Independent Predictor Of Poor Survival Research Articles

246 Residential aged care facility (RACF) residency is an independent predictor of poorer survival from out-of-hospital cardiac arrest in older persons in Perth, Australia

246 Residential aged care facility (RACF) residency is an independent predictor of poorer survival from out-of-hospital cardiac arrest in older persons in Perth, Australia

Machine learning-based identification of CYBB and FCAR as potential neutrophil extracellular trap-related treatment targets in sepsis.

Sepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis. Datasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN). Analysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level. CYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.

Characteristics and risk factors for advanced lung cancer with pulmonary embolism: A cross-sectional, case-control study.

Pulmonary embolism (PE) is a life-threatening complication that can occur in patients with lung cancer. In this study, we aimed to identify risk factors and examine the clinical characteristics of advanced lung cancer patients with PE. We conducted a retrospective review of patients admitted to our two hospitals between January 2020 and June 2022. The case group consisted of patients with lung cancer and PE, and a closely matched control group was included to identify risk factors. Statistical analysis was conducted using R language. A total of 4957 patients were reviewed, and 162 patients (comprising 54 cases and 108 controls) were included in this study. The prevalence of lung cancer with PE in the study population was 1.08%. The majority of patients were male, and the most common histological subtype was adenocarcinoma (67%), followed by squamous cell carcinoma, small cell carcinoma, and poorly differentiated non-small cell lung cancer. The majority of patients had a high performance status (PS) score, with 50% experiencing respiratory failure (mainly hypoxia) and 33% with deep vein thrombosis (DVT). Forty-eight percent of patients were diagnosed with concurrent PE. Further analysis showed that PE was an independent predictor of poor survival, and a PS score of >1 was an independent risk factor for PE in patients with lung cancer. Our study provides valuable insights into the epidemiology and prognosis of PE in lung cancer patients and suggests that a poor ECOG PS, which has not been previously reported, is an independent risk factor for PE.

Pretreatment dual-energy CT for predicting early response to induction chemotherapy and survival in nasopharyngeal carcinoma.

To evaluate the predictive performance of pretreatment dual-energy CT (DECT) for early response to induction chemotherapy and survival in nasopharyngeal carcinoma (NPC). In this retrospective study, 56 NPC patients who underwent pretreatment DECT scans with posttreatment follow-up were enrolled. The DECT-derived normalised iodine concentration (nIC), effective atomic number (Zeff), 40-180keV (20keV interval), and Mix-0.3 value of the tumour lesions were measured to predict the early response to induction chemotherapy and survival in nasopharyngeal carcinoma. The Mann‒Whitney U test, ROC analysis, Kaplan‒Meier method with log-rank test, and Cox proportional hazards model were performed to evaluate the predictive performance of DECT parameters, respectively. Among all DECT-derived parameters, ROC analysis showed the predictive performances of nIC and Zeff values for early objective response to induction chemotherapy (AUCs of 0.803 and 0.826), locoregional failure-free survival (AUCs of 0.786 and 0.767), progression-free survival (AUCs of 0.856 and 0.731) and overall survival (AUCs of 0.765 and 0.799) in NPC patients, respectively (all p < 0.05). Moreover, multivariate analysis showed that a high nIC value was an independent predictor of poor survival in NPC. In addition, survival analysis indicated that NPC patients with higher nIC values in primary tumours tend to have lower 5-year locoregional failure-free survival, progression-free survival and overall survival rates than those with lower nIC values. DECT-derived nIC and Zeff values can predict early response to induction chemotherapy and survival in NPC; in particular, a high nIC value is an independent predictive factor of poor survival in NPC. Preoperative dual-energy computed tomography may provide predictive value for early response and survival outcomes in patients with nasopharyngeal carcinoma, and facilitate their clinical management. • Pretreatment dual-energy computed tomography helps to predict early response to therapy and survival in NPC. • NIC and Zeff values derived from dual-energy computed tomography can predict early objective response to induction chemotherapy and survival in NPC. • A high nIC value is an independent predictive factor of poor survival in NPC.

