Characterization of a predictive signature for tumor microenvironment and immunotherapy response in hepatocellular carcinoma involving neutrophil extracellular traps.

Neutrophil extracellular traps (NETs) and other factors play a significant role in impacting the prognosis of patients with Hepatocellular carcinoma (HCC). Nevertheless, further research is warranted to fully elucidate the prognostic implications of NETs in patients with HCC. We employed a hierarchical clustering technique to examine the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data and identified subtypes associated with NETs. Subsequently, we utilized LASSO regression analysis to identify a distinct gene expression pattern within these subtypes. The strength of this signature was further validated through analysis of TCGA-LIHC and International Cancer Genome Consortium-Liver Cancer (ICGC-LIRI-JP) data. Our findings resulted in the construction of a six-gene signature related to NETs, which can predict survival outcomes in HCC patients. To enhance the predictive accuracy of our tool, we developed a nomogram that integrates the NETs signature with clinicopathological characteristics. We validated the significance of NETs in HCC patients using qRT-PCR and immunohistochemistry assays, along with in vitro experiments targeting high-risk genes. Furthermore, our exploration of the immune microenvironment uncovered augmented immune-specific metrics within the low-risk cohort, implying potential disparities in immune-related attributes between the high-risk and low-risk contingents. In summary, the NETs signature we discovered serves as a valuable biomarker and provides guidance for personalized therapy in HCC patients.

DEP domain containing 1 as a biomarker for poor prognosis in lung adenocarcinoma.

Objective: The DEP domain-containing 1 (DEPDC1) gene is essential in the development and advancement of different types of cancer. This study is to examine the levels of DEPDC1 in lung adenocarcinoma (LUAD), and to determine its relationship with clinical results and immune response. The goal is to assess its potential as a biomarker and therapeutic target for LUAD. Methods: By comprehensively utilizing the Cancer Genome Atlas (TCGA), gene Expression Synthesis (GEO), UALCAN, cBioPortal, TISIDB databases and online platforms, we conducted a bioinformatics analysis to investigate DEPDC1 gene survival analysis, prognostic diagnosis, prognostic survival, immune cell infiltration, DNA methylation, and the correlation of genetic mutations in LUAD. The results were validated through cell assay and immunohistochemical staining. Results: DEPDC1 shows high levels of expression in the majority of tumors, with its expression being notably elevated in LUAD compablue to normal tissues. The expression of DEPDC1 varies based on the clinical characteristics of patients with LUAD. DEPDC1 expression affects the survival prognosis and prognostic model construction of LUAD patients. In addition, the presence of DEPDC1 is linked to immune infiltration. Various chemokines and chemokine receptors, immunoinhibitors and immune-stimulators in LUAD are significantly correlated with DEPDC1 methylation levels. Cell experiments confirmed through qPCR that the mRNA expression of DEPDC1 in LUAD was markedly elevated in comparison to the normal population, and immunohistochemistry showed positive DEPDC1 expression in LUAD pathological sections. Conclusion: Systematic analysis and experiments have verified that DEPDC1 serves as a biomarker for detecting early, prediction of survival, and evaluation of immune cell infiltration in LUAD.

The role of pre-onset hair hormone in predicting the prognosis of patients with severe pneumonia and acute COVID-19 outbreak.

Numerous research works have investigated the potential impact of endocrine hormones on the severity of COVID-19-related pneumonia in individuals. However, there are few studies on the effect of pre-onset neuroendocrine hormones on the prognosis of COVID-19 patients. This study looked into the prognostic value of pre-onset hair hormone levels in COVID-19 infected individuals. This study included 27 patients with COVID-19 and collected patient information and laboratory indicators. The hormone levels in hair were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Within 28 days, 63 % of the patients in this study passed away. With 28-day mortality as the outcome index, urea nitrogen, CURB-65 score and pneumonia severity score (PSI) of 2 groups were statistically significant (P < 0.05). Among all hormone levels detected in hair, only progesterone level was substantially correlated negatively with COVID-19 patients' 28-day mortality(P < 0.05). The level of progesterone in hair was substantially adversely connected with the death rate at 28 days of COVID-19 patients, according to correlation and logistic regression analysis(P < 0.05). Among patients with COVID-19 pneumonia, hair progesterone levels were strongly associated with 28-day mortality, which emphasizes hair progesterone's importance as a prognostic factor.

