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1.
J Stroke Cerebrovasc Dis ; 33(1): 107470, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38029458

RESUMEN

BACKGROUND: Incorporating cardiac CT with hyperacute stroke imaging may increase the yield for cardioembolic sources. It is not clarified whether stroke severity influences on rates of intracardiac thrombus. We aimed to investigate a National Institutes of Health Stroke Scale (NIHSS) threshold below which acute cardiac CT was unnecessary. METHODS: Consecutive patients with suspected stroke who underwent multimodal brain imaging and concurrent non-gated cardiac CT with delayed timing were prospectively recruited from 1st December 2020 to 30th November 2021. We performed receiver operating characteristics analysis of the NIHSS and intracardiac thrombus on hyperacute cardiac CT. RESULTS: A total of 314 patients were assessed (median age 69 years, 61% male). Final diagnoses were ischemic stroke (n=205; 132 etiology-confirmed stroke, independent of cardiac CT and 73 cryptogenic), transient ischemic attack (TIA) (n=21) and stroke-mimic syndromes (n=88). The total yield of cardiac CT was 8 intracardiac thrombus and 1 dissection. Cardiac CT identified an intracardiac thrombus in 6 (4.5%) with etiology-confirmed stroke, 2 (2.7%) with cryptogenic stroke, and none in patients with TIA or stroke-mimic. All of those with intracardiac thrombus had NIHSS ≥4 and this was the threshold below which hyperacute cardiac CT was not justified (sensitivity 100%, specificity 38%, positive predictive value 4.0%, negative predictive value 100%). CONCLUSIONS: A cutoff NIHSS ≥4 may be useful to stratify patients for cardiac CT in the hyperacute stroke setting to optimize its diagnostic yield and reduce additional radiation exposure.


Asunto(s)
Isquemia Encefálica , Cardiopatías , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Trombosis , Humanos , Masculino , Anciano , Femenino , Ataque Isquémico Transitorio/diagnóstico por imagen , Ataque Isquémico Transitorio/etiología , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Tomografía Computarizada por Rayos X/métodos , Isquemia Encefálica/diagnóstico por imagen , Cardiopatías/diagnóstico
2.
Eur Stroke J ; 9(1): 105-113, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37771138

RESUMEN

INTRODUCTION: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. PATIENTS AND METHODS: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. RESULTS: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). DISCUSSION AND CONCLUSION: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.


Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombosis de los Senos Intracraneales , Trombocitopenia , Vacunas , Humanos , Vacunas contra la COVID-19/efectos adversos , Trombocitopenia/inducido químicamente , Trombosis de los Senos Intracraneales/etiología
3.
Adv Sci (Weinh) ; 10(25): e2302663, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37377354

RESUMEN

Bimetallic nanoparticle (NP) catalysts are widely used in many heterogeneous gas-based reactions because they often outperform their monometallic counterparts. During these reactions, NPs often undergo structural changes, which impact their catalytic activity. Despite the important role of the structure in the catalytic activity, many aspects of how a reactive gaseous environment affects the structure of bimetallic nanocatalysts are still lacking. Here, using gas-cell transmission electron microscopy (TEM), it is shown that during a CO oxidation reaction over PdCu alloy NPs, the selective oxidation of Cu causes the segregation of Cu and transforms the NPs into Pd-CuO NPs. The segregated NPs are very stable and have high activity for the conversion of CO into CO2 . Based on the observations, the segregation of Cu from Cu-based alloys during a redox reaction is likely to be general and may have a positive impact on the catalytic activity. Hence, it is believed that similar insights based on direct observation of the reactions under relevant reactive conditions are critical both for understanding and designing high-performance catalysts.

