Survival Analysis Of Patients Research Articles

GCN-Based Risk Prediction for Necrosis Slide of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world which ranks fourth in cancer deaths. Primary pathological necrosis is an effective prognostic indicator for hepatocellular carcinoma. We propose a GCN-based approach that mimics the pathologist's perspective for global assessment of necrosis tissue distribution to analyze patient survival. Specifically, we introduced a graph convolutional neural network to construct a spatial map with necrotic tissue and tumor tissue as graph nodes, aiming to mine the contextual information between necrotic tissue in pathological sections. We used 1381 slides from 303 patients from the First Affiliated Hospital of Zhejiang University School to train the model and used TCGA-LIHC for external validation. The C-index of our method outperforms the baseline by about 4.45%, which proves that the information about the spatial distribution of necrosis learned by GCN is meaningful for guiding patient prognosis.

Pelvic Exenteration Surgery Outcomes Following Establishment of a Complex Pelvic Surgery Multidisciplinary Tertiary Unit

Background: Pelvic exenteration surgery (PES) is a complex operation associated with significant morbidity. PES requires sub-specialised multidisciplinary input along with expertise in complex pelvic surgery and anatomy. The majority of published data on PES comes from high volume units, however there is emerging evidence of comparable short and long-term outcomes in lower volume units where dedicated multidisciplinary teams are established. This study reports outcomes of PES in a lower volume centre with a collaborative multidisciplinary surgical approach. Methods: A retrospective review of patients who underwent PES for benign or malignant pathology at Liverpool and Macquarie University Hospitals between September 2015 and June 2022. Descriptive statistics were performed and KaplanMeier survival analysis for patients treated for malignancy with curative intent. Results: A total of 67 patients undergoing pelvic exenteration were included (53.8% female; with mean age 59 years). Indications for PES were colorectal cancer (56.7%), gynaecological cancer (22.4%), other malignancy (9.0%) and complex benign pathology (11.9%). Posterior or total pelvic exenteration was performed in 88.1%. Median hospital stay was 16 days. Clavien-Dindo grade III or IV complications occurred in 34.3%. There were two post-operative deaths (3.0%; one palliative intent). For patients treated with curative intent (n=51), R0 resection margin was achieved in 92.2%, and R1 margin in 7.8%. Estimated five-year disease-free survival was 57.1%, and five-year overall survival was 65.5%. Conclusion: Short and long-term outcomes of PES in a low volume unit with appropriate multidisciplinary expertise are comparable to published data on pelvic exenteration from higher volume units.

Overall survival and short-term efficacy analysis of cervical squamous cell carcinoma with skeletal muscle and 18F-FDG PET/CT parameters

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.

ROS-mediated up-regulation of SAE1 by Helicobacter pylori promotes human gastric tumor genesis and progression

Helicobacter pylori (H. pylori) is a major risk factor of gastric cancer (GC). The SUMO-activating enzyme SAE1(SUMO-activating enzyme subunit 1), which is indispensable for protein SUMOylation, involves in human tumorigenesis. In this study, we used the TIMER and TCGA database to explore the SAE1 expression in GC and normal tissues and Kaplan–Meier Plotter platform for survival analysis of GC patients. GC tissue microarray and gastric samples from patients who underwent endoscopic treatment were employed to detect the SAE1expression. Our results showed that SAE1 was overexpressed in GC tissues and higher SAE1 expression was associated with worse clinical characteristics of GC patients. Cell and animal models showed that H. pylori infection upregulated SAE1, SUMO1, and SUMO2/3 protein expression. Functional assays suggested that suppression of SAE1 attenuated epithelial-mesenchymal transition (EMT) biomarkers and cell proliferation abilities induced by H. pylori. Cell and animal models of ROS inhibition in H. pylori showed that ROS could mediate the H. pylori-induced upregulation of SAE1, SUMO1, and SUMO2/3 protein. RNA sequencing was performed and suggested that knockdown of SAE1 could exert an impact on IGF-1 expression. General, increased SUMOylation modification is involved in H. pylori-induced GC.