Immunological features of ESRD patients undergoing hemodialysis of various ages.

To investigate the immunological characteristics of hemodialysis (HD) patients with end-stage renal disease (ESRD) of various ages, and the impact of age-related immune alterations on these patients, with a focus on peripheral T cells. From September 2016 to September 2019, HD patients were enrolled and followed prospectively for 3years. Patients were divided into three groups based on their ages: < 45, 45 to 64, and ≥ 65. The distribution of T cell subsets in different age groups was investigated and compared. The effects of altered T cell subsets on overall survival were also investigated. A total of 371 HD patients were enrolled. The reduced number of naive CD8+ T cells (P < 0.001) and increased number of EMRA CD8+ T cells (P = 0.024) were independently associated with theadvanced age among all T cell subsets studied. Patient survival may be affected by numerical changes in naive CD8+ T cells. However, when HD patients were < 45 or ≥ 65years, the reduction had no significant impacton survival. Only in HD patients aged 45 to 64years, the number of naïve CD8+ T cells found to be insufficient but not deficient, identified as an independent predictor of poor survival. The most significant age-related immune change in HD patients was a decrease in peripheral naive CD8+ T cells, which was an independent predictor of 3-year overall survival in HD patients aged 45 ~ 64years.

#3160 IMPACT OF HEART FUNCTION ON ELDERLY INCIDENT HEMODIALYSIS PATIENTS

Abstract Background and Aims Cardiovascular disease (CVD) is the most common cause of death in patients on hemodialysis (HD). Indeed, left ventricular (LV) dysfunction, symptomatic congestive heart failure and arrhythmia are independent predictors of poor survival and hospitalization in these patients. Among the patients who initiated HD, the proportions of the elderly patients aged &amp;gt;65 years are increasing worldwide. According to the Korean Renal Data System, the percentage of incident HD patients aged&amp;gt;65 years increased from 11% in 1990 to 53% in 2022. In addition, the prevalence of CVD increases with age. Therefore following these trends, investigating the impact of heart function on prognosis in elderly patients on HD is important for predicting prognosis and making appropriate treatment plans. This study aims to investigate the all-cause mortality in elderly incident HD patients according to heart function and presence of arrhythmia. Method 1,002 incident HD patients aged &amp;gt;70 years were recruited from a retrospective cohort of the Korean Society of Geriatric Nephrology. The primary outcome is all-cause mortality (6 months, overall) according to the LV function and presence of arrhythmia. To analyze, patients were divided into 6 groups according to the LV function (LV ejection fraction [LVEF]≥50%, 40≤LVEF&amp;lt;50%, LVEF&amp;lt;40%) and the presence of arrhythmia. The secondary outcome is all-cause mortality (6 months, overall) according to the LV function or presence of arrhythmia. To analyze, patients were divided into 3 groups according to the LV function and separately divided into 2 groups according to the presence of arrhythmia. Cox regression univariate and multivariate analyses was used. Results 1,002 patients were divided into 6 groups (LVEF≥50% without arrhythmia [N = 707, 70.6%], 40≤LVEF&amp;lt;50% without arrhythmia [N = 71, 7.1%], LVEF&amp;lt;40% without arrhythmia [N = 66, 6.6%], LVEF≥50% with arrhythmia [N = 124, 12.4%], 40≤LVEF&amp;lt;50% with arrhythmia [N = 15, 1.5%], LVEF&amp;lt;40% with arrhythmia [N = 19, 1.8%]). There were no differences of 6-month all-cause mortality among the groups. Compared with LVEF≥50% without arrhythmia group, 40≤LVEF&amp;lt;50% without arrhythmia (hazard ratio [HR], 1.59; 95% confidence interval [95% CI], 1.21-2.09; P = 0.001), LVEF≥50% with arrhythmia (HR, 1.39; 95% CI, 1.12-1.74, P = 0.003) and LVEF&amp;lt;40% with arrhythmia groups (HR, 1.95; 95% CI, 1.19-3.17, P = 0.007) showed higher all-cause mortality of overall period. According to the LVEF groups, there were no differences of 6-month all-cause mortality among the groups. Compared with LVEF≥50% group, 40≤LVEF&amp;lt;50% group showed higher all-cause mortality of overall period (HR, 1.51; 95% CI, 1.18-1.94, P = 0.001). According to the arrhythmia groups, there were no differences of 6-month all-cause mortality between the groups. The presence of arrhythmia was associated with higher all-cause mortality of overall period (HR, 1.39; 95% CI, 1.15-1.69, P = 0.001). Conclusion Decreased heart function and presence of arrhythmia have negative impact on all-cause mortality of overall period, but not on 6-month all-cause mortality in elderly patients on incident HD. Therefore, evaluation of the heart function and detection of arrhythmia in elderly patients who start HD and providing the appropriate treatment to these patients would be helpful for improving the prognosis.

