Lower Survival Research Articles

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

Association between KRAS mutation and alcohol consumption in Brazilian patients with colorectal cancer

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Detection before metastasis and efficient treatment of disease significantly improve patient survival and quality of life. However, limitations in diagnosis and postoperative surveillance are associated with low CRC detection and survival rates. Thus, this project aimed to evaluate the molecular profile of patients diagnosed with CRC, as molecular biomarkers constitute a new frontier for diagnosis, treatment and prognosis. Methods and Results: 42 patients were included in the study, predominantly male (59.5%), with a median age of 63 years (SD: 10.0; min: 41; max: 83). The majority of primary tumors were located in the rectum (38.1%), in the sigmoid (33.3%) and in the ascending (21.4%) colon. We evaluated the genes KRAS, NRAS, BRAF, EGFR and TP53 using Sanger sequencing. Somatic and germline mutations were found in the KRAS, EGFR and TP53 genes, with the most common somatic alteration being rs121913529 in KRAS. This variant was also strongly associated with alcoholism (p = 0.002). Furthermore, patients with somatic mutations in TP53 had significantly higher mortality compared to those with wild-type alleles (OR: 11.2; 95% CI 1.25–2.45). Conclusions: Our findings support a relationship between alcohol consumption and the rs121913529 mutation, which is classified as pathogenic for colorectal cancer. Thus, further studies investigating the link between alcohol consumption, colorectal carcinogenesis and tumor progression ought to be conducted.

NCAPD3 is a prognostic biomarker and is correlated with immune infiltrates in glioma.

Non-SMC Condensin II Complex Subunit D3 (NCAPD3) has been linked with the genesis and progression of multiple human cancers. Nevertheless, the scientific value and molecular process of NCAPD3 in glioma remain unclear. We explored the level of NCAPD3 expression in pan-cancer by multiple online databases. And we focused on the level and prognostic value of NCAPD3 expression in glioma by immunohistochemistry (IHC) and survival analysis. Meanwhile, we verified the relationship between NCAPD3, biological function and immune infiltration in glioma by Linkedomics and SangerBox databases. The expression of NCAPD3 was increased in a variety of cancers, including glioma. Its high expression was strongly related to WHO grade (P=0.002) and programmed cell death ligand 1 (PD-L1) expression of glioma (P=0.001). Patients with a high level of NCAPD3 expression had a lower overall survival (OS) in glioma than patients with a low level of NCAPD3 expression. Multivariate statistical analyses showed NCAPD3 expression (P=0.040), WHO grade (P<0.001), 1p/19q codeletion (P<0.001), recurrence (P<0.001), age (P=0.023), and chemotherapy status (P=0.001) were meaningful independent prognostic factors in patients with glioma. Furthermore, bioinformatics analysis proved that NCAPD3 has been linked to immune infiltration in glioma. High level of NCAPD3 expression may serve as a promising prognostic biomarker and correlate with dendritic cell infiltration, representing a potential immunotherapy target in glioma.

Thyroid and growth hormone endocrine disruption and mechanisms of homosalate and octisalate using wild-type, thrαa-/-, and dre-miR-499-/- zebrafish embryo/larvae

Homosalate (HS) and octisalate (OS), which are used in sunscreen for the purpose of blocking ultraviolet rays, are frequently detected in water environment. Although effects on estrogens and androgens have been reported, studies on thyroid and growth hormone endocrine disruption are limited. In the present study, larval mortality was compared in wild-type and two knockout fish (thyroid hormone receptor alpha a knockout (thrαa-/-) and dre-miR-499 knockout (dre-miR-499-/-)) after 96 h of exposure to HS and OS (0, 0.003, 0.03, 0.3, 3, 30 and 300 µg/L). To investigate the mechanisms of thyroid and growth hormone endocrine disruption, we measured the levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), and insulin-like growth factor-1 (IGF-1), and the regulation of representative genes related to the hypothalamus-pituitary-thyroid (HPT) and GH/IGF axis in wild-type zebrafish exposed to target chemicals. The significantly lower larval survival rate of thrαa-/- and dre-miR-499-/- fish exposed to 300 μg/L of HS and OS suggest that thyroid hormone receptors and dre-miR-499 play a crucial role in the toxic effects of HS and OS. The finding of a significant increase in T3 and T4 in zebrafish larvae exposed to HS and OS supports a significant decrease in the crh gene. The reduction of GH and IGF-1 in fish exposed to HS and OS is well supported by the regulation of genes involved in the GH/IGF axis. Our observations suggest that exposure to HS and OS affects not only thyroid hormone receptors and their associated miRNAs, but also the feedback routes of HPT and GH/IGF axes, ultimately leading to growth reduction.