Survival Analysis of Patients with COVID-19 using Deep Neural Network and Random Forrest Techniques

Introduction: The prediction of the survival chance of coronavirus disease 2019 (COVID-19) patients is as important as the early detection of the coronavirus. Since patient mortality, factors may differ by location, this study concentrated on identifying the influential factors and predicting survival for COVID-19 patients using machine learning methods in Fars province, Iran.Material and Methods: The research dataset was extracted in the period January 21, 2020, to September 25, 2020, and contains 25858 hospitalized patients’ records with 51 features. These records were classified into two categories: death (label 1) and survival (label 0). The methodology of this research is CRISP standard. A comparison was made between the efficiency of two deep neural network and random forest algorithms in predicting survival. Modeling steps were done with Python language in the Google Colab environment.Results: Experimental results demonstrated that the deep neural network algorithm had better performance than random forest with accuracy, precision, recall, F-score, and receiver operating characteristic of 97.2%, 100%, 93.54%, 96.66%, and 97.9%, respectively. Based on the results of the random forest model, history of hypertension, chronic neurological disorders, chronic lung diseases, asthma, chronic kidney disease and, heart disease were the most important risk factors related to death.Conclusion: Deployment of our proposed model allows medical professionals to exercise greater caution during the treatment of patients who are most likely to die due to their medical conditions.

Conditional survival analysis and dynamic prediction of long-term survival in Merkel cell carcinoma patients.

Merkel cell carcinoma (MCC) is a rare type of invasive neuroendocrine skin malignancy with high mortality. However, with years of follow-up, what is the actual survival rate and how can we continually assess an individual's prognosis? The purpose of this study was to estimate conditional survival (CS) for MCC patients and establish a novel CS-based nomogram model. This study collected MCC patients from the Surveillance, Epidemiology, and End Results (SEER) database and divided these patients into training and validation groups at the ratio of 7:3. CS refers to the probability of survival for a specific timeframe (y years), based on the patient's survival after the initial diagnosis (x years). Then, we attempted to describe the CS pattern of MCCs. The Least absolute shrinkage and selection operator (LASSO) regression was employed to screen predictive factors. The Multivariate Cox regression analysis was applied to demonstrate these predictors' effect on overall survival and establish a novel CS-based nomogram. A total of 3,843 MCC patients were extracted from the SEER database. Analysis of the CS revealed that the 7-year survival rate of MCC patients progressively increased with each subsequent year of survival. The rates progressed from an initial 41-50%, 61, 70, 78, 85%, and finally to 93%. And the improvement of survival rate was nonlinear. The LASSO regression identified five predictors including patient age, sex, AJCC stage, surgery and radiotherapy as predictors for CS-nomogram development. And this novel survival prediction model was successfully validated with good predictive performance. CS of MCC patients was dynamic and increased with time since the initial diagnosis. Our newly established CS-based nomogram can provide a dynamic estimate of survival, which has implications for follow-up guidelines and survivorship planning, enabling clinicians to guide treatment for these patients better.

Multi-Centre UK Analysis of Simultaneous Pancreas and Kidney (SPK) Transplant in Recipients With Type 2 Diabetes Mellitus.

