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Background: Exonuclease 1 (EXO1), a protein involved in mismatch repair and recombination processes, has been identified as a prognostic biomarker in lung adenocarcinoma (LUAD). Nevertheless, its role in LUAD progression remains elusive. This study seeks to elucidate the functional significance of EXO1 in LUAD and evaluate its potential as a therapeutic target. Materials and methods: Patient RNA-seq and clinical data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Subsequently, a protein-protein interaction (PPI) network was constructed using differentially expressed genes (DEGs) to identify pivotal genes. Validation of the expression of signature genes was carried out through quantitative real-time PCR (qRT-PCR). Additionally, the association between EXO1 expression and clinical data was investigated. Immunohistochemistry was utilized to assess EXO1 expression in 93 cases of invasive pulmonary adenocarcinoma. Finally, cellular functional assays were conducted to investigate the impact of EXO1 on LUAD cells. Results: Ten key molecules (PBK, ASPM, NCAPG, EXO1, MKI67, RRM2, AURKA, DLGAP5, UBE2C, and CDC6) exhibited significantly elevated expression levels in LUAD tissues. Moreover, elevated levels of EXO1 gene expression correlated strongly with advanced T, N, and M stages and were significantly associated with immune cell infiltration in LUAD. Furthermore, marked increases in EXO1 protein expression were observed in patients diagnosed with invasive pulmonary adenocarcinoma. Notably, patients diagnosed with invasive pulmonary adenocarcinoma who exhibited elevated EXO1 expression levels exhibited increased lymph node metastasis, pleural invasion, poor tumor differentiation, and advanced clinical stage. Additionally, this study employed wound healing assay and CCK-8 cell proliferation assays to investigate the significant role of EXO1 in promoting the growth and migration of lung adenocarcinoma cells. Conclusions: This study identified ten hub genes associated with the initiation and progression of LUAD. Additionally, EXO1 may serve as a prognostic marker for LUAD patients, offering new perspectives for clinical treatments. [ABSTRACT FROM AUTHOR]

Background: Suppression of viral load is a targeted strategy for the prevention of HIV transmission. Viral load (VL) testing can be done at all health centres in Palembang City with free services. Purpose: This study aims to evaluate VL suppression and factors associated with VL suppression. Methods: The study design of this research was a cross-sectional study with data analysis using the Chi-square and binomial logistic regression tests. The population in this study was all HIV patients who accessed health services for VL testing. Data sources were obtained from the HIV/AIDS Information System (SIHA) for the period 2023 - June 2024. Results: The majority of PLHIV cases were male (1072 people) (83%) and unmarried (802 people) (62.1%). The transmission group was male-sexual males, 54.88%, with an average age of 36.62 years. The results of multivariate analysis showed that there were three variables associated with viral load levels, namely age with a p-value

Background Knee osteoarthritis (KOA) is a common clinical condition with a decades-long course. Long-term and personalised health management in community hospitals is the best way to prevent and treat KOA, and non-surgical treatment is an effective way to slow joint degeneration and postpone joint replacement surgery. Objective To understand the population characteristics, clinical staging and treatment modality characteristics of the population attending community hospitals for knee osteoarthritis, in order to provide a basis for optimising the treatment protocol for knee osteoarthritis at the grassroots level. Method All streets in the urban area of Beijing were randomly selected for the study using the whole cluster sampling method, and Hepingli Street in Dongcheng District, Beijing was censored for all patients who attended all community hospitals (7) belonging to the street from January to June 2022, and general information, medical history, personal history, clinical staging, K-L grading and treatment modalities were collected. Results A total of 3 615 KOA patients were included in this study, including 1 327 males (36.71%) and 2 288 females (63.29%), aged (71.8±13.3) years. There were 867 cases (23.98%) in the onset period, 2009 cases (55.57%) in the remission period and 739 cases (20.45%) in the rehabilitation period. Gender and age of patients with different clinical stages were not correlated with clinical stages (P>0.05), while BMI (K=0.235) and KL grading (K=0.406) were correlated with clinical stages (P

Background: Frozen shoulder (FS) is a common disorder causing shoulder pain and limited motion. Magnetic resonance imaging (MRI) is expected to help diagnose FS and realize the disease stage if stage-specific features are present. We aimed to survey stage-related MRI findings of FS in the literature. Methods: MEDLINE, SCOPUS, and Google Scholar databases were searched with search terms ''frozen shoulder'' or ''adhesive capsulitis'' combined with ''magnetic resonance imaging.'' Studies that discussed MRI findings in relation to FS stages were retrieved. The course of FS was divided into stages 1 to 4 according to Hannafin and Chiaia. Results: Two of the noncontrast-enhanced MRI findings were stage-related. T2 signal hyperintensity of the joint capsule was more frequent in stages 1 and 2. The axillary capsule thickness was greater in stages 1 and 2. However, these findings were also seen in the later stages to a lesser degree. Effusion around the long head of biceps, subcoracoid fat obliteration, and coracohumeral ligament thickening were common in FS but their relation to the stages was not evident. Signal enhancement on contrast-enhanced MRI was not consistently linked to stages. Conclusion: T2 signal hyperintensity and axillary capsule thickening are characteristic of the early stages of FS, although MRI alone cannot completely define the disease stage.