Which is the best TACE agent for patients with different NLR hepatocellular carcinomas? A systematic review and network meta-analysis.

Background: Transarterial chemoembolization (TACE) is a common treatment for hepatocellular carcinoma (HCC), but the best therapeutic agent for TACE treatment has not been determined. The neutrophil/lymphocyte ratio (NLR) is a systemic immune system marker; however, the ability of the NLR to predict the prognosis of patients with HCC is unknown, and no studies have been conducted to determine the most appropriate TACE regimen for HCC patients with different NLRs. Methods: The PubMed, Embase, Web of Science, and CNKI databases were searched through May 28, 2023. Comparisons of overall survival (OS) among cohort studies with different NLRs and different TACE treatment regimens were performed with a random effects model. Findings: Thirty-five studies involving 9210 patients were included in this meta-analysis. The results showed that Group 3-4 (NLR<2.5) patients had a significantly longer OS than Group 1-2 (NLR 2.5-5.0). Among the patients, Group 1-3 (NLR 2.0-5.0) patients had the best survival after treatment with adriamycin (lnHR (95 % CI = 0.48 [0.31, 0.75] and lnHR (95 % CI = 0.41 [0.19, 0.91]). Among the Group 4 patients (NLR<2.0), the best outcome was obtained with platinum + adriamycin (lnHR (95 % CI = 0.59 [0.45, 0.78]), followed by adriamycin. A subgroup analysis of TACE combined with other treatments showed that adriamycin combined with sorafenib was the most effective and superior to the other treatment agents. Interpretation: The NLR can be used to predict the prognosis of HCC patients treated with TACE; the higher the NLR is, the worse the prognosis. Adriamycin may be the best therapeutic agent for HCC patients treated with TACE.

Comparison of Prognosis and Metachronous Gastric Tumor Rates After Endoscopic Submucosal Dissection Between Gastric Neoplasm of Fundic Gland Type Neoplasms and Conventional Gastric Adenocarcinoma.

INTRODUCTION: Gastric neoplasm of the fundic gland type (GNFG) is a tumor with a good prognosis. However, since it has not been compared with conventional gastric adenocarcinoma (CGA), it is unknown whether it has a good prognosis or requires surveillance after treatment. The purpose of this study was to determine the prognosis and metachronous gastric tumor rates compared with those of CGA. METHODS: We conducted a single-center, retrospective, matched-cohort study using our database from January 2010 to December 2021. We extracted GNFG data from the endoscopic submucosal dissection (ESD) database and matched patients with conventional early gastric cancer as controls in a 1:4 ratio by age and sex. GNFG and CGA were compared for the overall survival (OS), disease-specific survival, progression-free survival, and metachronous gastric tumor rates. RESULTS: Overall, 43 lesions were GNFG and 164 CGAs were matched. There were three deaths in the GNFG group and 11 deaths in the CGA group. There was no significant difference in the OS between the two groups (P=0.81). The five-year OS rates for the GNFG and CGA groups were 90.9% and 92.9%, respectively. No disease-specific deaths or recurrences were observed in either group. There was no significant difference in the cumulative metachronous gastric tumor rate between the two groups (P=0.17). The cumulative five-year metachronous gastric tumor rates for the GNFG and CGA groups were 6.6% and 2.5%, respectively. CONCLUSIONS: The prognosis for GNFG is good, however, not better than that for CGA. The metachronous gastric tumor rate after ESD in GNFG was not lower than that in CGA. Therefore, after ESD, GNFG may need to be managed in the same way as CGA.

Jugular Venous Response for Risk Stratification in Heart Failure.

