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1.
Trials ; 25(1): 353, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822392

RESUMO

BACKGROUND: The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers. METHODS: Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs. RESULTS: SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard. CONCLUSIONS: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Fatores de Tempo , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Guias de Prática Clínica como Assunto , Interpretação Estatística de Dados , Medição de Risco , Projetos de Pesquisa/normas , Fatores de Risco , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Viés , Análise de Sobrevida , Seguimentos , Resultado do Tratamento , Simulação por Computador , Estimativa de Kaplan-Meier
2.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 164-176, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836665

RESUMO

The prognosis of patients with multiple myeloma (MM) has significantly improved over the past ten years because of several innovative treatments, including the proteasome inhibitor Bortezomib and immunomodulatory drugs (IMiDs) like Thalidomide and Lenalidomide. The present study aimed to determine the effectiveness of Bortezomib-based regimens on survival state of MM patients. This retrospective study included 204 newly diagnosed MM patients who were registered at Nanakali Hospital for Blood Diseases and Cancer, Erbil- Iraq, between April 2008 and April 2022. The patients were split into two primary groups: those receiving treatment with Bortezomib and those not. Clinical and laboratory data, treatment type, responsiveness to induction therapy, and survival results were examined in the enrolled patients' medical records. The mean patient age was 60 years, males constituted 55.8% of the included patients. At the time of diagnosis, 98 individuals (48%) had stage 3 illness. Except for the LDH, which was noticeably higher in the non-Bortezomib group, the patients laboratory results did not substantially change between the Bortezomib and non-Bortezomib groups (p = 0.001). In patients treated with Bortezomib, the complete response (CR) rate following induction was substantially greater (35.2%) than in those treated without Bortezomib (9.1%). Compared to the non-Bortezomib group, the median survival time of the Bortezomib group was considerably greater (p < 0.001). Bortezomib has a significant role in inducing a CR before bone marrow (BM) transplantation, and it has a significant role in the survival outcome in MM.


Assuntos
Bortezomib , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Bortezomib/uso terapêutico , Bortezomib/administração & dosagem , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise de Sobrevida
3.
Medicine (Baltimore) ; 103(23): e38230, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847674

RESUMO

The prognosis of acromelanomas (AM) is worse. The objective of this study was to investigate the clinical features of distant metastasis of AM and the factors affecting the survival and prognosis of patients. In this study, a retrospective study was conducted to select 154 AM patients admitted to Nanjing Pukou People's Hospital from January 2018 to April 2021 for clinical research. The clinical characteristics of distant metastasis were statistically analyzed, and the survival curve was drawn with 5-year follow-up outcomes. The median survival time of the patients was calculated, and the clinicopathological features and peripheral blood laboratory indexes of the surviving and dead patients were analyzed. Logistic regression model was used to analyze the risk factors affecting the prognosis of AM patients. In this study, 154 patients with AM were treated, including 88 males and 76 females, aged from 27 to 79 years old, with an average age of (59.3 ±â€…11.7) years old. Among them, 90 cases had distant metastasis. The main metastatic sites were lung (47.78%) and lymph nodes (42.22%). Among them, single site metastasis accounted for 41.11% and multiple site metastasis 58.89%. 89 cases survived and 65 cases died. The survival time was 22 months to 60 months, and the median survival time was 48.0 months. The Breslow thickness, stage at diagnosis, distant metastasis, site of metastasis and ulceration were compared between the survival group and the death group (P < .05). serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) were compared between the survival group and the death group (P < .05). The results of Logistic regression model showed that LDH ≥ 281 U/L, NLR ≥ 2.96, LMR ≤ 3.57, newly diagnosed stage > stage II, distant metastasis, multiple site metastasis and tumor ulcer were independent risk factors for poor prognosis of AM patients (P < .05). Patients with AM had a higher proportion of distant metastasis, mainly lung and lymph node metastasis. Increased LDH, increased NLR, decreased LMR, higher initial stage, distant metastasis, multiple site metastasis, and combined tumor ulcer were closely related to the poor prognosis of patients after surgery.


