Prognostic nomogram for patients with advanced unresectable hepatocellular carcinoma treated with TAE combined with HAIC.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and often arises in the context of chronic liver disease, such as hepatitis B or C infection, and cirrhosis. Advanced unresectable HCC (uHCC) presents significant treatment challenges due to its advanced stage and inoperability. One efficient treatment method for advanced uHCC is the use of hepatic arterial infusion chemotherapy (HAIC) combined with transcatheter arterial embolization (TAE). Patients and Methods: In this study, we conducted a retrospective collection of clinical data, including basic information, radiological data, and blood test parameters, for patients with advanced uHCC who underwent TAE + HAIC treatment from August 2020 to February 2023. A total of 743 cases involving 262 patients were included. Ultimately, the covariates included in the analysis were the Child-Pugh score, extrahepatic metastasis, tumor number, tumor size, and treatment method. Results: In the study, we performed univariable and multivariable analysis on 23 clinical factors that were screened by LASSO regression, indicating that the five variables aforementionedly were identified as independent factors influencing patient prognosis. Then we developed a nomogram of the sensitive model and calculated concordance indices of prognostic survival models. Conclusion: Based on the uHCC patient cohort, we have developed a prognostic model for OS in patients who received TAE + HAIC treatment. This model can accurately predict OS and has the potential to assist in personalized clinical decision-making.

Molecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology.

OBJECTIVES: MET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC. MATERIALS AND METHODS: NSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences. Immune cell fractions were estimated from bulk RNA sequencing (quanTIseq). Real-world survival data (mOS) was calculated from insurance claims. Statistical analyses employed Chi-square, Fisher's exact, or Mann-Whitney U and log-rank tests and were corrected for hypothesis testing where applicable. RESULTS: A total of 711 METex14+ cases were detected. Of 575 cases of defined histology, 77 (13.6 %) were squamous (Sq), 474 (82.3 %) were nSq (non-squamous), and 24 (4.1 %) were adenosquamous. Mutations in POT1 and BRCA2 were enriched, and amplifications in MDM2, HMGA2, CDK4, and MET were common in METex14+ tumors. TMB-high and TP53 mutated tumors were reduced in METex14+ independent of histology. KEAP1 (2.1 vs 14.7 %) and STK11 mutations (0.8 vs 17.1 %) were reduced only in METex14+ nSq (vs METex14+ Sq, q < 0.05). While the prevalence of PD-L1 high tumors was enriched in METex14+ independent of histology, T-cell inflamed tumors were enriched only in nSq METex14+. B-cells and CD8+ T-cells (1.07-1.43-fold) were enriched in nSq METex14+, and dendritic cells (0.32 fold) were reduced only in METex14+ Sq. METex14+ tumors had a modest improvement in mOS compared to METex14- tumors (mOS = 22.9 m vs 18.6 m, HR = 0.914, p = 0.04). Moreover, METex14+ tumors who received immunotherapy (IO) had a modest improvement in survival (mOS = 27.5 m vs 21.8 m; HR = 0.803, p = 0.03) compared to those who did not receive IO. METex14+ nSq tumors were associated with improved mOS compared to METex14+ Sq tumors (mOS = 27.7 vs 8.9 m, HR = 0.493, p < 0.0001). CONCLUSION: METex14+ alterations are a heterogeneous subgroup of NSCLC. Our analysis reveals that METex14+ nSq exhibit improved survival compared to METex14+ Sq. The distinct genomic and transcriptomic variations across histologies warrant clinical consideration.

Breast cancer survival analysis in the Republic of Mauritius by age, stage at diagnosis and molecular subtype: A retrospective cohort study.