Over-expression of Transmembrane Protein 158 Predicts Aggressive Tumor Behavior and Poor Prognosis in Lung Cancer.

Transmembrane protein 158 (TMEM158) has emerged as a potential contributor to cancer progression. While TMEM158 has been studied in various cancer types, its role in lung cancer remains unclear. Kaplan-Meier curves were used to evaluate the association between TMEM158 expression and overall survival rates. Gene set enrichment analysis (GSEA) was performed to explore pathways related to TMEM158, and sequence analysis was conducted to identify putative hypoxia-responsive element (HRE) sites in the TMEM158 promoter region. Hypoxic conditions were induced, and TMEM158 expression levels were measured by qPCR. The effect of hypoxia-inducible factor-1α (HIF-1α) depletion on TMEM158 expression was also examined. Additionally, lung cancer cells with either over-expressed or reduced TMEM158 levels were analyzed for epithelial-mesenchymal transition (EMT) and cell migration. Analysis of clinical datasets revealed elevated TMEM158 expression in tumors, particularly in patients with advanced stages. High TMEM158 expression was correlated with lower overall survival. TMEM158 was associated with EMT, hypoxia, and other tumor-promoting pathways. Under hypoxic conditions, TMEM158 expression was at least partially induced in a HIF-1α-dependent manner. Functional studies showed that over-expression of TMEM158 promoted EMT and increased lung cancer cell migration, while depletion of TMEM158 reduced these effects, indicating its role in aggressive tumor behavior. TMEM158 is highly expressed in lung cancer, is associated with hypoxia, and promotes EMT and cell migration. These findings suggest TMEM158 as a potential target for lung cancer therapies.

Ascending aortic length predicts adverse outcomes in type a intramural hematoma.

Ascending aortic length has recently been recognized as a novel predictor of adverse events in aortic diseases, but its prognostic value in type A intramural haematoma is unknown. We aimed to evaluate the association between ascending aortic length and outcomes in patients with type A intramural haematoma initially managed medically. We retrospectively analyzed patients with acute type A intramural haematoma. Ascending aortic length was measured by computed tomography. The primary outcome was aortic progression, defined as aortic intervention or aortic-related death. A total of 98 patients were enrolled. During a median follow-up of 2.6 years, aortic progression occurred in 27 patients (27.6%), ie, 9 events per 100 patient-years). Patients with ascending aortic length ≥11 cm had significantly higher rates of aortic progression (54.2% [20.9 events per 100 patient-years] vs 18.9% [6.1 events per 100 patient-years], p = 0.001), surgical intervention (45.8% vs 12.2%, p = 0.001), and presence of ulcer-like projection (25.0% vs 2.7%, p = 0.002) compared to those with ascending aortic length <11 cm. Kaplan-Meier analysis demonstrated lower progression-free survival in the ascending aortic length ≥11 cm group (p = 0.0021). Ascending aortic length had a sensitivity of 61.9% and specificity of 77.8% for predicting aortic progression, with an area under the curve of 0.756 (95% confidence interval: 0.649-0.862). Ascending aortic elongation may identify a high-risk subgroup of acute type A intramural haematoma patients initially managed medically who could potentially benefit from early surgery. Ascending aortic length should be considered in the risk stratification and management of these patients.

The benefits of prophylactic defibrotide: Are the tides turning?

