia/métodos , Infecciones del Ojo/terapia , Lesiones Oculares/diagnóstico , Lesiones Oculares/terapia , Personal Militar , Ceguera/etiología , Ceguera/prevención & control , Síndromes Compartimentales/diagnóstico , Síndromes Compartimentales/terapia , Infecciones del Ojo/diagnóstico , Lesiones Oculares/complicaciones , Lesiones Oculares/fisiopatología , Humanos , Presión Intraocular , Fracturas Orbitales/diagnóstico , Fracturas Orbitales/terapia , Guías de Práctica Clínica como Asunto , Derivación y Consulta , Hemorragia Retrobulbar/diagnóstico , Hemorragia Retrobulbar/terapia , Telemedicina , Factores de Tiempo , Estados Unidos , Pruebas de Visión , Agudeza Visual , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/terapiaRESUMEN
BACKGROUND: This report describes a rapid method of vision correction used by Special Operations Medics in multiple operational engagements. METHODS: Between 2011 and 2015, Special Operations Medics used an algorithm- driven refraction technique. A standard block of instruction was provided to the medics, along with a packaged kit. The technique was used in multiple operational engagements with host nation military and civilians. Data collected for program evaluation were later analyzed to assess the utility of the technique. RESULTS: Glasses were distributed to 230 patients with complaints of either decreased distance or near (reading). Most patients (84%) with distance complaints achieved corrected binocular vision of 20/40 or better, and 97% of patients with near-vision complaints achieved corrected near-binocular vision of 20/40 or better. There was no statistically significant difference between the percentages of patients achieving 20/40 when medics used the technique under direct supervision versus independent use. CONCLUSION: A basic refraction technique using a designed kit allows for meaningful improvement in distance and/or near vision at austere locations. Special Operations Medics can leverage this approach after specific training with minimal time commitment. It can serve as a rapid, effective intervention with multiple applications in diverse operational environments.
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Algoritmos , Anteojos , Hiperopía/rehabilitación , Medicina Militar , Miopía/rehabilitación , Presbiopía/rehabilitación , Trastornos de la Visión/rehabilitación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Hiperopía/diagnóstico , Masculino , Persona de Mediana Edad , Miopía/diagnóstico , Presbiopía/diagnóstico , Errores de Refracción/diagnóstico , Errores de Refracción/rehabilitación , Factores de Tiempo , Trastornos de la Visión/diagnóstico , Adulto JovenRESUMEN
BACKGROUND: Concomitant cranial and ocular injuries were frequently seen in combat casualties during Operation Iraqi Freedom. The incidence of these injuries is reported along with an interventional case series. METHODS: A retrospective review was conducted of all surgical patients treated by U.S. Army neurosurgeons and ophthalmologists in Iraq from December 2005 to April 2006. RESULTS: Out of 104 patients with cranial trauma and 158 patients with ocular trauma, 34 had both cranial and ocular injuries (32.7 and 21.5% of patients with cranial and ocular injuries, respectively). Neurosurgical procedures included exploratory craniotomy, decompressive craniectomy, and frontal sinus surgery. Ophthalmologic surgical procedures included globe exploration, open globe repair, primary enucleation, orbital fracture repair, lateral canthotomy and cantholysis, and repair of lid and periocular lacerations. Patients with cranial trauma had a higher incidence of orbital fracture, orbital compartment syndrome, and multiple ocular injuries compared with patients without cranial trauma (odds ratio 6.4, 3.9, and 3.3, respectively). CONCLUSION: A strong association exists between cranial and ocular trauma in combat casualties treated during Operation Iraqi Freedom. Combat health support personnel should maintain a high level of suspicion for one of these injuries when the other is present. Co-locating neurosurgeons and ophthalmologists in support of combat operations facilitates the optimal treatment of patients with these combined injuries.
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Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/epidemiología , Lesiones Oculares/complicaciones , Lesiones Oculares/epidemiología , Guerra de Irak 2003-2011 , Traumatismo Múltiple/epidemiología , Traumatismos por Explosión/complicaciones , Traumatismos por Explosión/epidemiología , Traumatismos por Explosión/cirugía , Lesiones Encefálicas/cirugía , Estudios de Cohortes , Lesiones Oculares/cirugía , Femenino , Humanos , Masculino , Traumatismo Múltiple/cirugía , Estudios Retrospectivos , Heridas por Arma de Fuego/complicaciones , Heridas por Arma de Fuego/epidemiología , Heridas por Arma de Fuego/cirugíaRESUMEN
Two structurally distinct classes of peptides were recently identified by phage display that bind the high-affinity IgE receptor, FcepsilonRI, and block IgE binding and subsequent receptor activation. Both classes adopt highly stable structures in solution, one forming a beta hairpin, with the other forming a helical "zeta" structure. Despite these differences, the two classes bind competitively to the same site on the receptor. Structural analyses of both peptide-receptor complexes by NMR spectroscopy and/or X-ray crystallography reveal that the unrelated peptide scaffolds have nevertheless converged to present a similar three-dimensional surface to interact with FcepsilonRI and that their modes of interaction share a key feature of the IgE-FcepsilonRI complex, the proline/tryptophan sandwich.
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Unión Competitiva , Inmunoglobulina E/metabolismo , Péptidos/química , Receptores de IgE/metabolismo , Secuencia de Aminoácidos , Células Cultivadas , Cristalografía por Rayos X , Humanos , Inmunoglobulina E/química , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Péptidos/metabolismo , Unión Proteica , Conformación Proteica , Receptores de IgE/química , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
Recently we described a family of peptides, unrelated in sequence to IgE, that form stable beta-hairpins in solution and inhibit IgE activity in the microM range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. & Lowman, H. B. (2001) Biochemistry 40, 9828-9835]. Using an expanded set of peptide-phage libraries, we found a simpler motif, X(2)CPX(2)CYX, for binding to the high-affinity IgE receptor. In solution, one of these peptides spontaneously formed a covalent antiparallel dimer. We subsequently linked these monomers in a single-chain construct on phage and optimized receptor binding. Ultimately, peptides with 30 nM affinity were produced. NMR studies showed that the peptide adopts a stable fold consisting of two "zeta" (zeta)-shaped moieties. Structure-activity analyses reveal a single binding site created by the zeta-dimer, with two tyrosine residues important for structural stability and two proline residues important for Fc epsilon RI binding. The peptides inhibit histamine release from cultured cells and are extremely stable in biological fluids. The zeta peptides appear to act as competitive IgE inhibitors and suggest possibilities for design of novel IgE antagonists.