Breast cancer is by far the leading cancer both in terms of incidence and mortality in the Republic of Mauritius, a Small Island Developing State (SIDS). However, few studies assessed its survival by age, stage at diagnosis and molecular subtype. We identified 1399 breast cancer cases newly diagnosed between 2017 and 2020 at the Central Health Laboratory, Victoria Hospital. Cancers were categorized into five molecular subtypes: (1) luminal A, (2) luminal B Her2 negative, (3) luminal B Her2 positive, (4) Her2 enriched and (5) Triple negative. The net 1 and 3-year survival were estimated for different age groups, staging at time of diagnosis and molecular subtype. We also estimated the excess hazards using a multivariate Cox proportional hazards model. While early stage at diagnosis (stage 1 [44.4%] and stage 2 [20.1%]) were most common compared to late presentation (Stage 3 [25.4%] and stage 4 [10.1%]), luminal B Her2 negative (36.7%) was the most frequent molecular subtype. The net 1- and 3-year breast cancer survival rates were 93.9% (92.3-95.4) and 83.4% (80.4-86.4), respectively. Breast cancer three-year survival rates were poorest among the youngest patients (<50 years), 77.1% (70.7-83.5), those diagnosed with stage 4 (28.5% [17.1-39.9]) and cancer with a triple negative molecular subtype (71.3% [63.3-79.3]). Emphasis on a national breast cancer screening programme, down staging breast cancer at diagnosis and systematic molecular subtyping of all breast tissues could be pivotal in improving breast cancer survival outcomes in the Republic of Mauritius.

A unified web cloud computing platform MiMedSurv for microbiome causal mediation analysis with survival responses.

In human microbiome studies, mediation analysis has recently been spotlighted as a practical and powerful analytic tool to survey the causal roles of the microbiome as a mediator to explain the observed relationships between a medical treatment/environmental exposure and a human disease. We also note that, in a clinical research, investigators often trace disease progression sequentially in time; as such, time-to-event (e.g., time-to-disease, time-to-cure) responses, known as survival responses, are prevalent as a surrogate variable for human health or disease. In this paper, we introduce a web cloud computing platform, named as microbiome mediation analysis with survival responses (MiMedSurv), for comprehensive microbiome mediation analysis with survival responses on user-friendly web environments. MiMedSurv is an extension of our prior web cloud computing platform, named as microbiome mediation analysis (MiMed), for survival responses. The two main features that are well-distinguished are as follows. First, MiMedSurv conducts some baseline exploratory non-mediational survival analysis, not involving microbiome, to survey the disparity in survival response between medical treatments/environmental exposures. Then, MiMedSurv identifies the mediating roles of the microbiome in various aspects: (i) as a microbial ecosystem using ecological indices (e.g., alpha and beta diversity indices) and (ii) as individual microbial taxa in various hierarchies (e.g., phyla, classes, orders, families, genera, species). To illustrate its use, we survey the mediating roles of the gut microbiome between antibiotic treatment and time-to-type 1 diabetes. MiMedSurv is freely available on our web server ( http://mimedsurv.micloud.kr ).

Recipient functional status impacts on short and long-term intestinal transplant outcomes in United States adults.

BACKGROUND: Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart, liver and kidney transplants. However, information on how functional status, before and after transplant impacts post-transplant survival outcomes is lacking. AIM: To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults. METHODS: We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022. The primary outcome was mortality. Using the Karnofsky Performance Status, functional impairment was categorized as severe, moderate and normal. Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression. RESULTS: The median age was 41 years, majority (53.4%) were women. Severe impairment was present in 28.3% of recipients. The median survival time was 906.6 days. The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively. Recipients with severe impairment had a 56% higher risk of mortality at one year [Hazard ratio (HR) = 1.56; 95%CI: 1.23-1.98; P < 0.001] and 58% at five years (HR = 1.58; 95%CI: 1.24-2.00; P < 0.001) compared to patients with no functional impairment. Recipients with worse functional status after transplant also had poor survival outcomes. CONCLUSION: Pre- and post-transplant recipient functional status is an important prognostic indicator for short- and long-term intestinal transplant outcomes.

Multidisciplinary team meetings and their impact on survival in rectal cancer. Population-based analysis in Catalonia (Spain).