4.
Sci Adv ; 9(24): eadf3120, 2023 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-37327346

RESUMEN

Human cord blood-derived γδ T cells (CBγδ) display a highly diverse TCRγδ repertoire and have a unique subtype composition different from fetal or adult peripheral blood counterparts. We expanded CBγδ in vitro using an irradiated Epstein-Barr virus-transformed feeder cell-based modified rapid expansion protocol (REP). Single-cell RNA sequencing tracked progressive differentiation of naïve CBγδ into cells expressing neoantigen-reactive tumor-infiltrating lymphocyte as well as tissue-resident memory precursor-like and antigen-presenting cell-like gene signatures. TCRγδ clonal tracing revealed a bias toward cytotoxic effector differentiation in a much larger proportion of Vδ2- clones compared to Vδ2+ clones, resulting in the former being more cytotoxic at the population level. These clonotype-specific differentiation dynamics were not restricted to REP and were recapitulated upon secondary nonviral antigen stimulations. Thus, our data showed intrinsic cellular differences between major subtypes of human γδ T cells already in operation at early postnatal stage and highlighted key areas of consideration in optimizing cell manufacturing processes.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfocitos T , Adulto , Humanos , Sangre Fetal , Herpesvirus Humano 4 , Receptores de Antígenos de Linfocitos T gamma-delta/genética
5.
Eur Stroke J ; 8(1): 191-198, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-37021178

RESUMEN

Introduction: The very elderly (⩾80 years) are under-represented in randomised endovascular thrombectomy (EVT) clinical trials for acute ischaemic stroke. Rates of independent outcome in this group are generally lower than the less-old patients but the comparisons may be biased by an imbalance of non-age related baseline characteristics, treatment related metrics and medical risk factors. Patients and methods: We compared outcomes between very elderly (⩾80) and the less-old (<80 years) using retrospective data from consecutive patients receiving EVT from four comprehensive stroke centres in New Zealand and Australia. We used propensity score matching or multivariable logistic regression to account for confounders. Results: We included 600 patients (300 in each age cohort) after propensity score matching from an initial group of 1270 patients. The median baseline National Institutes of Health Stroke Scale was 16 (11-21), with 455 (75.8%) having symptom free pre-stroke independent function, and 268 (44.7%) receiving intravenous thrombolysis. Good functional outcome (90-day modified Rankin Scale 0-2) was achieved in 282 (46.8%), with very elderly patients having less proportion of good outcome compared to the less-old (118 (39.3%) vs 163 (54.3%), p < 0.01). There was no difference between the very elderly and the less-old in the proportion of patients who returned to baseline function at 90 days (56 (18.7%) vs 62 (20.7%), p = 0.54). All-cause 90-day mortality was higher in the very elderly (75 (25%) vs 49 (16.3%), p < 0.01), without a difference in symptomatic haemorrhage (very elderly 11 (3.7%) vs 6 (2.0%), p = 0.33). In the multivariable logistic regression models, the very elderly were significantly associated with reduced odds of good 90-day outcome (OR 0.49, 95% CI 0.34-0.69, p < 0.01) but not with return to baseline function (OR 0.85, 90% CI 0.54-1.29, p = 0.45) after adjusting for confounders. Conclusion: Endovascular thrombectomy can be successfully and safely performed in the very elderly. Despite an increase in all-cause 90-day mortality, selected very elderly patients are as likely as younger patients with similar baseline characteristics to return to baseline function following EVT.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Anciano , Accidente Cerebrovascular/cirugía , Isquemia Encefálica/cirugía , Estudios Retrospectivos , Puntaje de Propensión , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Trombectomía/efectos adversos , Accidente Cerebrovascular Isquémico/cirugía
6.
Cluster Comput ; 26(1): 181-195, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35464821

