Survival Status Of Patients Research Articles

Mitochondria-Related TFAM and POLG Gene Variants and Associations with Tumor Characteristics and Patient Survival in Head and Neck Cancer.

In 2020, 878,348 newly reported cases and 444,347 deaths related to head and neck cancer were reported. These numbers suggest that there is still a need for molecular biomarkers for the diagnosis and prognosis of the disease. In this study, we aimed to analyze mitochondria-related mitochondrial transcription factor A (TFAM) and DNA polymerase γ (POLG) single-nucleotide polymorphisms (SNPs) in the head and neck cancer patient group and evaluate associations between SNPs, disease characteristics, and patient outcomes. Genotyping was performed using TaqMan probes with Real-Time polymerase chain reaction. We found associations between TFAM gene SNPs rs11006129 and rs3900887 and patient survival status. We found that patients with the TFAM rs11006129 CC genotype and non-carriers of the T allele had longer survival times than those with the CT genotype or T-allele carriers. Additionally, patients with the TFAM rs3900887 A allele tended to have shorter survival times than non-carriers of the A allele. Our findings suggest that variants in the TFAM gene may play an important role in head and neck cancer patient survival and could be considered and further evaluated as prognostic biomarkers. However, due to the limited sample size (n = 115), further studies in larger and more diverse cohorts are needed to confirm these findings.

The relationship between tumor infiltrating immune cells and the prognosis of patients with lung adenocarcinoma.

To depict the immune infiltration characteristics of tumor cells in patients with lung adenocarcinoma (LUAD) and evaluate the predictive value and significance of tumor immune cells on the prognosis of LUAD patients. The clinical characteristics and transcriptome of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), and the immune cell abundance in LUAD tissue was evaluated using the CIBERSORT algorithm. We created a simplified immune cell-based Cox regression model according to the survival status of patients and clarified the correlation between the survival status of patients and seven types of immune cells. An immune cell-based risk prediction model was created by Cox proportional hazards regression. Subsequently, the gene expression profile of LUAD patients was obtained from the Gene Expression Omnibus (GEO) database to validate the tumor immune infiltration and patient prognosis prediction model attained using the CIBERSORT algorithm. The abundance of 22 tumor-infiltrating immune cells in these patients was detected using the CIBERSORT algorithm. According to Pearson correlation analysis, the immune cells appeared to be closely related to each other. The immune cell composition was remarkably different between the LUAD tumor tissue and paracancerous tissue. The simplified COX model showed that seven kinds of immune cells have predictive value for the prognosis and survival status of LUAD. The receiver operating characteristic curve (ROC) curve confirmed that the prediction model performed well for 1-, 3-, and 5-year survival status. The calibration curve suggested that the prediction model was consistent with the clinical results. Correlation analysis revealed that the clinical features were significantly related to immune cell infiltration. A total of 246 LUAD specimens were from the GEO database, and the risk score model suggested that high risk scores were indicative of a poor prognosis. Finally, enzyme-linked immunosorbent assay (ELISA) revealed that the expressions of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), IL-6, and interferon-γ (IFN-γ) in tumor tissues were remarkably higher compared with those in adjacent tissues. There is a close correlation between the tumor-infiltrating immune cells and the prognosis and clinical characteristics of LUAD patients. The risk score model based on TCGA and GEO designed in this study can be applied in clinical practice.

Survival Analysis and Its Predictors Among Hemodialysis Patients at Saint Paul Hospital Millennium Medical College and Myungsung Christian Medical Center in Addis Ababa, Ethiopia, 2021.