Assuntos
Neoplasias Pulmonares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Prognóstico , Fatores de Risco , Análise de Sobrevida , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Metástase Linfática , Metástase Neoplásica , China/epidemiologia
4.
Medicine (Baltimore) ; 103(23): e38470, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847690

RESUMO

Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and adolescents. Improvements in our understanding of the OS pathogenesis and metastatic mechanism on the molecular level might lead to notable advances in the treatment and prognosis of OS. Biomarkers related to OS metastasis and prognosis were analyzed and identified, and a prognostic model was established through the integration of bioinformatics tools and datasets in multiple databases. 2 OS datasets were downloaded from the Gene Expression Omnibus database for data consolidation, standardization, batch effect correction, and identification of differentially expressed genes (DEGs); following that, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs; the STRING database was subsequently used for protein-protein interaction (PPI) network construction and identification of hub genes; hub gene expression was validated, and survival analysis was conducted through the employment of the TARGET database; finally, a prognostic model was established and evaluated subsequent to the screening of survival-related genes. A total of 701 DEGs were identified; by gene ontology and KEGG pathway enrichment analyses, the overlapping DEGs were enriched for 249 biological process terms, 13 cellular component terms, 35 molecular function terms, and 4 KEGG pathways; 13 hub genes were selected from the PPI network; 6 survival-related genes were identified by the survival analysis; the prognostic model suggested that 4 genes were strongly associated with the prognosis of OS. DEGs related to OS metastasis and survival were identified through bioinformatics analysis, and hub genes were further selected to establish an ideal prognostic model for OS patients. On this basis, 4 protective genes including TPM1, TPM2, TPM3, and TPM4 were yielded by the prognostic model.


Assuntos
Neoplasias Ósseas , Biologia Computacional , Osteossarcoma , Mapas de Interação de Proteínas , Osteossarcoma/genética , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Humanos , Biologia Computacional/métodos , Prognóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Mapas de Interação de Proteínas/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Bases de Dados Genéticas , Análise de Sobrevida , Metástase Neoplásica/genética
6.
BMC Med Inform Decis Mak ; 24(1): 120, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715002

RESUMO

In recent times, time-to-event data such as time to failure or death is routinely collected alongside high-throughput covariates. These high-dimensional bioinformatics data often challenge classical survival models, which are either infeasible to fit or produce low prediction accuracy due to overfitting. To address this issue, the focus has shifted towards introducing a novel approaches for feature selection and survival prediction. In this article, we propose a new hybrid feature selection approach that handles high-dimensional bioinformatics datasets for improved survival prediction. This study explores the efficacy of four distinct variable selection techniques: LASSO, RSF-vs, SCAD, and CoxBoost, in the context of non-parametric biomedical survival prediction. Leveraging these methods, we conducted comprehensive variable selection processes. Subsequently, survival analysis models-specifically CoxPH, RSF, and DeepHit NN-were employed to construct predictive models based on the selected variables. Furthermore, we introduce a novel approach wherein only variables consistently selected by a majority of the aforementioned feature selection techniques are considered. This innovative strategy, referred to as the proposed method, aims to enhance the reliability and robustness of variable selection, subsequently improving the predictive performance of the survival analysis models. To evaluate the effectiveness of the proposed method, we compare the performance of the proposed approach with the existing LASSO, RSF-vs, SCAD, and CoxBoost techniques using various performance metrics including integrated brier score (IBS), concordance index (C-Index) and integrated absolute error (IAE) for numerous high-dimensional survival datasets. The real data applications reveal that the proposed method outperforms the competing methods in terms of survival prediction accuracy.


