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BACKGROUND: Treatment options for human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases (BCBMs) remain limited. We previously reported central nervous system (CNS) activity for neratinib and neratinib-capecitabine. Preclinical data suggest that neratinib may overcome resistance to ado-trastuzumab emtansine (T-DM1) when given in combination. In Translational Breast Cancer Research Consortium (TBCRC) 022's cohort 4, we examined the efficacy of neratinib plus T-DM1 in patients with HER2-positive BCBM. PATIENTS AND METHODS: In this multicenter, phase II study, patients with measurable HER2-positive BCBM received neratinib 160 mg daily plus T-DM1 3.6 mg/kg intravenously every 21 days in three parallel-enrolling cohorts [cohort 4A-previously untreated BCBM, cohorts 4B and 4C-BCBM progressing after local CNS-directed therapy without (4B) and with (4C) prior exposure to T-DM1]. Cycle 1 diarrheal prophylaxis was required. The primary endpoint was the Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) by cohort. The overall survival (OS) and toxicity were also assessed. RESULTS: Between 2018 and 2021, 6, 17, and 21 patients enrolled in cohorts 4A, 4B, and 4C. Enrollment was stopped prematurely for slow accrual. The CNS objective response rate in cohorts 4A, 4B, and 4C was 33.3% [95% confidence interval (CI) 4.3% to 77.7%], 35.3% (95% CI 14.2% to 61.7%), and 28.6% (95% CI 11.3% to 52.2%), respectively; 38.1%-50% experienced stable disease for ≥6 months or response. Diarrhea was the most common grade 3 toxicity (22.7%). The median OS was 30.2 [cohort 4A; 95% CI 21.9-not reached (NR)], 23.3 (cohort 4B; 95% CI 17.6-NR), and 20.9 (cohort 4C; 95% CI 14.9-NR) months. CONCLUSIONS: We observed intracranial activity for neratinib plus T-DM1, including those with prior T-DM1 exposure, suggesting synergistic effects with neratinib. Our data provide additional evidence for neratinib-based combinations in patients with HER2-positive BCBM, even those who are heavily pretreated.
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BACKGROUND: Acquired ESR1 mutations in estrogen receptor-positive (ER+) metastatic breast cancer (mBC) drive treatment resistance and tumor progression; new treatment strategies are needed. Lasofoxifene, a next-generation, oral, endocrine therapy and tissue-specific ER antagonist, provided preclinical antitumor activity, alone or combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in ESR1-mutated mBC. PATIENTS AND METHODS: In the open-label, phase II, ELAINE 2 trial (NCT04432454), women with ESR1-mutated, ER+/human epidermal growth factor receptor 2-negative (HER2-) mBC who progressed on prior therapies (including CDK4/6i) received lasofoxifene 5 mg/day and abemaciclib 150 mg b.i.d until disease progression/toxicity. The primary endpoint was safety/tolerability. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and objective response rate (ORR). RESULTS: Twenty-nine women (median age 60 years) participated; all but one were previously treated with a CDK4/6i (median duration 2 years). The lasofoxifene-abemaciclib combination was well tolerated with primarily grade 1/2 treatment-emergent adverse events (TEAEs), most commonly diarrhea, nausea, fatigue, and vomiting. One patient (with no prior CDK4/6i) discontinued treatment due to grade 2 diarrhea. No deaths occurred during the study. Median PFS was 56.0 weeks [95% confidence interval (CI) 31.9 weeks-not estimable; â¼13 months]; PFS rates at 6, 12, and 18 months were 76.1%, 56.1%, and 38.8%, respectively. CBR at 24 weeks was 65.5% (95% CI 47.3% to 80.1%). In 18 patients with measurable lesions, ORR was 55.6% (95% CI 33.7% to 75.4%). ESR1-mutant circulating tumor DNA (ctDNA) allele fraction decreased from baseline to week 4 in 21/26 (80.8%) patients. CONCLUSIONS: Lasofoxifene plus abemaciclib had an acceptable safety profile, was well tolerated, and exhibited meaningful antitumor activity in women with ESR1-mutated, ER+/HER2- mBC after disease progression on prior CDK4/6i. Observed decreases in ESR1-mutant ctDNA with lasofoxifene concordant with clinical response suggest target engagement. If the ELAINE 2 findings are confirmed in the initiated, phase III, ELAINE 3 trial, these data could be practice-changing and help address a critical unmet need.