RESUMEN

There are thousands of flights carrying millions of passengers each day, having three or more Internet-connected devices with them on average. Usually, onboard devices remain idle for most of the journey (which can be of several hours), therefore, we can tap on their underutilized potential. Although these devices are generally becoming more and more resourceful, for complex services (such as related to machine learning, augmented/virtual reality, smart healthcare, and so on) those devices do not suffice standalone. This makes a case for multi-device resource aggregation such as through femto-cloud. As our first contribution, we present the utility of femto-cloud for aerial users. But for that sake, a reliable and faster Internet is required (to access online services or cloud resources), which is currently not the case with satellite-based Internet. That is the second challenge we try to address in our paper, by presenting an adaptive beamforming-based solution for aerial Internet provisioning. However, on average, most of the flight path is above waters. Given that, we propose that beamforming transceivers can be docked on stationery ships deployed in the vast waters (such as the ocean). Nevertheless, certain services would be delay-sensitive, and accessing their on-ground servers or cloud may not be feasible (in terms of delay). Similarly, certain complex services may require resources in addition to the flight-local femto-cloud. That is the third challenge we try to tackle in this paper, by proposing that the traditional fog computing (which is a cloud-like but localized pool of resources) can also be extended to the waters on the ships harboring beamforming transceivers. We name it Floating Fog. In addition to that, Floating Fog will enable several new services such as live black-box. We also present a cost and bandwidth analysis to highlight the potentials of Floating Fog. Lastly, we identify some challenges to tackle the successful deployment of Floating Fog.

8.
Front Neurorobot ; 16: 1073881, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36451678
9.
Stroke ; 53(10): 3206-3210, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36082668

RESUMEN

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Trombosis Intracraneal , Trombocitopenia , Trombosis , Vacunas , Trombosis de la Vena , Adulto , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Hemorragia Cerebral , Femenino , Humanos , Trombosis Intracraneal/diagnóstico , Masculino , Factores de Riesgo , SARS-CoV-2
10.
Sensors (Basel) ; 22(16)2022 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-36015782

RESUMEN

With the significant rise in demand for network utilization, such as data transmission and device-to-device (D2D) communication, fifth-generation (5G) networks have been proposed to fill the demand. Deploying 5G enhances the utilization of network channels and allows users to exploit licensed channels in the absence of primary users (PUs). In this paper, a hybrid route selection mechanism is proposed, and it allows the central controller (CC) to evaluate the route map proactively in a centralized manner for source nodes. In contrast, source nodes are enabled to make their own decisions reactively and select a route in a distributed manner. D2D communication is preferred, which helps networks to offload traffic from the control plane to the data plane. In addition to the theoretical analysis, a real testbed was set up for the proof of concept; it was composed of eleven nodes with independent processing units. Experiment results showed improvements in traffic offloading, higher utilization of network channels, and a lower interference level between primary and secondary users. Packet delivery ratio and end-to-end delay were affected due to a higher number of intermediate nodes and the dynamicity of PU activities.


Asunto(s)
Algoritmos , Redes de Comunicación de Computadores , Comunicación
11.
J Stroke Cerebrovasc Dis ; 31(7): 106468, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35523051

RESUMEN

OBJECTIVES: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). MATERIALS AND METHODS: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. RESULTS: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P<0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. CONCLUSION: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended.


Asunto(s)
COVID-19 , Trombosis de los Senos Intracraneales , Adulto , COVID-19/diagnóstico , COVID-19/epidemiología , Hospitalización , Humanos , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Trombosis de los Senos Intracraneales/diagnóstico , Trombosis de los Senos Intracraneales/epidemiología , Trombosis de los Senos Intracraneales/terapia
12.
Aust J Rural Health ; 30(3): 337-342, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35412702

RESUMEN

OBJECTIVE: Report on feasibility, use and effects on investigations and treatment of a neurologist-supported stroke clinic in rural Australia. DESIGN: Data were collected prospectively for consecutive patients referred to atelehealth stroke clinic from November 2018 to August 2021. SETTINGS, PARTICIPANTS AND INTERVENTIONS: Patients attended the local hospital, with a rural stroke care coordinator, and were assessed by stroke neurologist over videoconference. MAIN OUTCOME MEASURES: The following feasibility outcomes on the first appointments were analysed: (1) utility (a) change in medication, (b) request of additional investigations, (c) enrolment/offering clinical trials or d) other; (2) acceptability (attendance rate); and (3) process of care (waiting time to first appointment, distance travelled). RESULTS: During the study period, 173 appointments were made; 125 (73.5%) were first appointments. The median age was 70 [63-79] years, and 69 patients were male. A diagnosis of stroke or transient ischemic attack was made by the neurologist in 106 patients. A change in diagnosis was made in 23 (18.4%) patients. Of the first appointments, 102 (81.6%) resulted in at least one intervention: medication was changed in 67 (53.6%) patients, additional investigations requested in 72 (57.6%), 15 patients (12%) were referred to a clinical trial, and other interventions were made in 23 patients. The overall attendance rate of booked appointments was high. The median waiting time and distance travelled (round-trip) for a first appointment were 38 [24-53] days and 60.8 [25.6-76.6] km respectively. CONCLUSION: The telestroke clinic was very well attended, and it led to high volume of interventions in rural stroke patients.