Assuntos
Redes Neurais de Computação , Humanos , Análise de Sobrevida , Estatísticas não Paramétricas , Biologia Computacional/métodos
7.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 233-241, 2024 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-38716594

RESUMO

Objective: To retrospectively analyze the clinical characteristics and prognosis of 85 newly diagnosed patients with follicular lymphoma (FL), as well as the prognostic value of comprehensive geriatric assessment (CGA) in patients with FL aged ≥ 60 years old. Methods: The clinical data and prognosis of 85 newly diagnosed FL patients admitted from August 2011 to June 2022 were collected. The clinical features, laboratory indicators, therapeutic efficacy, survival and prognostic factors of patients were statistically analyzed, and the prognosis of patients was stratified using various geriatric assessment tools. Results: ① The patients with FL were mostly middle-aged and older, with a median age of 59 (20-87) years, including 41 patients (48.2%) aged ≥60 years. The ratio of male to female was 1∶1.36. Overall, 77.6% of the patients were diagnosed with Ann Arbor stage Ⅲ-Ⅳ, and 17 cases (20.0%) were accompanied by B symptoms. Bone marrow involvement was the most common (34.1%). ②Overall, 71 patients received immunochemotherapy. The overall response rate was 86.6%, and the complete recovery rate was 47.1% of 68 evaluated patients. Disease progression or relapse in the first 2 years was observed in 23.9% of the patient. Overall, 14.1% of the patients died during follow-up. ③Of the 56 patients receiving R-CHOP-like therapies, the 3-year and 5-year progression-free survival (PFS) rates were 85.2% and 72.8%, respectively, and the 3-year and 5-year overall survival (OS) rates were 95.9% and 88.8%, respectively. The univariate analysis showed that age ≥60 years old (HR=3.430, 95% CI 1.256-9.371, P=0.016), B symptoms (HR=5.030, 95% CI 1.903-13.294, P=0.016), Prognostic Nutritional Index (PNI) <45.25 (HR=3.478, 95% CI 1.299-9.310, P=0.013), Follicular Lymphoma International Prognostic Index (FLIPI) high-risk (HR=2.918, 95% CI 1.074-7.928, P=0.036), and PRIMA-prognostic index (PRIMA-PI) high-risk (HR=2.745, 95% CI 1.057-7.129, P=0.038) significantly predicted PFS. Moreover, age ≥60 years old and B symptoms were independent risk factors for PFS. Progression of disease within 24 months (POD24) significantly predicted OS in the univariate analysis. Conclusions: FL is more common among middle-aged and older women. Age, B symptoms, PNI score, FLIPI high-risk, PRIMA-PI high-risk, and POD24 influenced PFS and OS. The CGA can be used for treatment selection and risk prognostication in older patients with FL.


Assuntos
Avaliação Geriátrica , Linfoma Folicular , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Idoso de 80 Anos ou mais , Avaliação Geriátrica/métodos , Análise de Sobrevida , Adulto , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
8.
Rev Col Bras Cir ; 51: e20243595, 2024.
Artigo em Inglês, Português | MEDLINE | ID: mdl-38716912

RESUMO

INTRODUCTION: severe abdominal sepsis, accompained by diffuse peritonitis, poses a significant challenge for most surgeons. It often requires repetitive surgical interventions, leading to complications and resulting in high morbidity and mortality rates. The open abdomen technique, facilitated by applying a negative-pressure wound therapy (NPWT), reduces the duration of the initial surgical procedure, minimizes the accumulation of secretions and inflammatory mediators in the abdominal cavity and lowers the risk of abdominal compartment syndrome and its associated complications. Another approach is primary closure of the abdominal aponeurosis, which involves suturing the layers of the abdominal wall. METHODS: the objective of this study is to conduct a survival analysis comparing the treatment of severe abdominal sepsis using open abdomen technique versus primary closure after laparotomy in a public hospital in the South of Brazil. We utilized data extracted from electronic medical records to perform both descriptive and survival analysis, employing the Kaplan-Meier curve and a log-rank test. RESULTS: the study sample encompassed 75 laparotomies conducted over a span of 5 years, with 40 cases employing NPWT and 35 cases utilizing primary closure. The overall mortality rate observed was 55%. Notably, survival rates did not exhibit statistical significance when comparing the two methods, even after stratifying the data into separate analysis groups for each technique. CONCLUSION: recent publications on this subject have reported some favorable outcomes associated with the open abdomen technique underscoring the pressing need for a standardized approach to managing patients with severe, complicated abdominal sepsis.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais , Laparotomia , Técnicas de Abdome Aberto , Sepse , Humanos , Masculino , Feminino , Sepse/mortalidade , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Análise de Sobrevida , Índice de Gravidade de Doença , Adulto , Peritonite/cirurgia , Peritonite/mortalidade , Peritonite/etiologia , Tratamento de Ferimentos com Pressão Negativa
9.
Clin Exp Med ; 24(1): 95, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717497