BACKGROUND: Multidisciplinary team meetings (MTMs) are considered a pillar of cancer care; however, evidence of the independent benefit of MTMs on survival in rectal cancer is controversial. METHODS: This population-based cohort analysis included patients undergoing surgery for primary rectal cancer with curative intent. We drew data derived from three clinical audits conducted in Catalonia from 2011 to 2020. The primary outcome was 2-year survival. Multivariable Cox regression analysis was used to assess the hazard ratio for death in patients whose cases were versus were not discussed in a preoperative MTM. RESULTS: A total of 5249 patients were included (66.1 % male, 58.3 % aged 60-79 years, 63.2 % receiving anterior resection): 4096 cases were discussed in a preoperative MTM, and 1153 were not. Multivariable Cox proportional hazards regression analysis showed that the MTM group had better survival than those with no preoperative MTM (hazard ratio 1.22, 95 % confidence interval 1.02-1.48), after adjusting for potential confounders. CONCLUSIONS: Preoperative MTM may be associated with improved survival in patients with rectal cancer in Catalonia. Efforts to ensure universal access to MTMs for all newly diagnosed patients should be supported.

Survival Analysis, Clinical Characteristics, and Predictors of Cerebral Metastases in Patients with Colorectal Cancer.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer globally and a leading cause of cancer-related deaths. While liver metastasis is common, brain metastasis (BM) is rare, occurring in 0.1% to 14% of cases. Risk factors for BM include lung metastasis at diagnosis, rectal cancer, and mutations in RAS and KRAS genes. Due to its rarity, guidelines for BM screening and treatment are limited. The aim of this study is to identify the clinical characteristics and predictors of BM at the time of the initial diagnosis of CRC. METHODS: We evaluated patients ≥18 years old with metastatic colorectal cancer and brain metastases at diagnosis from the SEER database (2010-2021). A retrospective cohort study was conducted to analyze overall survival and predictive factors for brain metastasis, utilizing multivariate logistic regression, Kaplan-Meier survival analysis, and the Cox proportional hazards models, with p-values < 0.05 considered significant. RESULTS: Out of 24,703 patients with metastatic colorectal cancer (mCRC), 228 (0.92%) had brain metastasis (BM) at diagnosis. BM was more prevalent in average-onset mCRC (≥50 years) compared to early-onset (<50 years) (1% vs. 0.55%, p = 0.004). Certain factors, such as older age and adenocarcinoma subtype, were associated with BM. Additionally, Asians/Pacific-Islanders (HR 1.83 CI: 1.01-3-33, p = 0.045) and American Indians/Alaska Natives (HR 4.79 CI 1.15-19.97, p = 0.032) had higher mortality rates, while surgical treatment and chemotherapy were linked to decreased mortality. Patients with BM had significantly worse overall survival (6 months vs. 21 months, p < 0.001). CONCLUSION: BM in mCRC is uncommon, but it is associated with significantly worse outcomes, including markedly reduced overall survival. Our study highlights several critical factors associated with the presence of BM, such as older age and specific racial/ethnic groups, which may inform risk stratification and early-detection strategies. Our findings emphasize the need for heightened awareness and screening for BM in high-risk mCRC patients, as well as the inclusion of these patients in clinical trials to explore tailored therapeutic approaches aimed at improving survival and quality of life.

Relevance, Risks, and Benefits of Early-Phases Clinical Trials Participations for Patients With Hematological Malignancies From 2008 to 2023.

