Single-cell RNA Sequencing Demonstrates the Heterogeneity of Different Molecular Subtypes in Gastric Cancer.

Gastric cancer is a disease with high molecular and phenotypic heterogeneity. We integrated 119,878 cells from different molecular subtypes of gastric cancer and conducted comprehensive analysis. We found that patients with different molecular subtypes of gastric cancer showed significantly different cell composition heterogeneity, and the proportion of plasma cells was higher in GS tumors. After that, we constructed subtype-specific lncRNA-gene regulatory networks and identified subtype-specific lncRNA-related biological functions and pathways. Our study found that MALAT1-CTNNB1 regulatory pairs existed in CIN subtype, XIST-KLF2 regulatory pairs existed in GS subtype, and KCNQ1OT1-CCND2 regulatory pairs existed in MSI subtype. Next, we identified subtype-specific lncRNAs associated with prognosis. Our study found that NEAT1 could be used as prognostic factors for CIN tumors, and MALAT1 and XIST could be used as prognostic factors for GS tumors. In addition, we characterized the interactions between tumor cells and tumor microenvironment cells in different molecular subtypes of gastric cancer. In conclusion, we revealed the heterogeneity among different TCGA molecular subtypes of gastric cancer at the single-cell level, and identified the subtype-specific lncRNAs associated with prognosis. Our study may contribute to the in-depth understanding of the heterogeneity of gastric cancer and the prediction of patient prognosis.

Laparoscopic Duodenum and Spleen-Preserving Subtotal or Total Pancreatectomy: A Parenchyma-Sparing Strategy for Main Duct Intraductal Papillary Mucinous Neoplasms (with Video).

BACKGROUND: For premalignant main duct intraductal papillary mucinous neoplasms (MD-IPMN), laparoscopic duodenum and spleen-preserving subtotal or total pancreatectomy (LDSP-STP/TP) seems to be a viable option for parenchyma-sparing pancreatectomy. PATIENTS AND METHODS: On the basis of the imaging features, family history, genomic alterations, intraoperative ultrasound examination, and frozen section evaluation, we have proposed patient selection strategies for the LDSP-STP/TP technique for the first time. Additionally, a comprehensive step-by-step overview of this technique has been provided. To date, we have performed five LDSP-STP procedures and one LDSP-TP procedure. RESULTS: We successfully performed selective resection of the affected pancreatic parenchyma while preserving the duodenum, common bile duct (CBD), spleen, and splenic artery and vein. The operation time ranged from 295 to 495 min, with blood loss ranging from 100 to 300 mL. Postoperative pathological results revealed low-grade dysplasia in the resected pancreatic samples and margins. The patients resumed eating within 3-5 days after surgery, and all postoperative complications were classified as grade I according to the Clavien-Dindo classification. At the 3-month follow-up, there were no cases of CBD ischemic stenosis, splenic ischemia, or pseudocyst formation observed. For patients who received LDSP-STP, the longitudinal diameter of the remaining pancreatic tail ranged from 2.2 to 4.6 cm, and they demonstrated satisfactory long-term blood glycemic control. CONCLUSIONS: LDSP-STP/TP demonstrates technical feasibility and safety. It allows for the selective resection of the affected pancreatic parenchyma, thereby minimizing the impact of pancreatic functional impairment. However, it is crucial to validate this technique through long-term prospective observations.

Dissecting the clinicopathological, genomic, and prognostic significance of ALK rearrangement in resected lung adenocarcinoma.