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Neoplasias de la Mama , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Progresión de la Enfermedad , Mutación , Diarrea/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosAsunto(s)
COVID-19 , Encefalomielitis Aguda Diseminada , Glioblastoma , Vacunas contra la COVID-19 , Humanos , Sobrediagnóstico , SARS-CoV-2RESUMEN
Consumption of seafood contaminated with ciguatoxins (CTXs) leads to a foodborne disease known as ciguatera. Primary producers of CTXs are epibenthic dinoflagellates of the genera Gambierdiscus and Fukuyoa. In this study, thirteen Gambierdiscus and Fukuyoa strains were cultured, harvested at exponential phase, and CTXs were extracted with an implemented rapid protocol. Microalgal extracts were obtained from pellets with a low cell abundance (20,000 cell/mL) and were then analyzed with magnetic bead (MB)-based immunosensing tools (colorimetric immunoassay and electrochemical immunosensor). It is the first time that these approaches are used to screen Gambierdiscus and Fukuyoa strains, providing not only a global indication of the presence of CTXs, but also the ability to discriminate between two series of congeners (CTX1B and CTX3C). Analysis of the microalgal extracts revealed the presence of CTXs in 11 out of 13 strains and provided new information about Gambierdiscus and Fukuyoa toxin profiles. The use of immunosensing tools in the analysis of microalgal extracts facilitates the elucidation of further knowledge regarding these dinoflagellate genera and can contribute to improved ciguatera risk assessment and management.
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Ciguatoxinas/aislamiento & purificación , Colorimetría/métodos , Dinoflagelados/química , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Ciguatoxinas/clasificación , Especificidad de la EspecieRESUMEN
BACKGROUND: Synovial sepsis of unknown origin is a rare cause of lameness in the adult horse, and a haematogenous pathogenesis has been proposed in previous cases. OBJECTIVES: To describe the features and outcome of synovial sepsis of unknown origin in adult Thoroughbred racehorses. STUDY DESIGN: Retrospective case series. METHODS: Hospital records for admissions between 2005 and 2015 were reviewed to identify adult horses diagnosed with synovial sepsis of unknown origin. Presentation, clinicopathological, microbiological and diagnostic imaging findings were recorded. Treatment methods, surgical findings, complications and long-term outcome were evaluated. RESULTS: Eleven cases were identified over the study period. Diagnosis was established from clinical examination and clinicopathologic findings, which were comparable to other aetiologies of synovial sepsis. Affected structures included synovial joints, tendon sheaths and bursae. Concurrent osteochondritis dissecans or articular cartilage lesions were evident during arthroscopic surgery in three cases. Significant intrasynovial haemorrhage was not identified. Microbial culture of synovial fluid or synovial biopsy was positive in 6/11 of cases, with all isolates being Gram-positive cocci. Of the 6 positive microbial cultures, all isolates demonstrated in vitro sensitivity to a cephalosporin antimicrobial agent. A concurrent remote wound was present in a single case. No other potential origins of bacteraemia were identified. Treatment methods included endoscopic surgery, standing multineedle lavage, intravenous regional limb perfusion, intrasynovial medication and/or systemic antimicrobial administration. All horses survived to hospital discharge. For the 6/11 cases that raced following synovial sepsis, the median period for return to racing was 221 days. MAIN LIMITATIONS: A small study population, which was retrospectively reviewed. CONCLUSIONS: Synovial sepsis of unknown origin is rare in the adult Thoroughbred racehorse and can affect a range of synovial structures. A concurrent potential source of bacteraemia is rarely identified. With appropriate management, the prognosis to return to racing is fair.