Vitamin D Status, Cdx2 Genotype, and Colorectal Cancer Survival: Population-Based Patient Cohort.

According to recent evidence, the prognostic value of Vitamin D (VitD) status for colorectal cancer (CRC) patients might be confined to patients with the GG genotype of Cdx2, a functional polymorphism of the VitD receptor gene. We aimed to validate these findings in a cohort of CRC patients. Post-operative serum 25-hydroxyvitamin D concentration was determined by mass spectrometry and Cdx2 genotyping was performed from blood or buccal swabs using standard methods. Joint associations of VitD status and Cdx2 with overall survival (OS), CRC-specific survival (CSS), recurrence-free survival (RFS), and disease-free survival (DFS) were assessed using Cox regression. For patients with GG genotype, adjusted hazard ratios (95% confidence interval) for the associations of sufficient compared with deficient VitD were 0.63 (0.50-0.78), 0.68 (0.50-0.90), 0.66 (0.51-0.86), and 0.62 (0.50-0.77) for OS, CSS, RFS, and DFS, respectively. These associations were weaker and not statistically significant for the AA/AG genotype. Interaction between VitD status and genotype did not reach statistical significance. VitD deficiency is an independent predictor of poorer survival, particularly for the GG Cdx2 carriers, suggesting a potential role of VitD supplementation according to VitD status and genotype, which should be evaluated in randomised trials.

A multicenter study on adjuvant chemotherapy of S-1 versus observation for resected perihilar cholangiocarcinoma.

e16201 Background: The prognosis of perihilar cholangiocarcinoma (PHC) is poor even after curative resection. The efficacy of adjuvant S-1 chemotherapy for resected PHC is unclear. This study aimed to assess the efficacy of adjuvant S-1 chemotherapy after major hepatectomy for PHC. Methods: Consecutive patients with PHC who underwent major hepatectomy (hemihepatectomy or trisectionectomy extending to segment 1 with extrahepatic bile duct resection) at three high-volume centers in Japan from 2007 to 2020 were retrospectively evaluated. Patients with Clavien-Dindo grade V complications, pStage I or IVB disease, and those who underwent adjuvant radiation therapy were excluded from analysis. Propensity score matching analysis was performed to compare the disease-specific survival (DSS) of patients who underwent adjuvant S-1 chemotherapy with those who underwent observation. Results: Of 480 patients, 373 were eligible for the study, 81 of whom underwent adjuvant S-1 chemotherapy, and 146 underwent observation. In the global cohort, DSS in the S-1 and observation groups were similar ( P = 0.18). In the matched cohort as well (S-1: n=44, Observation: n=44), DSS was similar between the S-1 and observation groups ( P = 0.09). On multivariate analysis, performance of percutaneous biliary drainage, CA19-9 levels at operation ≥ 300 U/ml, and lymph node (LN) metastasis were independent predictors of poor survival following major hepatectomy for PHC. In subgroup analysis of patients with LN metastasis, DSS in the S-1 group was better than in the observation group ( P = 0.001). Conclusions: Adjuvant S-1 chemotherapy after major hepatectomy might be effective in PHC patients with LN metastasis.