BACKGROUND:  The response of jugular venous pressure (JVP) to increased preload with inspiration has been recognized as a method of stratifying risk in the management of heart failure (HF). Whether the JVP response to inspiration may be more effective than other simple approaches in this setting remains unclear. METHODS:  This study enrolled 79 patients with stable HF. JVP was assessed from the right internal jugular vein in the sitting position and was considered high if visible above the right clavicle at rest. JVP responses to inspiration, the five-repetition sit-to-stand test (5-STS), and squatting were also evaluated. The primary outcome was a composite of all-cause death and hospitalization for worsening HF. RESULTS:  JVP assessment after 5-STS and during squatting was not conducted in two and 14 HF patients, respectively, due to physical limitations. During a mean follow-up of 837 days, the primary outcome was associated with a high JVP at rest (hazard ratio, 2.47; 95% confidence interval [CI], 1.09 to 5.60; P <0.05), with inspiration (hazard ratio, 2.53; 95% CI, 1.17 to 5.46; P <0.05), after 5-STS (hazard ratio, 2.61; 95% CI, 1.23 to 5.97; P <0.05), and during squatting (hazard ratio, 2.40; 95% CI, 1.03 to 6.06; P <0.05). Among patients without a high JVP at rest, the specificity of the primary outcome at one year was greater for the JVP response to inspiration (89%) and squatting (92%) than for the response to 5-STS (80%). CONCLUSIONS:  JVP response to increased preload with inspiration may be a simple and practical method for risk assessment in patients with stable HF.

Prenatal Diagnosis of Vasa Previa in the Second Trimester of Pregnancy Based on Non-typical Ultrasound Findings: A Case Report and Mini-Review of the Literature.

Vasa previa is a rare disorder of the placenta. The absence of a prenatal diagnosis is associated with increased perinatal morbidity and mortality. In our patient, ultrasound findings, although atypical, successfully established the prenatal diagnosis of vasa previa in the second trimester of pregnancy. Despite the fact that the placenta was not low-lying, that it was not possible to visualize the site of umbilical cord insertion into the placental tissue, and that vasa previa was not directly visualized, the presence of blood flow near and around the internal cervical os, as seen on transvaginal Doppler ultrasound in the second and third trimesters of pregnancy, raised serious suspicion of their presence. With the completion of the 36th gestational week, it was decided to proceed with a scheduled cesarean section. One week earlier, a course of corticosteroids was administered. The cesarean section was performed without complications. After placental delivery, the presence of velamentous umbilical cord insertion was noted, with umbilical vessels coursing unprotected by the placental tissue or umbilical cord within the fetal membranes. The puerperant and the newborn were discharged from the obstetrics clinic of the General Hospital of Trikala in excellent condition. This paper highlights the importance of transvaginal color Doppler ultrasound in the prenatal diagnosis of vasa previa, which, while posing little risk to the mother, can often be fatal to the fetus.

Acute Kidney Injury Duration and 20-Year Risks of CKD and Cardiovascular Disease.

Introduction: Acute kidney injury (AKI) is associated with chronic kidney disease (CKD) and cardiovascular disease (CVD); however, it is unclear whether AKI duration affects the long-term risks of CKD and CVD. Therefore, we performed a population-based cohort study examining the associations between AKI duration and CKD and CVD. Methods: We identified patients with laboratory-recorded AKI in Denmark from 1990 through 2018. AKIs were categorized as rapid reversal AKI (≤48 hours), persistent AKI (2-7 days), and acute kidney disease (AKD) (>7 days). We estimated 20-year risks and adjusted hazard ratios (aHRs) of incident CKD and CVD. Results: The study comprised 169,582 patients with AKI, with 100,478 and 76,838 included in the analysis of CKD and CVD, respectively. The 20-year risks of CKD were 26.3%, 29.5%, and 28.7% for rapid reversal AKI, persistent AKI, and AKD, respectively. Compared with rapid reversal AKI, aHRs were 1.13 (95% confidence interval [CI], 1.08-1.19) for persistent AKI and 1.36 (95% CI, 1.30-1.41) for AKD. Risks and rates of overall CVD were similar for rapid reversal AKI, persistent AKI, and AKD. However, persistent AKI was associated with a slightly increased aHR of heart failure (1.09; 95% CI, 1.02-1.16), and aHRs of heart failure, ischemic heart disease, and peripheral artery disease were slightly increased for AKD (1.09 [95% CI, 1.03-1.15], 1.11 [95% CI, 1.03-1.19], and 1.10 [95% CI, 1.02-1.17], respectively). Conclusion: AKI duration was associated with development of CKD, but not overall CVD; however, rates of heart failure, ischemic heart disease, and peripheral artery disease increased slightly with AKI duration.