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Antibacterianos/uso terapéutico , Artroscopía/veterinaria , Enfermedades de los Caballos/diagnóstico , Sinovectomía/veterinaria , Sinovitis/veterinaria , Animales , Enfermedades de los Caballos/patología , Caballos , Estudios Retrospectivos , Membrana Sinovial , Sinovitis/patología , Sinovitis/terapia , Irrigación Terapéutica/veterinaria , Resultado del TratamientoRESUMEN
The evolution in foodstuff-monitoring processes has increased the number of studies on biogenic amines (BAs), in recent years. This trend with future perspective needs to be assembled to address the associated health risks. Thus, this study aims to cover three main aspects of BAs: (i) occurrence, physiology, and toxicological effects, most probable formation mechanisms and factors controlling their growth; (ii) recent advances, strategies for determination, preconcentration steps, model technique, and nature of the matrix; and (iii) milestone, limitations with existing methodologies, future trends, and detailed expected developments for clinical use and on-site ultra-trace determination. The core of the ongoing review will discuss recent trends in pre-concentration toward miniaturization, automation, and possible coupling with electrochemical techniques, surface-enhanced Raman scattering, spectrofluorimetry, and lateral flow protocols to be exploited for the development of rapid, facile, and sensitive on-site determination strategies for BAs.
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Aminas Biogénicas/análisis , Técnicas de Química Analítica/métodos , Animales , Análisis de los Alimentos , HumanosRESUMEN
INTRODUCTION: One in eight paediatric primary care presentations is for a musculoskeletal (MSK) disorder. These patients are frequently referred to paediatric orthopaedic surgeons; however, up to 50% of referrals are for normal variants. This results in excessive wait-times and impedes access for urgent surgical cases. Adult MSK medicine has successfully utilised advanced practice physiotherapists (APP) managing non-surgical candidates, with documented benefits both to patients and services. There is a gap in the literature with regard to APP in paediatric orthopaedics. AIM: In this review, we investigate demands on paediatric orthopaedic services, examine the literature regarding APP in paediatric orthopaedics and explore the value the role has to offer current outpatient services. RESULTS: Paediatric orthopaedic services are under-resourced with concurrent long wait times. Approximately 50% of referrals are for normal variants, which do not require specialist intervention. Poor musculoskeletal examination skills and low diagnostic confidence amongst primary care physicians have been identified as a cause of inappropriate referrals. APP clinics for normal variants have reported independent management rate and discharge rates of 95% and marked reduction in patient wait times. CONCLUSION: There is limited evidence to support the APP in paediatric orthopaedics. Further studies are needed investigating diagnostic agreement, patient/stakeholder satisfaction, patient outcomes and economic evaluation. Paediatric orthopaedics is in crisis as to how to effectively manage the overwhelming volume of referrals. Innovative multidisciplinary solutions are required so that the onus is not solely on physicians to provide all services. The APP in paediatric orthopaedics may be part of the solution.
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Enfermedades Musculoesqueléticas/terapia , Ortopedia/métodos , Modalidades de Fisioterapia/estadística & datos numéricos , Adulto , Niño , Humanos , MasculinoRESUMEN
Spores of Bacillus anthracis deposited on surfaces can become airborne again as a result of air currents and mechanical forces. As such, they are a potential source of infection by inhalation. Spores of Bacillus thuringiensis were used to quantify this phenomenon in a simulation of outdoor conditions. Concrete and turf surfaces were inoculated by aerosol to produce high spore densities (greater than 1 × 109 CFU per m2 ) which were then subjected to the passage of air at 10 ms-1 with and without simulated walking. Re-aerosolized spores were sampled by wetted wall cyclone air samplers. The mean total re-aerosolization rate from concrete (m-2 min-1 ) was 1·16 × 10-3 for wind alone and 3·2 × 10-3 for wind and simulated walking while for turf the respective values were 2·7 × 10-4 and 6·7 × 10-4 . SIGNIFICANCE AND IMPACT OF THE STUDY: Following the malicious and/or accidental release of an aerosol of Bacillus anthracis spores, the immediate risk of human inhalation would decrease as the spores were deposited on surfaces or diluted by wind flow. There is, however, a concern that the deposited spores could become re-aerosolized and so present an ongoing hazard. Using an accurate simulant for B. anthracis spores a method is reported here that allowed the enumeration of re-aerosolized spores from concrete and turf by wind flow and footfall. Under the conditions used, the rates of re-aerosolization were low. These findings will need to be verified under real outdoor conditions before the true significance in terms of secondary exposure to pathogenic spores can be assessed.