90% of the UK diabetic population are classified as T2DM. This study aims to compare outcomes after SPK transplant between recipients with T1DM or T2DM. Data on all UK SPK transplants from 2003-2019 were obtained from the NHSBT Registry (n = 2,236). Current SPK transplant selection criteria for T2DM requires insulin treatment and recipient BMI < 30kg/m2. After exclusions (re-transplants/ambiguous type of diabetes) we had a cohort of n = 2,154. Graft (GS) and patient (PS) survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Complications were compared using chi-squared analyses. 95.6% of SPK transplants were performed in recipients with T1DM (n = 2,060). Univariate analysis showed comparable outcomes for pancreas GS at 1year (p = 0.120), 3years (p = 0.237), and 10years (p = 0.196) and kidney GS at 1year (p = 0.438), 3years (p = 0.548), and 10years (p = 0.947). PS was comparable at 1year (p = 0.886) and 3years (p = 0.237) and at 10years (p = 0.161). Multi-variate analysis showed comparable outcomes in pancreas GS (p = 0.564, HR 1.221, 95% CI 0.619, 2.406) and PS(p = 0.556, HR 1.280, 95% CI 0.563, 2.911). Comparable rates of common complications were demonstrated. This is the largest series outside of the US evaluating outcomes after SPK transplants and shows similar outcomes between T1DM and T2DM recipients. It is hoped dissemination of this data will lead to increased referral rates and assessment of T2DM patients who could benefit from SPK transplantation.

Retrospective study of combined pelvic exenteration in the treatment of primary and recurrent pelvic malignant tumors.

Pelvic malignant tumors often originate in the rectum, bladder, uterus, and other organs. In patients with locally advanced tumours in the presence of direct invasion of one or more organs, negative tumor resection margin (R0) resection can be very beneficial to patient survival if it can be performed. As a multidisciplinary and high-risk surgical method, the pelvic exenteration (PE) procedure has only been reported in a few medical centres internationally. We retrospectively analyzed the clinical data of patients who had undergone PE surgery in our hospital, in order to provide ideas for the best treatment of patients with pelvic malignant tumors. A retrospective analysis was conducted of 59 patients with pelvic malignant tumors admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to July 2021, all of whom received PE surgery. They were divided into two groups according to the location of the disease: the rectal cancer group (n=40) and the cervical cancer group (n=19). Statistical analysis was performed on the baseline and follow-up data of the two groups of patients. (I) Patient baseline data. Compared to the rectal cancer group, more patients in the cervical cancer group received preoperative radiotherapy and chemotherapy (P=0.013), and had a lower R0 resection rate (P=0.037). Postoperative complications in patients with rectal cancer and cervical cancer were 27.5% and 47.3%, respectively. (II) Patient survival analysis after PE surgery. The 5-year survival rate was 36.6% in the rectal cancer group and 25.3% in the cervical cancer group. In the rectal cancer group, for the primary tumor, if there was no lymph node metastasis or no postoperative complications in the postoperative pathology, the patient had a good survival prognosis. Univariate analysis showed that recurrent rectal cancer, postoperative lymph node metastasis, postoperative complications, and microsatellite stability (MSS) were significant predictors of poor survival outcomes. Multivariate analysis showed that lymph node metastasis and postoperative complications were independent prognostic factors for patient survival. PE is a viable option for pelvic malignancies; aggressive radical resection of lesions and reduced postoperative complications can effectively improve patient outcomes.

Analysis of real-world survival for patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or abiraterone acetate (ABI) in an oncology database: ROMA study.

58 Background: Androgen receptor signaling inhibitors (ARSI), including APA and ABI plus prednisone, are approved for the treatment of mCSPC. However, studies evaluating survival for these agents in clinical trials or the real-world have not been investigated. This study describes real-world survival among men with mCSPC who initiated APA or ABI in the United States (US). Methods: Data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry Electronic DataMart (1/1/2013–05/31/2023) was used to identify ARSI-naïve patients with chart-confirmed metastasis and without evidence of castration resistance at ARSI initiation. Patients were classified into two treatment cohorts based on the start date for APA or ABI (index date) on/after 9/17/2019. Patients had ≥12 months of clinical data pre-index and were followed from the index date until the earliest of 24 months post-index, end of clinical activity, or end of data availability. Patients’ date of death was obtained by integrating data from electronic medical records, the Social Security Death Index, and or other confirmed sources. Using an intention-to-treat approach, Kaplan-Meier analysis was used to describe the proportion of patients surviving by 24 months post-index. An unadjusted Cox proportional hazards model was used to describe crude differences in survival rates between patients initiating APA and ABI. Results: This study included 242 APA (mean age: 73.0 years; 60.3% White, 13.6% Black) and 607 ABI (mean age: 73.1 years; 57.3% White, 16.8% Black) patients. APA median time on-treatment was 11.4 months over a median observation period of 14.3 months. ABI median time on-treatment was 10.8 months over a median observation of 14.0 months. By 24 months, 85.7% of the APA cohort and 75.9% of the ABI cohort were living (unadjusted hazard ratio=0.60, 95% confidence interval: 0.38, 0.96; p=0.033; Table). Conclusions: In this study, we observed that more ARSI-naïve patients with mCSPC survived by 24 months after initiating APA than those who initiated ABI. While the current study presents unadjusted comparisons, additional causal analyses controlling for confounding variables should be conducted to confirm these initial findings. [Table: see text]