BACKGROUND: Early-phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early-phases clinical trials participation for patients with hematological malignancies remain poorly evaluated. PATIENTS AND METHODS: All early-phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed. Patient's demographics, tumor type categories, therapeutic responses, mortality, overall survival (OS), and investigational product (IP) were assessed. RESULTS: Over the period 2008-2023, 736 patients participating in 92 different early-phases clinical trials, were analyzed. The most common tumor categories were diffuse large B-cell lymphoma (n = 253; 34.4%), acute myeloid leukemia/myelodysplastic syndrome (n = 164; 22.3%) and multiple myeloma (n = 100; 13.6%). The median OS was 14.8 (95% CI: 12.4-17.9) months and response rate 31.9%, including complete responses in 13.5% of patients. By tumor categories, the highest and lowest median duration of OS were observed for patients with Hodgkin lymphoma (99.8; [95% CI: 47.0-not reached] months) and peripheral T-cell lymphoma (8.9 [95% CI: 5.3-12.0] months), respectively. The on-protocol and treatment-related mortality rates were 5.43% and 0.54%, respectively. Overall response rate was 29.1% including 13.5% of complete response. Overall, 202 (27.5%) patients received an IP later approved by the health authorities, and those patients had better OS (18.2 months vs. 12.1 months HR: 1.160 [95% CI; 0.6977-1.391], p = 0.0283). CONCLUSION: In conclusion, patients with hematologic malignancies who have participated in early-phases clinical trials over the past 15 years have achieved variable therapeutic response rates, acceptable risk/benefit ratio and potentially significant therapeutic advantages. This study provides framework material for hematologists to further discuss clinical trial participation with their patients.

Food Consumption and Risk of Islet Autoimmunity and Type 1 Diabetes in Children at Increased Genetic Susceptibility for Type 1 Diabetes.

BACKGROUND: Prospective longitudinal evidence considering the entire childhood food consumption in relation to development of islet autoimmunity (IA or) type 1 diabetes is lacking. OBJECTIVES: We studied the associations of consumption of various foods and their combinations with IA and type 1 diabetes risk. METHODS: Children with genetic susceptibility to type 1 diabetes born in 1996-2004 were followed from birth up to 6 years of age in the prospective birth cohort Type 1 Diabetes Prediction and Prevention Study (n=5674). Exposure variables included 34 food groups covering the entire diet based on repeated 3-day food records at age 3 months to 6 years. Endpoints were islet cell antibodies (ICA) plus biochemical IA (n=247), multiple biochemical IA (n=206), and type 1 diabetes (n=94). We analyzed associations between longitudinally observed foods and the risk of IA/type 1 diabetes using a Bayesian approach to joint models in one-food and multi-food models adjusted for energy intake, sex, human leukocyte antigen (HLA) genotype, and familial diabetes. RESULTS: The final multi-food model for ICA plus biochemical IA included oats [hazard ratio (HR) 1.09, 95% credible interval (CI) 1.04-1.14], banana (HR 1.07, 95% CI 1.03-1.11), and cruciferous vegetables (HR 0.83, 95% CI 0.73-0.94). The final model for multiple biochemical IA included, in addition to above-mentioned foods, fermented dairy (HR 1.42, 95% CI 1.12-1.78) and wheat (HR 1.10, 95% CI 1.03-1.18). The final multi-food model for type 1 diabetes included rye (HR 1.27, 95% CI 1.07-1.50), oats (HR 1.15, 95% CI 1.03-1.26), fruits (HR 1.05, 95% CI 1.01-1.09), and berries (HR 0.67, 95% CI 0.50-0.93). CONCLUSIONS: Higher consumption of oats, gluten-containing cereals, and fruits was associated with increased and that of cruciferous vegetables with decreased risk of several type 1 diabetes related endpoints when considering all the foods in combination. Further etiological and mechanistic studies are warranted.

The short- and mid-term mortality trends in out-of-hospital cardiac arrest survivors: insights from a 5-year multicenter retrospective study in Taiwan.