OBJECTIVES: The ALINA trial introduced anaplastic lymphoma kinase (ALK) inhibitors in an early-stage context, generating notable interest. This study aims to investigate the characteristics and prognostic implications of ALK rearrangement in patients with resected lung adenocarcinoma (LUAD). METHODS: We retrospectively evaluated resected LUAD cases with documented ALK status from 2008 to 2020. The association between ALK positivity and clinicopathological characteristics, molecular profiles, and outcomes was explored. RESULTS: Among 4944 cases, 238 (4.8%) were ALK-positive, correlating with younger age and non-smokers. ALK positivity was also significantly associated with pure-solid nodules, spread through air spaces, and solid-predominant adenocarcinoma. ALK-positive tumors exhibited an overall low frequency of co-mutations (e.g., TP53, STK11). ALK positivity was associated with inferior recurrence-free survival (RFS) in stage I patients who did not receive adjuvant chemotherapy while with prolonged RFS in stage II and III patients who received adjuvant chemotherapy. Notably, six patients treated with adjuvant ALK inhibitors experienced no recurrence or metastasis during the follow-up period. Additionally, the administration of ALK inhibitors significantly improved post-recurrence survival in ALK-positive patients. CONCLUSIONS: ALK positivity was associated with specific aggressive pathological features and inferior RFS in stage I LUAD. ALK-positive patients seemed to benefit more from adjuvant chemotherapy. Active treatment with ALK inhibitors or chemotherapy should be considered for ALK-positive LUAD, although further evidence is warranted to expand their utility in early-stage disease management.

An integrative pan-cancer analysis of MASP1 and the potential clinical implications for the tumor immune microenvironment.

Mannose-binding lectin-associated serine protease 1 (MASP1) plays a crucial role in the complement lectin pathway and the mediation of immune responses. However, comprehensive research on MASP1 across various cancer types has not been performed to date. This study aimed to evaluate the significance of MASP1 in pan-cancer. The Cancer Genome Atlas (TCGA), UCSC Xena and Genotype Tissue Expression (GTEx) databases were used to evaluate the expression profiles, genomic features, prognostic relevance, and immune microenvironment associations of MASP1 across 33 cancer types. We observed significant dysregulation of MASP1 expression in multiple cancers, with strong associations between MASP1 expression levels and diagnostic value as well as patient prognosis. Mechanistic insights revealed significant correlations between MASP1 levels and various immunological and genomic factors, including tumor-infiltrating immune cells (TIICs), immune-related genes, mismatch repair (MMR), tumor mutation burden (TMB), and microsatellite instability (MSI), highlighting a critical regulatory function of MASP1 within the tumor immune microenvironment (TIME). In vitro and in vivo experiments demonstrated that MASP1 expression was markedly decreased in liver hepatocellular carcinoma (LIHC). Moreover, the overexpression of MASP1 in hepatocellular carcinoma (HCC) cell lines significantly inhibited their proliferation, invasion and migration. In conclusion, MASP1 exhibits differential expression in the pan-cancer analyses and might play an important role in TIME. MASP1 is a promising prognostic biomarker and a potential target for immunological research, particularly in LIHC.

[Review of 10 patients with pure perilunate carpal dislocation at a minimum of 18years follow-up]. / Revue à 18ans de recul minimum, de 10 patients présentant une luxation périlunaire isolée du carpe.

OBJECTIVE: To evaluate, in long-term, the functional abilities and the occurrence of osteoarthritis in patients treated for a posterior perilunate carpal dislocation without bone lesion associated. PATIENTS AND METHOD: This was a monocentric retrospective observational study on patients operated on at the University Hospital of Guadeloupe for a posterior perilunate dislocation without bone lesion associated with a minimum of 18years of follow-up. Ten patients were included with a mean follow-up of 22.8years. The evaluation criteria were clinical (PRWE, QuickDASH, pain, grip strength, wrist joint mobility, Watson and Reagan tests, Cooney functional score) and radiographic (Gilula curves, carpal height, carpal ulnar translation, scapholunate and radiolunar angles, scapholunate and triquetro-lunar interlines in statics and dynamics, Herzberg's classification of complications). RESULTS: The average Cooney score was 67.5/100. Mean PRWE and QuickDASH scores were 33.9 and 24.8 respectively. The mean flexion-extension arc on the injured side was 71.5° (66.7% compared to the healthy side). Mean grip strength was 27kg (72.8% compared to the healthy side). The prevalence of osteoarthritis was 60%, with three A types, two A1 types, one B type and four B1 types according to Herzberg. CONCLUSION: The factors influencing the long-term prognosis are the initial displacement of the lunate, the quality of the reduction and the presence of chronic carpal instability, particularly scapholunate. The high prevalence of osteoarthritis in our series (60%) is apparently not correlated with the functional capacities of patients over the long term.