A nationwide analysis of the treatment patterns, survival, and medical costs in Korean patients with relapsed or refractory diffuse large B-cell lymphoma.

Approximately one-third of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to treatment or experience relapse after initial therapy. Unfortunately, treatment options for older patients and those who experience relapse or become refractory to hematopoietic stem cell transplantation (HSCT) are limited. This nationwide population-based study aimed to identify treatment patterns, survival times, and treatment costs in patients with relapsed/refractory DLBCL (R/R DLBCL). Between 2011 and 2020, data on patients with R/R DLBCL were retrieved from the Korean Health Insurance Review & Assessment Service, encompassing the entire population. We identified the treatment patterns for each treatment line using a Sankey diagram and calculated the median time to the subsequent treatment in line. Median overall and progression-free survival times were estimated using the Kaplan-Meier survival curves. Finally, the medical costs incurred during DLBCL treatment were calculated for each treatment line and the costs related to HSCT were summarized at the episode level. A total of 864 patients with R/R DLBCL who received second-line treatment were identified, and a regimen of ifosfamide, carboplatin, and etoposide (ICE) was administered the most. Among them, 353 were refractory or relapsed cases that were treated with third-line treatments. The median times for second-line to third-line, third-line to fourth-line, fourth-line to fifth-line, and fifth-line to sixth-line treatment failures gradually decreased (3.93, 2.86, 1.81, and 1.38 months, respectively). The median overall survival time was 8.90 and 4.73 months following the second-line and third-line treatments, respectively. In the third-line treatment setting, the patients did not show a significant difference in survival time after HSCT. The median medical cost was $39,491 across all treatment lines including the cost of HSCT which was $22,054. The treatment patterns in patients with R/R DLBCL, especially at third-line treatments and thereafter, were complicated, and their prognosis was poor despite the high medical costs. Novel and effective treatment options are expected to improve the prognosis and alleviate the economic burden of patients with R/R DLBCL.

Clinical characteristics and survival analysis in patients with isolated pulmonary metastases from colorectal cancer (CRC).

60 Background: Recent studies seem to indicate that patients with metastatic colorectal cancer (mCRC) with exclusive pulmonary metastatic disease have better outcomes than those with other metastatic sites. The aim of this study is to identify differences in clinical and survival characteristics between the two groups in a cohort of a third level hospital. Methods: We retrospectively analyzed a sample of 569 patients with mCRC in a tumor registry from 2015 to 2021, studying clinical and molecular characteristics, as well as overall survival data of patients with isolated pulmonary metastases, versus the rest of patients. Results: Of the total sample analyzed, 61 patients (10.7%) had isolated pulmonary metastases. In these patients, several clinical characteristics were more frequent: primary rectal tumor (52.5% vs 23.4%, p &lt; 0.000), resected primary tumor (95.1% vs 78.9%, p = 0.0026), metachronous metastatic disease (62.3% vs 42%, p = 0.0025) and complete response rate to the first line of treatment (19.3% vs 9.9%, p = 0.026). Furthermore, analytically, these patients were more likely to have normal CEA (75% vs 38.3%, p &lt; 0.000), CA 19.9 (84.3% vs 57.7%, p = 0.0002) and LDH (91.1% vs 66.5%, p = 0.0007) levels. In our cohort, we found no statistically significant differences in tumor mutational status (KRAS, NRAS, BRAF, PI3K and HER2). There were no patients with exclusive pulmonary metastatic disease and microsatellite instability (MSI). 70.3% of patients with isolated pulmonary metastases received lung metastasectomy, and up to 58.3% received a second metastases surgery. We also found a numerical benefit in terms of overall survival (OS) in patients with exclusive metastatic lung disease, although it did not reach statistical signification (median OS 77.3 vs 58.1 months, HR for death 0.70, 95% CI, 0.49 – 1.01, p = 0.083). Conclusions: In our cohort, patients with isolated pulmonary metastases were more likely to have rectal tumors, primary tumor resection, metachronous metastatic disease, higher rate of complete responses and normal CEA, CA 19.9 and LDH levels, with a possible benefit in terms of OS.