RESUMO

The prognostication of survival trajectories in multiple myeloma (MM) patients presents a substantial clinical challenge. Leveraging transcriptomic and clinical profiles from an expansive cohort of 2,088 MM patients, sourced from the Gene Expression Omnibus and The Cancer Genome Atlas repositories, we applied a sophisticated nested lasso regression technique to construct a prognostic model predicated on 28 gene pairings intrinsic to cell death pathways, thereby deriving a quantifiable risk stratification metric. Employing a threshold of 0.15, we dichotomized the MM samples into discrete high-risk and low-risk categories. Notably, the delineated high-risk cohort exhibited a statistically significant diminution in survival duration, a finding which consistently replicated across both training and external validation datasets. The prognostic acumen of our cell death signature was further corroborated by TIME ROC analyses, with the model demonstrating robust performance, evidenced by AUC metrics consistently surpassing the 0.6 benchmark across the evaluated arrays. Further analytical rigor was applied through multivariate COX regression analyses, which ratified the cell death risk model as an independent prognostic determinant. In an innovative stratagem, we amalgamated this risk stratification with the established International Staging System (ISS), culminating in the genesis of a novel, refined ISS categorization. This tripartite classification system was subjected to comparative analysis against extant prognostic models, whereupon it manifested superior predictive precision, as reflected by an elevated C-index. In summation, our endeavors have yielded a clinically viable gene pairing model predicated on cellular mortality, which, when synthesized with the ISS, engenders an augmented prognostic tool that exhibits pronounced predictive prowess in the context of multiple myeloma.


Assuntos
Morte Celular , Mieloma Múltiplo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Humanos , Prognóstico , Masculino , Feminino , Medição de Risco , Perfilação da Expressão Gênica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Idoso , Análise de Sobrevida
10.
Pediatr Transplant ; 28(4): e14742, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38702926

RESUMO

BACKGROUND: As more pediatric patients become candidates for heart transplantation (HT), understanding pathological predictors of outcome and the accuracy of the pretransplantation evaluation are important to optimize utilization of scarce donor organs and improve outcomes. The authors aimed to investigate explanted heart specimens to identify pathologic predictors that may affect cardiac allograft survival after HT. METHODS: Explanted pediatric hearts obtained over an 11-year period were analyzed to understand the patient demographics, indications for transplant, and the clinical-pathological factors. RESULTS: In this study, 149 explanted hearts, 46% congenital heart defects (CHD), were studied. CHD patients were younger and mean pulmonary artery pressure and resistance were significantly lower than in cardiomyopathy patients. Twenty-one died or underwent retransplantation (14.1%). Survival was significantly higher in the cardiomyopathy group at all follow-up intervals. There were more deaths and the 1-, 5- and 7-year survival was lower in patients ≤10 years of age at HT. Early rejection was significantly higher in CHD patients exposed to homograft tissue, but not late rejection. Mortality/retransplantation rate was significantly higher and allograft survival lower in CHD hearts with excessive fibrosis of one or both ventricles. Anatomic diagnosis at pathologic examination differed from the clinical diagnosis in eight cases. CONCLUSIONS: Survival was better for the cardiomyopathy group and patients >10 years at HT. Prior homograft use was associated with a higher prevalence of early rejection. Ventricular fibrosis (of explant) was a strong predictor of outcome in the CHD group. We presented several pathologic findings in explanted pediatric hearts.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Cardiopatias Congênitas , Transplante de Coração , Humanos , Criança , Masculino , Feminino , Pré-Escolar , Lactente , Adolescente , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/patologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Seguimentos , Cardiomiopatias/cirurgia , Cardiomiopatias/patologia , Reoperação , Recém-Nascido , Análise de Sobrevida
11.
BMC Med Res Methodol ; 24(1): 107, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724889