Veno-occlusive disease (VOD) is a life-threatening endotheliopathy that can occur after stem cell transplant (SCT). Numerous risk factors contribute to the development of VOD during SCT, and the role of prophylactic defibrotide (DF) in mitigating these risks remains unclear. We compare not only the incidence of VOD development, but also the severity of VOD and survival outcomes between patients who did and did not develop VOD and did or did not receive prophylactic DF. In this single-center retrospective study of 58 pediatric SCT patients from 2008 to 2022, we compare the demographics, risk profiles, and outcomes within three cohorts: Group 1: prophylactic DF and no VOD (n=5), Group 2: prophylactic DF and development of VOD (n=6), and Group 3: treatment DF for patients who developed VOD (n=47). Patients with VOD who did not receive prophylactic DF had higher severity classification of disease at onset (very severe 80.9% vs. 66.7%, p=.592) and at maximum severity (very severe 89.4% vs. 83.3%, p=.532), as opposed to mild, moderate, or severe categorization compared to those who did not receive prophylactic DF. Patients who developed VOD and did not receive prophylactic DF had a lower 1-year survival probability compared to those who received prophylactic DF and still developed VOD (51.1% vs. 75% alive at 1year, excluding the two subjects without adequate follow-up time, p=.266). Although, not statistically significant in our small retrospective study, there is potential overall survival and decreased VOD severity benefits of prophylactic DF.

Initial sarcopenia and body composition changes as prognostic factors in cervical cancer patients treated with concurrent chemoradiation: An artificial intelligence-based volumetric study

ObjectivesThis study aimed to investigate the influence of baseline sarcopenia and changes in body composition on survival during cervical cancer treatment. MethodsPatients diagnosed with stage IB1-IVB cervical cancer who underwent primary concurrent chemoradiation therapy (CCRT) between 2002 and 2022 were included. The exclusion criteria were prior radical hysterectomy, lack of pretreatment computed tomography (CT) imaging, or significant comorbidities. An artificial intelligence-based automatic segmentation program assessed body composition by analyzing CT images, defining L3 sarcopenia (L3 skeletal muscle index [SMI] <39cm2/m2) and volumetric sarcopenia (volumetric SMI <180.4 cm3/m3). Comparative and multivariate analyses identified the prognostic factors. The impact of body component changes during CCRT was explored. ResultsAmong 347 patients, there were 125 recurrences and 59 deaths (median follow-up, 50.5 months). Seven patients were excluded from the volumetric sarcopenia analysis because of incomplete baseline CT data, and 175 patients were included in the analysis of body composition changes. Patients with L3 sarcopenia had a lower 5-year progression-free survival (PFS) rate (55.6% vs. 66.2%, p = 0.027), while those with volumetric sarcopenia showed a poorer 5-year overall survival rate (76.5% vs. 85.1%, p = 0.036). Patients with total fat loss during CCRT had a worse 5-year PFS rate than those with total fat gain (61.9% vs. 73.8%, p = 0.029). Multivariate analyses revealed that total fat loss (adjusted hazard ratio [aHR], 2.172; 95% confidence interval [CI], 1.066–4.424; p = 0.033) was a significant factor for recurrence, whereas L3 sarcopenia was not. Volumetric sarcopenia increased the risk of death by 1.75-fold (aHR, 1.750; 95% CI, 1.012–3.025; p = 0.045). ConclusionsAmong patients with cervical cancer undergoing CCRT, initial volumetric sarcopenia and fat loss during treatment are survival risk factors. These findings suggest the potential importance of personalized supportive care, including tailored nutrition and exercise interventions.

Sick without signs. Subclinical infections reduce local movements, alter habitat selection, and cause demographic shifts

In wildlife populations, parasites often go unnoticed, as infected animals appear asymptomatic. However, these infections can subtly alter behaviour. Field evidence of how these subclinical infections induce changes in movement behaviour is scarce in free-ranging animals, yet it may be crucial for zoonotic disease surveillance. We used an ultra-high-resolution tracking system (ATLAS) to monitor the movements of 60 free-ranging swallows every 8 seconds across four breeding seasons, resulting in over 1 million localizations. About 40% of these swallows were naturally infected with haemosporidian parasites. Here, we show that infected individuals had reduced foraging ranges, foraged in lower quality habitats, and faced a lowered survival probability, with an average reduction of 7.4%, albeit with some variation between species and years. This study highlights the impact of subclinical infections on movement behaviour and survival, emphasizing the importance of considering infection status in movement ecology. Our findings provide insights into individual variations in behaviour and previously unobservable local parasite transmission dynamics.