The Role of SOX2 and SOX9 in Radioresistance and Tumor Recurrence.

Head and neck squamous cell carcinoma (HNSCC) exhibits considerable variability in patient outcome. It has been reported that SOX2 plays a role in proliferation, tumor growth, drug resistance, and metastasis in a variety of cancer types. Additionally, SOX9 has been implicated in immune tolerance and treatment failures. SOX2 and SOX9 induce treatment failure by a molecular mechanism that has not yet been elucidated. This study explores the inverse association of SOX2/SOX9 and their distinct expression in tumors, influencing the tumor microenvironment and radiotherapy responses. Through public RNA sequencing data, human biopsy samples, and knockdown cellular models, we explored the effects of inverted SOX2 and SOX9 expression. We found that patients expressing SOX2LowSOX9High showed decreased survival compared to SOX2HighSOX9Low. A survival analysis of patients stratified by radiotherapy and human papillomavirus brings additional clinical relevance. We identified a gene set signature comprising newly discovered candidate genes resulting from inverted SOX2/SOX9 expression. Moreover, the TGF-β pathway emerges as a significant predicted contributor to the overexpression of these candidate genes. In vitro findings reveal that silencing SOX2 enhances tumor radioresistance, while SOX9 silencing enhances radiosensitivity. These discoveries lay the groundwork for further studies on the therapeutic potential of transcription factors in optimizing HNSCC treatment.

Treatment patterns and survival analysis in patients with unresectable stage III EGFR-mutated non-small cell lung cancer.

To investigate the treatment patterns and survival outcomes in patients with unresectable Stage III EGFR-mutated non-small cell lung cancer (NSCLC). A retrospective analysis was conducted on patients with unresectable Stage III EGFR-mutated NSCLC spanning from 2012 to 2022. Treatment patterns were outlined, and survival comparisons between different treatment groups were performed using Kaplan-Meier methods. A total of 88 patients were included: 62.5% received TKI alone, 26.1% received TKI+chemotherapy, 4.5% received radiotherapy, 4.5% participated in clinical trials, and 2.4% received TKI+antiangiogenic drugs. Prior to propensity score matching, TKI+chemotherapy and TKI alone groups demonstrated similar progression-free survival (hazard ratio [HR] = 1.56, 95% confidence interval [CI]: 0.87-2.80; P = 0.134), overall survival (HR = 1.12, 95% CI: 0.59-2.13; P = 0.733), and locoregional-free survival (HR = 1.46; 95% CI: 0.75-2.81; P = 0.267). However, TKI+chemotherapy showed reduced distant metastasis-free survival compared to TKI alone (HR = 2.39, 95% CI: 1.11-5.18; P = 0.022). After propensity score matching, no significant differences were observed in progression-free survival (P = 0.435), overall survival (P = 0.205), locoregional-free survival (P = 0.706), and distant metastasis-free survival (P = 0.171) between the TKI+chemotherapy and TKI alone groups. The addition of chemotherapy to TKI did not enhance survival outcomes compared to TKI monotherapy in patients with unresectable Stage III EGFR-mutated NSCLC.