RESUMO

BACKGROUND: Semiparametric survival analysis such as the Cox proportional hazards (CPH) regression model is commonly employed in endometrial cancer (EC) study. Although this method does not need to know the baseline hazard function, it cannot estimate event time ratio (ETR) which measures relative increase or decrease in survival time. To estimate ETR, the Weibull parametric model needs to be applied. The objective of this study is to develop and evaluate the Weibull parametric model for EC patients' survival analysis. METHODS: Training (n = 411) and testing (n = 80) datasets from EC patients were retrospectively collected to investigate this problem. To determine the optimal CPH model from the training dataset, a bi-level model selection with minimax concave penalty was applied to select clinical and radiomic features which were obtained from T2-weighted MRI images. After the CPH model was built, model diagnostic was carried out to evaluate the proportional hazard assumption with Schoenfeld test. Survival data were fitted into a Weibull model and hazard ratio (HR) and ETR were calculated from the model. Brier score and time-dependent area under the receiver operating characteristic curve (AUC) were compared between CPH and Weibull models. Goodness of the fit was measured with Kolmogorov-Smirnov (KS) statistic. RESULTS: Although the proportional hazard assumption holds for fitting EC survival data, the linearity of the model assumption is suspicious as there are trends in the age and cancer grade predictors. The result also showed that there was a significant relation between the EC survival data and the Weibull distribution. Finally, it showed that Weibull model has a larger AUC value than CPH model in general, and it also has smaller Brier score value for EC survival prediction using both training and testing datasets, suggesting that it is more accurate to use the Weibull model for EC survival analysis. CONCLUSIONS: The Weibull parametric model for EC survival analysis allows simultaneous characterization of the treatment effect in terms of the hazard ratio and the event time ratio (ETR), which is likely to be better understood. This method can be extended to study progression free survival and disease specific survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT03543215, https://clinicaltrials.gov/ , date of registration: 30th June 2017.


Assuntos
Neoplasias do Endométrio , Imageamento por Ressonância Magnética , Modelos de Riscos Proporcionais , Humanos , Feminino , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Análise de Sobrevida , Idoso , Curva ROC , Adulto , Modelos Estatísticos , Radiômica
12.
Invest Ophthalmol Vis Sci ; 65(5): 10, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709525

RESUMO

Purpose: The purpose of this study was to investigate the incidence of foveal involvement in geographic atrophy (GA) secondary to age-related macular degeneration (AMD), using machine learning to assess the importance of risk factors. Methods: Retrospective, longitudinal cohort study. Patients diagnosed with foveal-sparing GA, having GA size ≥ 0.049 mm² and follow-up ≥ 6 months, were included. Baseline GA area, distance from the fovea, and perilesional patterns were measured using fundus autofluorescence. Optical coherence tomography assessed foveal involvement, structural biomarkers, and outer retinal layers thickness. Onset of foveal involvement was recorded. Foveal survival rates were estimated using Kaplan-Meier curves. Hazard ratios (HRs) were assessed with mixed model Cox regression. Variable Importance (VIMP) was ranked with Random Survival Forests (RSF), with higher scores indicating greater predictive significance. Results: One hundred sixty-seven eyes (115 patients, average age = 75.8 ± 9.47 years) with mean follow-up of 50 ± 29 months, were included in this study. Median foveal survival time was 45 months (95% confidence interval [CI] = 38-55). Incidences of foveal involvement were 26% at 24 months and 67% at 60 months. Risk factors were GA proximity to the fovea (HR = 0.97 per 10-µm increase, 95% CI = 0.96-0.98), worse baseline visual acuity (HR = 1.37 per 0.1 LogMAR increase, 95% CI = 1.21-1.53), and thinner outer nuclear layer (HR = 0.59 per 10-µm increase, 95% CI = 0.46-0.74). RSF analysis confirmed these as main predictors (VIMP = 16.7, P = 0.002; VIMP = 6.2, P = 0.003; and VIMP = 3.4, P = 0.01). Lesser baseline GA area (HR = 1.09 per 1-mm2 increase, 95% CI = 1.01-1.16) and presence of a double layer sign (HR = 0.42, 95% CI = 0.20-0.88) were protective but less influential. Conclusions: This study identifies anatomic and functional factors impacting the risk of foveal involvement in GA. These findings may help identify at-risk patients, enabling tailored preventive strategies.