Machine Learning-Based Discrimination of Cardiovascular Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background: Current risk stratification strategies for patients with hypertrophic cardiomyopathy (HCM) are limited to traditional methodologies. Objectives: The authors aimed to establish machine learning (ML)-based models to discriminate major cardiovascular events in patients with HCM. Methods: We enrolled consecutive HCM patients from 2 tertiary referral centers and used 25 clinical and echocardiographic features to discriminate major adverse cardiovascular events (MACE), including all-cause death, admission for heart failure (HF-adm), and stroke. The best model was selected for each outcome using the area under the receiver operating characteristic curve (AUROC) with 20-fold cross-validation. After testing in the external validation cohort, the relative importance of features in discriminating each outcome was determined using the SHapley Additive exPlanations (SHAP) method. Results: In total, 2,111 patients with HCM (age 61.4 ± 13.6 years; 67.6% men) were analyzed. During the median 4.0 years of follow-up, MACE occurred in 341 patients (16.2%). Among the 4 ML models, the logistic regression model achieved the best AUROC of 0.800 (95% CI: 0.760-0.841) for MACE, 0.789 (95% CI: 0.736-0.841) for all-cause death, 0.798 (95% CI: 0.736-0.860) for HF-adm, and 0.807 (95% CI: 0.754-0.859) for stroke. The discriminant ability of the logistic regression model remained excellent when applied to the external validation cohort for MACE (AUROC = 0.768), all-cause death (AUROC = 0.750), and HF-adm (AUROC = 0.806). The SHAP analysis identified left atrial diameter and hypertension as important variables for all outcomes of interest. Conclusions: The proposed ML models incorporating various phenotypes from patients with HCM accurately discriminated adverse cardiovascular events and provided variables with high importance for each outcome.

Invasive papillary carcinoma of the breast: A case report.

Invasive papillary carcinoma (IPC) of the breast is a rare form of cancer. The current report documents a case of IPC characterized by a large tumor size and skin involvement. Surgical exploration revealed no evidence of axillary lymph node metastasis in breast cancer. Due to financial constraints, the patient opted solely for anastrozole endocrine therapy at a dosage of 1 mg/day for a period of 5 years post-surgery, foregoing other treatments such as radiotherapy and chemotherapy. Since discharge, 2.5 years have passed, during which the patient has been followed up via phone every 3 months, showing a good prognosis. A literature review indicated that IPC is prevalent amongst the elderly population and can be misdiagnosed due to its morphological, cytomorphological and immunophenotypic overlap with other types of papillary neoplasms. This tumor exhibits a more favorable prognosis compared with IDC, primarily attributed to its advantageous gene and molecular expression patterns, coupled with its decreased invasiveness. Despite limited evidence-based research on the treatment of IPC, the present case report, albeit with limitations, underscores the importance of avoiding over-treatment and suggests the feasibility of combining surgery with endocrine therapy for IPC.

Bilirubin Elevation During Hospitalization Post Radiofrequency Catheter Ablation of Persistent Atrial Fibrillation: Variation Trend, Related Factors, and Relevance to 1-Year Recurrence.

Background: The role of total bilirubin (TBIL) in cardiovascular disease has been increasingly recognized in recent decades. Studies have shown a correlation between total bilirubin levels and the prognosis of patients after heart surgery. This study aimed to investigate the clinical significance of bilirubin elevation in persistent atrial fibrillation (PAF) patients who received radiofrequency catheter ablation (RFCA). Methods and Results: A total of 184 patients with PAF who received RFCA were retrospectively studied. Laboratory examinations and demographic data were analyzed to identify independent predictors of TBIL elevation. The relationship between TBIL and prognosis was further investigated. Our results indicated that TBIL increased significantly after RFCA. Multiple linear regression analysis showed that TBIL elevation owned a negative correlation with the percentile of low voltage areas (LVAs) in left atria (ß=-0.490, P<0.001). In contrast, a positive correlation was observed with the white blood cell (WBC) ratio (ß=0.153, P=0.042) and left atrial diameter (LAD) (ß=0.232, P=0.025). It was found that postoperative TBIL levels increased and then gradually decreased to baseline within 5 days without intervention. The bilirubin ratio <1.211 indicated the possibility of 1-year AF recurrence after ablation with a predictive value of 0.743 (specificity = 75.00%, sensitivity = 66.67%). Conclusion: Bilirubin elevation post PAF RFCA was a common phenomenon and was associated with 1-year recurrence of AF in PAF patients after RFCA.

