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Positron emission tomography is a widely used imaging platform for studying physiological processes. Despite the proliferation of modern synthetic methodologies for radiolabeling, the optimization of these reactions still primarily relies on inefficient one-factor-at-a-time approaches. High-throughput experimentation (HTE) has proven to be a powerful approach for optimizing reactions in many areas of chemical synthesis. However, to date, HTE has rarely been applied to radiochemistry. This is largely because of the short lifetime of common radioisotopes, which presents major challenges for efficient parallel reaction setup and analysis using standard equipment and workflows. Herein, we demonstrate an effective HTE workflow and apply it to the optimization of copper-mediated radiofluorination of pharmaceutically relevant boronate ester substrates. The workflow utilizes commercial equipment and allows for rapid analysis of reactions for optimizing reactions, exploring chemical space using pharmaceutically relevant aryl boronates for radiofluorinations, and constructing large radiochemistry data sets.
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Cobre , Tomografía de Emisión de Positrones , Radioquímica , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Radioisótopos de FlúorRESUMEN
Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of HiChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we reveal previously unappreciated variation in the epigenetic profiles of young TE loci in mouse and human cells. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.
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Cromatina , Elementos Transponibles de ADN , Animales , Cromatina/genética , Elementos Transponibles de ADN/genética , Regulación de la Expresión Génica , Genómica , Humanos , RatonesRESUMEN
This report describes the development of a Zn(OTf)2 -mediated method for converting α-tertiary haloamides to the corresponding fluorine-18 labelled α-tertiary fluoroamides with no-carrier-added [18 F]tetramethylammonium fluoride. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4â GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C-H radiofluorination process using N-sulphonyloxyamide substrates.
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Protein binding to negatively charged lipids is essential for maintaining numerous vital cellular processes where its dysfunction can lead to various diseases. One such protein that plays a crucial role in this process is lactadherin, which competes with coagulation factors for membrane binding sites to regulate blood clotting. Despite identifying key binding regions of these proteins through structural and biochemical studies, models incorporating membrane dynamics are still lacking. In this study, we report on the multimodal binding of lactadherin and use it to gain insight into the binding mechanisms of its C domain homologs, factor V and factor VIII. Molecular dynamics simulations enhanced with the highly mobile mimetic model enabled the determination of lactadherin's multimodal binding on membranes that revealed critical interacting residues consistent with prior NMR and mutagenesis data. The binding occurred primarily via two dynamic structural ensembles: an inserted state and an unreported, highly conserved side-lying state driven by a cationic patch. We utilized these findings to analyze the membrane binding domains of coagulation factors V and VIII and identified their preferred membrane-bound conformations. Specifically, factor V's C domains maintained an inserted state, while factor VIII preferred a tilted, side-lying state that permitted antibody binding. Insight into lactadherin's atomistically resolved membrane interactions from a multistate perspective can guide new therapeutic opportunities in treating diseases related to blood coagulation.
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Factor VIII , Factor V , Factor VIII/química , Factor VIII/metabolismo , Factor V/química , Factor V/metabolismo , Sitios de Unión , Unión Proteica , Conformación MolecularRESUMEN
Radiocyanation is an attractive strategy for incorporating carbon-11 into radiotracer targets, particularly given the broad scope of acyl moieties accessible from nitriles. Most existing methods for aromatic radiocyanation require elevated temperatures (Cu-mediated reactions of aryl halides or organometallics) or involve expensive and toxic palladium complexes (Pd-mediated reactions of aryl halides). The current report discloses a complementary approach that leverages the capture of aryl radical intermediates by a Cu-11CN complex to achieve rapid and mild (5 min, room temperature) radiocyanation. In a first example, aryl radicals are generated via the reaction of a CuI mediator with an aryldiazonium salt (a Sandmeyer-type reaction) followed by radiocyanation with Cu-11CN. In a second example, aryl radicals are formed from aryl iodides via visible-light photocatalysis and then captured by a Cu-11CN species to achieve aryl-11CN coupling. This approach provides access to radiocyanated products that are challenging to access using other methods (e.g., ortho-disubstituted aryl nitriles).
