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1.
Int J Cancer ; 154(8): 1484-1491, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38158593

RESUMO

Irinotecan plays a crucial role in the neoadjuvant chemoradiotherapy (nCRT) of rectal cancer, but its optimal dosing is still unclear. In this study, we included 101 eligible patients with the UGT1A1*28 genotype of UGT1A1*1*1 (74.3%) and UGT1A1*1*28 (25.7%) and UGT1A1*6 genotypes of GG (63.4%), GA (32.7%), and AA (3.9%). All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m2 ; UGT1A1*1*28: 65 mg/m2 ) and capecitabine (CapIri). SN-38 concentrations were measured at 1.5, 24, and 49 h post-administration. Patients were divided into four groups (Q1-Q4) based on the SN-38 concentration. The complete-response (CR) rate was the primary endpoint. The analysis demonstrated that the 49 h SN-38 concentration was relatively optimal for predicting efficacy and toxicity. The Q4 group had a significantly higher CR rate than the Q1 group (p = .019), but also higher rates of adverse events (p = .009). We screened the recommended 49 h SN-38, with a 0.5-1.0 ng/mL concentration range. We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Irinotecano , Camptotecina , Terapia Neoadjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/genética , Segunda Neoplasia Primária/etiologia , Genótipo , Quimiorradioterapia/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Epilepsy Behav ; 156: 109829, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761451

RESUMO

In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a number of limbic and thalamo-cortical related structures involved in the processing of musical emotion (exposure), including the amygdala (arousal, expression of mood, fear), hippocampus (memory, regulation of HPA axis, stress), parahippocampal gyrus (recognition, memory retrieval), insula (valence), temporal poles (connectivity), ventral striatum (expectation and experience of reward), orbitofrontal cortex (valence) and cingulate cortex (autonomic regulation). One method is to audify (a form of sonification) EEG activity to find music by feedback to entrain abnormal EEG activity. We discuss various methods and our use of X-System (https://www.x-system.co.uk/) which is a computational model of the musical brain capable of predicting the neurophysiological effects of music. It models structures and pathways related to responses to music, including the cochlea, brain stem, auditory and motor cortex, as well as basal ganglia, cerebellum and limbic structures. It can predict autonomic and endocrine activity as well as the substrates of electrical activity to select music which can regularise EEG abnormalities to decrease epileptic activity and seizures, especially in those unresponsive to antiepileptic medication or invasive treatments.


Assuntos
Epilepsia , Musicoterapia , Música , Humanos , Epilepsia/terapia , Epilepsia/fisiopatologia , Musicoterapia/métodos , Eletroencefalografia , Encéfalo/fisiopatologia , Percepção Auditiva/fisiologia , Medicina de Precisão/métodos
3.
Colorectal Dis ; 26(4): 660-668, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38345176

RESUMO

AIM: The optimum surgical approach to splenic flexure cancers (SFCs) remains uncertain. The aim of this survey was to explore the opinions of an international surgical community on the management and outcomes of SFC. METHOD: A questionnaire was constructed comprising five sections (information about respondents; definition and prognosis of SFC; operative approach; approach in specific scenarios; outcomes) and circulated through an international dissemination committee and social media. RESULTS: The survey received 576 responses over 4 weeks across 50 countries. There was no consensus regarding the definition of the splenic flexure, whilst the proportion of respondents who did and did not think that patients with SFC had a worse outcome was equal. The overall preferred operative approach was left hemicolectomy [203 (35.2%)], followed by segmental resection [167 (29%)], extended right hemicolectomy [126 (21.9%)] and subtotal colectomy [7 (12%)]. The stated pedicles for ligation varied between resection types and also within the same resection. One hundred and sixty-six (28.8%) respondents thought a segmental resection was associated with the worst survival and 190 (33%) thought it was associated with the best quality of life. CONCLUSION: This survey confirms a lack of consensus across all aspects SFC treatment. The differing approaches described are likely to represent different beliefs around the variable anatomy of this region and the associated lymphatic drainage. Future studies are required to address such inconsistencies and identify the optimum surgical strategy, whilst also incorporating quality-of-life metrics and patient-reported outcomes. A one-size-fits-all approach is probably not appropriate with SFC, and a more bespoke approach is required.