Diabetes mellitus and hypertension are the most prominent conditions causing chronic kidney disease and eventually end-stage renal disease. Renal replacement therapy, particularly hemodialysis (HD), is the mainstay of treatment. The aim of this study is to assess the overall survival status of HD patients and potential survival predictors at Saint Paul hospital millennium medical college (SPHMMC) and Myungsung Christian Medical Center (MCM) in Addis Ababa, Ethiopia. A retrospective cohort study was conducted on HD patients at SPHMMC and MCM general hospital from January 1, 2013 to December 30, 2020. Kaplan Meier, Log-rank, and Cox proportional regression models were used for the analysis. Estimated risks were reported as hazard ratios with 95% confidence intervals and P<0.05 was considered as having a significant association. A total of 128 patients were included in the study. Median survival time was 65 months. The predominant co-morbid condition was found to be diabetes mellitus with hypertension (42%). The total risk time for these patients was 143,617 person years. The overall incidence rate of death was 2.9 per 10,000 person years (95% CI=2.2-4). Patients who developed blood stream infection were 2.98-times more likely to die than those without infection. Those using an arteriovenous fistula were 66% less likely to die than those using a central venous catheter. Additionally, patients treated in a government-owned facility were 79% less likely to die. The study identified that the median survival time of 65 months was comparable with developed nations. Significant predictors of death were found to be blood stream infection and type of vascular access. Government-owned treatment facilities showed better patient survival.

Implications of Extra-cardiac Disease in Patient Selection for Heart Transplantation: Considerations in Cardiac Amyloidosis.

Disease-modifying therapies in both light chain and transthyretin amyloidosis have improved patient functional status and survival. Conceivably, as heart failure may progress despite amyloid therapies, more patients may be considered for heart transplantation. In earlier eras, extra-cardiac amyloid deposits significantly reduced post-heart transplant patient survival and functional status compared to the non-amyloid population. In the modern era, transplant centres have reported improved outcomes in amyloidosis as patient selection has grown more stringent. Importantly, systematic candidate evaluation should assess the degree of extra-cardiac involvement, the effectiveness of disease-modifying therapies and downstream effects on patients' nutrition and frailty. This review outlines such an overall approach while also considering that organ-specific selection criteria may vary between individual transplant centres. A methodical approach to patient evaluation will promote better understanding of the prevalence and severity of extra-cardiac disease in amyloidosis patients referred for heart transplantation and of any disparities in decision outcomes in this population.

Association of Neutrophil-to-Lymphocyte Ratio and Bloodstream Infections with Survival after Curative-Intent Treatment in Elderly Patients with Oral Cavity Squamous Cell Carcinoma.

Patients with oral cavity squamous cell carcinoma (OSCC) undergoing curative-intent treatment may become immunocompromised. This study aimed to investigate the association of pretreatment sarcopenia, nutritional status, comorbidities, and blood-based inflammation prognostic biomarkers in bloodstream infection (BSI) with survival status in elderly patients with OSCC. Retrospective data were collected from 235 patients who were newly diagnosed with OSCC, were aged ≥ 65 years, had undergone curative-intent treatment, and were classified into either the BSI group or the no-BSI group within 6 months after surgery and/or adjuvant therapy initiation. Of the 235 elderly patients, 27 presented with BSI episodes. A preoperative high neutrophil-to-lymphocyte ratio (NLR) was a significant independent risk factor for BSI. BSI was not significantly associated with survival status. Ever betel nut chewing, hypoalbuminemia, and advanced tumor stage were associated with shorter overall survival. Moreover, a high NLR was an independent risk factor associated with disease-free survival. A high NLR was associated with BSI and resistance to curative-intent treatment. Pretreatment of NLR could act as an independent prognostic indicator and help inform treatment strategies for older patients with OSCC.

Survival analysis of early-onset locally advanced rectal cancer: a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database