Background: Suppression of viral load is a targeted strategy for preventing HIV transmission. Viral load (VL) testing can be done at all health centers in Palembang City with free services. Purpose: This study aims to evaluate VL suppression and factors associated with VL suppression. Methods: The study design of this research was a cross-sectional study with data analysis using the Chi-square and binomial logistic regression tests. The population in this study was all HIV patients who accessed health services for VL testing. Data sources were obtained from the HIV/AIDS Information System (SIHA) for the period 2023-June 2024. Results: The majority of PLHIV cases were male (1072 people) (83%) and unmarried (802 people) (62.1%). The transmission group was male-sexual males, 54.88%, with an average age of 36.62 years. The results of multivariate analysis showed that there were three variables associated with viral load levels, namely age with a p-value <0.03, AOR = 1.59 (95% CI: 1.04-2.43), ARV adherence with a p-value < 0.00, AOR = 1.76 (95% CI: 1.18-2.61), and clinical stage with a p-value < 0.04, AOR = 1.02 (95% CI: 1.02-2.07). Conclusion: Adherence to ART therapy, prevention of opportunistic infections, and early detection of clinical stage are predictors of successful viral load suppression. The role and responsibility of the community and the active participation of health workers in early detection, treatment, and care are needed. [ABSTRACT FROM AUTHOR]

Objective: To analyze the association of CD19+ CD24hiCD27+ regulatory B cells (Bregs) with ankylosing spondylitis (AS) . Methods: Eighty patients with AS in Ganzhou People's Hospital from January 2019 to December 2021 were enrolled as observation group, meantime, another 60 healthy individuals were set as control group. Observation group was further divided into subgroups according to clinical stages and disease activity, advanced stage, ankylosis stage, active stage and non-active stage. Percentage of CD19+ CD24hiCD27+Bregs in CD19+ cells in peripheral blood of observation group and control group, and observation group patients with different stages were detected and compared, thereafter, relationship between percentage of CD19+CD24hiCD27+ Bregs and clinical characteristics of AS patients were discussed, such as course of disease, duration of morning stiffness, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), IL-10, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and X-ray classification of sacroiliitis. Results: Percentage of CD19+ CD24hiCD27+Bregs in peripheral blood in observation group was higher than that in control group. Percentage of CD19+ CD24hiCD27+Bregs in CD19+ cells in AS patients at ankylosis stage was higher than that in patients at advanced stage, and percentage of CD19+CD24hiCD27+Bregs in peripheral blood of patients with bony ankylosis stage was higher than that in patients with fibrous ankylosis stage. Percentage of CD19+ CD24hiCD27+Breg in CD19+B cells in active AS patients was significantly higher than that of patients with stable AS (P<0.05) . Serum IL-10 level in observation group was lower than that in control group, while ESR and CRP levels were higher than those in control group, with statistical significance (P<0.05) . Percentage of CD19+ CD24hiCD27+Breg in CD19+B cells in peripheral blood of AS patients was positively correlated with BASDAI score and serum IL-10 level, while negatively correlated with ESR and CRP levels, and had no correlation with morning stiffness time and X-ray classification of sacroiliitis. Conclusion: Percentage of CD19+ CD24hiCD27+Bregs in peripheral blood is reduced in AS patients, moreover, percentage is closely related to disease stage, activity and laboratory indicators IL-10, ESR and CRP, which may be involved in the occurrence and development of AS. [ABSTRACT FROM AUTHOR]

Clinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. In this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. We identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both "understaging" (path > clinical) and "overstaging" (clinical > path) were associated with inferior survival. Inaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy. [ABSTRACT FROM AUTHOR]