Spatial Immunoprofiling of Adenoid Cystic Carcinoma Reveals B7-H4 Is a Therapeutic Target for Aggressive Tumors.

Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets. Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm software. The B7-H4 antibody-drug conjugate AZD8205 was tested in ACC patient-derived xenografts (PDX). RNA deconvolution revealed that most ACCs are immunologically "cold," with approximately 30% being "hot." ACC-I tumors with a poor prognosis harbored a higher density of immune cells; however, spatial analysis by IMC revealed that ACC-I immune cells were significantly restricted to the stroma, characterizing an immune-excluded TME. ACC-I tumors overexpressed the immune checkpoint B7-H4, and the degree of immune exclusion was directly correlated with B7-H4 expression levels, an independent predictor of poor survival. Two ACC-I/B7-H4-high PDXs obtained 90% complete responses to a single dose of AZD8205, but none were observed with isotype-conjugated payload or in an ACC-II/B7-H4 low PDX. Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.

Characterization and prognostic factors of secondary to MDS/MPN and therapy-related AML: a single-center study

Introduction: Secondary acute myeloid leukemia (sAML) accounts for 15–30% of overall AML cases and is associated with shorter survival compared to de novo AML. The pathogenetic spectrum of sAML is heterogeneous, i.e. therapy-related AML (tAML) arises from prior cytotoxic, radiation, or immunosuppressive therapy, while myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)-AML develops from a previous clonal disorder of hematopoiesis. Material and methods: We performed a single-center retrospective analysis of MDS/MPN-AML and tAML patients diagnosed between 2013 and 2018 in the Hematology Department of the Medical University in Lodz, Poland. Simultaneously, demographic data, clinical factors, and laboratory findings were collected. For statistical analysis, we used Cox proportional hazard models and log-rank tests. Results: The study included 110 patients with either MDS/MPN-AML (n = 78) or tAML (n = 32), with a median age of 66 years (range 31–86). The median follow-up was 3.2 months [95% confidence interval (CI): 2.5–5.3]. The median overall survival (OS) for MDS/MPN-AML patients was 4.1 months (95% CI: 2.5–7.0) and for tAML it was 2.8 months (95% CI: 1.6-5.6). In multivariate Cox regression model for OS, factors such as age at diagnosis [hazard ratio (HR) 1.03, 95% CI: 1.00–1.06], higher Eastern Cooperative Oncology Group score (HR 1.85, 95% CI: 1.08–3.15), hypoalbuminemia (HR 3.20, 95% CI: 1.95–5.24) and percentage of bone marrow blasts infiltration (HR 1.01, 95% CI: 1.00–1.03) were independent predictors of poor survival for the whole cohort. On the other hand, the intensive treatment approach was related to longer survival (HR 0.42, 95% CI: 0.21–0.82). There were no differences in OS between MDS/MPN-AML and tAML ( p = 0.81). Conclusion: The poor treatment outcomes for sAML consist of a combination of low response rate and high early mortality. The positive influence of intensive chemotherapy should be highlighted, but nevertheless, optimizing treatment for thishigh-risk subpopulation remains crucial.

Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs

Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006-2020) in Italy. Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006-2010; 2011-2015; 2016-2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol+ metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients' eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance.