[Long-term hypomethylating agents in patients with myelodysplastic syndromes: a multi-center retrospective study].

Objective: To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) . Methods: A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results: Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype (P=0.02, OR=0.39, 95%CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation (P=0.02, OR=0.22, 95%CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95%CI 21.14-30.19) months. HMA response (P=0.036, HR=0.47, 95%CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype (P=0.024, HR=2.14, 95%CI 1.10-4.15) , leukemia transformation (P<0.001, HR=2.839, 95%CI 1.64-4.92) , and TP53 mutation (P=0.012, HR=2.19, 95%CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion: Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Excavating regulated cell death signatures to predict prognosis, tumor microenvironment and therapeutic response in HR+/HER2- breast cancer.

Regulated cell death (RCD) has been documented to have great potentials for discovering novel biomarkers and therapeutic targets in malignancies. But its role and clinical value in HR+/HER2- breast cancer, the most common subtype of breast cancer, are obscure. In this study, we comprehensively explored 12 types of RCD patterns and found extensive mutations and dysregulations of RCD genes in HR+/HER2- breast cancer. A prognostic RCD scoring system (CDScore) based on six critical genes (LEF1, SLC7A11, SFRP1, IGFBP6, CXCL2, STXBP1) was constructed, in which a high CDScore predicts poor prognosis. The expressions and prognostic value of LEF1 and SFRP1were also validated in our tissue microarrays. The nomogram established basing on CDScore, age and TNM stage performed satisfactory in predicting overall survival, with an area under the ROC curve of 0.89, 0.82 and 0.8 in predicting 1-year, 3-year and 5-year overall survival rates, respectively. Furthermore, CDScore was identified to be correlated with tumor microenvironments and immune checkpoints by excavation of bulk and single-cell sequencing data. Patients in CDScore high group might be resistant to standard chemotherapy and target therapy. Our results underlined the potential effects and importance of RCD in HR+/HER2- breast cancer and provided novel biomarkers and therapeutic targets for HR+/HER2- breast cancer patients.

Implementing machine learning to predict survival outcomes in patients with resected pulmonary large cell neuroendocrine carcinoma.

BACKGROUND: The post-surgical prognosis for Pulmonary Large Cell Neuroendocrine Carcinoma (PLCNEC) patients remains largely unexplored. Developing a precise prognostic model is vital to assist clinicians in patient counseling and creating effective treatment strategies. RESEARCH DESIGN AND METHODS: This retrospective study utilized the Surveillance, Epidemiology, and End Results database from 2000 to 2018 to identify key prognostic features for Overall Survival (OS) in PLCNEC using Boruta analysis. Predictive models employing XGBoost, Random Forest, Decision Trees, Elastic Net, and Support Vector Machine were constructed and evaluated based on Area Under the Receiver Operating Characteristic Curve (AUC), calibration plots, Brier scores, and Decision Curve Analysis (DCA). RESULTS: Analysis of 604 patients revealed eight significant predictors of OS. The Random Forest model outperformed others, with AUC values of 0.765 and 0.756 for 3 and 5-year survival predictions in the training set, and 0.739 and 0.706 in the validation set, respectively. Its superior validation cohort performance was confirmed by its AUC, calibration, and DCA metrics. CONCLUSIONS: This study introduces a novel machine learning-based prognostic model with a supportive web-based platform, offering valuable tools for healthcare professionals. These advancements facilitate more personalized clinical decision-making for PLCNEC patients following primary tumor resection.

ZFP1 is a biomarker related to poor prognosis and immunity in gastric cancer.