Assuntos
Colectomia , Colo Transverso , Neoplasias Colorretais , Humanos , Colectomia/métodos , Colo Transverso/cirurgia , Inquéritos e Questionários , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Masculino , Feminino , Resultado do Tratamento , Pessoa de Meia-Idade , Prognóstico , Idoso
4.
Int J Mol Sci ; 25(16)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39201610

RESUMO

The global burden of liver cancer is increasing. Timely diagnosis is important for optimising the limited available treatment options. Understanding the metabolic consequences of hepatocellular carcinoma (HCC) may lead to more effective treatment options. We aimed to document metabolite differences between HCC and matched surrounding tissues of varying aetiology, obtained at the time of liver resection, and to interpret metabolite changes with clinical findings. High-resolution magic angle spinning nuclear magnetic resonance (HRMAS-NMR) spectroscopy analyses of N = 10 paired HCC and surrounding non-tumour liver tissue samples were undertaken. There were marked HRMAS-NMR differences in lipid levels in HCC tissue compared to matched surrounding tissue and more subtle changes in low-molecular-weight metabolites, particularly when adjusting for patient-specific variability. Differences in lipid-CH3, lipid-CH2, formate, and acetate levels were of particular interest. The obvious differences in lipid content highlight the intricate interplay between metabolic adaptations and cancer cell survival in the complex microenvironment of liver cancer. Differences in formate and acetate might relate to bacterial metabolites. Therefore, documentation of metabolites in HCC tissue according to histology findings in patients is of interest for personalised medicine approaches and for tailoring targeted treatment strategies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fígado , Espectroscopia de Ressonância Magnética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Masculino , Espectroscopia de Ressonância Magnética/métodos , Feminino , Pessoa de Meia-Idade , Fígado/metabolismo , Fígado/patologia , Idoso , Metabolismo dos Lipídeos , Lipídeos/análise , Adulto , Metaboloma
5.
BMC Med ; 20(1): 45, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101059

RESUMO

BACKGROUND: Donepezil, galantamine, rivastigmine and memantine are potentially effective interventions for cognitive impairment in dementia, but the use of these drugs has not been personalised to individual patients yet. We examined whether artificial intelligence-based recommendations can identify the best treatment using routinely collected patient-level information. METHODS: Six thousand eight hundred four patients aged 59-102 years with a diagnosis of dementia from two National Health Service (NHS) Foundation Trusts in the UK were used for model training/internal validation and external validation, respectively. A personalised prescription model based on the Recurrent Neural Network machine learning architecture was developed to predict the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores post-drug initiation. The drug that resulted in the smallest decline in cognitive scores between prescription and the next visit was selected as the treatment of choice. Change of cognitive scores up to 2 years after treatment initiation was compared for model evaluation. RESULTS: Overall, 1343 patients with MMSE scores were identified for internal validation and 285 [21.22%] took the drug recommended. After 2 years, the reduction of mean [standard deviation] MMSE score in this group was significantly smaller than the remaining 1058 [78.78%] patients (0.60 [0.26] vs 2.80 [0.28]; P = 0.02). In the external validation cohort (N = 1772), 222 [12.53%] patients took the drug recommended and reported a smaller MMSE reduction compared to the 1550 [87.47%] patients who did not (1.01 [0.49] vs 4.23 [0.60]; P = 0.01). A similar performance gap was seen when testing the model on patients prescribed with AChEIs only. CONCLUSIONS: It was possible to identify the most effective drug for the real-world treatment of cognitive impairment in dementia at an individual patient level. Routine care patients whose prescribed medications were the best fit according to the model had better cognitive performance after 2 years.


Assuntos
Disfunção Cognitiva , Demência , Idoso , Idoso de 80 Anos ou mais , Inteligência Artificial , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Demência/diagnóstico , Demência/tratamento farmacológico , Demência/psicologia , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Medicina de Precisão , Medicina Estatal
6.
J Pathol ; 250(5): 475-479, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32346919

RESUMO

This year's Annual Review Issue of The Journal of Pathology contains 18 invited reviews on current research areas in pathology. The subject areas reflect the broad range of topics covered by the journal and this year encompass the development and application of software in digital histopathology, implementation of biomarkers in pathology practice; genetics and epigenetics, and stromal influences in disease. The reviews are authored by experts in their field and provide comprehensive updates in the chosen areas, in which there has been considerable recent progress in our understanding of disease. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Biomarcadores Tumorais , Inflamação/patologia , Neoplasias/patologia , Microambiente Tumoral/genética , Animais , Epigênese Genética , Humanos , Neoplasias/genética , Microambiente Tumoral/imunologia , Reino Unido
7.
BMC Med ; 18(1): 318, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33172445

RESUMO

BACKGROUND: Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. METHODS: Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. RESULTS: The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). CONCLUSIONS: The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.