Objective: To investigate the factors influencing tumor-specific survival of early-onset locally advanced rectal cancer. Methods: All-age patients with primary locally advanced rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2019) were included in this study. Early- and late-onset locally advanced rectal cancer was defined according to age of 50 years at diagnosis. Early-onset locally advanced rectal cancer was divided into five age groups for subgroup analyses. Age, sex, tumor-specific survival time and survival status of patients at diagnosis, pathological grade, TNM stage, perineural invasion, tumor deposits, tumor size, pretreatment CEA , radiotherapy, chemotherapy, and number of lymph node dissections were included. Progression-free survival (PFS) was analyzed and compared between patients with early- and late-onset rectal cancer. Results: A total of 5,048 patients with locally advanced rectal cancer were included in the study (aged 27-70 years): 1,290 (25.55%) patients with early-onset rectal cancer and 3,758 (74.45%) patients with late-onset rectal cancer. Patients with early-onset rectal cancer had a higher rate of perineural invasion (P<0.001), more positive lymph nodes dissected (P<0.001), higher positive lymph node ratios (P<0.001), and a higher proportion receiving preoperative radiotherapy (P=0.002). Patients with early-onset rectal cancer had slightly better short-term survival than those with late-onset rectal cancer (median (IQR ): 54 (33-83) vs 50 (31-79) months, χ2=5.192, P=0.023). Multivariate Cox regression for all patients with locally advanced rectal cancer showed that age (P=0.008), grade of tumor differentiation (P=0.002), pretreatment CEA (P=0.008), perineural invasion (P=0.021), positive number (P=0.004) and positive ratio (P=0.001) of dissected lymph nodes, and sequence of surgery and radiotherapy (P=0.005) influenced PFS. This suggests that the Cox regression results for all patients may not be applicable to patients with early-onset cancer. Cox analysis showed tumor differentiation grade (patients with low differentiation had a higher risk of death, P=0.027), TNM stage (stage III patients had a higher risk of death, P=0.025), T stage (higher risk of death in stage T4, P<0.001), pretreatment CEA (P=0.002), perineural invasion (P<0.001), tumor deposits (P=0.005), number of dissected lymph nodes (patients with removal of 12-20 lymph nodes had a lower risk of death, P<0.001), and positive number of dissected lymph nodes (P<0.001) were independent factors influencing PFS of patients with early-onset locally advanced rectal cancer. Conclusion: Patients with early-onset locally advanced rectal cancer were more likely to have adverse prognostic factors, but an adequate number of lymph node dissections (12-20) resulted in better survival outcomes.

A machine learning model for predicting the three-year survival status of patients with hypopharyngeal squamous cell carcinoma using multiple parameters.

This study aimed to establish a model for predicting the three-year survival status of patients with hypopharyngeal squamous cell carcinoma using artificial intelligence algorithms. Data from 295 patients with hypopharyngeal squamous cell carcinoma were analysed retrospectively. Training sets comprised 70 per cent of the data and test sets the remaining 30 per cent. A total of 22 clinical parameters were included as training features. In total, 12 different types of machine learning algorithms were used for model construction. Accuracy, sensitivity, specificity, area under the receiver operating characteristic curve and Cohen's kappa co-efficient were used to evaluate model performance. The XGBoost algorithm achieved the best model performance. Accuracy, sensitivity, specificity, area under the receiver operating characteristic curve and kappa value of the model were 80.9 per cent, 92.6 per cent, 62.9 per cent, 77.7 per cent and 58.1 per cent, respectively. This study successfully identified a machine learning model for predicting three-year survival status for patients with hypopharyngeal squamous cell carcinoma that can offer a new prognostic evaluation method for the clinical treatment of these patients.

Identification of immunocell infiltrates and effective diagnostic biomarkers in laryngeal carcinoma.

Laryngeal cancer (LC) is a malignant tumor that occurs in the head and neck. Laryngeal cancer is one of the most common cancers of the neck and head, and its prognosis has always been poor. The incidence of LC increased gradually and showed an early rising trend. Laryngeal cancer is rarely studied in relation to immunity, Malignant tumors will change the state of the human body in various ways to adapt to their own survival and avoid the immune system. This study aims to explore the immune molecular mechanism of laryngeal cancer through bioinformatics analysis. The gene expression data was downloaded for 3 microarray datasets: GSE27020, GSE59102, and GSE51985. CIBERSORT algorithm was performed to evaluate immune cell infiltration in tissues between LC and healthy control (HC). Differentially expressed genes (DEGs) were screened. Functional correlation of DEGs were analyzed by Gene Ontology, Gene Set Enrichment Analysis and Kyoto encyclopedia of genes and genomes. Candidate biomarkers were identified by cytoHubba of Cytoscape. Spearman correlations between the above biomarkers and infiltrating immune cells were explored using R software analysis. The immune cell types of LC and HC were significantly different. Twenty-one DEGs were obtained by cross-screening. The function of DEGs is closely related to the number of immune cells. Five central genes (TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4) were screened. The HUB gene was demonstrated to have the ability to diagnose LC and HC with good specificity and sensitivity. The correlation between immune cells and biomarkers showed that hub gene was positively correlated with macrophages and dendritic cells, and negatively correlated with CD4 + T cell. TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4 can be used as diagnostic biomarker for LC. Macrophages, dendritic cells and CD4 + T cell may participate in the occurrence and development of LC.