Deciphering the role of NcRNAs in Pancreatic Cancer immune evasion and drug resistance: a new perspective for targeted therapy

Pancreatic cancer (PC) is a very aggressive digestive system tumor, known for its high mortality rate, low cure rate, low survival rate and poor prognosis. In particular, pancreatic ductal adenocarcinoma (PADC), which accounts for more than 90% of PC cases, has an overall 5-year survival rate of only 5%, which is an extremely critical situation. Early detection and effective treatment of PC is extremely difficult, which leads many patients to despair. In the current medical context, targeted therapy, as an important strategy for cancer treatment, is expected. However, the problems of immune escape and drug resistance in PC have become two major obstacles that are difficult to be overcome by targeted therapy. How to break through these two difficulties has become a key issue to be solved in the field of PC therapy. In recent years, non-coding RNAs (ncRNAs) have continued to heat up in the field of cancer research. NcRNAs play a pivotal role in gene regulation, cell differentiation, development, and disease processes, and their important roles in the genesis, development, and therapeutic response of PC have been gradually revealed. More importantly, ncRNAs have many advantages as therapeutic targets, such as high specificity and low side effects, making them a new favorite in the field of PC therapy. Therefore, the aim of this paper is to provide new ideas and methods for the targeted therapy of PC by reviewing the mechanism of action of four major ncRNAs (circRNAs, lncRNAs, miRNAs, siRNAs) in both immune escape and drug resistance of PC. It is expected that an effective way to overcome immune escape and drug resistance can be found through in-depth study of ncRNA, bringing a ray of hope to PC patients.

Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA-matched stem-cell transplantation for acute myeloid leukemia.

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.

Clinical and prognostic significance of Hec1 expression in patients with Cervical Cancer

ObjectiveHec1 is a component of the Ndc80 kinetochore complex and is frequently upregulated in various cancers. However, the clinical significance of Hec1 in cervical cancer remains largely unknown. This study aimed to investigate the expression patterns of Hec1 in cervical cancer and its relationship with the clinicopathological characteristics of patients diagnosed with the disease.MethodsImmunohistochemistry was used to assess the expression of Hec1 in 136 cervical cancer tissue samples and 82 normal cervical tissue samples. The relationship between Hec1 protein expression and the clinicopathological characteristics of cervical cancer patients was analyzed using the Chi-square test. Additionally, the association between Hec1 protein expression and patient survival was examined using Kaplan-Meier survival curves. Independent risk factors affecting the prognosis of cervical cancer patients were analyzed using the Cox proportional hazards regression model.ResultsThe positive expression rate of Hec1 protein in cervical cancer tissues was 83.82%, significantly higher than the 7.31% in normal cervical tissues. Compared to patients with negative Hec1 expression, those with positive expression exhibited significantly higher FIGO staging, increased lymph node metastasis, greater depth of tumor stromal infiltration, and larger tumor diameter. Multivariable analysis using the Cox proportional hazards regression model indicated that Hec1 positive expression was an independent risk factor for both overall survival (HR = 2.79, 95% CI: 1.65–4.05, p = 0.012) and progression-free survival (HR = 1.81, 95% CI: 1.22-3.18, p = 0.002) in cervical cancer patients. Kaplan-Meier survival curve analysis showed that patients with positive Hec1 expression experienced a lower overall survival (HR: 2.72, 95% CI: 1.15–4.52, p = 0.004) and progression-free survival (HR: 3.12, 95% CI: 1.62–5.03, p = 0.002) when compared to those with negative Hec1 expression.ConclusionHec1 is significantly upregulated in cervical cancer tissues and associated with poor prognosis in cervical cancer patients. Therefore, Hec1 could be a novel biomarker, not only for the diagnosis and treatment evaluation of cervical cancer but also as an indicator for predicting the prognosis of cervical cancer patients.