BackgroundExonuclease 1 (EXO1), a protein involved in mismatch repair and recombination processes, has been identified as a prognostic biomarker in lung adenocarcinoma (LUAD). Nevertheless, its role in LUAD progression remains elusive. This study seeks to elucidate the functional significance of EXO1 in LUAD and evaluate its potential as a therapeutic target.Materials and methodsPatient RNA-seq and clinical data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Subsequently, a protein-protein interaction (PPI) network was constructed using differentially expressed genes (DEGs) to identify pivotal genes. Validation of the expression of signature genes was carried out through quantitative real-time PCR (qRT-PCR). Additionally, the association between EXO1 expression and clinical data was investigated. Immunohistochemistry was utilized to assess EXO1 expression in 93 cases of invasive pulmonary adenocarcinoma. Finally, cellular functional assays were conducted to investigate the impact of EXO1 on LUAD cells.ResultsTen key molecules (PBK, ASPM, NCAPG, EXO1, MKI67, RRM2, AURKA, DLGAP5, UBE2C, and CDC6) exhibited significantly elevated expression levels in LUAD tissues. Moreover, elevated levels of EXO1 gene expression correlated strongly with advanced T, N, and M stages and were significantly associated with immune cell infiltration in LUAD. Furthermore, marked increases in EXO1 protein expression were observed in patients diagnosed with invasive pulmonary adenocarcinoma. Notably, patients diagnosed with invasive pulmonary adenocarcinoma who exhibited elevated EXO1 expression levels exhibited increased lymph node metastasis, pleural invasion, poor tumor differentiation, and advanced clinical stage. Additionally, this study employed wound healing assay and CCK-8 cell proliferation assays to investigate the significant role of EXO1 in promoting the growth and migration of lung adenocarcinoma cells.ConclusionsThis study identified ten hub genes associated with the initiation and progression of LUAD. Additionally, EXO1 may serve as a prognostic marker for LUAD patients, offering new perspectives for clinical treatments.

Abstract Breast cancer, as the most common cancer, has surpassed lung cancer worldwide. The neutrophil-to-lymphocyte ratio (NLR) has been linked to the onset of cancer and its prognosis in recent studies. However, quite a few studies have shown that there is a link between NLR and lymph node metastases in cN0 hormone receptor-positive (HR(+)) breast cancer. The purpose of this study was to evaluate the correlation between NLR and lymph node metastases in cN0 HR(+) breast cancer patients. From January 2012 to January 2022, 220 patients with cN0 HR(+) invasive breast cancers were enrolled in this study. The relationship between NLR and pathological data was statistically examined. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff of NLR, a chi-squared test was used for the univariate analysis, and logistic analysis was used for the multivariate analysis. The NLR had an optimal cutoff of 2.4 when the Jorden index was at a maximum. Patients with axillary lymph node metastases had a higher NLR (P

Real-life estimations of survival by stage in colorectal cancer are scanty. We estimated population-based net survival by pathological stage and location, and for rectal cancer by patterns of evolution according to clinical and pathological stage with regard to neoadjuvant therapy. Age-standardized net survival was estimated on 19,630 colorectal cancers diagnosed between 2009 and 2015. Five-year net survival was 64 % for colon and 62 % for rectal cancer. The highest absolute difference between colon and rectum was 12 % for stage II women aged 75 (91% vs. 79 %). Among patients with clinical stage III rectal cancer, 67 % no longer had pathological node involvement after neoadjuvant treatment. Survival was similar in clinical stage I, II or III and pathological stage III after neoadjuvant treatment and in pathological stage III without neoadjuvant treatment (between 67 % and 72 %). It ranged between 80 and 82 % in pathological stage II, without neoadjuvant treatment or with clinical stage I, II or III before neoadjuvant treatment. Survival ranged between 93 % and 95 % in pathological stage I, treated with surgery only or with clinical stage II or III before neoadjuvant treatment. Prognosis is associated with stage determined on surgical specimens rather than stage at the initial workup. [ABSTRACT FROM AUTHOR]

Summary: Treatment of rare/ultra-rare tumors is an unmet need due to a lack of standardized therapies and clinical trials. We developed the Molecular Tumor Board (MTB), a multidisciplinary team that integrates molecular profiling to generate personalized, N-of-One treatments for advanced cancers. This study evaluates 112 patients with rare/ultra-rare tumors who presented to the MTB and were evaluable for clinical therapeutic outcome. Overall, 46/112 patients (41%) received a treatment regimen with a high degree of matching between tumor molecular alterations and drugs given (reflected by a high Matching Score (≥50%)). Patients with a high versus low Matching Score experienced significantly longer progression-free survival (p = 0.005) and overall survival (p = 0.047), and higher rates of clinical benefit (stable disease ≥6 months, partial response, or complete response) (54% vs. 32% p = 0.027). The MTB facilitated personalized N-of-One matching of drugs to tumor molecular alterations, which was associated with improved clinical outcomes in patients with rare/ultra-rare cancers.