Background: The survival trend and factors influencing short- and mid-term mortality in Asian out-of-hospital cardiac arrest (OHCA) survivors should be elucidated. We performed survival analyses on days 3 and 30, hypothesizing decreased survival rates within the initial 3 days post-resuscitation. Additionally, variables linked to mortality at these two timepoints were examined. Methods: We performed a retrospective analysis on adult nontraumatic OHCA survivors admitted to the National Taiwan University Hospital and its branches between 2017 and 2021. We collected the following variables from the NTUH-Integrative Medical Database: basic characteristics, cardiopulmonary resuscitation events, inotrope administration, and post-resuscitation management. The outcomes included 3- and 30-day mortality. Subgroup analyses with the Kaplan-Meier method explored the survival probability of the OHCA survivors and assessed differences in cumulative survival among subgroups. Cox proportional hazards model was used to estimate adjusted hazard ratios with 95% confidence interval. Results: Of the 967 survivors, 273 (28.2%) and 604 (62.5%) died within 3 and 30 days, respectively. The 30-day survival curve after OHCA showed an uneven decline, with the most significant decrease within the first 3 days of admission. Various risk factors influence mortality at 3- and 30-day intervals. Although increased age, noncardiac etiology, and prolonged low-flow time increased mortality risks, bystander CPR, targeted temperature management, and continuous renal replacement therapy were associated with reduced mortality at 3- and 30-day timeframes. Conclusion: Survival declined in most OHCA survivors within 3 days post-resuscitation. The risk factors associated with mortality at 3- and 30-day intervals varied in this population.

Delta radiomics to track radiation response in lung tumors receiving stereotactic magnetic resonance-guided radiotherapy.

Background and purpose: Lung cancer is a leading cause of cancer-related mortality, and stereotactic body radiotherapy (SBRT) has become a standard treatment for early-stage lung cancer. However, the heterogeneous response to radiation at the tumor level poses challenges. Currently, standardized dosage regimens lack adaptation based on individual patient or tumor characteristics. Thus, we explore the potential of delta radiomics from on-treatment magnetic resonance (MR) imaging to track radiation dose response, inform personalized radiotherapy dosing, and predict outcomes. Materials and methods: A retrospective study of 47 MR-guided lung SBRT treatments for 39 patients was conducted. Radiomic features were extracted using Pyradiomics, and stability was evaluated temporally and spatially. Delta radiomics were correlated with radiation dose delivery and assessed for associations with tumor control and survival with Cox regressions. Results: Among 107 features, 49 demonstrated temporal stability, and 57 showed spatial stability. Fifteen stable and non-collinear features were analyzed. Median Skewness and surface to volume ratio decreased with radiation dose fraction delivery, while coarseness and 90th percentile values increased. Skewness had the largest relative median absolute changes (22 %-45 %) per fraction from baseline and was associated with locoregional failure (p = 0.012) by analysis of covariance. Skewness, Elongation, and Flatness were significantly associated with local recurrence-free survival, while tumor diameter and volume were not. Conclusions: Our study establishes the feasibility and stability of delta radiomics analysis for MR-guided lung SBRT. Findings suggest that MR delta radiomics can capture short-term radiographic manifestations of the intra-tumoral radiation effect.

Updated review on pulmonary arterial hypertension: Differences between down syndrome and non-down syndrome populations.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a major concern in patients with Down syndrome (DS) and congenital heart disease (CHD). Understanding the unique characteristics of PAH in these populations is essential for developing tailored management strategies. This review examines differences in PAH between DS and non-DS (nDS) patients with CHD, focusing on pathophysiology, clinical presentation, hemodynamic profiles, and treatment outcomes. METHODS: A retrospective analysis of 93 adults with PAH was conducted, including 18 with DS and 75 with CHD but without DS (nDS). Data on demographics, clinical presentations, comorbidities, and hemodynamic parameters were collected using echocardiography and right heart catheterization. Statistical analyses included Mann-Whitney U tests, Student's t-tests, and Kaplan-Meier survival analysis to compare the DS and nDS groups. RESULTS: DS patients presented with PAH at a younger age (mean age 25.06 years) compared to nDS patients (mean age 42.4 years; p < 0.001). Hypothyroidism was more prevalent in DS patients (61.1 %) than in nDS patients (29.3 %; p = 0.012). Hemodynamic assessments showed lower mean arterial pressure (MAP) in DS patients (76.24 ± 11.6 mmHg) versus nDS patients (93.95 ± 15 mmHg; p < 0.001), and a higher TAPSE/PASP ratio (0.41 vs. 0.23; p = 0.009), suggesting less severe right ventricular dysfunction. DS patients had a significant survival advantage over nDS patients (p = 0.043). CONCLUSIONS: DS patients have distinct clinical and hemodynamic profiles in PAH, requiring personalized management. Early detection and tailored treatment are crucial for improving outcomes. Further research should refine these strategies and explore new therapies.