Enhancing outcomes: neurosurgical resection in brain metastasis patients with poor Karnofsky performance score - a comprehensive survival analysis.

A reduced Karnofsky performance score (KPS) often leads to the discontinuation of surgical and adjuvant therapy, owing to a lack of evidence of survival and quality of life benefits. This study aimed to examine the clinical and treatment outcomes of patients with KPS < 70 after neurosurgical resection and identify prognostic factors associated with better survival. Patients with a preoperative KPS < 70 who underwent surgical resection for newly diagnosed brain metastases (BM) between 2007 and 2020 were retrospectively analyzed. The KPS, age, sex, tumor localization, cumulative tumor volume, number of lesions, extent of resection, prognostic assessment scores, adjuvant radiotherapy and systemic therapy, and presence of disease progression were analyzed. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with better survival. Survival > 3 months was considered favorable and ≤ 3 months as poor. A total of 140 patients were identified. Median overall survival was 5.6 months (range 0-58). There was no difference in the preoperative KPS between the groups of > 3 and ≤ 3 months (50; range, 20-60 vs. 50; range, 10-60, p = 0.077). There was a significant improvement in KPS after surgery in patients with a preoperative KPS of 20% (20 vs 40 ± 20, p = 0.048). In the other groups, no significant changes in KPS were observed. Adjuvant radiotherapy was associated with better survival (44 [84.6%] vs. 32 [36.4%]; hazard ratio [HR], 0.0363; confidence interval [CI], 0.197-0.670, p = 0.00199). Adjuvant chemotherapy and immunotherapy resulted in prolonged survival (24 [46.2%] vs. 12 [13.6%]; HR 0.474, CI 0.263-0.854, p = 0.013]. Systemic disease progression was associated with poor survival (36 [50%] vs. 71 [80.7%]; HR 5.975, CI 2.610-13.677, p < 0.001]. Neurosurgical resection is an appropriate treatment modality for patients with low KPS. Surgery may improve functional status and facilitate further tumor-specific treatment. Combined treatment with adjuvant radiotherapy and systemic therapy was associated with improved survival in this cohort of patients. Systemic tumor progression has been identified as an independent factor for a poor prognosis. There is almost no information regarding surgical and adjuvant treatment in patients with low KPS. Our paper provides novel data on clinical outcome and survival analysis of patients with BM who underwent surgical treatment.

Xie-Bai-San increases NSCLC cells sensitivity to gefitinib by inhibiting Beclin-1 mediated autophagosome formation

BackgroundAutophagy, a cellular process involving lysosomal self-digestion, plays a crucial role in recycling biomolecules and degrading dysfunctional proteins and damaged organelles. However, in non-small cell lung cancer (NSCLC), cancer cells can exploit autophagy to survive metabolic stress and develop resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which reduce treatment efficacies. Currently, most studies have found that late-stage autophagy inhibitors can hinder EGFR-TKIs resistance, while research on early-stage autophagy inhibitors is still limited. PurposeThis study investigates the mechanism via which the Xie-Bai-San (XBS) formula enhances NSCLC cell sensitivity to gefitinib, revealing the relationship between XBS-induced cell death and the inhibition of autophagosome formation. MethodsCell viability was assessed using CCK-8 and EdU assays, lentivirus transfection was utilized to generate PC9 cells harboring the PIK3CA E545K mutation (referred to as PC9-M), autophagic flux was monitored using mCherry-GFP-LC3 adenovirus. Protein expression and colocalization were observed through immunofluorescence staining. The interaction between Bcl-2 and Beclin-1 in PC9-GR and PC9-M cells was determined via co-immunoprecipitation (Co-IP) assay, cell apoptosis was assessed by flow cytometry and PI staining, and overall survival analysis of lung adenocarcinoma patients was conducted using the TCGA database. In vivo experiments included a patient-derived xenograft (PDX) model with EGFR and PIK3CA mutations and subcutaneous mice xenografts of NSCLC cell lines (PC9 and PC9-GR). In addition, autophagic vesicles in mouse tumor tissues were observed via transmission electron microscopy analysis. ResultsXBS effectively inhibits the proliferation of gefitinib-resistant NSCLC cells and induces apoptosis both in vitro and in vivo. Mechanistically, XBS suppresses gefitinib-induced autophagic flux by inhibiting autophagy through the upregulation of p-mTOR and Bcl-2 and downregulation of Beclin-1. Additionally, XBS enhances the interaction between Bcl-2 and Beclin-1, and the overexpression of Beclin-1 promotes NSCLC cell proliferation and counteracts XBS-induced cell death, while XBS demonstrates minimal impact on autophagosome-lysosome fusion or lysosome function. ConclusionThis study reveals a novel role for the XBS formula in impeding autophagy initiation and demonstrates its potential as a candidate drug to counteract autophagy-induced treatment resistance in NSCLC.