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Aerosoles/efectos adversos , Bacillus anthracis/aislamiento & purificación , Bacillus thuringiensis/aislamiento & purificación , Material Particulado/efectos adversos , Esporas Bacterianas/aislamiento & purificación , Humanos , Microbiología del SueloRESUMEN
Diatoms are single cell microalgae with a silica shell (frustule), which possess a micro/nanoporous pattern of unparalleled diversity far beyond the possibilities of current micro- and nanofabrication techniques. To explore diatoms as natural three-dimensional nanostructured supports in sensing and biosensing devices, a simple, rapid and stable method to immobilize diatoms via gold electrodeposition is described. In this process, gold microstructures are formed, immobilizing diatoms by entrapment or crossing their nanopores. Varying the applied potential, time and HAuCl4 concentration, gold deposits of different morphologies and roughness are obtained, thereby determining the diatom immobilization process. Optical and scanning electron microscopy have been used to characterize diatom immobilization yields, the morphology of the gold microstructures, and the morphological integrity of diatoms. Cyclic voltammetry has been performed to characterize the gold deposits and to demonstrate the enhanced electrocatalytic activity of the gold-diatom electrodes. Electro-addressed immobilization of different diatoms on specific bands of interdigitated electrode arrays has been achieved, highlighting the potential application of diatoms for site-specific immobilization on microarrays. The feasibility to combine tailored immobilization with diatom biofunctionalization has also been demonstrated. Antibody-functionalized diatoms were immobilized on electrodes retaining their ability to detect its cognate antigen. The reported method exploits the natural three-dimensional nanostructures of diatoms together with their easy modification with biomolecules and the simplicity of gold electrodeposition to produce micro/nanostructured and highly electrocatalytic electrodes, providing low-cost and eco-friendly platforms and arrays with potential application in biosensing devices.
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Diatomeas/química , Oro/química , Anticuerpos Inmovilizados/química , Anticuerpos Inmovilizados/inmunología , Técnicas Biosensibles , Catálisis , Células Inmovilizadas/química , Técnicas Electroquímicas , Electrodos , Galvanoplastia , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Peróxido de Hidrógeno/química , Metosulfato de Metilfenazonio/química , Microcistinas/análisis , Microcistinas/inmunología , Microscopía Electrónica de Rastreo , Nanoporos , Nanoestructuras/química , Oxidación-ReducciónRESUMEN
The aim of this study was to evaluate a number of foot-and-mouth disease (FMD) test methods for use in red deer. Ten animals were intranasally inoculated with the FMD virus (FMDV) O UKG 11/2001, monitored for clinical signs, and samples taken regularly (blood, serum, oral swabs, nasal swabs, probang samples and lesion swabs, if present) over a 4-week period. Only one animal, deer 1103, developed clinical signs (lesions under the tongue and at the coronary band of the right hind hoof). It tested positive by 3D and IRES real-time reverse transcription polymerase chain reaction (rRT-PCR) in various swabs, lesion materials and serum. In a non-structural protein (NSP) in-house ELISA (NSP-ELISA-IH), one commercial ELISA (NSP-ELISA-PR) and a commercial antibody NSP pen side test, only deer 1103 showed positive results from day post-inoculation (dpi) 14 onwards. Two other NSP-ELISAs detected anti-NSP serum antibodies with lower sensitivity. It also showed rising antibody levels in the virus neutralization test (VNT), the in-house SPO-ELISA-IH and the commercial SPO-ELISA-PR at dpi 9, and in another two commercial SPO-ELISAs at dpi 12 (SPO-ELISA-IV) and dpi 19 (SPO-ELISA-IZ), respectively. Six of the red deer that had been rRT-PCR and antibody negative were re-inoculated intramuscularly with the same O-serotype FMDV at dpi 14. None of these animals became rRT-PCR or NSP-ELISA positive, but all six animals became positive in the VNT, the in-house SPO-ELISA-IH and the commercial SPO-ELISA-PR. Two other commercial SPO-ELISAs were less sensitive or failed to detect animals as positive. The rRT-PCRs and the four most sensitive commercial ELISAs that had been used for the experimentally inoculated deer were further evaluated for diagnostic specificity (DSP) using 950 serum samples and 200 nasal swabs from non-infected animals. DSPs were 100% for the rRT-PCRs and between 99.8 and 100% for the ELISAs.