An excessive weight loss percentage over the two years before treatment is an independent prognostic factor for operated patients with advanced oral squamous cell carcinoma.

The aim of this study was to assess the prognostic value of the weight loss percentage (WLP) over the 2 years pre-treatment for operated patients with advanced oral squamous cell carcinoma (OSCC). This cohort study included 506 operated patients who were diagnosed with advanced primary OSCC between October 2001 and March 2022, and who were followed up until July 2022. Fine-Gray models, marginal structural models with stabilized inverse probability of treatment weighting, and Cox proportional hazards models were utilized to evaluate the prognostic significance of pre-treatment WLP for disease-specific survival (DSS). The median follow-up time was 32.6 months (interquartile range 13.0-71.6 months). A high pre-treatment WLP (>9.23%) was significantly associated with worse DSS (multivariate Fine-Gray model: hazard ratio (HR) 2.04, 95% confidence interval (CI) 1.29-3.22, P = 0.002; multivariate Cox: HR 2.01, 95% CI 1.28-3.16, P = 0.002). In the weighted cohort, a similar association pattern was observed (marginal structural model: HR 2.26, 95% CI 1.28-3.98, P = 0.005; multivariate Cox: HR 2.28, 95% CI 1.38-3.76, P = 0.001). In subgroup analyses, high WLP could predict worse DSS among patients with buccal mucosa/other cancer sites (not including the oral tongue), moderate tumor differentiation, and larger cancer size (>1.8 cm) (all P < 0.05). Pre-treatment WLP over 2 years might be a useful tool to predict the prognosis of operated patients with advanced OSCC.

Is Lycorma delicatula (Hemiptera: Fulgoridae) a blooming threat to citrus?

Examining the host range of emerging invasive insects is essential to assess their invasion potential and to anticipate the negative impacts of their spread. The ongoing North American invasion of spotted lanternfly (SLF) [Lycorma delicatula (White, 1845)] threatens agricultural, urban, and natural areas. The survival and development of SLF nymphs on Washington navel orange [Citrus sinensis (L.) Osbeck (Sapindales: Rutaceae)] trees were assessed in a quarantine facility. Results indicated that SLF nymphs can develop to at least the third instar by feeding exclusively on Washington navel orange. This finding suggests that, at least up to the third stage of nymphal development, Washington navel orange might be a suitable host for SLF, highlighting the possibility that this invasive pest represents an unrecognized threat to this globally important crop and possibly to other Citrus species.

Integrating amyloid imaging and genetics for early risk stratification of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) initiates years prior to symptoms, underscoring the importance of early detection. While amyloid accumulation starts early, individuals with substantial amyloid burden may remain cognitively normal, implying that amyloid alone is not sufficient for early risk assessment. METHODS: Given the genetic susceptibility of AD, a multi-factorial pseudotime approach was proposed to integrate amyloid imaging and genotype data for estimating a risk score. Validation involved association with cognitive decline and survival analysis across risk-stratified groups, focusing on patients with mild cognitive impairment (MCI). RESULTS: Our risk score outperformed amyloid composite standardized uptake value ratio in correlation with cognitive scores. MCI subjects with lower pseudotime risk score showed substantial delayed onset of AD and slower cognitive decline. Moreover, pseudotime risk score demonstrated strong capability in risk stratification within traditionally defined subgroups such as early MCI, apolipoprotein E (APOE) ε4+ MCI, APOE ε4- MCI, and amyloid+ MCI. DISCUSSION: Our risk score holds great potential to improve the precision of early risk assessment. HIGHLIGHTS: Accurate early risk assessment is critical for the success of clinical trials. A new risk score was built from integrating amyloid imaging and genetic data. Our risk score demonstrated improved capability in early risk stratification.