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Endothelial activation and sickle red blood cell (RBC) adhesion are central to the pathogenesis of sickle cell disease (SCD). Quantitatively, RBC-derived extracellular vesicles (REVs) are more abundant from SS RBCs compared with healthy RBCs (AA RBCs). Sickle RBC-derived REVs (SS REVs) are known to promote endothelial cell (EC) activation through cell signalling and transcriptional regulation at longer terms. However, the SS REV-mediated short-term non-transcriptional response of EC is unclear. Here, we examined the impact of SS REVs on acute microvascular EC activation and RBC adhesion at 2 h. Compared with AA REVs, SS REVs promoted human pulmonary microvascular ECs (HPMEC) activation indicated by increased von Willebrand factor (VWF) expression. Under microfluidic conditions, we found abnormal SS RBC adhesion to HPMECs exposed to SS REVs. This enhanced SS RBC adhesion was reduced by haeme binding protein haemopexin or VWF cleaving protease ADAMTS13 to a level similar to HPMECs treated with AA REVs. Consistent with these observations, haemin- or SS REV-induced microvascular stasis in SS mice with implanted dorsal skin-fold chambers that was inhibited by ADAMTS13. The adhesion induced by SS REVs was variable and was higher with SS RBCs from patients with increased markers of haemolysis (lactate dehydrogenase and reticulocyte count) or a concomitant clinical diagnosis of deep vein thrombosis. Our results emphasise the critical contribution made by REVs to the pathophysiology of SCD by triggering acute microvascular EC activation and abnormal RBC adhesion. These findings may help to better understand acute pathophysiological mechanism of SCD and thereby the development of new treatment strategies using VWF as a potential target.
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Anemia de Células Falciformes , Células Endoteliales , Humanos , Animales , Ratones , Células Endoteliales/patología , Factor de von Willebrand/metabolismo , Adhesión Celular , Eritrocitos/metabolismoRESUMEN
INTRODUCTION: Medulloblastoma is the commonest malignant brain tumour in children. Pre-operative hydrocephalus is present in up to 90% of these patients at presentation. Following posterior fossa surgery, despite resolution of fourth ventricular obstruction, a proportion of these children will still require cerebrospinal fluid (CSF) diversion for management of persistent or new hydrocephalus. Various scoring systems have been developed to predict the risk for CSF diversion following posterior fossa surgery. However, no accurate tool exists regarding which pathological subset or group of medulloblastoma patients will require a shunt post-operatively. In this study we investigated the impact of molecular subgroup of medulloblastoma on shunt dependency post-operatively in paediatric patients. METHODS: We undertook a retrospective multi-centre study of children with medulloblastoma who underwent tumour resection. Those with available molecular subgroup were identified. Demographic data and clinical parameters including age, sex, presence of pre-operative hydrocephalus, extent of surgical resection, evidence of metastasis/leptomeningeal disease and need for CSF diversion post-operatively were further analysed. RESULTS: Sixty-nine children with medulloblastoma with available molecular data were identified during the study period with male to female ratio of 1.5:1 (42M:27F). Twelve patients (17.4%) belonged to SHH, 10 (14.5%) Wnt, 19 (27.5%) Group 3 and 15 (21.7%) Group 4; 13 (18.8%) were non-specified Group 3 or 4. A total of 18 (26%) patients had evidence of leptomeningeal disease at presentation (20% of Wnt, 42% of Group 3, 33% of group 4, 23% of group 3/4, and 0% of SHH). Fifteen patients (22%) underwent post-operative ventriculoperitoneal (VP) shunt insertion. No patient in the Wnt group required ventriculoperitoneal (VP) shunt post-operatively in this cohort. Need for shunt was associated with pre-operative hydrocephalus, leptomeningeal disease, with molecular group 3 or 4 demonstrating higher rate of leptomeningeal disease, and pre-operative hydrocephalus. Age, extent of resection and pre-operative EVD were not associated with need for shunt in this cohort. Regression analysis identified only pre-operative hydrocephalus and leptomeningeal disease as independent predictors of need for shunt post-resection in this cohort. CONCLUSION: All patients requiring permanent post-operative VP shunt belonged to non-Wnt groups, particularly group 3 and 4. Although medulloblastoma subgroup does not independently predict need for post-operative shunt, presence of leptomeningeal disease and pre-operative hydrocephalus, and their higher prevalence in group 3 and 4, likely account for observed higher rate of shunting in these groups.