We aimed to determine the prognostic significance of ZFP1 in gastric cancer (GC), its role in the immune microenvironment, and its potential as a therapeutic target using data from The Cancer Genome Atlas (TCGA) database. ZFP1 overexpression was closely associated with tumour T stage and histological grade. Patients with GC and high ZFP1 expression had poor outcomes. Lower ZFP1 expression was associated with longer symptom-free intervals and disease-specific survival. Subgroup analyses of T3 and T4, N0, N1, and M0 patients showed that overall survival (OS), disease-specific survival, and progression-free interval (PFI) were worse in those with high ZFP1 expression. ZFP1 expression in GC was moderately to strongly positively correlated with the infiltration levels of effector central memory T cells and T helper cells and negatively correlated with Th17 cells and NK CD56bright cells. The lncRNA-miRNA-ZFP1 axis was predicted using a public database. CCK8, colony formation, and wound healing assays were conducted to investigate whether ZFP1 promoted the proliferation and migration of GC cells. Our study suggests that ZFP1 plays a key role in the prognosis, immune response, and progression of GC and is a significant factor in the diagnosis and treatment of this disease.

Exploring extrahepatic metastasis of hepatocellular carcinoma based on methylation driver genes and establishing a prognostic model for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), theseventh most common cancer worldwide, is characterized by a high mortality rate, advanced diagnosis, and susceptibility to extrahepatic metastasis. Numerous studies have shown that DNA methylation is a crucial factor in epigenetic modifications and regulation of carcinogenesis. METHODS: HCC patient data were sourced from the TCGA dataset as a training set, while GSE116174 was used as an external validation set for verification. Differential methylation and expression analyses were performed on HCC samples with and without extrahepatic metastasis. In the intersecting genes, the relationship between methylation and expression levels of the intersecting genes was analyzed. Genes with a correlation coefficient≥|0.30| and P<0.05 were identified as methylation driver genes. Cox regression analysis was conducted to identify genes associated with HCC prognosis and establish a risk score. Subsequently, a prognostic model was established and validated using Cox regression analysis incorporating the risk score and other clinical factors. Using immunohistochemistry to evaluate the expression of DHX58 and EIF5A2 in HCC tissues with and without extrahepatic metastasis. Immunoinfiltration analysis was performed on the HCC samples using CIBERSORT. RESULTS: Our research identified eight methylation driver genes for HCC extrahepatic metastasis, of which two genes (DHX58 and EIF5A2) were associated with HCC patient prognosis. And the study further constructed and validated the risk score and prognostic model. Immunoinfiltration analysis showed that M0 macrophage abundance was correlated with the prognosis of HCC patients. Immunohistochemistry revealed differences in DHX58 and EIF5A2 expression between HCC tissues with and without extrahepatic metastasis, consistent with our bioinformatics findings.

Radiotherapy is recommended for hormone receptor-negative older breast cancer patients after breast conserving surgery.

In this study, the necessity of radiotherapy (RT) for hormone receptor-negative older breast cancer patients after breast-conserving surgery (BCS) was investigated. The data of hormone receptor-negative invasive breast cancer patients who underwent BCS were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All patients were separated into two groups, namely, the RT group and the no radiotherapy (No RT) group. The 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were compared between the No RT and RT groups after propensity score matching (PSM). The nomograms for predicting the survival of patients were constructed from variables identified by univariate or multivariate Cox regression analysis. A total of 2504 patients were enrolled in the training cohort, and 630 patients were included in the validation cohort. After PSM, 738 patients were enrolled in the No RT group and RT group. We noted that RT can improve survival in hormone receptor-negative older breast cancer patients who undergo BCS. Based on the results of multivariate Cox analysis, age, race, tumour grade, receipt of RT and chemotherapy, pathological T stage, N status, M status and HER2 status were linked to OS and CSS for these patients, and nomograms for predicting OS and CSS were constructed and validated. Moreover, RT improved OS and CSS in hormone receptor-negative older breast cancer patients who underwent BCS. In addition, the proposed nomograms more accurately predicted OS and CSS for hormone receptor-negative older breast cancer patients after BCS.

Lymphopenia associated with whole-brain radiotherapy and its effects on clinical outcomes of patients with brain metastases.