A Sequent of Gram-Negative Co-Infectome-Induced Acute Respiratory Distress Syndrome Are Potentially Subtle Aggravators Associated to the SARS-CoV-2 Evolution of Virulence.

Acute respiratory distress syndrome (ARDS) is one of the major problems in COVID-19 that is not well understood. ARDS is usually complicated by co-infections in hospitals. Although ARDS is inherited by Europeans and Africans, this is not clear for those from the Middle East. There are severe limitations in correlations made between COVID-19, ARDS, co-infectome, and patient demographics. We investigated 298 patients for associations of ARDS, coinfections, and patient demographics on COVID-19 patients' outcomes. Of the 149 patients examined for ARDS during COVID-19, 16 had an incidence with a higher case fatality rate (CFR) of 75.0% compared to those without ARDS (27.0%) (p value = 0.0001). The co-infectome association showed a CFR of 31.3% in co-infected patients; meanwhile, only 4.8% of those without co-infections (p value = 0.01) died. The major bacteria were Acinetobacter baumannii and Escherichia coli, either alone or in a mixed infection with Klebsiella pneumoniae. Kaplan-Meier survival analysis of COVID-19 patients with and without ARDS revealed a significant difference in the survival time of patients with ARDS (58.8 +/- 2.7 days) and without ARDS (41.9 +/- 1.8 days) (p value = 0.0002). These findings prove that increased hospital time was risky for co-infectome-induced SDRS later on. This also explained that while empiric therapy and lethal ventilations delayed the mortality in 75% of patients, they potentially did not help those without co-infection or ARDS who stayed for shorter times. In addition, the age of patients (n = 298) was significantly associated with ARDS (72.9 +/- 8.9) compared to those without it (56.2 +/- 15.1) and was irrespective of gender. However, there were no significant differences neither in the age of admitted patients before COVID-19 (58.5 +/- 15.3) and during COVID-19 (57.2 +/- 15.5) nor in the gender and COVID-19 fatality (p value 0.546). Thus, Gram-negative co-infectome potentially induced fatal ARDS, aggravating the COVID-19 outcome. These findings are important for the specific differential diagnosis of patients with and without ARDS and co-infections. Future vertical investigations on mechanisms of Gram-negative-induced ARDS are imperative since hypervirulent strains are rapidly circulating. This study was limited as it was a single-center study confined to Ha'il hospitals; a large-scale investigation in major national hospitals would gain more insights.

Factors associated with antibiotic resistance and survival analysis of severe pneumonia patients infected with Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa: A retrospective cohort study in Jakarta, Indonesia.