Thoraco-Omphalopagus Conjoined Twins: A Rare Presentation in the Dominican Republic.

The case involves a 23-year-old Dominican woman's admission to Hospital Docente Nuestra Señora De la Altagracia for an elective cesarean section at 38 weeks gestation with conjoined twins. Despite effective treatment for syphilis in the third trimester, her medical history complicated the situation. The twins, thoraco-omphalopagus conjoined, share vital organs and exhibit congenital anomalies, posing unique diagnostic and management challenges. This case contributes to the scarce literature on conjoined twins, especially in the Dominican Republic. It highlights the complexities of diagnosis, prognosis, and management strategies for such rare cases. This emphasizes the importance of ongoing research and medical intervention in addressing these challenges.

Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Chemotherapy remains one dominant therapeutic strategy, while a substantial proportion of patients may develop chemotherapeutic resistance; therefore, it is particularly significant to identify the patients who could achieve maximum benefits from chemotherapy. Presently, four pyroptosis genes are reported to correlate with the chemotherapeutic response or prognosis of HNSCC, while no study has assessed the combinatorial predicting efficacy of these four genes. Hence, this study aims to evaluate the predictive value of a multi-gene pyroptosis model regarding the prognosis and chemotherapeutic responsiveness in HNSCC. Methods: By utilizing RNA-sequencing data from The Cancer Genome Atlas database and the Gene Expression Omnibus database, the pyroptosis-related gene score (PRGscore) was computed for each HNSCC sample by performing a Gene Set Variation Analysis (GSVA) based on four genes (Caspase-1, Caspase-3, Gasdermin D, Gasdermin E). The prognostic significance of the PRGscore was assessed through Cox regression and Kaplan-Meier survival analyses. Additionally, chemotherapy sensitivity stratified by high and low PRGscore was examined to determine the potential association between pyroptosis activity and chemosensitivity. Furthermore, chemotherapy sensitivity assays were conducted in HNSCC cell lines in vitro. Results: As a result, our study successfully formulated a PRGscore reflective of pyroptotic activity in HNSCC. Higher PRGscore correlates with worse prognosis. However, patients with higher PRGscore were remarkably more responsive to chemotherapy. In agreement, chemotherapy sensitivity tests on HNSCC cell lines indicated a positive association between overall pyroptosis levels and chemosensitivity to cisplatin and 5-fluorouracil; in addition, patients with higher PRGscore may benefit from the immunotherapy. Overall, our study suggests that HNSCC patients with higher PRGscore, though may have a less favorable prognosis, chemotherapy and immunotherapy may exhibit better benefits in this population.

TUBB, a robust biomarker with satisfying abilities in diagnosis, prognosis, and immune regulation via a comprehensive pan-cancer analysis.

Purpose: TUBB can encode a beta-tubulin protein. At present, the role of TUBB has not been ascertained in cancers. Hence, the importance of further systematic pan-cancer analyses is stressed to explore its value in the diagnosis, prognosis, and immune function of cancers. Methods: By collecting and handling integrative data from the TCGA, Firehose, UCSC Xena, cBioPortal, GEO, CPTAC, TIMER2.0, TISCH, CellMiner, GDSC, and CTRP databases, we explored the potential diagnostic and prognostic roles of TUBB in pan-cancers from multiple angles. Moreover, the GSEA analysis was conducted to excavate the biological functions of TUBB in pan-cancers. In addition, survival profiles were described, and the differential expressions of TUBB in different molecular subtypes were discussed. Also, we utilized the cMAP function to search drugs or micro-molecules that have an impact on TUBB expressions. Results: Based on the TCGA data, we found that TUBB was differentially expressed in a variety of tumors and showed an early-diagnostic value. Mutations, somatic copy number alterations, and DNA methylation would lead to its abnormal expression. TUBB expressions had relations with many clinical features. What's more, TUBB expressions were validated to be related to many metabolism-related, metastasis-related, and immune-related pathways. High TUBB expressions were proved to have a great impact on the prognosis of various types of cancers and would affect the sensitivity of some drugs. We also demonstrated that the expression of TUBB was significantly correlated to immunoregulator molecules and biomarkers of lymphocyte subpopulation infiltration. Conclusion: TUBB and its regulatory genes were systemically analyzed in this study, showing that TUBB had satisfying performances in disease diagnosing and prognosis predicting of multiple cancers. It could remodel the tumor microenvironment and play an integral role in guiding cancer therapies and forecasting responses to chemotherapy.