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Ciervos , Pruebas Diagnósticas de Rutina/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Virus de la Fiebre Aftosa/aislamiento & purificación , Fiebre Aftosa/diagnóstico , Proteínas no Estructurales Virales/análisis , Animales , Anticuerpos Antivirales/sangre , Pruebas Diagnósticas de Rutina/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Fiebre Aftosa/virología , Virus de la Fiebre Aftosa/inmunología , Masculino , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
BACKGROUND: Proton therapy (PT) is a radiotherapy treatment modality that uses protons, rather than conventional photons. PT is often used in paediatric oncology due to its reported capability to reduce acute and late adverse treatment effects. As PT is unavailable in Ireland, patients are referred abroad for treatment. AIMS: To: (1) produce a descriptive study of Irish children referred abroad for PT, and (2) discuss the case for PT in general. METHODS: A retrospective review of all children referred for PT before October 2015 was performed. Information was gathered regarding demographics, diagnosis, referral timeline, adverse effects attributable to PT, current status and cost. A review of the relevant literature was performed. RESULTS: Seventeen children treated in Ireland have been referred abroad for PT. The largest number was in the 0-4 year old group. At initial diagnosis the median age was 4.8 years. The average cost per child was 37,312. Two patients suffered disease relapse. Four have encountered PT-related adverse effects. CONCLUSION: Despite the fact that >100,000 patients worldwide have been treated with PT, the level of published evidence to support superiority over conventional treatment remains low. It is debated that randomised control trials in this area would be inconsistent with the principle of clinical equipoise. In contrast, there is a call for level 1 evidence to justify drastic changes in patient care, particularly in light of recent reports of unexpected toxicities. In time, careful evaluation, follow-up and clinical trials will likely support the preferential use of PT in children.
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Oncología Médica/métodos , Terapia de Protones/métodos , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Irlanda , Masculino , Estudios RetrospectivosRESUMEN
PURPOSE: Improved therapies and imaging modalities are needed for the treatment of breast cancer brain metastases (BCBM). ANG1005 is a drug conjugate consisting of paclitaxel covalently linked to Angiopep-2, designed to cross the blood-brain barrier. We conducted a biomarker substudy to evaluate 18F-FLT-PET for response assessment. METHODS: Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m2 IV every 21 days. Before and after cycle 1, patients underwent PET imaging with 18F-FLT, a thymidine analog, retention of which reflects cellular proliferation, for comparison with gadolinium-contrast magnetic resonance imaging (Gd-MRI) in brain metastases detection and response assessment. A 20 % change in uptake after one cycle of ANG1005 was deemed significant. RESULTS: Thirty-two target and twenty non-target metastatic brain lesions were analyzed. The median tumor reduction by MRI after cycle 1 was -17.5 % (n = 10 patients, lower, upper quartiles: -25.5, -4.8 %) in target lesion size compared with baseline. Fifteen of twenty-nine target lesions (52 %) and 12/20 nontarget lesions (60 %) showed a ≥20 % decrease post-therapy in FLT-PET SUV change (odds ratio 0.71, 95 % CI: 0.19, 2.61). The median percentage change in SUVmax was -20.9 % (n = 29 lesions; lower, upper quartiles: -42.4, 2.0 %), and the median percentage change in SUV80 was also -20.9 % (n = 29; lower, upper quartiles: -49.0, 0.0 %). Two patients had confirmed partial responses by PET and MRI lasting 6 and 18 cycles, respectively. Seven patients had stable disease, receiving a median of six cycles. CONCLUSIONS: ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and 18F-FLT-PET imaging.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Paclitaxel/análogos & derivados , Péptidos/uso terapéutico , Adulto , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Biomarcadores , Biomarcadores de Tumor , Neoplasias Encefálicas/diagnóstico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Terapia Combinada , Femenino , Fluorodesoxiglucosa F18 , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Imagen por Resonancia Magnética , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Péptidos/administración & dosificación , Péptidos/efectos adversos , Tomografía de Emisión de Positrones , Resultado del TratamientoRESUMEN
PURPOSE: Objectives of this systematic review were to summarize how fatigue has been described from the perspective of children and adolescents with cancer, the impact of fatigue on quality of life, and child reported contributing factors and potential alleviators of fatigue. METHODS: We conducted electronic searches of Ovid Medline, EMBASE, PsycInfo, Science Citation, Social Science Citation (Web of Science), and CINAHL. We included studies of children and adolescents with cancer in which the experience of fatigue was described by the child/adolescent. The search was restricted to publications in English. Themes were summarized. RESULTS: Eleven studies were represented in 18 publications. Ages of included children ranged from 6 to 19 years. Majority of studies used semi-structured interviews to elicit participant's perceptions of fatigue. Terms used to describe fatigue included the following: tiredness, weary, loss of strength, dizziness, feeling drained, feeling drowsy, lacking motivation, exhaustion, and feeling emotional. Impact of fatigue related to not being able to participate in regular activities; needing to sleep or rest more; and impact on psychosocial health. Perceived alleviators of fatigue included exercise, distraction, rest, eating, and drinking. CONCLUSIONS: Fatigue is impactful from the perspective of children and adolescents. Future research should focus on prospective exploration of the impact of fatigue on pediatric cancer patients and identifying approaches to reduce fatigue.