Study on HBV-related acute-on-chronic liver failure risk factors and novel predictive survival model

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.

Expression and function of myelin expression factor 2 in hepatocellular carcinoma

IntroductionHepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world and has a high mortality rate. However, the pathogenesis of HCC remains unclear. This study aimed to investigate the potential biomarkers of HCC.MethodsONCOMINE, HCCDB and THE HUMAN PROTEIN ATLAS were used to identify myelin expression factor 2 (MYEF2) as a potential biomarker for HCC. The Cancer Genome Atlas database was used to further validate and analyse the value of MYEF2. Kaplan–Meier Plotter was used for the prognostic analysis. The COX regression model and Kaplan–Meier method were used to investigate the clinical value of MYEF2 in the prognosis of HCC by reviewing the survival status of patients. Fluorescent quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to detect the expressions of the MYEF2 mRNA and protein in HCC tissues and cell lines. qPCR and Western blotting were used to validate the efficiency of MYEF2 knockout and overexpression in HCC cells. The invasion and migration abilities regulated by MYEF2 were detected by performing transwell and wound healing assays.ResultsMYEF2 is significantly upregulated in HCC and is mainly located in the nucleus of HCC cells. MYEF2 expression is significantly associated with the tumour stage, histological grade and TNM stage. High MYEF2 expression is an independent prognostic factor for patients with HCC. Functionally, elevated MYEF2 facilitated cell migration and invasion in vitro. In contrast, decreased MYEF2 inhibited cell migration and invasion.ConclusionsMYEF2 may be a novel biomarker with potential diagnosis and prognosis values and as a potential therapeutic target for HCC.

High-intensity mechanical bowel preparation before curative colorectal surgery is associated with poor long-term prognosis.

Mechanical bowel preparation (MBP) has been widely used to reduce intestinal feces and bacteria and is considered necessary to prevent surgical infections. However, it is still controversial which intensity level of MBP is the most beneficial for patients before colorectal surgery. Our study aimed to determine the impact of different intensity levels of MBP on the progression-free survival (PFS) and overall survival (OS) for colorectal cancer (CRC) patients. We evaluated 694 patients pathologically diagnosed with CRC and underwent MBP before surgery at 4 general hospitals from January 2011 to December 2015. The survival status of patients, the disease progression, and the time of death or progression were obtained through telephone follow-up at the deadline October 10, 2018. Hazard ratios were estimated by Cox proportional hazard models. Survival was assessed using the Kaplan-Meier method followed by the log-rank test. Of 694 patients included, 462 received low-intensity MBP and 232 received high-intensity MBP. A significantly higher PFS in low-intensity MBP was observed (p = 0.009). PFS at 2000days was 69.331% in the low-intensity arm and 58.717% in the high-intensity arm. Patients who underwent low-intensity MBP also showed higher OS (p = 0.009). Nine patients in the low-intensity MBP group received secondary surgery, and two patients in the high-intensity MBP group received secondary surgery. In this retrospective cohort, low-intensity MBP was associated with better PFS and OS, which could provide a reference for doctors when choosing the intensity of MBP.

Establishment of prognostic models of adrenocortical carcinoma using machine learning and big data.