Background: MicroRNAs (miRNAs) are key regulators of gene expression that have been implicated in gynecological and breast cancers. Understanding the cancer stage-wise expression patterns of miRNAs and their interactions with other RNA molecules in cancer is crucial to improve cancer diagnosis and treatment planning. Comprehensive web tools that integrate data on the transcriptome, circulating miRNAs, and their validated targets to derive beneficial conclusions in cancer research are lacking. Methods: Using the Shiny R package, we developed a web tool called ExplORRNet that integrates transcriptomic profiles from The Cancer Genome Atlas and miRNA expression data derived from various sources, including tissues, cell lines, exosomes, serum, and plasma, available in the Gene Expression Omnibus database. Differential expression analyses between normal and tumor tissue samples as well as different stages of cancer, accompanied by gene enrichment and survival analyses, can be performed using specialized R packages. Additionally, a miRNA-messenger RNA (mRNA)-long non-coding RNA (lncRNA) networks are constructed to identify regulatory modules. Results: Our tool identifies cancer stage-wise differentially regulated miRNAs, mRNAs, and lncRNAs in gynecological and breast cancers. Survival analysis identifies miRNAs associated with patient survival, and functional enrichment analysis provides insights into dysregulated miRNA-related biological processes and pathways. The miRNA–mRNA–lncRNA networks highlight interconnected regulatory molecular modules driving cancer progression. Case studies demonstrate the utility of the ExplORRNet for studying gynecological and breast cancers. Conclusion: ExplORRNet is an intuitive and user-friendly web tool that provides a deeper understanding of dysregulated miRNAs and their functional implications in gynecological and breast cancers. We hope our ExplORRNet tool has potential utility among the clinical and basic researchers and will be beneficial to the entire cancer genomics community to encourage and facilitate mining the rapidly growing public databases to progress the field of precision oncology. The ExplORRNet is available at https://mirna.cs.ut.ee.

Objective To evaluate the relationship between TCGA molecular typing with FIGO grade and clinical stage of endometrial carcinoma. Methods The clinical studies about TCGA molecular typing of endometrial cancer in PubMed, Web of Science, EMBASE, CNKI and Wanfang databases were retrieved by computer. The retrival time was from the establishment of the database to December 2021. The literatures were screened according to the inclusion and exclusion criteria for conducting the data extraction. The RevMan 5. 3 and SPSS 21. 0 softwares were used for the meta analysis. Results A total of 10 related articles were included, 6 articles in English and 4 articles literatures in Chinese. There were 3 813 cases of endometrial cancer, including 213 cases (5.6%) of POLE mutation type, 1 103 cases (28.9%) of MSI-H type, 1 954 cases (51.2%) of CN-L type and 543 cases (14.2%) of CN-H type. A total of 10 articles analyzed the relationship between TCGA molecular subgroups and FIGO grade, 8 articles analyzed the relationship with the clinical stage, depth of muscular infiltration and lymph node metastasis, 9 articles analyzed the relationship with the histological typing and LVSI, and 2 articles analyzed the cytological statistics of peritoneal lavage fluid. In the comparison between FIGO G3 and G1-2 stage, OR of POLE mutant type was 1. 46 (95%CI 1.06-2.03); OR of MSI-H type was 1. 42(95%CI 1. 16-1.74); OR of CN-L type was 0.20 (95%CI 0.14-0.29); OR of CN-H type was 9. 62(95%CI 4.61-16.67). In the comparision between FIGO II-IV and FIGO I,OR of POLE mutant type was 0. 44 (95%CI 0.27-0.72); OR of MSI-H type was 1. 12(95%CI 0.92-1. 37; OR of CN-L type was 0. 51(95%CI 0.36-0.74; OR of CN-H type was 2. 81(95%CI 2. 23-3.53). Conclusion The patients with FIGO G3 grade and FIGO stage I endometrial cancer are more likely to develop POLE mutation, and the patients with FIGO G3 grade and II-IV stage are more likely to develop high copy number variation. Clinicopathological features should be combined with molecular type to guide the prognosis and treatment of the patients. [ABSTRACT FROM AUTHOR]