Assuntos
Fóvea Central , Atrofia Geográfica , Aprendizado de Máquina , Tomografia de Coerência Óptica , Humanos , Fóvea Central/patologia , Fóvea Central/diagnóstico por imagem , Masculino , Feminino , Atrofia Geográfica/diagnóstico , Idoso , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Fatores de Risco , Idoso de 80 Anos ou mais , Acuidade Visual/fisiologia , Seguimentos , Angiofluoresceinografia/métodos , Incidência , Pessoa de Meia-Idade , Análise de Sobrevida
13.
BMC Public Health ; 24(1): 1255, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714963

RESUMO

BACKGROUND: In Thailand, the national health care system and nationwide standard treatment protocols have evolved over time, potentially influencing the trends in the incidence and survival rates of childhood cancers. However, further investigations are required to comprehensively study these trends in Khon Kaen, Thailand. METHODS: Childhood cancer patients aged 0-14 years (n = 541) who were diagnosed with one of the five most common cancers between 2000 and 2019 from the population-based Khon Kaen Cancer Registry were enrolled. Descriptive statistics were used to analyse the demographic data, which are presented as numbers, percentages, means, and standard deviations. The trends in incidence between 2000 and 2019, including age-standardized incidence rates (ASRs) and annual percent changes (APCs), were analysed using the Joinpoint regression model. Survival analysis was performed for 5-year relative survival rates (RSRs) according to the Pohar Perme estimator and Kaplan-Meier survival curves. RESULTS: The ASRs of the overall top 5 childhood cancer groups were 67.96 and 106.12 per million person-years in 2000 and 2019, respectively. Overall, the APC significantly increased by 2.37% each year for both sexes. The overall 5-year RSRs were 60.5% for both sexes, 58.2% for males, and 63.9% for females. The highest 5-year RSR was for germ cell tumours (84.3%), whereas the lowest 5-year RSR was for neuroblastoma (29.1%). CONCLUSIONS: The incidence and survival rates of childhood cancers in Khon Kaen, Thailand, varied according to sex. The incidence trends increased over time, meanwhile, the relative survival rates rose to satisfactory levels and were comparable to those of other nations with similar financial status. The implementation of national health policies and adherence to national treatment guidelines have improved cancer diagnosis and treatment outcomes.


Assuntos
Neoplasias , Sistema de Registros , Humanos , Tailândia/epidemiologia , Feminino , Masculino , Pré-Escolar , Criança , Lactente , Incidência , Adolescente , Neoplasias/mortalidade , Neoplasias/epidemiologia , Recém-Nascido , Taxa de Sobrevida , Análise de Sobrevida
14.
BMJ Open ; 14(5): e073384, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697761

RESUMO

OBJECTIVES: This study aimed to evaluate competing risks and functional ability measures among patients who had a stroke. DESIGN: A joint model comprising two related submodels was applied: a cause-specific hazard submodel for competing drop-out and stroke-related death risks, and a partial proportional odd submodel for longitudinal functional ability. SETTING: Felege Hiwot Referral Hospital, Ethiopia. PARTICIPANTS: The study included 400 patients who had a stroke from the medical ward outpatient stroke unit at Felege Hiwot Referral Hospital, who were treated from September 2018 to August 2021. RESULTS: Among the 400 patients who had a stroke, 146 (36.5%) died and 88 (22%) dropped out. At baseline, 14% of patients had no symptoms and/or disability while 24% had slight disability, and 25% had severe disability. Most patients (37.04%) exhibited moderate functional ability. The presence of diabetes increased the cause-specific hazard of death by 3.95 times (95% CI 2.16 to 7.24) but decreased the cause-specific hazard of drop-out by 95% (aHR 0.05; 95% CI 0.01 to 0.46) compared with non-diabetic patients who had a stroke. CONCLUSION: A substantial proportion of patients who had a stroke experienced mortality and drop-out during the study period, highlighting the importance of considering competing risks in stroke research. Age, diabetes, white cell count and stroke complications were significant covariates affecting both longitudinal and survival submodels. Compared with stand-alone models, the joint competing risk modelling technique offers comprehensive insights into the disease's transition pattern.