Assuntos
Pressão Sanguínea/genética , Hipertensão/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Riboflavina/metabolismo , Idoso , Anti-Hipertensivos/uso terapêutico , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Polimorfismo de Nucleotídeo Único , Fatores de Risco
8.
Int J Mol Sci ; 20(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035344

RESUMO

Glioblastoma multiforme is the most aggressive and malignant primary brain tumour, with a median survival rate of between 15 to 17 months. Heterogeneous regions occur in glioblastoma as a result of oxygen gradients which ranges from 0.1% to 10% in vivo. Emerging evidence suggests that tumour hypoxia leads to increased aggressiveness and chemo/radio resistance. Yet, few in vitro studies have been performed in hypoxia. Using three glioblastoma cell-lines (U87, U251, and SNB19), the adaptation of glioblastoma cells in a 1% (hypoxia) and 20% (normoxia) oxygen microenvironment on proliferation, metabolism, migration, neurosphere formation, CD133 and VEGF expression was investigated. Compared to cells maintained in normoxia (20% oxygen), glioblastoma cells adapted to 1% oxygen tension by reducing proliferation and enhancing metabolism. Both migratory tendency and neurosphere formation ability were greatly limited. In addition, hypoxic-mediated gene upregulation (CD133 and VEGF) was reversed when cells were removed from the hypoxic environment. Collectively, our results reveal that hypoxia plays a pivotal role in changing the behaviour of glioblastoma cells. We have also shown that genetic modulation can be reversed, supporting the concept of reversibility. Thus, understanding the degree of oxygen gradient in glioblastoma will be crucial in personalising treatment for glioblastoma patients.


Assuntos
Antígeno AC133/metabolismo , Glioblastoma/metabolismo , Oxigênio/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Hipóxia Tumoral/genética , Hipóxia Tumoral/fisiologia , Microambiente Tumoral/genética , Microambiente Tumoral/fisiologia
9.
J Theor Biol ; 448: 66-79, 2018 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-29625204

RESUMO

Atopic dermatitis (AD) is a common inflammatory skin disease, whose incidence is currently increasing worldwide. AD has a complex etiology, involving genetic, environmental, immunological, and epidermal factors, and its pathogenic mechanisms have not yet been fully elucidated. Identification of AD risk factors and systematic understanding of their interactions are required for exploring effective prevention and treatment strategies for AD. We recently developed a mathematical model for AD pathogenesis to clarify mechanisms underlying AD onset and progression. This model describes a dynamic interplay between skin barrier, immune regulation, and environmental stress, and reproduced four types of dynamic behaviour typically observed in AD patients in response to environmental triggers. Here, we analyse bifurcations of the model to identify mathematical conditions for the system to demonstrate transitions between different types of dynamic behaviour that reflect respective severity of AD symptoms. By mathematically modelling effects of topical application of antibiotics, emollients, corticosteroids, and their combinations with different application schedules and doses, bifurcation analysis allows us to mathematically evaluate effects of the treatments on improving AD symptoms in terms of the patients' dynamic behaviour. The mathematical method developed in this study can be used to explore and improve patient-specific personalised treatment strategies to control AD symptoms.


Assuntos
Dermatite Atópica/tratamento farmacológico , Modelos Teóricos , Medicina de Precisão/métodos , Dermatite Atópica/etiologia , Humanos , Fenótipo , Resultado do Tratamento
10.
Neuropsychol Rehabil ; 28(4): 602-613, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27219068

RESUMO

Cognitive deficits are a well-recognised issue for individuals diagnosed with schizophrenia spectrum disorders. Despite positive group findings for the use of cognitive remediation (CR) interventions, there are substantial individual differences in response to treatment. In addition, the aggregate CR literature reports low moderate effect sizes for cognitive and functional outcomes. Based on personalised medicine theory, this paper uses extant CR literature to examine the individual characteristics determined to predict treatment response. These characteristics, which fall into the broad categories of cognitive, psychological, and biological can be used as tailoring variables to personalise CR to an individual's unique profile. Personalisation through the use of these tailoring variables has the potential to improve the delivery of CR to maximise treatment outcomes.