Antimicrobial resistance is one of the most significant challenges to global public health and the risk factors in severe pneumonia are constantly growing. Therefore, this study aimed to identify factors associated with antimicrobial resistance and conduct survival analysis of severe pneumonia patients with single and multiple pathogens in the National Referral Hospital, Jakarta, Indonesia. A retrospective method was used, and secondary data were collected from severe pneumonia patients admitted to the intensive care unit at Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia, from January 2016 to December 2022. Respiratory specimens were collected through bronchial washing. Furthermore, univariate and multivariate analyses were performed to analyze factors associated with antimicrobial resistance. Kaplan‒Meier survival curves were generated with the log-rank test to compare 30-day mortality between patients infected with single, dual, and multiple pathogens. The results showed that a total of 333 patients from 415 enrolled were analyzed. Klebsiella pneumoniae (35.4%), Acinetobacter baumannii (29.3%), and Pseudomonas aeruginosa (15.4%) were the most frequently isolated Gram-negative pathogens. Factors associated with resistance to aminoglycoside, carbapenem, and quinolone were sepsis, cerebrovascular disease, and ventilator-associated pneumonia, as indicated by p < 0.05. In addition, the Kaplan-Meier curves showed that multiple pathogens influenced the survival rate of severe pneumonia patients (p < 0.05). Sepsis, cerebrovascular disease, and ventilator-associated pneumonia were associated with antimicrobial resistance in severe pneumonia patients. The survival rate of patients infected with multiple pathogens was low. This suggests the importance of further awareness regarding empirical antibiotic stewardship and mortality assessment in severe pneumonia patients.

Survival Analysis of Patients with Bladder Cancer after Radical Cystectomy

Abstract: One of the most commonly used surgical operations among patients with bladder cancer (BC) is radical cystectomy (RC), which includes the removal of the entire bladder along with the surrounding lymph nodes and other nearby organs that are affected by malignant neoplasms. During this operation, the most important stage that has a direct impact on the further quality of life of the patient is the choice of the method of uroderivation (UD). Patients and Methods: Have been reviewed retrospectively the clinical records of 586 patients who had BC RC at the Oncourological Department of the Sverdlovsk Regional Oncological Dispensary (SROD) between December 2001 and May 2021 after RC with three methods of UD: external urine removal, internal urine removal, intestinal reservoir. Results: The direct dependence of the presence and severity of some complications after RC on the method of urine removal chosen by the oncologist surgeon were determined. The analysis of survival curves was carried out, as well as the 5- and 10-year survival rate of patients of the SROD after RC. According to the results of the analysis, it was found that the worst survival was observed in patients with external urine diversion, the best survival was found in patients with internal urine diversion (p &lt; 0.05). Conclusions: Urinary diversion is definitely an important stage in the performance of such a surgical intervention as RC. The study revealed statistically significant differences between patient survival curves (p &lt; 0.05) plotted for different groups of urinary diversion and differences between the medians of several types of survival for the groups considered (p &lt; 0.05).

Survival analysis of patients with rare tumors of the uterine corpus – carcinosarcoma

Background/Aim. Uterine carcinosarcoma (UCS), formerly known as malignant mixed M?llerian tumor, is a rare, aggressive malignancy of the female genital tract. The aim of this study was to analyze the most important clinical and pathohistological characteristics of UCSs on operated patients, as well as to determine which of those factors are affecting progression-free survival (PFS) and overall survival (OS) of patients. Methods. The study was conducted as a retrospective analysis of medical data documentation of patients with a diagnosis of UCS who were surgically treated at the Department of Gynecology, Clinic for Operative Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, in 10 years? period (from the beginning of 2009 to the end of 2018). The analysis included data for a total of 31 patients. Results. Of all the examined parameters (age of the patient, clinical stage of the disease, histological grade, depth of myometrial invasion, and lymphovascular invasion ? LVI), the greatest influence on the choice of therapeutic procedure had a histological tumor grade. Conclusion. Our research showed the joint influence of the examined clinical and pathohistological factors on PFS and OS of patients with UCS. The only independent parameter that showed a statistically significant impact on survival is LVI.

Expression of the stem cell biomarker (CK19) – analysis of general and disease-free survival in resected patients with hepatocellular carcinoma

Expression of the stem cell biomarker (CK19) – analysis of general and disease-free survival in resected patients with hepatocellular carcinoma