Asunto(s)
Pacientes Ambulatorios , Accidente Cerebrovascular , Anciano , Instituciones de Atención Ambulatoria , Citas y Horarios , Femenino , Humanos , Masculino , Población Rural , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Comunicación por Videoconferencia
13.
Ann Diagn Pathol ; 58: 151935, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35313158

RESUMEN

The study aimed to evaluate the impact of the updated 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) testing in invasive breast cancer compared with previous 2013 guidelines. Between Jan 2014 and May 2020, 3364 consecutive invasive breast carcinomas with concurrent HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results were retrospectively reviewed for HER2 status. Both 2013 and 2018 testing criteria were applied to establish the HER2 status. The testing algorithms involved testing of invasive breast carcinomas by IHC, with equivocal results being reflexed to FISH assays. Concordance rate improved from 92.7% to 94.1% in the non-equivocal IHC cases with the 2018 guidelines. Comparing 2013 versus 2018 criteria, HER2 non-amplified cases increased significantly from 73.7% (n = 2478) to 76.8% (n = 2585), HER2 amplified cases remained similar from 23.4% (n = 789) to 23.2% (n = 779) while equivocal cases decreased from 2.9% (n = 97) to 0% with the new guidelines. Thus, 107 cases (3.2%) were reclassified from HER2 equivocal (n = 97) and amplified (n = 10) to non-amplified with the updated 2018 guidelines. Under the 2018 criteria, a total of 259 cases (7.7%) belonged to the uncommon categories (groups 2 to 4), with group 3 being the most frequent (4.6%), followed by group 4 (2.9%) and group 2 (0.2%). Implementation of 2018 guidelines resulted in a significant increase in HER2 non-amplified cases, mainly due to the abolishment of the equivocal FISH group. This has helped resolve the clinical practice dilemma by providing a more definitive HER2 gene status.


Asunto(s)
Neoplasias de la Mama , Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Oncología Médica , Patólogos , Guías de Práctica Clínica como Asunto , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Estados Unidos
14.
Cardiol Res ; 13(6): 380-392, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36660064

RESUMEN

Background: Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients. There is a need for early detection through risk factor identification. To date, no large multicenter study has been conducted to describe the incidence, risk factors and clinical and demographic profiles of breast cancer patients with anthracycline-induced cardiotoxicity (AIC) in the Philippines. Methods: This was a nationwide multicenter retrospective cohort study among adult breast cancer patients who underwent anthracycline chemotherapy from 2015 to 2020 in 10 sites in the Philippines. Baseline characteristics and possible risk factors for AIC were retrieved from medical records and cancer registries. AIC was defined as a reduction of left ventricular ejection fraction (LVEF) by > 10% from baseline to a value of < 53% or the development of overt left ventricular systolic dysfunction or heart failure (HF). Odds ratios from logistic regression were computed to determine risk factors associated with AIC using STATA-15.0 software. Results: Out of 341 patients included, 33 had AIC, accounting for an incidence of 9.68%. Nine patients (2.6%) had clinical HF. AIC patients had a mean age of 53.91 ± 10.84 years. Breast cancer AIC patients were significantly older and had lower body mass index (BMI) than those without AIC. AIC patients had significantly more comorbidities, especially hypertension and atrial fibrillation. Multivariate analysis showed that patients with any preexisting comorbidity are approximately 12.37 times as likely to have AIC, while those with concurrent chemotherapy are 0.07 times or 93% less likely to have AIC. Conclusion: Among adult breast cancer patients undergoing anthracycline chemotherapy, we determined a high incidence of cardiotoxicity at 9.68%. Having preexisting comorbidities gave patients 12 times increased odds of developing anthracycline cardiotoxicity. The presence of concurrent non-anthracycline chemotherapy showed an inverse association with the development of AIC which we attribute largely to patient selection in a retrospective study. The significantly higher propensity for AIC development in patients with preexisting comorbidities may warrant closer monitoring and control of patient comorbidities such as hypertension among patients undergoing anthracycline chemotherapy.