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Neoplasias Encefálicas , Neoplasias Cerebelosas , Hidrocefalia , Meduloblastoma , Niño , Humanos , Masculino , Femenino , Meduloblastoma/genética , Meduloblastoma/cirugía , Neoplasias Encefálicas/cirugía , Derivación Ventriculoperitoneal , Hidrocefalia/etiología , Hidrocefalia/cirugía , Hidrocefalia/epidemiología , Estudios Retrospectivos , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/cirugíaRESUMEN
Objectives: Rapid Access Chest Pain Clinics (RACPCs) provide safe and efficient follow-up for outpatients presenting with new-onset chest pain. RACPC delivery by telehealth has not been reported. We sought to evaluate a telehealth RACPC established during the coronavirus disease 2019 (COVID-19) pandemic. There was a need to reduce the frequency of additional testing arranged by the RACPC during this time, and the safety of this approach was also explored. Methods: This was a prospective evaluation of a cohort of RACPC patients reviewed by telehealth during the COVID-19 pandemic compared with a historical control group of face-to-face consultations. The main outcomes included emergency department re-presentation at 30 days and 12 months, major adverse cardiovascular events at 12 months, and patient satisfaction scores. Results: One hundred forty patients seen in the telehealth clinic were compared with 1,479 in-person RACPC controls. Baseline demographics were similar; however, telehealth patients were less likely to have a normal prereferral electrocardiogram than RACPC controls (81.4% vs. 88.1%, p = 0.03). Additional testing was ordered less often for telehealth patients (35.0% vs. 80.7%, p < 0.001). Rates of adverse cardiovascular events were low in both groups. One hundred twenty (85.7%) patients reported being satisfied or highly satisfied with the telehealth clinic service. Conclusions: In the setting of COVID-19, a telehealth RACPC model with reduced use of additional testing facilitated social distancing and achieved clinical outcomes equivalent to a face-to-face RACPC control. Telehealth may have an ongoing role beyond the pandemic, supporting specialist chest pain assessment for rural and remote communities. Pending further study, it may be safe to reduce the frequency of additional testing following RACPC review.
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COVID-19 , Enfermedades Cardiovasculares , Telemedicina , Humanos , Clínicas de Dolor , Pandemias , COVID-19/epidemiología , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Dolor en el Pecho/epidemiologíaRESUMEN
The well-known epoxide-Ritter reaction generally affords oxazolines with poor to average regioselectivity. Herein, a mechanism-based study of the less known diol-Ritter reaction has provided a highly regioselective procedure for the synthesis of 1-vic-amido-2-esters from either terminal epoxides or 1,2-diols via Lewis acid-catalyzed monoesterification. When treated with a stoichiometric Lewis acid catalyst (BF3), these diol monoesters form dioxonium cation intermediates that are ring-opened with nitrile nucleophiles to form nitrilium intermediates, which undergo rapid and irreversible hydration to give the desired amidoesters. Diester byproduct formation is irreversible and appears to occur through disproportionation of diol monoester. With chiral epoxide starting materials, the formation of amidoester occurs with retention of configuration and no apparent erosion of optical purity as determined by single-crystal X-ray analyses and chiral chromatography, respectively. The direct access to chiral vic-amidoesters is especially practical with regard to the synthesis of antibacterial oxazolidinone analogues of the Zyvox antimicrobial family.
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Amino Alcoholes , Compuestos Epoxi , Catálisis , Compuestos Epoxi/química , EstereoisomerismoRESUMEN
OBJECTIVES: The purpose of this study was to measure the indices of radiographic developmental dysplasia of the hip (DDH) in a cross-sectional study of an elderly Japanese population. METHODS: Hip radiographs of 427 informed, voluntary Japanese community-dwelling individuals (279 female and 148 male) aged 50-96 years-old were obtained from Miyagawa village in Japan through a health screening. The hip radiographs were measured by a custom-written, semi-automated MATLAB program. The center edge (CE) angle, acetabular roof obliquity (ARO), acetabular head index (AHI), and minimum joint space width (mJSW) were measured. We examined the associations between gender, side-of-hip, and age group on radiographic DDH and hip osteoarthritis (OA). RESULTS: The mean CE angle was 31.0°. The mean ARO was 5.8°. The mean AHI was 88.2%. The mean mJSW was 4.0 mm. Of the total population, 29.9% had DDH and 4.0% had hip OA. Of those who had hip OA, 41.2% were secondary OA, and 58.8% were primary OA. The relationship between DDH and OA was not significant. CONCLUSION: DDH is unlikely to be an important cause of hip OA in the present population-based study.