Assuntos
Terapia Cognitivo-Comportamental , Disfunção Cognitiva/terapia , Medicina de Precisão/métodos , Esquizofrenia/complicações , Atenção , Disfunção Cognitiva/etiologia , Humanos , Motivação , Esquizofrenia/genética , Psicologia do Esquizofrênico , Resultado do Tratamento
11.
Cancer Rep (Hoboken) ; 7(10): e70016, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39410867

RESUMO

BACKGROUND: Prostate cancer is the second leading cause of cancer deaths in men, second only to lung cancer. Despite this, diagnosis and prognosis methods remain limited, with effective treatments being few and far between. Traditionally, prostate cancer is initially tested for through a prostate serum antigen (PSA) test and a digital rectum examination (DRE), followed by confirmation through an invasive prostate biopsy. The DRE and biopsy are uncomfortable for the patient, so less invasive, accurate diagnostic tools are needed. Current diagnostic tools, along with genes that hold possible biomarker uses in diagnosis, prognosis and indications for personalised treatment plans, were reviewed in this article. RECENT FINDINGS: Several genes from multiple families have been identified as possible biomarkers for disease, including those from the MYC and ETS families, as well as several tumour suppressor genes, Androgen Receptor signalling genes and DNA repair genes. There have also been advances in diagnostic tools, including MRI-targeted and liquid biopsies. Several personalised treatments have been developed over the years, including those that target metabolism-driven prostate cancer or those that target inflammation-driven cancer. CONCLUSION: Several advances have been made in prostate cancer diagnosis and treatment, but the disease still grows year by year, leading to more and more deaths annually. This calls for even more research into this disease, allowing for better diagnosis and treatment methods and a better chance of patient survival.


Assuntos
Biomarcadores Tumorais , Medicina de Precisão , Neoplasias da Próstata , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Masculino , Medicina de Precisão/métodos , Biomarcadores Tumorais/genética , Prognóstico
12.
Oral Health Prev Dent ; 22: 465-478, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264370

RESUMO

Dental caries, one of the most prevalent diseases globally, affects individuals throughout their lifetimes. Recently, researchers have increasingly focused on postbiotics for caries prevention. Postbiotics, comprising inanimate microorganisms and/or their components, confer health benefits to the host. Growing evidence suggests postbiotics' potential anticaries effects. Specifically, numerous postbiotics have demonstrated the ability to inhibit dental caries onset and progression by modulating oral flora microecology and reducing human caries susceptibility. This review elaborates on the current research regarding postbiotics' anticaries effects, highlights some studies' shortcomings, and innovatively proposes that postbiotics could potentially influence tooth development and salivary characteristics through epigenetic modifications. Furthermore, it anticipates postbiotics' future application in personalised caries treatment, given their multifaceted anticaries potential.


Assuntos
Cárie Dentária , Humanos , Cárie Dentária/prevenção & controle , Cárie Dentária/microbiologia , Suscetibilidade à Cárie Dentária , Saliva/microbiologia , Probióticos/uso terapêutico
13.
Psychiatry Res ; 336: 115910, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38608539

RESUMO

Approximately half of generalised anxiety disorder (GAD) patients do not recover from first-line treatments, and no validated prediction models exist to inform individuals or clinicians of potential treatment benefits. This study aimed to develop and validate an accurate and explainable prediction model of post-treatment GAD symptom severity. Data from adults receiving treatment for GAD in eight Improving Access to Psychological Therapies (IAPT) services (n=15,859) were separated into training, validation and holdout datasets. Thirteen machine learning algorithms were compared using 10-fold cross-validation, against two simple clinically relevant comparison models. The best-performing model was tested on the holdout dataset and model-specific explainability measures identified the most important predictors. A Bayesian Additive Regression Trees model out-performed all comparison models (MSE=16.54 [95 % CI=15.58; 17.51]; MAE=3.19; R²=0.33, including a single predictor linear regression model: MSE=20.70 [95 % CI=19.58; 21.82]; MAE=3.94; R²=0.14). The five most important predictors were: PHQ-9 anhedonia, GAD-7 annoyance/irritability, restlessness and fear items, then the referral-assessment waiting time. The best-performing model accurately predicted post-treatment GAD symptom severity using only pre-treatment data, outperforming comparison models that approximated clinical judgement and remaining within the GAD-7 error of measurement and minimal clinically important differences. This model could inform treatment decision-making and provide desired information to clinicians and patients receiving treatment for GAD.