Liver transplantation for biliary cysts: perioperative and long-term outcomes

BackgroundBiliary cysts (BC) is a rare indication for orthotopic liver transplantation (OLT). MethodsWe queried the UNOS dataset to identify patients who underwent OLT for Caroli's disease (CD) and choledochal cysts (CC). All patients with BC (CD + CC) were compared to a cohort of patients transplanted for other indications. Patients with CC were also compared to those with CD. Cox proportional hazard model was performed to assess predictors of graft and patient survival. Results261 patients underwent OLT for BC. Patients with BC had better pre-operative liver function compared to those transplanted for other indications. 5-year graft and patient survival were 72% and 81%, respectively, similar to those transplanted for other indications after matching. Patients with CC were younger and had increased preoperative cholestasis compared to those with CD. Donor age, race, and gender were predictors of poor graft and patient survival in patients transplanted for CC. ConclusionsPatients with BC have similar outcomes to those transplanted for other indications and more frequently require MELD score exception. In patients transplanted for choledochal cysts, female gender, donor age, and African-American race were independent predictors of poor survival. Pediatric patients transplanted for Caroli's disease had better survival compared to adults.

Body mass index percentage and survival in pediatric patients listed for lung transplantation: A modern-era multi-institutional analysis

Prior studies suggest that being underweight by body mass index percentiles (BMI%) or thinness grade did not affect post-transplant survival in pediatric lung transplant (LTx) recipients regardless of cystic fibrosis (CF) or non-CF diagnosis. Graft and overall survival from the time of listing was instead evaluated based on listing BMI%, the current standard of practice for BMI definitions in pediatrics, to ascertain the impact of a "severely low" subcategory. The UNOS registry was queried for children listed for LTx (aged 2 to <18 years) from January 1986 to March 2020. BMI% at listing and transplant were calculated per CDC guidelines according to age in years, sex, and reported BMI%. Patients were divided by listing BMI%: severely low (<3rd), low (3-<5th), normal (5-<85th), overweight (85-<95th), and obese (≥95th). Kaplan-Meier curves were generated to assess differences in overall survival since listing based on BMI% classes. Cox proportional-hazards models were developed to assess risk factors for overall and graft survival, including listing BMI%, transplant listing era (≥2005), and listing age, by reporting hazard ratios (HR). Listing BMI% was calculable for 1,876 patients. The proportion of patients with CF differed significantly between BMI% groups (p < 0.001). Patients listed with a non-CF diagnosis comprised 34% of those in the severely low category, and 88% of those listed with an obese BMI%. Compared to patients with a normal listing BMI%, the cohort with severely low BMI% had worse overall survival regardless of LTx (p=0.009) and graft survival (p=0.034). Compared to patients with a low BMI%, those with a severely low BMI% had significantly poorer graft survival as well (p=0.040). Mean graft survival was not significantly different between groups that remained at listing BMI% vs those that improved in category despite an overall small sample size. Independent predictors of poorer survival from the time of listing include severely low vs low-normal BMI% (HR=1.20) and listing age (HR=1.02). The proportion of children listed at severely low BMI% has steadily decreased with time, yet pediatric LTx candidates listed with a severely low BMI% had poorer graft and overall survival compared to those of normal BMI%. Severely low listing BMI% was an independent prognostic factor for higher mortality risk from the time of placement on the waitlist. BMI% may be a modifiable target for improving survival regardless of transplantation.

LncRNA LINC01833 is a Prognostic Biomarker and Correlates with Immune Infiltrates in Patients with Lung Adenocarcinoma by Integrated Bioinformatics Analysis.