Evaluation of BUBR1, MCM2, and GMNN as oral cancer biomarkers.

Oral cancer is a public health problem worldwide. Late diagnosis results in a low survival rate. However, this tumor can arise from oral precancerous lesions and identification of biomarkers in precursor lesions has the potential for early diagnosis, improving patient survival. In this context, proteins involved in the cell cycle control are potentially promising. This study aimed to evaluate the importance of immunohistochemical expression of BUBR1, MCM2, and GMNN as biomarkers of oral carcinogenesis considering different oral sites. Sixty-six samples of oral epithelial dysplasia (from 33 males and 33 females) and 63 samples of oral squamous cell carcinoma (from 44 males and 19 females) were subjected to immunohistochemistry to detect some human proteins. Ki67 expression was included as a marker of cell proliferation. Marker expression was quantified by manually counting at least 1000 cells, and the labeling index was used in all statistical analyses. GMNN, MCM2, BUBR1 (nuclear and cytoplasmic labeling), and Ki67 expression levels were higher in carcinomas than in dysplasia (P < 0.05). Cytoplasmic BUBR1 was a good marker of malignancy (AUC = 0.8525, P < 0.05), but Ki67 was not (AUC = 0.5943, P = 0.0713). GMNN, MCM2, BUBR1, and Ki67 had higher expression in carcinoma than in dysplasia, regardless of the site of the lesion. Cytoplasmic BUBR1 has the potential to be used as a marker of tumor progression.

High Stress Hyperglycemia Ratio Versus Absolute Hyperglycemia as a Predictor of Poor Outcome Among Patients With Type 2 Diabetes Mellitus and Moderate to Critical Covid-19 Infection Admitted at a Tertiary Hospital from 2020-21: A Retrospective Study

Background: Patients with diabetes are vulnerable and highly susceptible to contracting COVID-19. Stress hyperglycemia ratio (SHR) may provide prognostic information in hospitalized patients. It is debatable whether stress hyperglycemia directly leads to poor outcomes, or is simply a marker of increased stress and inflammation. Objective: This study investigates whether high SHR is associated with poor clinical outcomes among patients with type 2 diabetes mellitus (T2DM) and moderate to critical COVID-19 infection. Moreover, this study aims to compare high SHR versus absolute hyperglycemia as a predictor of poor outcomes. Methodology: A chart review was conducted on 146 COVID-19 patients with T2DM from March 2020 to December 2021. The area under the receiver operating curve was conducted to categorize SHR into low and high levels. The association of high SHR levels and absolute hyperglycemia with outcomes was analyzed using the regression analysis. Survival analysis was also utilized to allow differences in the time when in-hospital mortality occurred. Result: Patients with high SHR had a significantly higher proportion of mortality and invasive ventilation compared to those with low SHR. High SHR significantly increased the likelihood of invasive ventilation by 16.49 times and mortality hazards by 5.70 times compared to low SHR. Kaplan-Meier survival curves showed that those with high SHR had significantly lower survival rates than those with low SHR. In contrast, the survival estimates between those with and without absolute hyperglycemia were not statistically significant. Conclusion: High SHR (&gt;1.082) was associated with poorer outcomes, increased invasive mechanical ventilatory support and increased mortality. Keywords: Stress Hyperglycemia Ratio, Absolute Hyperglycemia, Type 2 Diabetes Mellitus, COVID-19, Poor outcome

Cutaneous Metastasis of Rectal Cancer as a Diagnostic Challenge: A Clinical Case and Literature Review