15.
Front Neurol ; 12: 745673, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34925211

RESUMEN

Background and Purpose: CT perfusion (CTP) has been implemented widely in regional areas of Australia for telestroke assessment. The aim of this study was to determine if, as part of telestroke assessment, CTP provided added benefit to clinical features in distinguishing between strokes and mimic and between transient ischaemic attack (TIA) and mimic. Methods: We retrospectively analysed 1,513 consecutively recruited patients referred to the Northern New South Wales Telestroke service, where CTP is performed as a part of telestroke assessment. Patients were classified based on the final diagnosis of stroke, TIA, or mimic. Multivariate regression models were used to determine factors that could be used to differentiate between stroke and mimic and between TIA and mimic. Results: There were 693 strokes, 97 TIA, and 259 mimics included in the multivariate regression models. For the stroke vs. mimic model using symptoms only, the area under the curve (AUC) on the receiver operator curve (ROC) was 0.71 (95% CI 0.67-0.75). For the stroke vs. mimic model using the absence of ischaemic lesion on CTP in addition to clinical features, the AUC was 0.90 (95% CI 0.88-0.92). The multivariate regression model for predicting mimic from TIA using symptoms produced an AUC of 0.71 (95% CI 0.65-0.76). The addition of absence of an ischaemic lesion on CTP to clinical features for the TIA vs. mimic model had an AUC of 0.78 (95% CI 0.73-0.83) Conclusions: In the telehealth setting, the absence of an ischaemic lesion on CTP adds to the diagnostic accuracy in distinguishing mimic from stroke, above that from clinical features.

16.
Artículo en Inglés | MEDLINE | ID: mdl-34250396

RESUMEN

PURPOSE: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS: One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION: Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.


Asunto(s)
Ensayos Clínicos como Asunto , Perfilación de la Expresión Génica , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisión , Adulto , Anciano , Anciano de 80 o más Años , Instituciones Oncológicas , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Singapur , Centros de Atención Terciaria , Adulto Joven
17.
Front Neurol ; 12: 645088, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33897601

RESUMEN

Introduction: A telestroke network in Northern New South Wales, Australia has been developed since 2017. We theorized that the telestroke network development would drive a progressive improvement in stroke care metrics over time. Aim: This study aimed to describe changes in acute stroke workflow metrics over time to determine whether they improved with network experience. Methods: We prospectively collected data of patients assessed by telestroke who received multimodal computed tomography (mCT) and were diagnosed with ischemic stroke or transient ischemic attack from January 2017 to July 2019. The period was divided into two phases (phase 1: January 2017 - October 2018 and phase 2: November 2018 - July 2019). We compared median door-to-call, door-to-image, and door-to-decision time between the two phases. Results: We included 433 patients (243 in phase 1 and 190 in phase 2). Each spoke site treated 1.5-5.2 patients per month. There were Door-to-call time (median 39 in phase 1, 35 min in phase 2, p = 0.18), and door-to-decision time (median 81.5 vs. 83 min, p = 0.31) were not improved significantly. Similarly, in the reperfusion therapy subgroup, door-to-call time (median 29 vs. 24.5 min, p = 0.12) and door-to-decision time (median 70.5 vs. 67.5 min, p = 0.75) remained substantially unchanged. Regression analysis showed no association between time in the network and door-to-decision time (coefficient 1.5, p = 0.32). Conclusion: In our telestroke network, acute stroke timing metrics did not improve over time. There is the need for targeted education and training focusing on both stroke reperfusion competencies and the technical aspects of telestroke in areas with limited workforce and high turnover.