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Luxación Congénita de la Cadera , Luxación de la Cadera , Osteoartritis de la Cadera , Acetábulo , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Luxación Congénita de la Cadera/complicaciones , Articulación de la Cadera/diagnóstico por imagen , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/diagnóstico por imagen , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/etiología , Prevalencia , Estudios RetrospectivosRESUMEN
We design and synthesize a set of homologous organic molecules by taking advantage of facile and tailorable Suzuki cross coupling reactions to produce triarylbenzene derivatives. By adjusting the number and the arrangement of conjugated rings, the identity of heteroatoms, lengths of fluorinated alkyl chains, and other interaction parameters, we create a library of glassformers with a wide range of properties. Measurements of the glass transition temperature (Tg) show a power-law relationship between Tg and molecular weight (MW), with of the molecules, with an exponent of 0.3 ± 0.1, for Tg values spanning a range of 300-450 K. The trends in indices of refraction and expansion coefficients indicate a general increase in the glass density with MW, consistent with the trends observed in Tg variations. A notable exception to these trends was observed with the addition of alkyl and fluorinated alkyl groups, which significantly reduced Tg and increased the dynamical fragility (which is otherwise insensitive to MW). This is an indication of reduced density and increased packing frustrations in these systems, which is also corroborated by the observations of the decreasing index of refraction with increasing length of these groups. These data were used to launch a new database for glassforming materials, glass.apps.sas.upenn.edu.
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PURPOSE: Two-dimensional (2D) analyses of intervertebral disc (IVD) height and foramen measurements following lateral lumbar interbody fusion (LLIF) have been reported. However, three-dimensional (3D) morphometric analysis of intervertebral structure using 3D computed tomography (3D CT) provides increased precision for measuring morphological changes. The purpose of this study was to evaluate 3D changes of lumbar IVD height and foramen diameter in degenerative lumbar disease patients following LLIF. METHODS: Subject-based 3D CT lumbar models were created for 26 patients before and following LLIF. IVD height (whole and five anatomical zones) and foramen diameter (minimum and maximum) were measured based on the model using custom software. The sagittal placement of cages (SPC) and cross-sectional area of the thecal sac (CSA) were measured. Changes in these parameters by LLIF were quantified and statistically analysed. RESULTS: Following LLIF, disc height increased by an average of 2.9 mm (P < 0.01). Post-operative measurements of both minimum and maximum diameters of the foramen were significantly increased by 1.0 mm and 1.9 mm, respectively (P < 0.01). Change in maximum foramen diameter was significantly correlated with change in disc height (P < 0.05). The SPC was significantly correlated with the changes in disc height and foraminal diameters (P < 0.05, respectively). No significant change between the change in disc height and CSA was found. CONCLUSION: This preliminary study quantifies disc height and foramen diameter changes in 3D following LLIF. The presented data provide baseline intervertebral changes for future comparisons with follow-up studies and clinical outcomes. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
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Disco Intervertebral , Fusión Vertebral , Humanos , Vértebras Lumbares , Región Lumbosacra , Tomografía Computarizada por Rayos XRESUMEN
A 38-year-old female with anomalous left coronary artery from the pulmonary artery presented with refractory angina (Canadian Cardiovascular Society [CCS] class 4). Having failed two previous internal mammary artery grafts to the left anterior descending artery and with no percutaneous revascularization options, she underwent coronary sinus reducer implantation, which improved her symptoms (CCS 0), quality of life, and corresponded to an improvement in ischemia on myocardial perfusion scanning. This case report describes an unusual case of refractory angina in the context of congenital heart disease, illustrates the benefit of this novel hourglass-shaped stent in improving ischemia, quality of life, depression and anxiety, and highlights the importance of managing these patients in multidisciplinary teams.