Transition is the next major hurdle in the field of HIV-infected youth, especially in sub-Saharan Africa. At St Camille Hospital in Ouagadougou, fully informed and compliant patients over 13-years-old were eligible for referral to the adult HIV/AIDS service, after completion of an individualized preparatory process. Transition consisted in at least two consecutive "joined-service" appointments in the respective facilities. We retrospectively compared immunological, clinical, and therapeutical data one year before transition, at transition and one year after transition. Between 2008 and 2019 73 patients (34 females, 39 males) were transitioned. All had been previously in pediatric care for at least 1 year and 66 were on HAART. Matched paired analysis of CD4 counts revealed a modest drop in CD4 cells over time (p < 0.05). Clinical data also showed strong fluctuation between WHO clinical stages over the three time points, with a clear trend towards increased severity especially post transfer. This large retrospective 12-year single-center experience from a Sahel country showed a 95.8% retention rate at one year. It demonstrates how a comprehensive plan, carefully implemented, can provide excellent retention, even in a low-resource setting. However, mild immunological decline was associated with a worrisome clinical deterioration, underlining the importance of assessing the latter after transition. [ABSTRACT FROM AUTHOR]

Objective: Investigate the expression and potential clinical significance of FK506-binding protein 38 (FKBP38) in breast cancer tissue. Methods: The expression of FKBP38 in 100 cases of normal breast tissue, 300 cases of invasive ductal carcinoma tissue (IDC) and 59 cases of invasive lobular carcinoma tissue (ILC) were detected by immunohistochemistry, and analyzed the relationship between the expression level of FKBP38 protein and clinicopathological parameters of breast cancer. Results: Immunohistochemical results showed that comparing with normal breast tissue, the expression levels of FKBP38 in invasive ductal carcinoma and invasive lobular carcinoma tissue significantly decreased, with a statistical difference (P<0.0001). Further analysis showed that in invasive ductal carcinoma, the expression level of FKBP38 protein was negatively correlated with the pathological grade and clinical stage, and there was a statistical difference, while the expression of FKBP38 protein was negatively correlated with the expression of PR protein. In addition, the current study demonstrated that the expression level of FKBP38 protein in triple-negative breast cancer (TNBC) was much higher than that in non-triple-negative breast cancer, and the expression of FKBP38 in TNBC was negatively correlated with the primary tumor stages. Conclusions: The expression level of FKBP38 protein significantly decreases in breast cancer patients, and it is related to the pathological grade and clinical stage of breast cancer. It is suggested that FKBP38 protein can be used as a potential target for the diagnosis and treatment of breast cancer, but the involving mechanism still needs further exploration. [ABSTRACT FROM AUTHOR]

Objective To explore the expression of programmed cell death protein 5 in cervical cancer and its relationship with lymph node metastasis. Methods 98 cases of cervical cancer patients admitted to our hospital were selected as the observation group, and 98 cases of cervical benign lesions were selected as the control group. The expression levels of PDCD5 in serum and lesion tissues of the two groups were compared to analyze the relationship between PDCD5 and pathological features of cervical cancer, and the diagnostic value of PDCD5 in lymph node metastasis of patients with cervical cancer was analyzed by ROC curve. Results The expression levels of PDCD5 in serum and lesion tissue of observation group were lower than those of control group (P < 0.05) . With the increase of clinical stage and pathological grade of cervical cancer, the expression of PDCD5 in serum and lesion tissue was significantly decreased (P < 0.05) . Among the 98 patients with cervical cancer, 32 had lymph node metastasis. The expression levels of PDCD5 in serum and lesion tissue of lymph node metastasis group were lower than those of non-lymph node metastasis group (P < 0.05) . ROC curve results showed that the AUCs of PDCD5 in serum and lesion tissue to predict lymph node metastasis of cervical cancer patients were 0.810 and 0.850, respectively, with no statistical significance (P > 0.05) . Conclusion The Programmed cell death protein 5 is closely related to the pathological features of patients with cervical cancer, and it has a good predictive effect on lymph node metastasis, which is worthy of further study and application. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether galectin-9 gene (LGALS9) expression is correlated with cervical cancer progression, clinicopathological characteristics, and overall survival. To determine the biological processes and the abundance of tumour infiltrating immune cells related to the expression of LGALS9.Patients and Methods: The study was conducted in two phases: 1) The expression level of LGALS9 was determined using the data of 193 squamous cell carcinoma (SCC) samples from The Cancer Genome Atlas (TCGA) database. Biological processes and tumour infiltrating cells associated to LGALS9 expression were evaluated using gene set enrichment analysis (GSEA) and tumour immune estimation resource (TIMER). 2) Independently, galectin-9 was identified in 40 SCC samples by immunohistochemistry and optical density quantified using ImagePro® software.Results: The LGALS9 gene showed increased expression in cervical cancer samples. A higher expression level in SCC was related to better overall survival and to early clinical stages. GSEA showed that tumours with higher expression of LGALS9 were enriched in immune pathways such as interferon_alpha_response, and complement, the analysis of TIMER database showed a positive correlation between the expression level of LGALS9 and the abundance of tumour infiltrating immune cells. In addition, higher expression of galectin-9 was found in biopsies of SCC patients at early clinical stages, showing a trend of better survival.Conclusion: Higher expression levels of LGALS9 and galectin-9 in SCC were related to early clinical stages and better prognosis. GSEA and TIMER analysis suggested that galectin-9 could play an antitumor role in cervical SCC. [ABSTRACT FROM AUTHOR]