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although neurexophilin 4 (NXPH4) has been investigated in several tumors, its role in COAD remains unclear. The aim of this study was to explore the prognostic value and potential functions of NXPH4 in COAD. Methods: The expression of NXPH4 in COAD were analyzed using The Cancer Genome Atlas (TCGA) and datasets from the Gene Expression Omnibus (GEO) database. The prognostic value of NXPH4 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NXPH4 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NXPH4 expression and immune cell infiltration levels was examined thorough single-sample gene set enrichment analysis (ssGSEA). Furthermore, the competing endogenous RNA (ceRNA) regulatory network that may be involved in NXPH4 in COAD was predicted and constructed through a variety of databases. Results: NXPH4 expression was significantly higher in COAD tissue compared with normal colon tissues. Meanwhile, high expression of NXPH4 was associated with poor prognosis in COAD patients. GO-KEGG and GSEA analyses indicated that NXPH4 was associated with glycolysis and hypoxia pathway, and may promote COAD progression and metastasis by modulating metabolic reprogramming. ssGSEA analysis demonstrated that NXPH4 expression also associated with immune infiltration. Furthermore, we identified various microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) as upstream regulators of NXPH4 in COAD. Conclusions: The present study revealed that high expression of NXPH4 is associated with tumor progression, metabolic reprogramming, and immune infiltration. These findings suggest that NXPH4 could serve as a reliable prognostic biomarker and a promising therapeutic target in COAD.

Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Background: Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. Methods: We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. Results: In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. Conclusions: The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Effect of perioperative blood transfusion on complications and prognosis after radical gastrectomy in elderly patients: a retrospective study of 1,666 cases.

Background: Multiple studies have examined the effect of perioperative blood transfusion (BTF) on postoperative complications and the prognosis of gastric cancer patients, but the conclusions remain controversial, and few studies related to elderly patients are present. This study sought to examine the effect of perioperative BTF on postoperative complications and the prognosis of elderly patients who underwent radical gastrectomy. Methods: The clinical data of 1,666 elderly patients (aged ≥60 years) at Xijing Hospital from October 2013 to October 2021 were retrospectively analyzed. The patients were stratified into the perioperative BTF group and the perioperative non-BTF group. The clinicopathological characteristics, postoperative complications, and long-term prognoses of the patients were compared. Results: There were significant differences in terms of sex, tumor location, tumor size, gastrectomy range, tumor differentiation, T stage, N stage, tumor-node-metastasis (TNM) stage, preoperative anemia, and intraoperative blood loss between the two groups (P<0.05). The incidence of postoperative fever in the BTF group was significantly higher than that in the non-BTF group (31.6% vs. 15.4%, P<0.001), but there were no significant differences in the other complications between the two groups (P>0.05). The survival analysis showed that in stage III patients, the prognosis of the BTF group was inferior to that of the non-BTF group [the 3-year overall survival (OS) rates of the groups were 33.7% vs. 47.9% respectively, P<0.001], while there was no significant difference between the two groups among the stage I and stage II patients (P>0.05). There was no significant difference in the prognosis of patients with different transfusion times (preoperative/intraoperative/postoperative) (P>0.05). The multivariate analysis indicated that perioperative BTF was not an independent risk factor for prognosis in elderly patients with gastric cancer overall or elderly patients with gastric cancer in stage III (P>0.05). Conclusions: Perioperative BTF may elevate the incidence of fever but has no significant effect on other complications in elderly patients after radical gastrectomy. Perioperative BTF is not an independent risk factor affecting the postoperative prognosis of elderly patients with gastric cancer.