Assuntos
Acidente Vascular Cerebral , Humanos , Etiópia/epidemiologia , Masculino , Feminino , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/epidemiologia , Pessoa de Meia-Idade , Estudos Longitudinais , Idoso , Análise de Sobrevida , Adulto , Fatores de Risco , Reabilitação do Acidente Vascular Cerebral , Avaliação da Deficiência , Encaminhamento e Consulta/estatística & dados numéricos
15.
Skin Res Technol ; 30(5): e13739, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38766879

RESUMO

BACKGROUND: Programmed cell death (PCD) pathways play crucial roles in the pathogenesis of skin cutaneous melanoma (SKCM). Understanding their prognostic significance and clinical implications is imperative for the development of personalized treatment strategies. METHODS: A total of 1466 PCD-related genes were analyzed using data from The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 353). Prognostic cell death index (CDI) was established and validated through survival analysis and predictive modeling. Functional enrichment, protein-protein interaction (PPI), consensus clustering, and tumor microenvironment assessment and drug sensitivity analysis were performed to elucidate the biological and clinical relevance of CDI. RESULTS: CDI effectively stratified SKCM patients into high and low-risk groups, demonstrating significant differences in survival outcomes. It exhibited predictive value for survival at 1, 3, and 5 years. The concordance index (C-index) was 0.794 in the training set, and 0.792 and 0.821 in the internal and external validation sets, respectively. The corresponding area under curve (AUC) was all above 0.75 in these data sets. Functional enrichment analysis revealed significant associations with immune response and inflammatory processes. PPI analysis identified key molecular modules associated with apoptosis and chemokine signaling. Consensus clustering unveiled three discernible subtypes demonstrating notable disparities in survival outcomes based on CDI expression profiles. Assessment of the tumor microenvironment highlighted correlations with immune cell infiltration such as M1 macrophages and T cells. Drug sensitivity analysis indicated tight correlations between CDI levels and response to immunotherapy. CONCLUSION: Our comprehensive analysis establishes the prognostic significance of PCD-related genes in SKCM. CDI emerges as a promising prognostic biomarker, offering insights into tumor biology and potential implications for personalized treatment strategies. Further validation and clinical integration of CDI are warranted to improve SKCM management and patient outcomes.


Assuntos
Melanoma , Neoplasias Cutâneas , Microambiente Tumoral , Humanos , Melanoma/genética , Melanoma/mortalidade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Microambiente Tumoral/genética , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Melanoma Maligno Cutâneo , Transcriptoma , Apoptose/genética , Perfilação da Expressão Gênica , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise de Sobrevida
16.
Clin Exp Med ; 24(1): 104, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761234

RESUMO

Recent research highlights the significance of exosomes and long noncoding RNAs (lncRNAs) in cancer progression and drug resistance, but their role in lung adenocarcinoma (LUAD) is not fully understood. We analyzed 121 exosome-related (ER) mRNAs from the ExoBCD database, along with mRNA and lncRNA expression profiles of TCGA-LUAD using "DESeq2", "survival," "ConsensusClusterPlus," "GSVA," "estimate," "glmnet," "clusterProfiler," "rms," and "pRRophetic" R packages. This comprehensive approach included univariate cox regression, unsupervised consensus clustering, GSEA, functional enrichment analysis, and prognostic model construction. Our study identified 134 differentially expressed ER-lncRNAs, with 19 linked to LUAD prognosis. These ER-lncRNAs delineated two patient subtypes, one with poorer outcomes. Additionally, 286 differentially expressed genes were related to these ER-lncRNAs, 261 of which also correlated with LUAD prognosis. We constructed an ER-lncRNA-related prognostic model and calculated an ER-lncRNA-related risk score (ERS), revealing that a higher ERS correlates with poor overall survival in both the Meta cohort and two validation cohorts. The ERS potentially serves as an independent prognostic factor, and the prognostic model demonstrates superior predictive power. Notably, significant differences in the immune landscape were observed between the high- and low-ERS groups. Drug sensitivity analysis indicated varying responses to common chemotherapy drugs based on ERS stratification, with the high-ERS group showing greater sensitivity, except to rapamycin and erlotinib. Experimental validation confirmed that thymidine kinase 1 enhances lung cancer invasion, metastasis, and cell cycle progression. Our study pioneers an ER-lncRNA-related prognostic model for LUAD, proposing that ERS-based risk stratification could inform personalized treatment strategies to improve patient outcomes.