Introduction: Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC. Methods: A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry. Results: The response of Th1 cytokines such as IFN-g and TNF-a against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001 and P < 0.05-0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells. Conclusion: There is a characteristic cytokine profile at each clinical stage of MAC. [ABSTRACT FROM AUTHOR]

Purpose: In testicular neoplasms, the interrelationship of elevations of the novel serum tumor marker microRNA-371a-3p (M371) and traditional markers with other clinical features is still incompletely understood. The present study evaluated marker expression rates in relation to various other clinical parameters. Methods: The following data were retrospectively registered from 641 consecutive patients with testicular neoplasms: histology, such as seminoma (n = 365), nonseminoma (n = 179), benign tumor (n = 79), other malignant tumor (n = 18); patients age (years); clinical stage (CS1, CS2a/b, CS2c, CS3); and preoperative elevation of beta HCG, AFP, LDH, M371 (yes/no). Descriptive statistical methods were employed with comparisons of various subgroups to disclose associations of marker expression rates with age, histology and CS, and of age with histology. Results: The histologic subgroups revealed significantly different expression rates of tumor markers. M371 performed best with expression rates of 82.69% and 93.58% in seminoma and in nonseminoma, respectively. In germ cell tumors, all markers had significantly higher expression rates in metastasized stages than in localized disease. All markers except LDH have significantly higher expression rates in younger than in older patients. Nonseminoma is most prevalent in the youngest age category, seminoma predominates in patients > 40 years, other malignancies were restricted to patients > 50 years. Conclusion: The study documented significant associations of serum marker expression rates with histology, age and clinical staging, with highest rates in nonseminomas, young age and advanced clinical stages. M371 showed significantly higher expression rates than other markers suggesting its superior clinical usefulness. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between quantitative parameters of ultrasound elastic imaging and clinical stage and pathological molecular classification of benign and malignant breast tumors. Methods: 85 patients with breast mass admitted to our hospital from January 2020 to December 2022 were selected to undergo ultrasound elastic imaging examination. The pathological examination results of 85 patients with breast mass were analyzed, elastic imaging parameters of benign and malignant tumors were compared, and ROC curves were drawn for elastic strain rate, diameter change rate, area ratio and the three combined. The elastic imaging parameters of different clinical stages of breast cancer patients and the elastic imaging parameters of pathological molecular classification of breast cancer patients were analyzed. Results: Among 85 patients with breast mass, 35 cases were benign and 50 cases were malignant.The elastic strain rate, mass diameter, diameter change rate, mass area and area ratio in the malignant group were significantly lower than those in the benign group (P<0.05). The area ratio ROC curve AUC was 0.580, with 1.73 as the critical value, the diagnostic sensitivity and specificity of breast malignant tumor were 73.5% and 38.5%. The ROC curve of diameter change rate was 0.630 with 0.28 as the critical value. The diagnostic sensitivity was 75.5% and the specificity was 47.5%. The ROC curve of elastic strain rate was 0.790, with 15.2 cm2 as the critical value, the diagnostic sensitivity was 64.5%, and the specificity was 83.5%. The ROC curve was drawn with the three factors combined, and the AUC was 0.920, the diagnostic sensitivity was 82.5%, and the specificity was 92.5%. There were significant differences in the elastic strain rate, mass diameter, diameter change rate, mass area and area ratio in patients with breast malignant tumor at TNM stage Ⅰ, Ⅱ, Ⅲ and Ⅳ (P<0.05). Among them, the elastic strain rate, mass diameter, diameter change rate, mass area and area ratio of stage Ⅳ were significantly higher than those of stage Ⅲ, Ⅱ and Ⅰ, stage Ⅲ was significantly higher than those of stage Ⅱ and Ⅰ, and stage Ⅱ was significantly higher than those of stage Ⅰ. The differences of elastic strain rate, mass diameter, rate of diameter change, mass area and area ratio in Luminal A, Liminal B, Her2 overexpression and basal-like patients with breast malignant tumor were statistically significant (P<0.05). The elastic strain rate, mass diameter, rate of diameter change, mass area and area ratio of the Liminal B type are significantly higher than those of Luminal A, Her2 overexpression and basal-like type, and the overexpression of Her2 is significantly higher than those of Luminal A and basal-like type (all P<0.05). There was no statistical significance between Luminal A type and basal-like type (P>0.05). Conclusion: Ultrasound elastic imaging can be used for the diagnosis of benign and malignant breast tumors, and the quantitative parameters of ultrasound elastic imaging can be used to judge the clinical stage of malignant breast tumors, the Liminal type B, the Her2 overexpression type. [ABSTRACT FROM AUTHOR]