Adrenocortical carcinoma (ACC) is a rare malignant tumor with a short life expectancy. It is important to identify patients at high risk so that doctors can adopt more aggressive regimens to treat their condition. Machine learning has the advantage of processing complicated data. To date, there is no research that tries to use machine learning algorithms and big data to construct prognostic models for ACC patients. Clinical data of patients with ACC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. These records were screened according to preset inclusion and exclusion criteria. The remaining data were applied to univariate survival analysis to select meaningful outcome-related candidates. Backpropagation artificial neural network (BP-ANN), random forest (RF), support vector machine (SVM), and naive Bayes classifier (NBC) were chosen as alternative algorithms. The acquired cases were grouped into a training set and a test set at a ratio of 8:2, and a 10-fold cross-validation method repeated 10 times was performed. Area under the receiver operating characteristic (AUROC) curves were used as indices of efficiency. The calculated 1-, 3-, 5-, and 10-year overall survival rates were 62.3%, 42.0%, 34.9%, and 26.1%, respectively. A total of 825 patients were included in the study. In the training set, the AUCs of BP-ANN, RF, SVM, and NBC for predicting 1-year survival status were 0.921, 0.885, 0.865, and 0.854; those for predicting 3-year survival status were 0.859, 0.865, 0.837, and 0.831; and those for 5-year survival status were 0.888, 0.872, 0.852, and 0.841, respectively. In the test set, AUCs of these four models for 1-year survival status were 0.899, 0.875, 0.886, and 0.862; those for 3-year survival status were 0.871, 0.858, 0.853, and 0.869; and those for 5-year survival status were 0.841, 0.783, 0.836, and 0.867, respectively. The consequences of the 10-fold cross-validation method repeated 10 times indicated that the mean values of 1-, 3-, and 5-year AUROCs of BP-ANN were 0.890, 0.847, and 0.854, respectively, which were better than those of other classifiers (P < 0.008). The model combined with BP-ANN and big data can precisely predict the survival status of ACC patients and has the potential for clinical application.

Five-Year Prognosis Model of Esophageal Cancer Based on Genetic Algorithm Improved Deep Neural Network

ObjectivesEsophageal cancer is a high occult malignant tumor. Even with good diagnosis and treatment, the 5-year survival rate of esophageal cancer patients is still less than 30%. Considering the influence of clinical characteristics on postoperative esophageal cancer patients, the construction of a neural network model will help improve the poor prognosis of patients in the five years. Material and methodsIn this study, genetic algorithm optimized deep neural network is exploited to the clinical dataset of esophageal cancer. The independent prognostic factors are screened by Relief algorithm and Cox proportional risk regression. FTD prognostic staging system is established to assess the risk level of esophageal cancer patients. ResultsFTD staging system and independent prognostic factors are integrated into the genetic algorithm optimized deep neural network. The Area Under Curve (AUC) of FTD staging system is 0.802. FTD staging system is verified by the Kaplan-Meier survival curve, and the median survival time is divided for different risk grades. The FTD staging system is superior to the TNM stages in the prognosis effect. The AUC of deep neural network optimized by genetic algorithm is 0.91. ConclusionThe deep neural network optimized by genetic algorithm has good performance in predicting the 5-year survival status of esophageal cancer patients. The FTD staging system has a significant prognostic effect. The FTD staging system and genetic algorithm optimized deep neural network can be successfully availed in clinical diagnosis and treatment.

Survival analysis and predictors of mortality among adult HIV/AIDS patients initiated antiretroviral therapy from 2010 to 2015 in Dubti General Hospital, Afar, Ethiopia: A retrospective cohort study