Association between Higher Expression of Vav1 in Hepatocellular Carcinoma and Unfavourable Clinicopathological Features and Prognosis.

OBJECTIVE: The aim was to investigate the potential relationship between Vav1 protein and prognosis in patients with hepatocellular carcinoma (HCC). METHODS: Samples were collected from 96 patients with HCC. For each patient, cancerous tissue and adjacent non-cancerous tissue were obtained. The Vav1 expression levels in these tissues were determined using immunohistochemistry. Chi-square and Fisher's exact tests were used to analyse the associations between Vav1 expression and clinicopathological characteristics. Kaplan- Meier analysis was used to assess the relationship between Vav1 expression and 5-year overall survival (OS). RESULTS: The expression level of Vav1 protein in primary tumour samples (64.46%; 59/96) was higher (33.33%; 32/96; P<0.001). Moreover, the high expression rate of Vav1 was correlated with tumour differentiation, TNM stage, and tumour recurrence (P<0.05). Univariate and multivariate Cox analysis further demonstrated that tumour differentiation, TNM stage, vascular invasion, tumour recurrence and Vav1 expression were independent prognostic factors for 5-year OS. Notably, follow-up analysis determined that patients with HCC with higher Vav1 expression levels have lower survival rates (P<0.05). CONCLUSION: Vav1 may serve as a promising molecular prognostic biomarker for patients diagnosed with HCC.

A Network-Constrain Weibull AFT Model for Biomarkers Discovery.

We propose AFTNet, a novel network-constraint survival analysis method based on the Weibull accelerated failure time (AFT) model solved by a penalized likelihood approach for variable selection and estimation. When using the log-linear representation, the inference problem becomes a structured sparse regression problem for which we explicitly incorporate the correlation patterns among predictors using a double penalty that promotes both sparsity and grouping effect. Moreover, we establish the theoretical consistency for the AFTNet estimator and present an efficient iterative computational algorithm based on the proximal gradient descent method. Finally, we evaluate AFTNet performance both on synthetic and real data examples.

Interleukin 16 and 25 (IL-17E) and Clinical Outcomes in Exacerbation of COPD-A Pilot Study.

Background: Exacerbation of chronic obstructive pulmonary disease (ECOPD) significantly impact health status, hospitalization rates, and disease progression, and are linked to increased mortality. Predictive factors for ECOPD are therefore of considerable interest. The limited understanding of interleukin 16 (IL-16) and IL-25 role in ECOPD provided the rationale for this study. Methods: Fifty ex-smokers diagnosed with COPD (22 ECOPD and 28 patients in the stable phase of the disease) underwent prospective analysis to evaluate the role of I IL-25 as predictive markers of clinical outcomes in ECOPD. Results: We observed a significantly lower IL-16 and higher IL-25 concentrations among ECOPD patients (p = 0.002 and p = 0.01 respectively). We also detected a significant negative correlation between IL-16 and neutrophil-to-lymphocyte ratio (NLR) (p = 0.04) and a significant negative correlation between IL-25 concentration and absolute eosinophil count (p = 0.04). In the entire group, we observed a positive correlation between IL-16 and both FEV1 and FVC, both expressed as a percentage of reference value, (p = 0.002 and p = 0.0004 respectively). However, after stratification to ECOPD and stable COPD group, significance maintained for FVC (p = 0.045 for ECOPD and p = 0.02 for stable COPD). In survival analysis, we detected significantly lower all-cause mortality for 3rd tertile of IL-16 concentrations, with a hazard ratio of 0.33 (95%CI: 0.11-0.98; p = 0.04). Conclusions: Lower IL-16 levels among ECOPD patients may indicate a feedback mechanism linked to heightened Th1 response activation. Observed correlations with ventilatory parameters and survival also seems to reflect this mechanism. The higher IL-25 concentrations observed in ECOPD patients, along with the negative correlation with absolute eosinophil count and eosinopenia, suggest multifactorial regulation and independent functions of eosinophils and IL-25. Hypothetically, this paradox may be related to the Th1/Th2 imbalance favoring Th1 response. Obtained results should be reproduced in larger size samples.

