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1.
Clin Exp Med ; 24(1): 95, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717497

RESUMEN

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.


Asunto(s)
Muerte Celular , Mieloma Múltiple , Mieloma Múltiple/patología , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Humanos , Pronóstico , Masculino , Femenino , Medición de Riesgo , Perfilación de la Expresión Génica , Persona de Mediana Edad , Estadificación de Neoplasias , Anciano , Análisis de Supervivencia
2.
BMC Med Res Methodol ; 24(1): 107, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724889

RESUMEN

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.


Asunto(s)
Neoplasias Endometriales , Imagen por Resonancia Magnética , Modelos de Riesgos Proporcionales , Humanos , Femenino , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/diagnóstico por imagen , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Análisis de Supervivencia , Anciano , Curva ROC , Adulto , Modelos Estadísticos , Radiómica
3.
Clin Respir J ; 18(5): e13772, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38725348

RESUMEN

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as an immune suppressor and a promising candidate for immunotherapy of cancer management. However, the association between Siglec-15 expression and clinicopathological features of lung adenocarcinoma (LUAD), especially the prognostic role, is not fully elucidated. In this present study, a serial of bioinformatics analyses in both tissue and cell levels were conducted to provide an overview of Siglec-15 expression. Real-time quantitative PCR (qPCR) test, western blotting assay, and immunohistochemistry (IHC) analyses were conducted to evaluate the expression of Siglec-15 in LUAD. Survival analysis and Kaplan-Meier curve were employed to describe the prognostic parameters of LUAD. The results of bioinformatics analyses demonstrated the up-regulation of Siglec-15 expression in LUAD. The data of qPCR, western blotting, and IHC analyses further proved that the expression of Siglec-15 in LUAD tissues was significantly increased than that in noncancerous tissues. Moreover, the expression level of Siglec-15 protein in LUAD was substantially associated with TNM stage. LUAD cases with up-regulated Siglec-15 expression, positive N status, and advance TNM stage suffered a critical unfavorable prognosis. In conclusion, Siglec-15 could be identified as a novel prognostic biomarker in LUAD and targeting Siglec-15 may provide a promising strategy for LUAD immunotherapy.


Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Neoplasias Pulmonares , Humanos , Pronóstico , Femenino , Masculino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/mortalidad , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Anciano , Inmunohistoquímica , Estadificación de Neoplasias , Regulación hacia Arriba , Inmunoglobulinas/metabolismo , Inmunoglobulinas/genética , Lectinas/metabolismo , Lectinas/genética , Análisis de Supervivencia , Proteínas de la Membrana
4.
BMJ Open ; 14(5): e073384, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697761

RESUMEN

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.


Asunto(s)
Accidente Cerebrovascular , Humanos , Etiopía/epidemiología , Masculino , Femenino , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/epidemiología , Persona de Mediana Edad , Estudios Longitudinales , Anciano , Análisis de Supervivencia , Adulto , Factores de Riesgo , Rehabilitación de Accidente Cerebrovascular , Evaluación de la Discapacidad , Derivación y Consulta/estadística & datos numéricos
5.
Parasitol Res ; 123(5): 211, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748261

RESUMEN

Ivermectin is one of the most widely used drugs for parasite control. Previous studies have shown a reduction in the abundance and diversity of "non-target" coprophilous organisms due to the presence of ivermectin (IVM) in bovine faecal matter (FM). Due to its breadth of behavioural habits, Calliphora vicina is a suitable dipteran species to evaluate the effects of IVM in FM. The aim of this work was to evaluate the effect of five concentrations of IVM in FM (3000, 300, 100, 30, and 3 ng/g) on the development of C. vicina. The following endpoints were evaluated: survival (between the first larval stage and emergence of new adults), larval development times to pupation and pupation times to adult, and adult emergence (% sex) and LC50. Sampling was performed from larval hatching at 60 and 120 min and at 3, 4, 5, and 12 h, and every 24 h specimens were weighed until pupae were observed. Data were analysed by ANOVA using a non-parametric Kruskal-Wallis test and as a function of elapsed development time and accumulated degree hours (ADH). Mortality at 3000 and 300 ng/g was 100% and 97%, respectively. There were statistically significant delays in adult emergence time (p = 0.0216) and in the ADH (p = 0.0431) between the control group (C) and 100 ng/g. The LC50 was determined at 5.6 ng/g. These results demonstrate the lethal and sub-lethal effects of IVM on C. vicina, while highlighting the usefulness of this species as a bioindicator for ecotoxicological studies.