There is increasing awareness of radiotherapy's potential side effects, such as lymphopenia. Therefore, this study aimed to establish the association between WBRT and the development of lymphopenia in patients with brain metastases undergoing brain radiotherapy (RT), along with evaluating the corresponding clinical outcomes. Including 116 patients with brain metastases undergoing brain radiotherapy, the study collected the absolute lymphocyte counts (ALC) within 2 weeks before brain radiotherapy (pre-radiotherapy, pre-RT), as well as ones at 1 and 2 months after completing RT (post-RT). Univariate and multivariate analyses were performed to identify associations between radiation modality and post-RT ALC. The relationships between post-RT ALC and overall survival were evaluated with Kaplan-Meier analysis and a multivariate Cox regression model. The median ALC definitely decreased at 1 month post-RT, but at 2 months post-RT, gradually rose but not to the pre-RT ALC. The multivariate analysis identified WBRT and lower pre-RT ALC as independent risk factors associated with the decrease in post-RT ALC at 1 month. It also revealed more than 4 brain metastases, G3-4 lymphopenia at 1 month and lower post-RT ALC at 2 months exhibited significantly worse prognosis regardless of the radiation modality. However, there was indeed an independent correlation between radiation modality and the outcome of intracranial progression-free survival (PFS). To approach the feasibility and reasonableness of treatment, clinicians should carefully consider various factors to achieve long-term survival of patients.

A scoring-based clinical grading model for xanthelasma palpebrarum: predicting treatment frequency and prognosis.

Xanthelasma palpebrarum is one of the most common cutaneous xanthomas in humans. Currently, there are various methods available for treating xanthelasma palpebrarum, but the high treatment frequency and recurrence rate remain significant challenges for patients. Therefore, it is necessary to establish a reasonable and effective clinical grading system to guide the diagnosis and treatment of xanthelasma palpebrarum. We developed a clinical scoring system related to local injection of pingyangmycin for the treatment of xanthelasma palpebrarum, which can be used to predict early prognosis and treatment outcomes in patients. We collected and retrospectively studied 246 outpatient cases of xanthelasma palpebrarum treated with local injection of pingyangmycin in the Department of Plastic Surgery at Shanghai East Hospital from February 2020 to August 2022. Potential independent risk factors for adverse outcomes (recurrence or non-recurrence) were considered in univariate and multivariate logistic regression models. Predictive factors were determined based on the multivariate logistic regression model and Cox model, and a scoring grading system was established. External validation was conducted on an independent cohort of 110 patients. Based on logistic regression analysis, the number, area, and color of lesions were identified as significant predictive indicators (P < 0.05), with respective AUCs of 0.710, 0.799, and 0.755. The Cox model established hazard ratios for four new severity indicators of xanthelasma palpebrarum: hyperlipidemia, number of lesions, lesion area, and lesion grayscale value. Based on these findings, a new clinical grading model was developed, which was validated to be effective in the external cohort. The new scoring-based clinical predictive model can effectively predict the number of pingyangmycin injection treatments and prognosis in patients with xanthelasma palpebrarum. It holds promise for broader application in clinical practice.

Outcomes in children with first-relapsed acute lymphoblastic leukemia in Japan: Results from JCCG Study JPLSG-ALL-R08.

BACKGROUND/OBJECTIVES: The Berlin-Frankfurt-Münster (BFM)-S classification is a crucial prognostic indicator in children experiencing first-relapsed acute lymphoblastic leukemia (ALL). Early molecular response to therapy, evaluated by measurable/minimal residual disease (MRD), has a significant impact on the survival of patients with childhood ALL. Applying risk stratification based on the BFM-S classification and MRD response after induction, the first nationwide prospective multicenter study, ALL-R08, was conducted in children with first-relapsed ALL in Japan. METHODS: The ALL-R08 study comprised two parts: ALL-R08-I, an observational study aimed at obtaining an overall picture of outcomes in first-relapsed childhood ALL, and ALL-R08-II, a clinical trial for the non-T-ALL S2 risk group. In ALL-R08-II, patients with an MRD level of ≥10-3 at the end of induction therapy were assigned to undergo allogeneic hematopoietic stem cell transplantation (allo-HCT), whereas those with an MRD level less than 10-3 and isolated extramedullary relapse continued to receive chemotherapy. RESULTS: In total, 163 patients were enrolled in the ALL-R08 study, and 82 and 81 patients were enrolled in the ALL-R08-I and the ALL-R08-II, respectively. In ALL-R08-I, the probability of 3-year event-free survival (EFS) for patients with S1, S2, S3, S4, and post-HCT groups was 83% ± 15%, 37% ± 11%, 28% ± 8%, 14% ± 7%, and 0%, respectively. In the ALL-R08-II trial, 3-year EFS in patients with post-induction MRD less than 10-3 and ≥10-3 was 70% ± 9% (n = 27) and 68% ± 8% (n = 31) (p = .591), respectively. CONCLUSIONS: ALL-REZ BFM-type treatment is equally effective for children with first-relapsed ALL treated according to the Japanese frontline protocols and for children with first-relapsed ALL treated according to the BFM-type frontline protocols.