Assuntos
Adenocarcinoma de Pulmão , Exossomos , Neoplasias Pulmonares , RNA Longo não Codificante , Microambiente Tumoral , Humanos , Exossomos/genética , Exossomos/metabolismo , RNA Longo não Codificante/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Prognóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Análise de Sobrevida
17.
J Transl Med ; 22(1): 472, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762511

RESUMO

BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC. METHODS: A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell's concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis. RESULTS: A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time. CONCLUSIONS: The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Idoso , Análise de Sobrevida , Estimativa de Kaplan-Meier , Reprodutibilidade dos Testes , Quinolinas/uso terapêutico , Compostos de Fenilureia
18.
Sci Rep ; 14(1): 11494, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769376

RESUMO

Gastrointestinal stromal tumors (GISTs) predominantly develop in the stomach. While nomogram offer tremendous therapeutic promise, there is yet no ideal nomogram comparison customized specifically for handling categorical data and model selection related gastric GISTs. (1) We selected 5463 patients with gastric GISTs from the SEER Research Plus database spanning from 2000 to 2020; (2) We proposed an advanced missing data imputation algorithm specifically designed for categorical variables; (3) We constructed five Cox nomogram models, each employing distinct methods for the selection and modeling of categorical variables, including Cox (Two-Stage), Lasso-Cox, Ridge-Cox, Elastic Net-Cox, and Cox With Lasso; (4) We conducted a comprehensive comparison of both overall survival (OS) and cancer-specific survival (CSS) tasks at six different time points; (5) To ensure robustness, we performed 50 randomized splits for each task, maintaining a 7:3 ratio between the training and test cohorts with no discernible statistical differences. Among the five models, the Cox (Two-Stage) nomogram contains the fewest features. Notably, at Near-term, Mid-term, and Long-term intervals, the Cox (Two-Stage) model attains the highest Area Under the Curve (AUC), top-1 ratio, and top-3 ratio in both OS and CSS tasks. For the prediction of survival in patients with gastric GISTs, the Cox (Two-Stage) nomogram stands as a simple, stable, and accurate predictive model with substantial promise for clinical application. To enhance the clinical utility and accessibility of our findings, we have deployed the nomogram model online, allowing healthcare professionals and researchers worldwide to access and utilize this predictive tool.


Assuntos
Tumores do Estroma Gastrointestinal , Nomogramas , Programa de SEER , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Feminino , Masculino , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Modelos de Riscos Proporcionais , Análise de Sobrevida , Algoritmos
19.
Biometrics ; 80(2)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38708764

RESUMO

When studying the treatment effect on time-to-event outcomes, it is common that some individuals never experience failure events, which suggests that they have been cured. However, the cure status may not be observed due to censoring which makes it challenging to define treatment effects. Current methods mainly focus on estimating model parameters in various cure models, ultimately leading to a lack of causal interpretations. To address this issue, we propose 2 causal estimands, the timewise risk difference and mean survival time difference, in the always-uncured based on principal stratification as a complement to the treatment effect on cure rates. These estimands allow us to study the treatment effects on failure times in the always-uncured subpopulation. We show the identifiability using a substitutional variable for the potential cure status under ignorable treatment assignment mechanism, these 2 estimands are identifiable. We also provide estimation methods using mixture cure models. We applied our approach to an observational study that compared the leukemia-free survival rates of different transplantation types to cure acute lymphoblastic leukemia. Our proposed approach yielded insightful results that can be used to inform future treatment decisions.


Assuntos
Modelos Estatísticos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Causalidade , Biometria/métodos , Resultado do Tratamento , Simulação por Computador , Intervalo Livre de Doença , Análise de Sobrevida
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