Asunto(s)
Calliphoridae , Heces , Ivermectina , Larva , Animales , Ivermectina/farmacología , Calliphoridae/efectos de los fármacos , Calliphoridae/crecimiento & desarrollo , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Heces/parasitología , Bovinos , Análisis de Supervivencia , Pupa/efectos de los fármacos , Pupa/crecimiento & desarrollo , Femenino , Antiparasitarios/farmacología , Masculino , Dosificación Letal Mediana , Dípteros/efectos de los fármacos , Dípteros/crecimiento & desarrollo
6.
Clin Exp Med ; 24(1): 99, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748269

RESUMEN

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.


Asunto(s)
Complejo CD3 , Inmunohistoquímica , Interferón gamma , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Interferón gamma/metabolismo , Anciano , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Complejo CD3/metabolismo , Antígenos CD8/metabolismo , Antígenos CD8/análisis , Adulto , Biomarcadores de Tumor/análisis , Análisis de Supervivencia , Anciano de 80 o más Años , Estimación de Kaplan-Meier , Células del Estroma/patología , Células del Estroma/metabolismo
7.
JAMA Netw Open ; 7(5): e2410260, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38743426

RESUMEN

Importance: Breast cancer is the most prevalent cancer globally with tremendous disparities both within specific regions and across different contexts. The survival pattern of patients with breast cancer remains poorly understood in sub-Saharan African (SSA) countries. Objective: To investigate the survival patterns of patients with breast cancer in SSA countries and compare the variation across countries and over time. Data Sources: Embase, PubMed, Web of Science, Scopus, and ProQuest were searched from inception to December 31, 2022, with a manual search of the references. Study Selection: Cohort studies of human participants that reported 1-, 2-, 3-, 4-, 5-, and 10-year survival from diagnosis among men, women, or both with breast cancer in SSA were included. Data Extraction and Synthesis: Independent extraction of study characteristics by multiple observers was performed using open-source software, then exported to a standard spreadsheet. A random-effects model using the generalized linear mixed-effects model was used to pool data. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guideline for reporting was followed. Main Outcome and Measures: Survival time from diagnosis. Results: Forty-nine studies were included in the review with a sample size ranging from 21 to 2311 (total, 14 459; 196 [1.35%] men, 13 556 [93.75%] women, and 707 [4.90%] unspecified; mean age range, 38 to 71 years), of which 40 were summarized using meta-analysis. The pooled 1-year survival rate of patients with breast cancer in SSA was 0.79 (95% CI, 0.67-0.88); 2-year survival rate, 0.70 (95% CI, 0.57-0.80); 3-year survival rate, 0.56 (95% CI, 0.45-0.67); 4-year survival rate, 0.54 (95% CI, 0.43-0.65); and 5-year survival rate, 0.40 (95% CI, 0.32-0.49). The subgroup analysis showed that the 5-year survival rate ranged from 0.26 (95% CI, 0.06-0.65) for studies conducted earlier than 2010 to 0.47 (95% CI, 0.32-0.64) for studies conducted later than 2020. Additionally, the 5-year survival rate was lower in countries with a low human development index (HDI) (0.36 [95% CI, 0.25-0.49) compared with a middle HDI (0.46 [95% CI, 0.33-0.60]) and a high HDI (0.54 [95% CI, 0.04-0.97]). Conclusions and Relevance: In this systematic review and meta-analysis, the survival rates for patients with breast cancer in SSA were higher in countries with a high HDI compared with a low HDI. Enhancing patient survival necessitates a comprehensive approach that involves collaboration from all relevant stakeholders.


Asunto(s)
Neoplasias de la Mama , Humanos , Neoplasias de la Mama/mortalidad , África del Sur del Sahara/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Tasa de Supervivencia , Anciano , Análisis de Supervivencia
8.
Sci Rep ; 14(1): 10902, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740898

RESUMEN

Calcification of the aortic valve (CAVDS) is a major cause of aortic stenosis (AS) leading to loss of valve function which requires the substitution by surgical aortic valve replacement (SAVR) or transcatheter aortic valve intervention (TAVI). These procedures are associated with high post-intervention mortality, then the corresponding risk assessment is relevant from a clinical standpoint. This study compares the traditional Cox Proportional Hazard (CPH) against Machine Learning (ML) based methods, such as Deep Learning Survival (DeepSurv) and Random Survival Forest (RSF), to identify variables able to estimate the risk of death one year after the intervention, in patients undergoing either to SAVR or TAVI. We found that with all three approaches the combination of six variables, named albumin, age, BMI, glucose, hypertension, and clonal hemopoiesis of indeterminate potential (CHIP), allows for predicting mortality with a c-index of approximately 80 % . Importantly, we found that the ML models have a better prediction capability, making them as effective for statistical analysis in medicine as most state-of-the-art approaches, with the additional advantage that they may expose non-linear relationships. This study aims to improve the early identification of patients at higher risk of death, who could then benefit from a more appropriate therapeutic intervention.


Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Calcinosis , Aprendizaje Profundo , Humanos , Válvula Aórtica/cirugía , Válvula Aórtica/patología , Calcinosis/cirugía , Calcinosis/mortalidad , Femenino , Masculino , Anciano , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/mortalidad , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Anciano de 80 o más Años , Análisis de Supervivencia , Factores de Riesgo , Modelos de Riesgos Proporcionales , Medición de Riesgo/métodos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Implantación de Prótesis de Válvulas Cardíacas/métodos , Persona de Mediana Edad
9.
Gastroenterol. hepatol. (Ed. impr.) ; 47(5): 448-456, may. 2024.
Artículo en Español | IBECS | ID: ibc-CR-354

RESUMEN

Introducción El colangiocarcinoma distal es una neoplasia epitelial maligna que afecta a los conductos biliares extrahepáticos, per debajo del conducto cístico. Existe poca evidencia sobre la relación entre factores perioperatorios y peor evolución a largo plazo tras la resección quirúrgica. Objetivo Analizar los factores de riesgo de mortalidad y recidiva a largo plazo del colangiocarcinoma distal de los pacientes resecados. Material y métodos Se ha analizado una base de datos prospectiva unicéntrica de pacientes intervenidos por colangiocarcinoma distal entre los años 1990 y 2021 con la finalidad de investigar los factores de mortalidad y recidiva. Resultados Se han intervenido 113 pacientes, con una supervivencia actuarial media de 100,2 (76-124) meses tras la resección. El estudio bivariante no evidenció diferencias entre los pacientes dependiendo de la edad o variables preoperatorias estudiadas. La presencia de adenopatías afectadas fue un factor de riesgo de mortalidad a largo plazo en el estudio multivariante. La presencia de adenopatías afectadas, la recidiva tumoral y la fístula biliar durante el postoperatorio implicaron peor supervivencia actuarial al comparar las curvas de Kaplan-Meier. Conclusiones La presencia de adenopatías afectadas influyen en el pronóstico de la enfermedad. La aparición de fístula biliar durante el postoperatorio del colangiocarcinoma distal podría agravar los resultados a largo plazo, hallazgo que debe ser reafirmado en futuros estudios. (AU)


Introduction Distal cholangiocarcinoma is a malignant epithelial neoplasia that affects the extrahepatic bile ducts, below the cystic duct. No relevant relationship between perioperative factors and worse long-term outcome has been proved. Objective To analyze the risk factors for mortality and long-term recurrence of distal cholangiocarcinoma in resected patients. Materials and methods A single-center prospective database of patients operated on for distal cholangiocarcinoma between 1990 and 2021 was analyzed in order to investigate mortality and recurrence factors. Results One hundred and thirteen patients have undergone surgery, with mean actuarial survival of 100.2 (76–124) months after resection. The bivariate study did not show differences between patients depending on age or preoperative variables studied. When multivariate analysis was performed, the presence of affected adenopathy was a risk factor for long-term mortality. The presence of affected lymph nodes, tumor recurrence, and biliary fistula during the postoperative period implied worse actuarial survival when comparing the Kaplan–Meier curves. Conclusions The presence of affected lymph nodes influence the prognosis of the disease. The occurrence of biliary fistula during postoperative cholangiocarcinoma distal could aggravate long-term outcomes, a finding that should be reaffirmed in future studies. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Pancreaticoduodenectomía/mortalidad , Colangiocarcinoma/mortalidad , Recurrencia Local de Neoplasia , Carcinoma , Conducto Cístico , Análisis de Supervivencia , Factores de Riesgo
10.
BMC Public Health ; 24(1): 1255, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714963

RESUMEN

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.


Asunto(s)
Neoplasias , Sistema de Registros , Humanos , Tailandia/epidemiología , Femenino , Masculino , Preescolar , Niño , Lactante , Incidencia , Adolescente , Neoplasias/mortalidad , Neoplasias/epidemiología , Recién Nacido , Tasa de Supervivencia , Análisis de Supervivencia
11.
PLoS Comput Biol ; 20(5): e1012024, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38717988

RESUMEN

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.