Prognosis evaluation and efficacy analysis of different treatment options for patients with visceral pleural invasion in stage IIA-IIB lung cancer.

OBJECTIVE: Controversy surrounds the treatment of visceral pleural invasion in lung cancer, and no studies have compared the efficacy of its four main treatment options (i.e., surgery, chemotherapy, targeted therapy, and immunotherapy). This study aims to compare and analyze surgery, chemotherapy, targeted therapy, and immunotherapy outcomes and explore the optimal treatment of visceral pleural invasion in lung cancer. METHODS: We searched electronic databases (i.e., Pubmed, Embase, Cochrane Library, CNKI, and Chinese Biomedical Literature Database Search) for relevant studies of treatment options for patients with visceral pleural invasion in stage IIA-IIB lung cancer. Searches times were limited to studies published between January 1, 2000 and February 20, 2021. Meta analysis was performed using RevMan 5.3 software We also downloaded original RNA transcription data about lung cancer invasion in the GEO and TCGA tumor databases, and used R 4.0.3 software to perform differential expression and co-expression gene network analyses. RESULTS: We included a total of 25 high-quality (i.e., Jadad score 4-7) studies. Meta-analysis found that surgical treatment was associated with a 3-year survival rate OR = 3.80 (95% CI 3.53, 4.09; P < 0.0001), 5-year survival rate OR = 4.10 (95% CI 3.72, 4.53; P < 0.0001), and median survival time OR = 2.71 (95% CI 2.53, 2.89; P < 0.0001). Chemotherapy was associated with a 3-year survival rate OR = 2.08 (95% CI 1.93, 2.25; P < 0.0001), 5-year survival rate OR = 1.68 (95% CI 1.49, 1.89; P < 0.0001), and median survival time OR = 1.84 (95% CI 1.66, 2.04; P < 0.0001). Targeted therapy was associated with a 3-year survival rate OR = 2.91 (95% CI 2.65, 3.19; P < 0.0001), 5-year survival rate OR = 1.83 (95% CI 1.39, 2.33; P < 0.0001), and median survival time OR = 1.76 (95% CI 1.59, 1.94; P < 0.0001). Finally, immunotherapy was associated with a 3-year survival rate OR = 1.89 (95% CI 1.73, 2.07; P < 0.0001), 5-year survival rate OR = 1.66 (95% CI 1.46, 1.88; P < 0.0001), and median survival time OR = 2.53 (95% CI 2.27, 2.82; P < 0.0001). After screening differential genes and co-expressed genes in tumor gene databases, we found that AC245595.1, ITGB1-DT and AL606489.1 may be involved in the process of lung cancer invasion, and macrophages M1 and M2, CD4+-Th1, CD8+-Th1 may participate in immune infiltration. CONCLUSIONS: In patients with visceral pleural invasion of stage IIA-IIB lung cancer, chemotherapy has shown a significant effect on improving prognosis and enhancing efficacy. However, surgical treatment did not significantly improve the overall prognosis. Therefore, the individual situation of the patient and the comprehensive benefits of the treatment program should be fully considered when developing the treatment program.