Abstract Background Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care. Methods Demographic and clinical information of 2901 young people who accessed mental health care at age 12–25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: ‘non-specific anxious or depressive symptoms’, 1b: ‘attenuated mood or psychotic syndromes’, 2+: ‘full-threshold mood or psychotic syndromes’). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care. Results Of the entire cohort, 2093 young people aged 12–25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60–4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36–3.28), develop suicidal ideations (OR=1.92; CI 1.30–2.84) and circadian disturbances (OR=1.94, CI 1.31–2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity. Conclusions The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages.

Objective To investigate the correlation between MRI diffusion kurtosis imaging (DKI) parameters and clinical stage of nasopharyngeal carcinoma (NPC). Methods 86 patients with pathologically proved NPC were scanned byDKI. DKI parameters included fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr). FA of kurtosis (FAK) value. The consistency of the parameters of tumor focus DKI measured by the two observers was tested by intraclass correlation coefficient (ICC). To analyze the correlation between DKI parameters and NPC clinical stage, T stage and N stage. When the parameter values between the two groups were in accordance with the normal distribution, the differences of different groups were compared by two independent sample t -test. Results The values of DKI parameters of nasopharyngeal carcinoma lesions measured by the two observers were in good agreement (ICC > 0.75). The MD values of DKI parameters in the high-grade group were lower than those in the low-grade group in the clinical stage, the MK value in the high-grade group was higher than the low-grade group in the clinical stage, the MD value in the T-stage high-grade group were lower than those in the low-grade group, and the MK value was In T stage, the high stage group was higher than the low stage group, the MD value in the N stage group were lower than those in the low stage group, and the MK value in the N stage high stage group was higher than the low stage group, and the difference was statistically significant (P < 0.05). The values of DKI parameters FA, Da, Dr, FAK, Ka and Kr were not statistically significant in NPC clinical stage, T stage and N stage. Conclusion The MD value and MK value of DKI parameters were related to the clinical stage, T and N stage of NPC. The clinical stage, T stage and N stage were high, the MD value decreased and the MK value increased. [ABSTRACT FROM AUTHOR]

Non-invasive diagnostic method based on radiomic features in patients with non-small cell lung cancer (NSCLC) has attracted attention. This study aimed to develop a CT image-based model for both histological typing and clinical staging of patients with NSCLC. A total of 309 NSCLC patients with 537 CT series from The Cancer Imaging Archive (TCIA) database were included in this study. All patients were randomly divided into the training set (247 patients, 425 CT series) and testing set (62 patients, 112 CT series). A total of 107 radiomic features were extracted. Four classifiers including random forest, XGBoost, support vector machine, and logistic regression were used to construct the classification model. The classification model had two output layers: histological type (adenocarcinoma, squamous cell carcinoma, and large cell) and clinical stage (I, II, and III) of NSCLC patients. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence interval (CI) were utilized to evaluate the performance of the model. Seven features were selected for inclusion in the classification model. The random forest model had the best classification ability compared with other classifiers. The AUC of the RF model for histological typing and clinical staging of NSCLC patients in the testing set was 0.700 (95% CI, 0.641–0.759) and 0.881 (95% CI, 0.842–0.920), respectively. The CT image-based radiomic feature model had good classification ability for both histological typing and clinical staging of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Surgery remains the preferred treatment option for early-stage gallbladder cancer (GBC). According to the anatomical position of the primary tumor, accurate preoperative stage and strict control of surgical indications, appropriate surgical strategies are selected to achieve the optimal surgical effect. However, most patients have already been at the locally advanced stage or the tumor has metastasized at the initial diagnosis. The postoperative recurrence rate and 5-year survival rate remain unsatisfactory even after radical resection for gallbladder cancer. Hence, there is an urgent need for more treatment options, such as neoadjuvant therapy, postoperative adjuvant therapy and first-line and second-line treatments of local progression and metastasis, in the whole-course treatment management of gallbladder cancer patients. In recent years, the application of molecular targeted drugs and immunotherapy has brought greater hope and broader prospects for the treatment of gallbladder cancer, but their effects in improving the prognosis of patients still lack sufficient evidence-based medicine evidence, so many problems should be addressed by further research. Based on the latest progress in gallbladder cancer research, this review systematically analyzes the treatment trends of gallbladder cancer. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a rare, progressive multi-system neurodegenerative disorder. Its clinical presentation varies considerably leading to delays in diagnosis, which has dire consequences in a disease where early intervention is key to optimize outcomes and limit care giver burden. There are a range of diagnostic criteria available to aid ALS diagnosis, as well staging methods to assess disease progression. However, they all suffer from inter-rater variability, complexity, and confusion in use. Such difficulties, when medical appointment times are limited and becoming more virtually based, have the potential to amplify uncertainty and errors in ALS diagnosis and prognosis. This review provides a clinical overview of the best way to balance the needs of evidence-based medicine and the patient. We focus on ALS diagnostic criteria and staging systems currently in use in clinical practice and explore factors that could enhance diagnostic efficiency and assessment of disease progression. [ABSTRACT FROM AUTHOR]