Asunto(s)
Biomarcadores de Tumor , Biología Computacional , Bases de Datos Genéticas , Internet , Neoplasias , Programas Informáticos , Humanos , Neoplasias/genética , Neoplasias/mortalidad , Análisis de Supervivencia , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biología Computacional/métodos , Pronóstico , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética
12.
Invest Ophthalmol Vis Sci ; 65(5): 10, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38709525

RESUMEN

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.


Asunto(s)
Fóvea Central , Atrofia Geográfica , Aprendizaje Automático , Tomografía de Coherencia Óptica , Humanos , Fóvea Central/patología , Fóvea Central/diagnóstico por imagen , Masculino , Femenino , Atrofia Geográfica/diagnóstico , Anciano , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Factores de Riesgo , Anciano de 80 o más Años , Agudeza Visual/fisiología , Estudios de Seguimiento , Angiografía con Fluoresceína/métodos , Incidencia , Persona de Mediana Edad , Análisis de Supervivencia
13.
Biometrics ; 80(2)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38708764

RESUMEN

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.


Asunto(s)
Modelos Estadísticos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Causalidad , Biometría/métodos , Resultado del Tratamiento , Simulación por Computador , Supervivencia sin Enfermedad , Análisis de Supervivencia
14.
BMC Med Inform Decis Mak ; 24(1): 120, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715002

RESUMEN

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.


Asunto(s)
Redes Neurales de la Computación , Humanos , Análisis de Supervivencia , Estadísticas no Paramétricas , Biología Computacional/métodos
15.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 233-241, 2024 Mar 14.
Artículo en Chino | MEDLINE | ID: mdl-38716594

RESUMEN

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.


Asunto(s)
Evaluación Geriátrica , Linfoma Folicular , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidad , Linfoma Folicular/terapia , Anciano , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Análisis de Supervivencia , Adulto , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
16.
Rev Col Bras Cir ; 51: e20243595, 2024.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-38716912

RESUMEN

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.


Asunto(s)
Técnicas de Cierre de Herida Abdominal , Laparotomía , Técnicas de Abdomen Abierto , Sepsis , Humanos , Masculino , Femenino , Sepsis/mortalidad , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Análisis de Supervivencia , Índice de Severidad de la Enfermedad , Adulto , Peritonitis/cirugía , Peritonitis/mortalidad , Peritonitis/etiología , Terapia de Presión Negativa para Heridas
17.
Pediatr Transplant ; 28(4): e14742, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38702926

RESUMEN

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.


Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Cardiopatías Congénitas , Trasplante de Corazón , Humanos , Niño , Masculino , Femenino , Preescolar , Lactante , Adolescente , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/patología , Rechazo de Injerto/patología , Rechazo de Injerto/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de Seguimiento , Cardiomiopatías/cirugía , Cardiomiopatías/patología , Reoperación , Recién Nacido , Análisis de Supervivencia
19.
BMC Oral Health ; 24(1): 519, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698358

RESUMEN

BACKGROUND: Oral cancer is a deadly disease and a major cause of morbidity and mortality worldwide. The purpose of this study was to develop a fuzzy deep learning (FDL)-based model to estimate the survival time based on clinicopathologic data of oral cancer. METHODS: Electronic medical records of 581 oral squamous cell carcinoma (OSCC) patients, treated with surgery with or without radiochemotherapy, were collected retrospectively from the Oral and Maxillofacial Surgery Clinic and the Regional Cancer Center from 2011 to 2019. The deep learning (DL) model was trained to classify survival time classes based on clinicopathologic data. Fuzzy logic was integrated into the DL model and trained to create FDL-based models to estimate the survival time classes. RESULTS: The performance of the models was evaluated on a test dataset. The performance of the DL and FDL models for estimation of survival time achieved an accuracy of 0.74 and 0.97 and an area under the receiver operating characteristic (AUC) curve of 0.84 to 1.00 and 1.00, respectively. CONCLUSIONS: The integration of fuzzy logic into DL models could improve the accuracy to estimate survival time based on clinicopathologic data of oral cancer.


Asunto(s)
Aprendizaje Profundo , Lógica Difusa , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/patología , Neoplasias de la Boca/mortalidad , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Análisis de Supervivencia , Anciano , Tasa de Supervivencia , Adulto
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