Type 2 diabetes mellitus negatively affects the functional performance of 6-min step test in chronic heart failure: a 3-year follow-up study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) present a decrease in functional capacity due to the intrinsic nature of both pathologies. It is not known about the potential impact of T2DM on functional capacity when assessed by 6-min step test (6MST) and its effect as a prognostic marker for fatal and non-fatal events in patients with CHF. OBJECTIVE: to evaluate the coexistence of T2DM and CHF in functional capacity through 6MST when compared to CHF non-T2DM, as well as to investigate the different cardiovascular responses to 6MST and the risk of mortality, decompensation of CHF and acute myocardial infarction (AMI) over 36 months. METHODS: This is a prospective cohort study with 36 months of follow-up in individuals with T2DM and CHF. All participants completed a clinical assessment, followed by pulmonary function testing, echocardiography, and 6MST. The 6MST was performed on a 20 cm high step and cardiovascular responses were collected: heart rate, systemic blood pressure, oxygen saturation, BORG dyspnea and fatigue. The risk of mortality, acute myocardial infarction and decompensation of CHF was evaluated. RESULTS: Eighty-six participants were included. The CHF-T2DM group had a significantly lower functional capacity than the CHF non-T2DM group (p < 0.05). Forced Expiratory Volume in one second (L), ejection fraction (%), gender and T2DM influence and are predictors of functional capacity (p < 0.05; adjusted R squared: 0.419). CHF-T2DM group presented a higher risk of mortality and acute myocardial infarction over the 36 months of follow-up (p < 0.05), but not to the risk of decompensation (p > 0.05). CONCLUSION: T2DM negatively affects the functional performance of 6MST in patients with CHF. Gender, ejection fraction (%), FEV1 (L) and T2DM itself negatively influence exercise performance.

Prognostic value of tumour-associated regulatory T-cells as a biomarker in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Tumour, nodes, and metastases (TNM) staging has been deficient in prognosticating in patients suffering from non-small cell lung cancer (NSCLC). To supplement TNM staging, this systematic review and meta-analysis aimed to evaluate the prognostic value of the regulatory T cells (Treg). METHODS: A keyword search was conducted in MEDLINE and EMBASE for full-text original human studies from any region published in English during the last 12 years. Eligible for inclusion were studies evaluating the prognostic value of the number of Treg cells in NSCLC except case studies, case series, systematic reviews, and meta-analyses. Two reviewers (one reviewer used an automation tool) independently screened the studies and assessed risk-of-bias using the Quality in Prognosis Studies (QUIPS) tool. Meta-analysis was done for studies reporting significant multivariate hazard ratio (HR). RESULTS: Out of 809 retrievals, 24 studies were included in the final review. The low number of Treg cells was found significantly associated with improved overall survival (pooled log OR, 1.646; 95% CI, 1.349, 1.944; p (2-tailed) < .001; SE, 0.1217), improved recurrence-free survival (HR, 1.99; 95% CI, 1.15, 3.46; p = .01), improved progression-free survival (pooled log OR, 2.231; 95% CI, 0.424, 4.038; p (2-tailed) .034; SE, 0.4200), and worse disease-free survival (pooled log OR, 0.992; 95% CI, 0.820, 1.163; p (2-tailed) .009; SE, 0.0135), especially when identified by forkhead box P3 (FOXP3), in any stage or non-metastatic NSCLC. CONCLUSION: A low number of Treg cells indicated better survival, suggesting its potential use as a prognostic biomarker in NSCLC. SYSTEMATIC REVIEW REGISTRATION: The protocol of this review was prospectively registered on PROSPERO on August 28, 2021, and was assigned the registration number CRD42021270598. The protocol can be accessed from PROSPERO website.

The red blood cell distribution width to albumin ratio was a potential prognostic biomarker for acute respiratory failure: a retrospective study.