Background/Objectives: Metastatic colorectal cancer remains a fatal disease, with a 5-year survival rate lower than 15%. The most common metastatic sites are the lungs and the liver, while skin metastases are very rare and often indicate a poor prognosis with a lower survival rate. Methods. Herein, we present the clinical case of a 62-year-old female patient with rectal cancer metastases to the skin of the anogenital and abdominal regions, diagnosed 2 years after completion of treatment of the underlying disease. Results: Histological examination of the skin lesions revealed adenocarcinoma, and expression of the same immunohistochemical markers was also found in the primary tumor and in the cutaneous metastases. However, next-generation sequencing demonstrated differences in the mutational profiles of the primary tumor and metastasis to the skin. Somatic mutations in the APC, TP53, and PTPN11 genes were revealed in primary rectal adenocarcinoma, but another pathogenic TP53 mutation and a frameshift variant in the DYNC1I1 gene were found in cutaneous metastases. The patient underwent several courses of FOLFOX6 chemotherapy in combination with bevacizumab, but the treatment was unsuccessful. An analysis of 50 clinical cases from the literature concerning various manifestations of cutaneous metastases of rectal cancer showed a median survival of 8.5 months from the time of detection of the skin lesions. Conclusions: In this regard, careful skin examination of patients with rectal cancer and timely detection of cutaneous metastases are essential steps in the follow-up of patients who have undergone treatment of the primary tumor.

Development of a web-based tool for estimating individualized survival curves in glioblastoma using clinical, mRNA, and tumor microenvironment features with fusion techniques.

Glioblastoma (GBM), one of the most common brain tumors, is known for its low survival rates and poor treatment responses. This study aims to create a robust predictive model that integrates multiple feature types, including clinical data, RNA expression, and tumor microenvironment data, using fusion techniques to enhance model performance. We obtained data from the SEER database to assess the impact of nine demographic and clinical features on the survival of 58,495 GBM patients and built predictive machine learning models. Additionally, mRNA expression data from 600 GBM patients from TCGA, CGGA, and GEO were analyzed. We used Cox regression and LASSO to create a gene signature, which was compared against 13 published signatures for accuracy. Twenty-one machine learning models were applied to predict survival at multiple time points. Finally, we integrated multiple feature types using fusion techniques and developed a Shiny app to provide survival predictions for GBM patients. Using the SEER database, we constructed machine learning models based on nine clinical variables: age, gender, marital status, race, tumor site, laterality, surgery, chemotherapy, and radiation therapy. The best-performing model achieved AUC values of 0.775, 0.728, 0.692, and 0.683 for predicting survival at 6, 12, 18, and 24months in the testing cohort. In the merged TCGA, CGGA, and GEO cohorts, we identified 11 genes to develop predictive models. These 11 genes outperformed 13 other published gene signatures in predicting the prognosis of GBM. When incorporating mRNA features, tumor microenvironment features, and clinical variables into the fusion models, the AUC values for predicting survival at 6, 12, 18, and 24months were 0.641, 0.624, 0.655, and 0.637, respectively. A user-friendly tool for predicting the survival curve of individual GBM patients is available at https://zzubioinfo.shinyapps.io/mlGBM/ . Our study provides a web-based tool that includes two modules: one for predicting survival curves using only clinical variables, and another that integrates multiple feature types for more comprehensive predictions.

Using a Bayesian analytic approach to identify county-level ecological factors associated with survival among individuals with early-onset colorectal cancer.

In the United States (US), incidence of early age of onset colorectal cancer (EOCRC, diagnosed <50 years of age) has been increasing. Using a Bayesian analytic approach, we evaluated the association between county-level ecological factors and survival among individuals with EOCRC and identified hotspot and coldspot counties with unexplained low and high survival, respectively. Principal component (PC) analysis was used to reduce dimensionality of 36 county-level social, behavioral, and preventive factors from the Centers for Disease Control and Prevention data. Survival information was derived from the Surveillance, Epidemiology, and End Results Program data from January 1, 2000 to December 31, 2019. The association between the identified PCs and survival was evaluated using multivariable spatial generalized linear mixed models. Counties with residual low and high survival (i.e., unexplained by the PCs) were classified as hotspots and coldspots, respectively. Four PCs were used to explain the spatial variability in 5-year survival among 75,215 individuals with EOCRC: PC1) poverty, chronic disease, health risk behaviors (β = -0.03, 95% credible interval (CrI): -0.04, -0.03); PC2) younger age, chronic disease-free, minority status (β = -0.01, 95% CrI: -0.02, 0.00); PC3) urban environment, preventive services (β = 0.02, 95% CrI: 0.00, 0.03); and PC4) older age (-0.04, 95% CrI: -0.06, -0.02). Among individuals with distant malignancies, the residual spatial variability remained high for two US counties: 1) Salt Lake County, UT residents experiencing 26.5% (95% CrI: 1.5%, 47.8%) lower odds of survival [hotspot], and 2) Riverside County, CA residents experiencing 37% (95% CrI: 7.97%, 78.8%) higher odds survival [coldspot] after adjustment for county-level factors. County-level ecological factors are strongly associated with survival among individuals with EOCRC. Yet there is some evidence of survival disparities among individuals with distant malignancies that remain unexplained by the included factors.