Due to the absence of accurate tools for early detection and successful treatment, lung adenocarcinoma (LUAD) is one of the most aggressive tumors with high morbidity and mortality globally. It is absolutely necessary to investigate the process behind its development and search for new biomarkers that could aid in the early detection of LUAD. There is a correlation between the immune microenvironment of the tumor and the prognosis of lung cancer as well as the efficacy of immunotherapy. Long noncoding RNAs (lncRNAs) have been identified as potential prognostic biomarkers linked to immunological activities. In this study, we identified 1 downregulated lncRNA and 76 upregulated lncRNAs in LUAD samples from TCGA datasets. Among the 77 dysregulated lncRNAs, our attention focused on lncRNA LINC01833 (LINC01833). When compared with nontumor specimens, the level of expression of LINC01833 was shown to be significantly elevated in LUAD samples. In addition, the data of the ROC study revealed that LUAD patients with high LINC01833 expression had an AUC value of 0.840 (95% confidence interval: 0.804 to 0.876). There was a correlation between high LINC01833 expression and an advanced clinical stage. Patients who had a high expression of LINC01833 were shown to have a lower overall survival rate (p < 0.001) and a lower disease-specific survival rate (p = 0.004) in comparison to patients who were in the low LINC01833 group, according to the data on survival. In addition, the results of the multivariate analysis revealed that high LINC01833 expression was an independent predictor of poor survival in LUAD. Moreover, the immune analysis revealed that we found that the expression of LINC01833 was positively associated with Th2 cells, aDC, and Tgd, while negatively associated with Mast cells, Tcm, Eosinophils, iDC, DC, Tem, Th17 cells, and pDC. Overall, our data point to the possibility that the unique lncRNA LINC01833 might be employed as a diagnostic and prognostic marker, and as a result, it has a significant impact on clinical practice.

Molecular characteristics and prognostic factors of leptomeningeal metastasis in non-small cell lung cancer

BackgroundNon-small cell lung cancer with leptomeningeal metastasis (NSCLC-LM) is emerging as a new management challenge for oncologists and is associated with poor prognosis. This study aimed to investigate the molecular characteristics and prognostic factors of NSCLC-LM. MethodsThis retrospective study included 97 patients with NSCLC-LM between January 2015 and October 2021. Progression-free survival (PFS) and overall survival (OS) were evaluated. Gene mutations were detected by next-generation sequencing (NGS). ResultsThe median PFS and OS were 8.4 (95 % confidence interval [CI]: 4.839–11.901) and 14.0 (95 % CI: 9.254–18.746) months, respectively. Sixty-seven patients harboured epidermal growth factor receptor-mutated (EGFRm): L858R (34), 19del (29), T790M (13), and G719C with L861Q (1). Other mutations included ALK (5), ROS1 (3), KRAS (1), TP53 (14), MET amplification (6). The detection rate and types of circulating tumour DNA (ctDNA) in the cerebrospinal fluid (CSF) samples were higher than the paired plasma samples. Patients with EGFR mutations had a longer median OS than those without mutations (19.0 vs. 13.0 months, P = 0.015). Patients with gene mutations had shorter median OS than those without mutations, such as ALK (11.8 vs. 19.9 months, P = 0.014), ROS1 (12.7 vs. 19.8 months, P = 0.014), KRAS (4.0 vs. 19.0 months, P = 0.005), TP53 (15.0 vs. 19.0 months, P = 0.014), and MET amplification (6.0 vs. 19.0 months, P = 0.003). Multivariate analysis indicated that MET amplification was an independent predictor of poor survival. Along with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 3, LM accompanied with brain parenchymal metastasis (BPM), extracranial disease, and seizures were independent predictors of poor survival, whereas intrathecal chemotherapy, and third-generation EGFR-TKIs were independent predictors of favorable survival. ConclusionsCSF ctDNA detected using NGS had a high sensitivity for NSCLC-LM, showing high potential in detecting driver and drug-resistant gene mutations. Genomic profiles, combined with clinically relevant prognostic factors, will guide individualised treatments and improve the outcomes of NSCLC-LM patients.

Human Immunodeficiency Virus Is Associated With Poor Overall Survival Among Patients With Head and Neck Cancer.