Assuntos
Transtornos de Ansiedade , Aprendizado de Máquina , Índice de Gravidade de Doença , Humanos , Transtornos de Ansiedade/terapia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Psicoterapia/métodos , Teorema de Bayes , Adulto Jovem
14.
Mult Scler Relat Disord ; 90: 105796, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39096666

RESUMO

BACKGROUND: Several studies reported lower drug concentrations with subcutaneous natalizumab compared to intravenous natalizumab. With the emergence of extended interval dosing, gaining more insight into lower concentrations after subcutaneous administration is essential. METHODS: We compared serum trough concentrations between subcutaneous and intravenous administration within a matched cohort (n = 50). RESULTS: Subcutaneous administration (n = 25) was associated with lower concentrations compared to intravenous administration (n = 25) (log-B=-0.28, p = 0.01). In an exploratory group of 11 patients receiving extended interval dosing of subcutaneous natalizumab, the median trough concentration was even lower. CONCLUSION: Subcutaneous natalizumab can lead to lower drug concentrations, potentially limiting extended interval dosing.


Assuntos
Administração Intravenosa , Fatores Imunológicos , Natalizumab , Humanos , Natalizumab/administração & dosagem , Natalizumab/sangue , Feminino , Masculino , Injeções Subcutâneas , Adulto , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacocinética , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/sangue
15.
Cancers (Basel) ; 16(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38254908

RESUMO

PURPOSE: To investigate the role of Dkk1 as a predictor of response to NACT in BC patients. METHODS: This retrospective monocentric study included 145 women who had undergone NACT followed by breast surgery. Dkk1 protein expression was assessed using immunohistochemistry staining in core needle biopsies and mammary carcinoma specimens. RESULTS: Dkk1 levels were lower in treated BC tumours than in untreated tumours. The outcomes of 68 matched pre- and post-therapy tissues showed that Dkk1 levels in mammary carcinoma tissues were significantly predicted by levels in core needle biopsies and that Dkk1 expression was reduced in 83% of cases. Smaller cT stage, positive Her2 expression, and decreased Dkk1-IRS in core needle biopsy tissues were all independent predictors of regression grade (R4), according to Sinn. However, the percentage of Dkk1 expression differences prior to and following NACT had no effect on PFS or OS. CONCLUSIONS: In this study, we demonstrated for the first time that Dkk1 could be identified as an independent predictor of NACT response in BC patients, particularly those with TNBC. Further research with a multicentric expanded (pre-/post-therapy) sample set and better-defined populations in terms of molecular subtypes, therapy modality, and long-term follow-up is recommended to obtain more solid evidence.

16.
J Clin Med ; 13(18)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39336866

RESUMO

Atrial wall thickness (AWT) is a significant factor in understanding the pathological physiological substrate of atrial fibrillation, with a potentially substantial impact on the outcomes of catheter ablation procedures. Precise measurements of the AWT may provide valuable insights for categorising patients with AF and planning targeted interventions. Objectives: The purpose of this study was to evaluate the characteristics of the left atrium (LA) using non-invasive multidetector computed tomography (MDCT) scans and subsequent three-dimensional (3D) image post-processing using novel software designed to calculate atrial thickness dimensions and mass. Methods: We retrospectively analysed 128 consecutive patients (33.6% females; mean age 55.6 ± 11.2 years) referred for AF ablation (37 with persistent AF and 91 with paroxysmal AF) who underwent preprocedural MDCT. The images were post-processed and analysed using the ADAS software (Galgo Medical), automatically calculating the LA volume and regional wall thickness. In addition, the software employed a regional semi-automatic LA parcellation feature that divided the atrial wall into 12 segments, generating atrial wall thickness (AWT) maps per segment for each patient. Results: This study demonstrated considerable variability in the average thickness of LA walls, with the anterior segments being the thickest across the cohort. Distinct sex-specific differences were observed, with males exhibiting greater anterior and septal wall thickness than females. No significant associations were identified between the average AWT and body mass index, LA volume, or sphericity. Survival analysis conducted over 24 months revealed a meaningful relationship between mean anterior wall thickness and recurrence-free survival, with increased thickness associated with a lower likelihood of AF-free survival. No such relationship was observed for the indexed LA volume. Conclusions: The variability in AWT and its association with recurrence-free survival following AF ablation suggest that AWT should be considered when stratifying patients for AF management and ablation strategies. These findings underscore the need for personalised treatment approaches and further research on the interplay of the structural properties of the left atrium as factors that can serve as important prognostic markers in AF treatment.