Sociodemographic Disparities in 1-Year Outcomes of Children With Community-Acquired Acute Kidney Injury

Racial disparities have been identified in pediatric community-acquired acute kidney injury (CA-AKI), and they are associated with increased risk of child mortality, morbidity, and progression of kidney disease. To assess clinical outcomes at 1 year among children with CA-AKI, stratified by age, race, and ethnicity. This retrospective cohort study is a population-based analysis of deidentified, aggregated electronic health record data collected by 61 large health care organizations from 2003 to 2023 and accessed through the TriNetX platform. Outcomes were assessed at 1 year after a CA-AKI episode. Participants included pediatric patients (aged <18 years) with AKI. Data were accessed in January 2024. A diagnosis of CA-AKI and sociodemographic factors such as race, ethnicity, and age, as reported in electronic health records. The primary end point of this study was to assess differences in clinical outcomes within 1 year of an episode of CA-AKI, including all-cause emergency department (ED) visits, intensive care unit (ICU) admissions, mechanical intubation and ventilation, and mortality. Risk was compared between White children and Asian (including Asian, Native Hawaiian, and Other Pacific Islander), Black, and Hispanic children, stratified by age group. Measures of association, Cox proportional hazard analyses, and Kaplan-Meier survival curves were performed within the TriNetX Advanced Analytics Platform between racial and ethnic groups for each analysis. From the total sample of 18 152 children, those with hospital-acquired AKI, chronic kidney disease, end-stage kidney failure, or dialysis dependence were excluded, leaving a final cohort of 17 125 children (mean [SD] age, 11.2 [5.2] years; 9424 male [55.3%]). Eligible patients were divided into racial and ethnic groups as follows: non-Hispanic Asian, 1169 children (6.5%); non-Hispanic Black, 4636 children (27.3%); Hispanic, 1786 children (10.2%); and non-Hispanic White, 9534 children (55.9%). Patients were further subdivided into groups aged 0 to 9 years (546 Asian children, 1675 Black children, 689 Hispanic children, and 3340 White children) and 10 to 18 years (623 Asian children, 2961 Black children, 1091 Hispanic children, and 6104 White children). Within 1 year of CA-AKI diagnosis, compared with White children, Black children experienced greater rates of ED visits (hazard ratio [HR], 1.53; 95% CI, 1.40-1.67), ICU admissions (HR, 1.31; 95% CI, 1.16-1.47), mechanical ventilation (HR, 1.33; 95% CI, 1.13-1.56), and all-cause mortality (HR, 1.27; 95% CI, 1.09-1.48), as well as the greatest risk for composite outcomes (HR, 1.43; 95% CI, 1.33-1.53). Hispanic children experienced greater rates of ED visits (HR, 1.40; 95% CI, 1.21-1.62) and the greatest risk of all-cause mortality (HR, 1.66; 95% CI, 1.31-2.09), whereas Asian children experienced greater rates of mechanical ventilation (HR, 1.69; 95% CI, 1.26-2.27), compared with White children. Black and Hispanic children aged 0 to 9 years were at greatest risk of experiencing poor clinical outcomes. Black children had a 11.41% lower survival probability and Hispanic children had a 7.14% lower survival probability compared with White children after an initial ED encounter. Among children with an identified episode of CA-AKI diagnosed in an ED, within 1 year, Black and Hispanic children had a poorer survival probability compared with White children. Future studies are needed to understand these disparities and improve awareness and follow-up after emergency care.