Increased co-expression of 4-1BB with PD-1 on CD8+ tumor-infiltrating lymphocytes is associated with improved prognosis and immunotherapy response in cervical cancer.

Background: The combination of agonistic antibodies with immune checkpoint inhibitors presents a promising avenue for cancer immunotherapy. Our objective is to explore the co-expression of 4-1BB, ICOS, CD28, with PD-1 on CD8+ T cells in the peripheral blood and tumor tissue of cervical cancer(CC) patients, with a specific focus on the association between the co-expression levels of 4-1BB with PD-1 and clinical features, prognosis as well as immunotherapy response. The goal is to offer valuable insights into cervical cancer immunotherapy. Methods: In this study, 50 treatment-naive patients diagnosed with CC were enrolled. Flow cytometry was used to detect PD-1/4-1BB, PD-1/ICOS and PD-1/CD28 co-expression on CD8+ T cells. Subsequent analysis aimed to investigate the differential co-expression between peripheral blood and cancer tissue, and also the correlation between co-expression and clinical features in these patients. Gene Expression Omnibus (GEO) datasets, The Cancer Genome Atlas (TCGA) cohort, The IMvigor210 cohort, The BMS038cohort and Immunophenoscores were utilized to investigate the correlation between PD-1/4-1BB and the immune microenvironment, prognosis, immunotherapy, and drug sensitivity in cervical cancer. Results: The co-expression levels of PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 on CD8+ tumor-infiltrating lymphocytes (TILs) were significantly higher in cervical cancer patients compared to those in peripheral blood. Clinical feature analysis reveals that on CD8+ TILs, the co-expression of PD-1/4-1BB is more closely correlated with clinical characteristics compared to PD-1/ICOS, PD-1/CD28, PD-1, and 4-1BB. Pseudo-time analysis and cell communication profiling reveal close associations between the subgroups harboring 4-1BB and PD-1. The prognosis, tumor mutation burden, immune landscape, and immunotherapy response exhibit statistically significant variations between the high and low co-expression groups of PD-1/4-1BB. The high co-expression group of PD-1/4-1BB is more likely to benefit from immunotherapy. Conclusion: PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 exhibit elevated co-expression on CD8+TILs of cervical cancer, while demonstrating lower expression in circulating T cells. The co-expression patterns of PD-1/4-1BB significantly contributed to the prediction of immune cell infiltration characteristics, prognosis, and tailored immunotherapy tactics. PD-1/4-1BB exhibits potential as a target for combination immunotherapy in cervical cancer.

Enhancing breast cancer outcomes with machine learning-driven glutamine metabolic reprogramming signature.

Background: This study aims to identify precise biomarkers for breast cancer to improve patient outcomes, addressing the limitations of traditional staging in predicting treatment responses. Methods: Our analysis encompassed data from over 7,000 breast cancer patients across 14 datasets, which included in-house clinical data and single-cell data from 8 patients (totaling 43,766 cells). We utilized an integrative approach, applying 10 machine learning algorithms in 54 unique combinations to analyze 100 existing breast cancer signatures. Immunohistochemistry assays were performed for empirical validation. The study also investigated potential immunotherapies and chemotherapies. Results: Our research identified five consistent glutamine metabolic reprogramming (GMR)-related genes from multi-center cohorts, forming the foundation of a novel GMR-model. This model demonstrated superior accuracy in predicting recurrence and mortality risks compared to existing clinical and molecular features. Patients classified as high-risk by the model exhibited poorer outcomes. IHC validation in 30 patients reinforced these findings, suggesting the model's broad applicability. Intriguingly, the model indicates a differential therapeutic response: low-risk patients may benefit more from immunotherapy, whereas high-risk patients showed sensitivity to specific chemotherapies like BI-2536 and ispinesib. Conclusions: The GMR-model marks a significant leap forward in breast cancer prognosis and the personalization of treatment strategies, offering vital insights for the effective management of diverse breast cancer patient populations.