BACKGROUND: The association between red blood cell distribution width (RDW) to albumin ratio (RAR) and prognosis in patients with acute respiratory failure (ARF) admitted to the Intensive Care Unit (ICU) remains unclear. This retrospective cohort study aims to investigate this association. METHODS: Clinical information of ARF patients was collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) version 2.0 database. The primary outcome was, in-hospital mortality and secondary outcomes included 28-day mortality, 60-day mortality, length of hospital stay, and length of ICU stay. Cox regression models and subgroup analyses were conducted to explore the relationship between RAR and mortality. RESULTS: A total of 4547 patients with acute respiratory failure were enrolled, with 2277 in the low ratio group (RAR < 4.83) and 2270 in the high ratio group (RAR > = 4.83). Kaplan-Meier survival analysis demonstrated a significant difference in survival probability between the two groups. After adjusting for confounding factors, the Cox regression analysis showed that the high RAR ratio had a higher hazard ratio (HR) for in-hospital mortality (HR 1.22, 95% CI 1.07-1.40; P = 0.003), as well as for 28-day mortality and 60-day mortality. Propensity score-matched (PSM) analysis further supported the finding that high RAR was an independent risk factor for ARF. CONCLUSION: This study reveals that RAR is an independent risk factor for poor clinical prognosis in patients with ARF admitted to the ICU. Higher RAR levels were associated with increased in-hospital, 28-day and 60-day mortality rates.

The significance of risk stratification through nomogram-based assessment in determining postmastectomy radiotherapy for patients diagnosed with pT1 - 2N1M0 breast cancer.

OBJECTIVE: To explore the high-risk factors affecting the prognosis of pT1 - 2N1M0 patients after mastectomy, establish a nomogram prediction model, and screen the radiotherapy benefit population. METHOD: The clinical data of 936 patients with pT1 - 2N1M0 who underwent mastectomy in the fourth hospital of Hebei Medical University from 2010 to 2016 were retrospectively analyzed. There were 583 patients received postmastectomy radiotherapy(PMRT), and 325 patients without PMRT. Group imbalances were mitigated using the propensity score matching (PSM) method, and the log-rank test was employed to compare overall survival (OS) and disease-free survival (DFS) between the cohorts. The efficacy of PMRT across various risk groups was evaluated using a nomogram model. RESULT: The median follow-up period was 98 months, Patients who received PMRT demonstrated significantly improved 5-year and 8-year OS and DFS compared to those who did not (P < 0.001). Multivariate analysis revealed that age, primary tumor site, positive lymph node, stage, and Ki-67 level independently influenced OS, while age, primary tumor site, and stage independently affected DFS. PMRT drastically enhanced OS in the high-risk group (P = 0.001), but did not confer benefits in the low-risk and intermediate risk groups (P = 0.057, P = 0.099). PMRT led to a significant improvement in disease-free survival (DFS) among patients in the intermediate and high-risk groups (P = 0.036, P = 0.001), whereas the low-risk group did not experience a significant benefit (P = 0.475). CONCLUSION: Age ≤ 40 years, tumor located in the inner quadrant or central area, T2 stage, 2-3 lymph nodes metastasis, and Ki67 > 30% were the high-risk factors affecting the prognosis of this cohort of patients. In OS nomogram, patients with a risk score of 149 or higher who received PMRT exhibited improved OS. Similarly, in DFS nomogram, patients with a risk score of 123 or higher who received PMRT demonstrated enhanced DFS.

Blood-, Tissue- and Urine-Based Prognostic Biomarkers of Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) is a rare but aggressive neoplasm. Currently, there are few reliable and widely used prognostic biomarkers of this disease. The purpose of this study was to assess the prognostic value of blood-, tissue- and urine-based biomarkers in patients with UTUC. A comprehensive literature search was conducted using the PubMed, Cochrane and Embase databases. Case reports, editorials and non-peer-reviewed literature were excluded from the analysis. As a result, 94 articles were included in this review. We evaluated the impact of 22 blood-based, 13 tissue-based and 4 urine-based biomarkers and their influence on survival outcomes. The neutrophil-lymphocyte ratio, albumin, C-reactive protein, De Ritis ratio, renal function and fibrinogen, which are currently mentioned in the European Association of Urology (EAU) guidelines, are well researched and most probably allow for a reliable prognosis estimate. However, our review highlights a number of other promising biomarkers that could potentially predict oncological outcomes in patients with UTUC. Nonetheless, the clinical value of some prognostic factors remains uncertain due to the lack of comprehensive studies.