Prognostic influence of the neurological complications in patients supported with venoarterial extracorporeal membrane oxygenation

Abstract Background Neurologic injuries including ischemic or hemorrhagic stroke and hypoxic-ischemic encephalopathy are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Purpose Our objective was to analyze the prognostic influence of neurological injuries on in-hospital survival. Methods Retrospective analysis of consecutive VA-ECMO cases in a referal center. We studied the neurological diagnoses and the results of complementary tests (brain computed tomography –CT- and electroencephalogram –EEG-) and their influence on in-hospital evolution. Results 238 VA-ECMO were implanted between oct 2013-jan 2024. Baseline, admission and evolution characteristics are collected in the table. 58.4% of patients had suffered cardiac arrest (prior to VA-ECMO implantation, and extracorporeal cardiopulmonary resuscitation was performed in 28.6% of cases. 6 (2.5%) suffered intracranial hemorrhage, 13 (5.5%) ischemic stroke and 40 (16.8%) some degree of hypoxic-ischemic encephalopathy. In-hospital survival was 32.4% (n=77). In 17.2% of the cases neurological damage influenced death (adequacy of therapeutic effort or non-escalation of therapies) and in 14.7% of cases death was directly due to neurological cause (table). Survival was lower in patients with ischemic (stroke survival 23.1% vs no stroke 33.2%, p=0.555) or hemorrhagic stroke (16.7% vs 33%, p=0.667), although without statistically significant differences. The presence of hypoxic brain damage was related to lower hospital survival (survival in patients with encephalopathy 15% vs. without 36.8%, p=0.009). Best EEG pattern registered was related to survival: I survival 33.3% and II 12.5% (good prognosis), III 25% (uncertain prognosis), IV 16.7% and V 0% (poor prognosis), p=0.048. The presence of status epilepticus showed a non-statistically significant trend towards lower survival (survival status 0% vs no estatus 25%, p=0.082). VA-ECMO preimplantation cardiac arrest was associated with the occurrence of encephalopathy (encephalopathy 84% vs. not 40%, p=0.049). The duration of cardiac arrest and lactate before VA-ECMO implantation were significantly higher as the EEG pattern was worse (figure). Conclusions Neurological damage is relevant in patients under VA-ECMO support, being a determining factor in death in up to 17.2% of patients. Hypoxic-ischemic encephalopathy was associated with lower survival, with the EEG pattern associated with previous cardiac arrest, its duration and lactate.Table.Baseline, admission and follow-upFigure.Cardiac arrest, lactate and EEG

Impact of Impella5.0/5.5 use on short-term prognosis in patients with AMI-related cardiogenic shock receiving Impella-incorporated MCS in Japan

Abstract Background The short-term prognosis in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS) remains unsatisfactory even in the era of Impella. The survival benefit of Impella 5.0/5.5 use remains uncertain. Purpose This study examined the clinical impact of Impella device type on clinical outcomes among patients with AMI-CS receiving Impella support using the prospective multi-center J-PVAD registry data. Methods We included patients with AMI-CS who received Impella-incorporated temporary MCS and were enrolled in the J-PVAD registry between Feb 2022 and Dec 2023. The primary outcome was 30-day survival. Results A total of 2405 patients (average 71 y; LVEF 30%; Lac 5.6 mmol/L) were included. 1409 (58.6%) patients received Impella alone and the others (41.4%) received ECPELLA support. Patients who received ECPELLA had a lower 30-day survival compared to those receiving Impella alone (46.1% vs 62.3%, p &amp;lt; 0.0001). Of note, patients who received ECMO with Impella5.0/5.5 had a greater survival compared to those who received ECMO with Impella2.5/CP (64.4% vs 43.0%, Figure 1). Conclusions Patients who received ECPELLA had a lower 30-day survival compared to Impella alone. Impella 5.0/5.5 use may improve prognosis for those with ECMO support in AMI-CS.