18.
Digit Health ; 9: 20552076221149651, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36636729

RESUMO

As simulation is playing an increasingly important role in medicine, providing the individual patient with a customised diagnosis and treatment is envisaged as part of future precision medicine. Such customisation will become possible through the emergence of digital twin (DT) technology. The objective of this article is to review the progress of prominent research on DT technology in medicine and discuss the potential applications and future opportunities as well as several challenges remaining in digital healthcare. A review of the literature was conducted using PubMed, Web of Science, Google Scholar, Scopus and related bibliographic resources, in which the following terms and their derivatives were considered during the search: DT, medicine and digital health virtual healthcare. Finally, analyses of the literature yielded 465 pertinent articles, of which we selected 22 for detailed review. We summarised the application examples of DT in medicine and analysed the applications in many fields of medicine. It revealed encouraging results that DT is being increasing applied in medicine. Results from this literature review indicated that DT healthcare, as a key fusion approach of future medicine, will bring the advantages of precision diagnose and personalised treatment into reality.

19.
Clin Oncol (R Coll Radiol) ; 35(1): e48-e59, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35781406

RESUMO

AIMS: Medication for advanced sarcomas has not improved for three decades. Patient-derived tumour xenografts (PDTX) are a promising solution for developing new therapies and real-time personalised medicine because of their highly effective prediction of drug efficacy. However, there is a dearth of PDTX models for sarcomas due to the scarcity and heterogeneity of the disease. MATERIALS AND METHODS: A multicentre clinical collaborative study (ChiCTR-OOC-17013617) was carried out. Fresh patient tumour tissues via resection or biopsy were used for the PDTX set-up. The standard medical care chosen by the physician was given to the patient, in parallel with testing on multiple regimens. The outcomes of patients' responses and PDTX tests were compared. Comprehensive analyses were carried out to assess the clinical value of PDTX for the treatment of sarcomas. Living tissues from successfully engrafted cases were deposited into a repository. RESULTS: Forty-two cases, including 36 bone sarcomas and six soft-tissue sarcomas, were enrolled; the overall engraftment rate was 73.8%. Histopathological examination showed a 100% consistency between primary tumours and tumour grafts. The engraftment rate was independent of age, gender and sampling methods, but was associated with subtypes of tumour. The outgrowth time of tumour grafts could be associated with prognosis. Major somatic mutations in tumour grafts occurred primarily in common tumour driver genes. Poor prognosis was associated with the KMT2C mutation. A drug efficacy test showed complete concordance between the PDTX model and patients' responses in 17 regimens. CONCLUSION: PDTX is an ideal preclinical model for sarcomas because of its faithful preservation of the heterogeneity of the disease, a satisfactory engraftment rate and high accuracy in its prediction of drug efficacy.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Animais , Humanos , Xenoenxertos , Medicina de Precisão/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Sarcoma/tratamento farmacológico , Sarcoma/genética , Modelos Animais de Doenças
20.
Cancers (Basel) ; 15(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38001698

RESUMO

Cancer remains a leading cause of death worldwide, despite many advances in diagnosis and treatment. Precision medicine has been a key area of focus, with research providing insights and progress in helping to lower cancer mortality through better patient stratification for therapies and more precise diagnostic techniques. However, unequal access to cancer care is still a global concern, with many patients having limited access to diagnostic tests and treatment regimens. Noninvasive liquid biopsy (LB) technology can determine tumour-specific molecular alterations in peripheral samples. This allows clinicians to infer knowledge at a DNA or cellular level, which can be used to screen individuals with high cancer risk, personalize treatments, monitor treatment response, and detect metastasis early. As scientific understanding of cancer pathology increases, LB technologies that utilize circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) have evolved over the course of research. These technologies incorporate tumour-specific markers into molecular testing platforms. For clinical translation and maximum patient benefit at a wider scale, the accuracy, accessibility, and affordability of LB tests need to be prioritized and compared with gold standard methodologies in current use. In this review, we highlight the range of technologies in LB diagnostics and discuss the future prospects of LB through the anticipated evolution of current technologies and the integration of emerging and novel ones. This could potentially allow a more cost-effective model of cancer care to be widely adopted.

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