BackgroundAlthough antiretroviral therapy (ART) is well accepted to increase survival of patients with HIV/AIDS, AIDS related deaths continue to be a major problem in sub-Saharan Africa like Ethiopia. Studies have showed variable findings in the survival status of patients with HIV/AIDS initiating ART, and there was no such study in the study area. Therefore, purpose of this study was to determine the survival and predictors of mortality among HIV/AIDS patients starting taking ART in Dubti General Hospital, Afar, Ethiopia. MethodsA 5 year retrospective cohort study was performed among 702 HIV/AIDS patients aged ≥15 years that started ART between December 31, 2010, and December 31, 2015 in Dubti General Hospital, Afar, Ethiopia. A simple random sampling technique was used to select the study subjects from each WHO stage based stratum. Socio-demographic, clinical and survival status data were extracted by reviewing patients’ records. Data were analyzed by using SPSS Version 21. Kaplan-Meier and Cox-regression models were used to estimate survival, and explore predictors of mortality. Variables with a p value of <0.05 in multivariate Cox regression analysis were considered statistically significant. ResultsAmong 702 study participants, 82 (11.7%) died during follow up, and the overall incidence rate of mortality was 5.81 per 100 person-years. Identified predictors of mortality were being not married (AHR = 3.71, 95% CI: 1.97–6.99), had no formal education (AHR = 2.33, 95% CI: 1.33–4.38), bedridden functional status (AHR = 5.91, 95% CI: 2.71–12.88), advanced WHO stage III and IV (AHR = 4.36, 95% CI: 2.20–8.64), BMI 16–18.4 kg/m2 (AHR = 3.03, 95% CI: 1.50–6.13), and BMI<16.0 kg/m2 (AHR = 5.47; 95% CI: 2.85–10.50), CD4 count ≤50 cells/mm3 (AHR = 6.62, 95% CI: 4.73–8.52), hemoglobin <8 g/dl (AHR = 5.21; 95% CI: 2.64–10.26), not used cotrimoxazole prophylaxis therapy (AHR = 2.78, 95% CI: 1.61–4.73), stavudine based regimen (AHR = 2.34, 95% CI: 1.32–4.13), and zidovudine based regimen (AHR = 2.49, 95% CI: 1.41–4.39). ConclusionHigh mortality was observed in this cohort, and participants with stage III and IV, low CD4 count, low hemoglobin level, bed ridden functional status, low BMI should be closely monitored even with the scarce resources. In addition, the use of cotrimoxazole prophylaxis therapy should be more encouraged to increase survival.

A case-cohort study of left ventricular diastolic dysfunction in patients with cirrhosis: the liver-heart axis.

Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis. We assessed the association of LVDD with the factors affecting cirrhosis patients' severity, complications, and survival. A total of 203 cirrhosis patients were enrolled and underwent investigations, including 2-dimensional echocardiography with tissue Doppler imaging, and 139 patients with LVDD (cases) were compared with 64 patients without LVDD (controls). Logistic regression and Kaplan-Meier analysis were applied. Mean age was 52.76±10 years. Among LVDD patients, 56% had grade-1, and 44% had grade-2 LVDD. Cirrhosis related to NASH had a more significant association with LVDD (P<0.001) than other etiologies. LVDD was significantly associated with a greater incidence of Child-Turcotte-Pugh (CTP) class C (P<0.001), higher model for end-stage liver disease scores (P=0.001), duration of cirrhosis >2 years since diagnosis (P=0.028), ascites (P<0.001), hepatic encephalopathy (P<0.010), hepatorenal syndrome (P<0.001), and a history of obesity (P=0.004). Multivariate analysis showed that higher CTP score, ascitic fluid protein and prolonged QTc interval were independently associated with LVDD (P=0.009; P=0.018; P=0.016, respectively). Kaplan-Meier survival analysis showed significantly poorer survival status in patients with higher grades of LVDD (P<0.001). The area under the receiver operating characteristic curve (0.78) was greatest for ascitic fluid protein in predicting LVDD, with a cutoff of >1 g/dL. Higher CTP score, prolonged QTc, higher ascitic fluid protein levels, and poor survival are significantly associated with LVDD. Ascitic fluid protein >1 g/dL could be an indicator for evaluating LVDD.