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Angina de Pecho/cirugía , Arteria Coronaria Izquierda Anómala/cirugía , Seno Coronario/cirugía , Procedimientos Quirúrgicos Vasculares/instrumentación , Adulto , Angina de Pecho/diagnóstico por imagen , Angina de Pecho/fisiopatología , Arteria Coronaria Izquierda Anómala/diagnóstico por imagen , Arteria Coronaria Izquierda Anómala/fisiopatología , Angiografía Coronaria , Seno Coronario/diagnóstico por imagen , Seno Coronario/fisiopatología , Femenino , Humanos , Calidad de Vida , Stents , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
PURPOSE: Craniopharyngioma is a rare low-grade neoplasm in children. Tumor progression occurs frequently, and survivors are at risk of long-term disease and treatment-related morbidities. We reviewed the population-based experience of managing pediatric craniopharyngioma in Hong Kong. METHODS: The Hong Kong Pediatric Hematology/Oncology Study Group database was interrogated for patients with craniopharyngioma younger than 18 years between 1999 and 2018. Patient demographics, clinical characteristics, outcomes, and long-term morbidities were summarized. RESULTS: Twenty-eight patients with craniopharyngioma were included (approximate incidence of 1.1 per 1,000,000 individuals). The treatment approaches were heterogeneous and included surgery only, surgery with adjuvant radiation, and surgery with intracystic interferon. With a median follow-up of 6.1 years, 12 (43%) patients experienced disease progression, and 3 patients died of progression, postoperative complication, and gastrointestinal bleeding. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 56.8% (± 10.0%) and 92.0% (± 5.4%), respectively. The 10-year PFS and OS rates were 37.3% (± 11.4) and 92.0% (± 5.4%), respectively. Patients receiving treatment in a high-volume center had significantly better outcomes than did those treated at other centers (PFS, p = 0.007; OS, p = 0.029). Period of diagnosis, sex, age at diagnosis, greatest tumor dimension, extent of resection, and radiotherapy use did not significantly affect patient survival. Long-term visual impairment (60%) and endocrinopathies (92%) were common. CONCLUSION: Prognosis of pediatric craniopharyngioma in Hong Kong compares unfavorably with published reports. Centralization and standardization of treatment may prove valuable in mitigating patient outcomes.
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Craneofaringioma , Hematología , Neoplasias Hipofisarias , Niño , China , Craneofaringioma/epidemiología , Craneofaringioma/terapia , Estudios de Seguimiento , Hong Kong/epidemiología , Humanos , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The choice of valve type for aortic valve replacement surgery is sometimes challenging. The main risk for bioprostheses is structural valve degeneration (SVD); however, little is known about what the most important risk factors are. We conducted a systematic review and meta-analysis to identify the risk factors and estimate their pooled effect sizes to aid the prosthesis choice for replacement. We followed PRISMA guidelines and systematically searched three electronic databases (PubMed, Scopus, and Web of Science) using appropriate key terms: 'aortic valve', 'bioprosthesis', 'degeneration', 'durability', 'prosthesis failure', etc. Hazard ratio (HR) and odds ratio (OR) and associated 95% confidence intervals (CI) were extracted. Pooled risk estimates were calculated using a random-effects model. Twenty-nine (29) observational studies were included with a total of 25,490 patients, 981 of whom developed SVD over a mean follow-up time of 18.5 years. Four (4) factors influencing bioprosthetic SVD were identified: increasing age was a protective factor (per 1-yr increase, HR: 0.91 [95% CI 0.89, 0.94], p<0.0001), whereas increased body surface area (HR 1.77 [1.04, 3.01], p=0.034), patient-prosthesis mismatch (HR 1.95 [1.56, 2.43], p<0.001), and smoking (HR 2.28 [1.37, 3.79], p=0.0015) were risk factors for SVD. We found younger age, patient-prosthesis mismatch, body surface area, and smoking, as risk factors for aortic SVD, which should be considered for valve selection. This study generates a further hypothesis that accelerated flow across the valve is a shared key component in the pathophysiology of SVD, thus future research should consider other high cardiac output states.