Bayesian identification and estimation of radon-related increased hazard rates of cancer death in the updated French cohort of uranium miners (1946-2014).

OBJECTIVE: A recent update of the French cohort of uranium miners added seven years of follow-up data. We use these new data to look for new possible radon-related increased risks and refine the estimation of the potential association between cumulative radon exposure and four cancer sites: lung cancer, kidney cancer, brain and central nervous system (CNS) cancer and leukemia (excluding chronic lymphocytic leukemia, which is not radiation-induced). METHODS: Several parametric survival models are proposed, fitted and compared under the Bayesian paradigm, to perform new and original exposure-risk analyses. In line with recent UNSCEAR recommendations, we consider time-related effect modifiers and exposure rate as potential effect modifying factors. We use Bayesian model selection criteria to identify radon-related increased hazard rates. RESULTS: Under the assumption of a linear exposure-risk relationship, we found a substantial evidence for a strictly positive effect of cumulative radon exposure on the hazard rate of death by lung cancer among French uranium miners. Given the current available data under the assumptions of a linear or log-linear exposure-risk relationship, it is not possible to conclude in favour of the absence or the existence of a strictly positive effect of chronic exposure to radon on the hazard rate of death by kidney cancer. Regarding death by brain and CNS cancer, there is a substantial evidence for the absence of radon-related effect. Finally, under the assumption of a log-linear exposure-risk relationship, a small positive radon-related effect appears when looking at the risk of death by leukemia (excluding CLL). CONCLUSION: This study investigates the existence of radon-related increased risk of death by lung cancer, kidney cancer, brain and CNS cancer and leukemia under a Bayesian framework and assumptions of linear and log-linear exposure-risk relationships. If there is no doubt in the interpretation of the results for lung cancer and brain and CNS cancer, the conclusion is less clear-cut in the case of kidney cancer and leukemia (excluding CLL). A future update of the French cohort, increasing the follow-up time for miners, may help to reach a clearer conclusion for these two cancer sites.

Four-year Outcomes of Class III and IV Anterior Restorations Based on a Subset of German Health Insurance Data.

PURPOSE: Numerous studies report on the outcome performance of posterior composite restorations. However, there are fewer studies providing data for anterior restorations. The aim of this study was to evaluate the clinical outcome performance of anterior permanent restorations by analyzing a large dataset from a German national health insurance company. MATERIALS AND METHODS: Routine claims data from a major German national health insurance company were assessed. Fee codes were used for tracing restoration careers on a day-count basis. The treatment was defined as a placed restoration (Class III and IV) on a mesial or distal tooth surface, irrespective of the extension. The restorations were placed between January 1, 2010 and December 31, 2013. Statistical analyses were conducted using Kaplan-Meier survival analysis to determine cumulative 4-year survival rates. The primary outcome was re-intervention on the same surface. Secondary outcomes were crowning and extraction which were analyzed separately. RESULTS: A total of 2,417,791 restorations involving mesial surfaces and a number of 2,409,031 restorations involving distal surfaces were observed. At 4 years, the cumulative survival rates concerning the primary outcome 're-intervention' were 79.9% for mesial and 80.9% for distal restorations. The respective annual failure rates (AFR) were 5.5% and 5.2%. Four-year survival rates for the secondary outcome 'crown' were 93.8% for mesial and 94.1% for distal anterior restorations. The respective AFRs were 1.6% and 1.5%. For the secondary outcome 'extraction,' the respective rates were 94.6% for mesial and 93.9% for distal restorations. The respective AFRs were 1.4% and 1.6%. CONCLUSION: The performance of permanent anterior restorations which were placed in general dental practices in Germany can be rated as acceptable.