Head and neck squamous cell cancer (HNSCC) occurs at higher rates among persons with HIV (PWH). This study compares the impact of sociodemographic and clinicopathologic characteristics on outcomes among PWH-HNSCC compared with HNSCC patients without HIV. Patient data from HNSCC individuals were collected at a single academic hospital center between 2002 and 2018. Forty-eight patients with HIV (HIV-HNSCC) and 2894 HNSCC patients without HIV were included. Multivariate analysis determined predictors of survival using Cox proportional hazards regression model. HIV-positive and -negative tumors were analyzed by quantitative immunofluorescence for expression of CD4, CD8, CD20 and PD-L1. HIV-HNSCC patients had a lower median overall survival than HNSCC patients without HIV (34 [18-84] vs 94 [86-103] months; P < .001). In multivariate analysis that included age, sex, race/ethnicity, stage, site, tobacco use, time to treatment initiation, and insurance status, HIV was an independent predictor of poorer survival, with a hazard ratio of 1.98 (95% CI: 1.32-2.97; P < .001). PWH with human papillomavirus (HPV)-positive oropharyngeal tumors also had worse prognosis than HPV-positive oropharyngeal tumors in the population without HIV (P < .001). The tumor microenvironment among HIV-HNSCC patients revealed lower intratumoral CD8 infiltration among HIV+ HPV+ tumors compared with HIV- HPV+ tumors (P = .04). HIV-HNSCC patients had worse prognosis than the non-HIV population, with HIV being an independent predictor of poor clinical outcomes when accounting for important sociodemographic and clinicopathologic factors. Our findings highlight differences in tumor biology that require further detailed characterization in large cohorts and increased inclusion of PWH in immunotherapy trials.

Indications for resection of recurrent lesions in patients with distal cholangiocarcinoma based on prognostic factors: a single-institute retrospective study and brief literature review

BackgroundTo evaluate the effectiveness of surgery for recurrent distal cholangiocarcinoma and determine surgical indications based on prognostic factors for the recurrence of distal cholangiocarcinoma.MethodsWe analysed the outcomes of 101 patients who underwent surgical resection for distal cholangiocarcinoma between 2000 and 2018. The clinicopathological factors and prognosis of primary and recurrent distal cholangiocarcinoma were investigated.ResultsOf the 101 patients with resected distal cholangiocarcinoma, 52 (51.5%) had relapsed. Seven (13.5%) and 45 patients (86.5%) underwent resection of recurrent lesions and palliative therapy, respectively. There were no major complications requiring therapeutic intervention after metastasectomy. The median overall survival in patients with and without surgery for recurrent lesions was 83.0 (0.0–185.6) and 34 months (19.0–49.0), respectively. Therefore, patients who had undergone surgery for recurrent lesions had a significantly better prognosis (p = 0.022). Multivariate analyses of recurrent distal cholangiocarcinoma revealed that recurrence within one year was an independent predictor of poor survival. Resection of recurrent lesions improved prognosis.ConclusionsRadical resection in recurrent distal cholangiocarcinoma may improve the prognosis in selected patients. Although time to recurrence is considered an important factor, the small number of cases of recurrence and resection of recurrent lesions in this study makes it difficult to conclude which patients are best suited for resection of recurrent lesions. This issue requires clarification in a multicentre prospective study, considering patients’ background, such as the recurrence site and number of metastases.

Sustained vasodilation after cold pressor test is an independent predictor of poor survival in primary AL amyloidosis