18.
ACS Appl Mater Interfaces ; 13(17): 20501-20510, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33891399

RESUMEN

Cerium(IV) oxide (CeO2), or ceria, is one of the most abundant rare-earth materials that has been extensively investigated for its catalytic properties over the past two decades. However, due to the global scarcity and increasing cost of rare-earth materials, efficient utilization of this class of materials poses a challenging issue for the materials research community. Thus, this work is directed toward an exploration of making ultrathin hollow ceria or other rare-earth metal oxides and mixed rare-earth oxides in general. Such a hollow morphology appears to be attractive, especially when the thickness is trimmed to its limit, so that it can be viewed as a two-dimensional sheet of organized nanoscale crystallites, while remaining three-dimensional spatially. This ensures that both inner and outer shell surfaces can be better utilized in catalytic reactions if the polycrystalline sphere is further endowed with mesoporosity. Herein, we have devised our novel synthetic protocol for making ultrathin mesoporous hollow spheres of ceria or other desired rare-earth oxides with a tunable shell thickness in the region of 10 to 40 nm. Our ceria ultrathin hollow spheres are catalytically active and outperform other reported similar nanostructured ceria for the oxidation reaction of carbon monoxide in terms of fuller utilization of cerium. The versatility of this approach has also been extended to fabricating singular or multicomponent rare-earth metal oxides with the same ultrathin hollow morphology and structural uniformity. Therefore, this approach holds good promise for better utilization of rare-earth metal elements across their various technological applications, not ignoring nano-safety considerations.

19.
Cancer Genet ; 252-253: 25-36, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33341677

RESUMEN

The detection of chromosomal abnormalities is important in the diagnosis, prognosis and disease monitoring in plasma cell neoplasia (PCN). However, the gold standard diagnostic techniques of conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) are hampered by culture difficulties and probe availability. Cytogenomic microarray (CMA), however, is able to surmount such limitations and generate a comprehensive genomic profile with the implementation of plasma cell (PC) enrichment. In this study, we examined 89 bone marrow specimens with CC and FISH without PC enrichment, 35 of which were examined with CMA after PC enrichment. Results revealed that after PC enrichment, CMA was able to detect chromosomal abnormalities in 34 of 35 specimens tested (97.1%), compared to 21 and 32 specimens (60% and 91.4%, respectively) achieved by CC and FISH, respectively, which were similar to the abnormality detection rates among all 89 specimens (59.5% by CC and 92.1% by FISH). In addition, as the only technique capable of detecting copy neutral loss of heterozygosity (CN-LOH) and chromothripsis, CMA appears to be the most powerful tool in risk stratification as it successfully re-stratified 9 (25.7%) and 12 (34.3%) specimens from standard risk (determined by CC and FISH, respectively) to high risk. Based on the encouraging data presented by our study and others, we conclude that implementation of CMA with PC enrichment is of great value in routine clinical workup in achieving a more complete genetic profile of patients with PCN.


Asunto(s)
Citogenética/métodos , Hibridación Fluorescente in Situ/métodos , Neoplasias de Células Plasmáticas/genética , Femenino , Humanos , Masculino , Neoplasias de Células Plasmáticas/patología , Células Plasmáticas , Pronóstico
20.
J Appl Stat ; 48(13-15): 2944-2960, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35707082

RESUMEN

Marketing mix models (MMMs) are statistical models for measuring the effectiveness of various marketing activities such as promotion, media advertisement, etc. In this research, we propose a comprehensive marketing mix model that captures the hierarchical structure and the carryover, shape and scale effects of certain marketing activities, as well as sign restrictions on certain coefficients that are consistent with common business sense. In contrast to commonly adopted approaches in practice, which estimate parameters in a multi-stage process, the proposed approach estimates all the unknown parameters simultaneously using a constrained maximum likelihood approach and a Hamiltonian Monte Carlo algorithm. We present results on real datasets to illustrate the use of the proposed solution algorithms.

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