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Válvula Aórtica/cirugía , Bioprótesis/efectos adversos , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Prótesis Valvulares Cardíacas/efectos adversos , Complicaciones Posoperatorias , Humanos , Diseño de Prótesis , Falla de Prótesis , Factores de RiesgoRESUMEN
Lipid droplets (LDs) utilize microtubules (MTs) to participate in intracellular trafficking of cargo proteins. Cancer cells accumulate LDs and acidify their tumor microenvironment (TME) by increasing the proton pump V-ATPase. However, it is not known whether these two metabolic changes are mechanistically related or influence LD movement. We postulated that LD density and velocity are progressively increased with tumor aggressiveness and are dependent on V-ATPase and the lipolysis regulator pigment epithelium-derived factor (PEDF). LD density was assessed in human prostate cancer (PCa) specimens across Gleason scores (GS) 6-8. LD distribution and velocity were analyzed in low and highly aggressive tumors using live-cell imaging and in cells exposed to low pH and/or treated with V-ATPase inhibitors. The MT network was disrupted and analyzed by α-tubulin staining. LD density positively correlated with advancing GS in human tumors. Acidification promoted peripheral localization and clustering of LDs. Highly aggressive prostate, breast, and pancreatic cell lines had significantly higher maximum LD velocity (LDVmax) than less aggressive and benign cells. LDVmax was MT-dependent and suppressed by blocking V-ATPase directly or indirectly with PEDF. Upon lowering pH, LDs moved to the cell periphery and carried metalloproteinases. These results suggest that acidification of the TME can alter intracellular LD movement and augment velocity in cancer. Restoration of PEDF or blockade of V-ATPase can normalize LD distribution and decrease velocity. This study identifies V-ATPase and PEDF as new modulators of LD trafficking in the cancer microenvironment.
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Proteínas del Ojo/metabolismo , Gotas Lipídicas/fisiología , Factores de Crecimiento Nervioso/metabolismo , Neoplasias de la Próstata/metabolismo , Serpinas/metabolismo , Microambiente Tumoral , ATPasas de Translocación de Protón Vacuolares/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Masculino , Clasificación del Tumor , Células PC-3 , Próstata/patología , Neoplasias de la Próstata/patologíaAsunto(s)
Enfermedad de la Arteria Coronaria , Seno Coronario , Imagen de Perfusión Miocárdica , Humanos , Seno Coronario/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Tomografía de Emisión de Positrones/métodos , Radioisótopos de Rubidio , Perfusión , Imagen de Perfusión Miocárdica/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Circulación Coronaria , RubidioRESUMEN
OBJECTIVES: To compare the outcomes and safety of a rapid access chest pain clinic (RACPC) in Australia with those of a general cardiology clinic. DESIGN: Prospective comparison of the outcomes for patients attending an RACPC and those of historical controls. SETTING: Royal Hobart Hospital cardiology outpatient department. PARTICIPANTS: 1914 patients referred for outpatient evaluation of new onset chest pain (1479 patients seen in the RACPC, 435 patients previously seen in the general cardiology clinic). MAIN OUTCOME MEASURES: Service outcomes (review times, number of clinic reviews); adverse events (unplanned emergency department re-attendances at 30 days and 12 months; major adverse cardiovascular events at 12 months, including unplanned revascularisation, acute coronary syndrome, stroke, cardiac death). RESULTS: Median time to review was shorter for RACPC than for usual care patients (12 days [IQR, 8-15 days] v 45 days [IQR, 27-89 days]). All patients seen in the RACPC received a diagnosis at the first clinic visit, but only 139 patients in the usual care group (32.0%). There were fewer unplanned emergency department re-attendances for patients in the RACPC group at 30 days (1.6% v 4.4%) and 12 months (5.7% v 12.9%) than in the control group. Major adverse cardiovascular events were less frequent among patients evaluated in the RACPC (0.2% v 1.4%). CONCLUSIONS: Patients were evaluated more efficiently in the RACPC than in a traditional cardiology clinic, and their subsequent rates of emergency department re-attendances and adverse cardiovascular events were lower.
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Servicio de Cardiología en Hospital/estadística & datos numéricos , Dolor en el Pecho/diagnóstico , Servicio de Urgencia en Hospital/estadística & datos numéricos , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Clínicas de Dolor/estadística & datos numéricos , Adulto , Anciano , Enfermedades Cardiovasculares/epidemiología , Dolor en el Pecho/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Derivación y Consulta , Factores de Tiempo , Victoria/epidemiologíaRESUMEN
The author "Ashish D. Diwan" receives educational consultant fees from Nuvasive Inc.