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Fatiga/psicología , Neoplasias/complicaciones , Adolescente , Adulto , Niño , Femenino , Humanos , Calidad de Vida , Adulto JovenRESUMEN
Asymmetric multiplex ligation-dependent probe amplification (MLPA) was developed for the amplification of seven breast cancer related mRNA markers and the MLPA products were electrochemically detected via hybridization. Seven breast cancer genetic markers were amplified by means of the MLPA reaction, which allows for multiplex amplification of multiple targets with a single primer pair. Novel synthetic MLPA probes were designed to include a unique barcode sequence in each amplified gene. Capture probes complementary to each of the barcode sequences were immobilized on each electrode of a low-cost electrode microarray manufactured on standard printed circuit board (PCB) substrates. The functionalised electrodes were exposed to the single-stranded MLPA products and following hybridization, a horseradish peroxidase (HRP)-labelled DNA secondary probe complementary to the amplified strand completed the genocomplex, which was electrochemically detected following substrate addition. The electrode arrays fabricated using PCB technology exhibited an excellent electrochemical performance, equivalent to planar photolithographically-fabricated gold electrodes, but at a vastly reduced cost (>50 times lower per array). The optimised system was demonstrated to be highly specific with negligible cross-reactivity allowing the simultaneous detection of the seven mRNA markers, with limits of detections as low as 25pM. This approach provides a novel strategy for the genetic profiling of tumour cells via integrated "amplification-to-detection".
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Neoplasias de la Mama/genética , Técnicas Electroquímicas/instrumentación , Reacción en Cadena de la Polimerasa Multiplex/instrumentación , Hibridación de Ácido Nucleico , ARN Mensajero/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Técnicas Biosensibles/instrumentación , Mama/patología , Neoplasias de la Mama/diagnóstico , Femenino , Humanos , ARN Mensajero/análisis , TranscriptomaRESUMEN
Breast cancer is the most common non-cutaneous malignancy among women, and there are over 3 million breast cancer survivors living in the United States today. Excellent cure rates with modern therapies are associated with substantial toxicities for many women; it is important that health care providers attend to the resulting symptoms and issues to optimize quality of life in this population. In this article, we review management options for potential long term toxicities in breast cancer survivors, with a particular focus on bone health, fertility preservation, premature menopause, cardiac dysfunction, and cognitive impairment.
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We report the labelling of dideoxy nucleotides (ddNTPs) for use in electrochemical array based primer extension for the detection of single nucleotide polymorphisms (SNPs). The results confirm the extension of the immobilised primers for each of the four ddNTPs, representing a significant advance in achieving a cost-effective platform for screening of disease-specific SNPs.