Sivas İli 2013-2019 Yılları Kanser İnsidansı ve Sağkalımı: Retrospektif Kohort Çalışması

Objective: This study's aim was to examine the incidence and survival of cancer in Sivas between 2013-2019. Material and Methods: In this retrospective cohort study, cancer registry data were analysed. Age, sex, treatment types, definitive pathological diagnosis results, and survival status of patients were questioned. Results: A total of 7,946 people were diagnosed with cancer in the years examined and 57.5% of the patients were male. Systemically the most common type of cancer was digestive organ cancers (20.2%) (stomach, colon, anorectal, respectively). The most common cancers in male were prostate (16%), skin (14%), and bronchopulmonary (12%). The most common cancers in female were breast (22%), thyroid (16%), and skin (14%). The cancer incidence was between 1.4 per thousand and 2.3 per thousand. Life expectancy was shorter (p<0.001), and the mortality risk was 1.6 times higher in male. The risk of cancer mortality increased with increasing age. Respiratory system and intrathoracic organ cancers were the cancers that caused the death and shortened the life span most (p<0.001). Conclusion: It was found that the cancer incidence tended to increase, and that the cancer mortality was higher in male and respiratory system organ cancers. It is important to keep detailed records (especially by including the stage and treatment protocols) in the follow-up of cancer cases.

Association of Augmented Immune-Staining of G-Quadruplex Tertiary DNA Structure in Chemo-Tolerant TNBC with Downregulation of WNT/Epidermal Growth Factor Receptor Pathway receptor Genes: A Pilot Clinicopathological Study

Purpose: The aim of the study is to understand the involvement of G-Quadruplex (G-Q) structures in altering the expression profile of WNT/epidermal growth factor receptor (EGFR) pathway receptor genes in chemo-tolerant Triple Negative Breast Cancer (TNBC) samples. Materials and Methods: At first, Gene Expression Omnibus datasets were mined where the expression profile of WNT/EGFR pathway genes in TNBC samples and MDA-MB-231, a TNBC cell line, were checked in response to doxorubicin, a chemotherapeutic drug. Next, to unveil the probable mechanism of regulation, the presence of G-Q structure was checked in in silico study and later validated by immunohistochemical analyses in our pool of sample. These observed results were correlated with patient's demography and survival status. Results: Expression of the receptors (FZD7, LRP6, EGFR) of the WNT/EGFR pathway were found to be differentially expressed in TNBC samples; further emphasized in our samples (n = 61). Notably, these G-Q structures were found in the promoter region of the WNT pathway receptor genes (FZD7, LRP6, and EGFR). Validating in our patient sample pool, a significant increase in G-Q immunostaining was observed in samples, after neoadjuvant chemotherapy (NACT) samples (n = 17) than the pretherapeutic samples (n = 44). Similar pattern of G-Q immunostaining was noticed in doxorubicin-treated MDA-MB-231 cell line. Intriguingly, low staining of G-Q among the pretherapeutic samples, but NACT TNBC samples, was found to be significantly correlated with lymph node metastasis. Conclusions: This study showed that the augmented immunostaining of G-Q structure might have an important involvement in regulating the expression pattern of the WNT/EGFR pathway genes in response to doxorubicin treatment of TNBC.

Outcomes of Declined Deceased Donor Kidney Offers That Are Subsequently Implanted: A UK Registry Study.

Deceased donor kidneys are often declined for ≥1 patients but then implanted into another. Studies are needed to guide transplant clinicians and patients, especially given the increasing age and comorbidity of donors. This study compares outcomes of recipients of transplanted kidneys that were initially declined with outcomes of patients who remained on the waiting list. This UK Transplant Registry study examined named-patient, adult donation after brain death donor single kidney-only offers that were declined for donor- or organ-related reasons (DORRs), in which the kidney was subsequently transplanted from January 1, 2010, to December 31, 2018. Outcomes included graft function and survival of kidneys transplanted following DORR decline, survival and transplant status of patients who had a kidney declined, and intercenter decline rates. A total of 4722 kidneys declined for DORRs, which eventually resulted in single kidney-only transplants, were examined. One year after the offer decline, 35% of patients for whom the organ was declined remained on the list, 55% received a deceased donor transplant at a median of 174 d after the initial offer decline, and 4% had been removed or died. For patients transplanted following offer decline, there was no significant difference in 5-y graft survival when comparing the outcomes to those recipients who received the declined kidney. There was significant variation in DORR decline rates between UK transplant units (17%-54%). This study shows reasonable outcomes of kidneys previously declined for DORRs and supports the utilization of those considered to be of higher risk for carefully selected recipients.