Abstract Background Primary AL amyloidosis is a rare yet lethal systemic disorder. Dysfunction of the autonomous nervous system due to disease-related nerve infiltration is a common manifestation of AL amyloidosis. Previously published own work indicated that AL patients present sustained paradoxical vasodilation in response to sympathetic stimulus, as assessed by cold pressor test (CPT). The clinical relevance of this finding is unknown. Purpose We sought to investigate the relationship between CPT-induced vascular response and mortality in AL amyloidosis. Methods We consecutively recruited 97 newly diagnosed patients with AL amyloidosis. CPT of the brachial artery was performed before treatment initiation. All measurements were assessed using high resolution ultrasonography (14.0Mhz multifrequency linear array probe, Vivid 7 Pro; General Electric Healthcare, Milwaukee, Wisconsin, USA). The maximum vasodilation of the brachial artery was measured during the sympathetic stimulus and 3 minutes after withdrawal (sustained response). All-cause mortality was defined as the primary end-point of the study. Results Mean age was 66 years with prevalence of male gender. Sustained vasodilation (but not vasodilation during CPT) was associated with heart failure, NYHA stage, BNP and peripheral vascular involvement (p&amp;lt;0.05 for all). Sustained vasodilation after withdrawal of the sympathetic stimulus was significantly associated with mortality as assessed by Cox regression analysis (HR: 1.149, 95% CI 1.042–1.269, p=0.005). This association remained significant after adjustment for age, sex, systolic blood pressure (SBP), nerve involvement and Mayo stage (HR: 1.123, 95% CI 1.014–1.243, p=0.026). A sustained vasodilation ≥3.35% from pre-stimulus diameter was associated with shorter survival (log-rank test, p=0.022, Figure 1). No association between vasodilation during sympathetic stress and mortality was observed. Conclusions In AL amyloidosis, sustained paradoxical vasodilation in response to sympathetic stimulus was associated with poor survival. The clinical utility of this index of vascular autonomic dysfunction as a potential prognostic and therapeutic biomarker in AL amyloidosis merits further investigation. Funding Acknowledgement Type of funding sources: None.

Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes.

Myelodysplastic syndrome is one of the main hematological malignancies that threaten the health of the elderly. However, biomarkers which predict the progression and prognosis of MDS are still controversial and puzzling. FOXO1 gene plays an important role in a variety of intracellular functions, including tumor suppression and cellular immune regulation. However, there is no research report on the correlation between FOXO1 and the clinical features of MDS including immune environment. In this study, we observed that FOXO1 expression is associated with neutrophil count, blasts, chromosome and different MDS scoring systems. FOXO1 expression is closely related to MDS cell immune polarization, and the increase expression of FOXO1 is significantly related to the amplification of immune cell polarization ratio. In addition, FOXO1 expression is associated with progression-free survival and overall survival in MDS patients. Moreover, in a multivariate model FOXO1 low-expression was an independent predictor of poor survival in MDS. In summary, FOXO1 may play a candidate tumor suppressor in MDS, and FOXO1 is a useful independent prognostic predictor in MDS, and it may provide a candidate target therapy in future.

Hippo-YAP signaling activation and cross-talk with PI3K in oral cancer: A retrospective cohort study.

This study aimed to investigate the clinical and prognostic relevance of the Hippo-YAP transactivators YAP1 and TAZ in oral squamous cell carcinoma, and their possible relationship with PI3K/mTOR pathway activation. Immunohistochemical analysis of YAP1, TAZ, PIK3CA (p110α), p-AKT (Ser473), and p-S6 (Ser235) was performed in paraffin-embedded tissue specimens from 165 OSCC patients. Correlations between protein expression and clinical data were further assessed. YAP1 expression was detected in both cytoplasm and nucleus of tumor cells, whereas TAZ expression was only found in the nucleus. Nuclear YAP1 was significantly associated with tumor size (p= 0.03), neck lymph node metastasis (p= 0.02), TNM stage (p= 0.02), and poor differentiation (p= 0.04). Nuclear TAZ was associated with tobacco (p= 0.03) and alcohol consumption (p= 0.04), and poor tumor differentiation (p= 0.04). There was a positive significant correlation between nuclear and cytoplasmic YAP1, nuclear TAZ, p110α expression, and mTORC1 activation p-S6 (S235). Combined expression of nuclear and cytoplasmic YAP1 was prognostic in both univariate and multivariate analyses. Active nuclear YAP1 was significantly and independently associated with poor disease-specific (p= 0.005, HR=2.520; 95%CI=1.319-4.816) and overall survival (p= 0.015, HR=2.126; 95%CI=1.155-3.916). Nuclear YAP1 is an independent predictor of poor survival in oral squamous cell carcinoma.