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Aortic valve stenosis and coronary artery disease (CAD) frequently coexist in elderly patients selected for transcatheter aortic valve implantation (TAVI). Therapeutic strategies to manage concomitant obstructive CAD are therefore an important consideration in the overall management of patients with severe aortic stenosis (AS) undergoing TAVI. Conventional surgical aortic valve replacement and coronary artery bypass grafting is the treatment of choice for low and intermediate risk patients with symptomatic severe AS and concomitant obstructive CAD. However, TAVI and percutaneous coronary intervention (PCI) are viable alternative options for high-risk or inoperable patients presenting with symptomatic severe AS. PCI has been shown to be feasible and safe in selected high-risk or inoperable patients with symptomatic severe AS. However, the optimal timing of PCI relative to the TAVI procedure has been a subject of debate. The most frequent approch is staged PCI typically performed a few weeks prior to TAVI. However, concomitant PCI has also been shown to be a feasible and safe approach, particularly in patients with a low level of CAD complexity and an absence of severe renal impairment. Conversely, staged PCI should be considered in patients with higher degrees of CAD complexity, particularly in the presence of severe renal impairment. The aim of the present review is to discuss the safety and feasibility of performing PCI in elderly patients with severe AS and the optimal timing of PCI relative to the TAVI procedure using the most up-to-date available evidence.
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Estenosis de la Válvula Aórtica/cirugía , Estenosis Coronaria/cirugía , Intervención Coronaria Percutánea/métodos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Algoritmos , Estenosis de la Válvula Aórtica/complicaciones , Contraindicaciones , Puente de Arteria Coronaria , Estenosis Coronaria/complicaciones , Stents Liberadores de Fármacos , Fluoroscopía , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/fisiopatología , Metaanálisis como Asunto , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Estudios Prospectivos , Radiografía Intervencional , Ensayos Clínicos Controlados Aleatorios como Asunto , Sistema de Registros , Índice de Severidad de la Enfermedad , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: Objective was to evaluate and refine a new instrument for paediatric cancer symptom screening named the Symptom Screening in Pediatrics Tool (SSPedi). METHODS: Respondents were children 8-18 years of age undergoing active cancer treatment and parents of eligible children. Respondents completed SSPedi once and then responded to semi-structured questions. They rated how easy or difficult SSPedi was to complete. For items containing two concepts, we asked respondents whether concepts should remain together or be separated into two questions. We also asked about each item's importance and whether items were missing. Cognitive probing was conducted in children to evaluate their understanding of items and the response scale. After each group of 10 children and 10 parents, responses were reviewed to determine whether modifications were required. Recruitment ceased with the first group of 10 children in which modifications were not required. RESULTS: Thirty children and 20 parents were required to achieve a final version of SSPedi. Fifteen items remain in the final version; the score ranges from 0 to 60. CONCLUSIONS: Using opinions of children with cancer and parents of paediatric cancer patients, we successfully developed a symptom screening tool that is easy to complete, is understandable and demonstrates content validity.
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Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Autoinforme , Adolescente , Antineoplásicos/uso terapéutico , Ansiedad/inducido químicamente , Ansiedad/diagnóstico , Niño , Femenino , Humanos , Masculino , Náusea/inducido químicamente , Náusea/diagnóstico , Neoplasias/patología , Dolor/inducido químicamente , Dolor/diagnósticoRESUMEN
The request of high specificity and selectivity sensors suitable for mass production is a constant demand in medical research. For applications in point-of-care diagnostics and therapy, there is a high demand for low cost and rapid sensing platforms. This paper describes the fabrication and functionalization of gold electrodes arrays for the detection of deoxyribonucleic acid (DNA) in printed circuit board (PCB) technology. The process can be implemented to produce efficiently a large number of biosensors. We report an electrolytic plating procedure to fabricate low-density gold microarrays on PCB suitable for electrochemical DNA detection in research fields such as cancer diagnostics or pharmacogenetics, where biosensors are usually targeted to detect a small number of genes. PCB technology allows producing high precision, fast and low cost microelectrodes. The surface of the microarray is functionalized with self-assembled monolayers of mercaptoundodecanoic acid or thiolated DNA. The PCB microarray is tested by cyclic voltammetry in presence of 5 mM of the redox probe K3Fe(CN6) in 0.1 M KCl. The voltammograms prove the correct immobilization of both the alkanethiol systems. The sensor is tested for detecting relevant markers for breast cancer. Results for 5 nM of the target TACSTD1 against the complementary TACSTD1 and non-complementary GRP, MYC, SCGB2A1, SCGB2A2, TOP2A probes show a remarkable detection limit of 0.05 nM and a high specificity.