A pyroptosis-related gene signature for prognostic and immunological evaluation in breast cancer.

Pyroptosis exerts an undesirable impact on the clinical outcome of breast cancer. Since any single gene is insufficient to be an appropriate marker for pyroptosis, our aim is to develop a pyroptosis-related gene (PRG) signature to predict the survival status and immunological landscape for breast cancer patients. The information of breast cancer patients was retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the gene expressions of this signature in breast cancer. Its prognostic value was evaluated by univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, receiver operating characteristics (ROCs), univariate/multivariate analysis, and nomogram. Analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to explore its potential biological function in breast cancer. The potential correlation between this signature and tumor immunity was revealed based on single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms. A PRG signature containing GSDMC, GZMB, IL18, and TP63 was created in a TCGA training cohort and validated in two validation GEO cohorts GSE58812 and GSE37751. Compared with a human mammary epithelial cell line MCF-10A, the expression levels of GSDMC, GZMB and IL18 were upregulated, while TP63 was found with lower expression level in breast cancer cells SK-BR-3, BT-549, MCF-7, and MDA-MB-231 using RT-qPCR assay. Based on univariate and multivariate Cox models, ROC curve, nomogram as well as calibration curve, it was revealed that this signature with high-risk score could independently predict poor clinical outcomes in breast cancer. Enrichment analyses demonstrated that the involved mechanism was tightly linked to immune-related processes. SsGSEA, ESTIMATE and CIBERSORT algorithms further pointed out that the established model might exert an impact on immune cell abundance, immune cell types and immune-checkpoint markers. Furthermore, individuals with breast cancer responded differently to these therapeutic agents based on this signature. Our data suggested that this PRG signature with high risk was tightly associated with impaired immune function, possibly resulting in an unfavorable outcome for breast cancer patients.

Survival analysis and prognostic factors of the carcinoma of gallbladder

BackgroundThe present study aims to evaluate the survival status of patients with gallbladder cancer (GBC) and explore the prognostic factors for the improvement and preventions.MethodsThe study consists of 176 patients with clinically diagnosed gallbladder cancer; the study was conducted between 2019 and 2021 registered at Kamala Nehru Memorial Cancer Hospital, Prayagraj, India. The survival rates were analyzed by the Kaplan-Meier method; survival rate difference was analyzed by log-rank test, prognosis factors; and hazard ratio for mortality outcomes was estimated using Cox regression method.ResultsThe overall median survival time of patients was 5 months with the 1-year, 2-year, and 3-year survival rates of 24.4%, 8.5%, and 4.5%, respectively. The 3-year survival for patients with jaundice was 2.9%, liver infiltration (4.2%), gallstones (0.8%), and with advanced tumor grade (1.4%). Elderly GBC patients had lower survival rates (3.8%), while the 3-year overall survival for patients residing in urban areas dropped to zero. No patients in the tumor stage (T3/T4) and with distance metastasis stage survived in 3 years, while only 1.1% of patients with advanced nodal stage survived. On receiving surgery and radiation therapy, the 3-year survival rate increased to 19.5% and 35%, respectively. The results of multivariate analysis showed that urban region (HR = 1.568, p = 0.040), gallstone or not (1.571, p = 0.049), N stage (HR = 1.468, p = 0.029), and M stage (HR = 2.289, p < 0.0001) were independent risk factors for prognosis, while surgery or not (HR = 0.573, p = 0.030) was the protective factor for the prognosis of GBC.ConclusionThe overall survival of GBC in the Gangetic belt is poor. The geographical region of patients, gallstones, and N and M stage was the risk factors for prognosis, while surgery or not was the protective factor for the prognosis of GBC.