Summary: Background: Essential indicators of health system performance for breast cancer are lacking in Mexico. We estimated survival and clinical stage distribution for women without social insurance who were treated under a health financing scheme that covered 60% of the Mexican population. Methods: We conducted a retrospective cohort study cross-linking reimbursement claims for 56,847 women treated for breast cancer between 2007 and 2016 to a mortality registry. We estimated overall- and clinical stage-specific survival and breast cancer survival according to patient age, state of residence, marginalization, type of treatment facility, and patient volume of the treatment facility. We also explored the distribution of clinical stage according to age, year of treatment initiation, and state where the woman was treated. We used log-rank tests and estimated 95% CIs to compare differences between patient groups. Findings: Median age was 52 years (interquartile range [IQR] 45, 61) (Sixty five percent patients (36,731/56,847) had advanced disease at treatment initiation. Five-year overall survival was 72.2% (95% CI 71.7, 72.6). For early disease (excluding stage 0), 5-year overall survival was 89.0% (95% CI 88.4, 89.5), for locally advanced disease 69.9% (95% CI 69.0, 70.2) and for metastatic 36.9% (95% CI 35.4, 38.4). Clinical stage at treatment initiation and breast cancer survival remained unchanged in the period analyzed. Clinical stage and survival differed across age groups, state of residence, and type of facility where women received treatment. Interpretation: In the absence of population-based cancer registries, medical claims data may be efficiently leveraged to estimate essential cancer-related performance indicators. Funding: The authors received no financial support for this research.

Summary: Background: Recurrent cancers of the head and neck are associated with poor survival outcome. Yet, their burden in Africa is not reliably known. We therefore aimed to estimate the prevalence of recurrence and the 5-year overall survival among patients treated for head and neck cancers (HNC) in Africa. Method: In this systematic review and meta-analysis, we searched four electronic databases (Pubmed, CINAHL, MEDLINE, and Web of Science) and the grey literature for studies reporting the prevalence of HNC recurrence and 5-year overall survival post treatment, published between January 1, 2002, and December 31, 2022. We contacted corresponding authors of relevant studies. Searches were extended to reference lists of review articles and other relevant sources for potentially eligible studies. Each record was assessed for inclusion or exclusion by two independent reviewers. Records with individual-level data on recurrence and survival conducted in Africa were included while exclusion was based on the study design and availability of relevant data. Data were independently extracted by three reviewers from eligible studies, and summary estimates were sought. Our primary outcomes were recurrence and 5-year overall survival of patients who have been treated for HNC, and our secondary outcomes included risk factors, tumor site, squamous cell histology, clinical stage of tumor, and treatment options received. Only records selected for primary outcomes were assessed for secondary outcome data extraction. Random-effects meta-analysis was conducted for each outcome. Meta-regression models were used in addressing sample heterogeneity among the studies. Protocol for this study was registered with PROSPERO, CRD42022372307. Findings: This systematic review and meta-analysis returned 3998 records, yielding 28 included studies after exclusion. Eighteen studies reported on the prevalence of HNC recurrence while 24 articles reported on the 5-year overall survival. Of the pooled total study population, 7199 (70.5%) of 10,218 patients were males while 2603 (25.5%) were females. We found that the prevalence of HNC recurrence was 15.4% (I2 = 96.2%; 95% CI: 9.5–22.3; n = 3214; k = 18), and the 5-year overall survival was 54.4% (I2 = 99.5%; 95% CI: 40.1–68.4; n = 9798; k = 24). We also found that the prevalence of smoking and alcohol consumption as risk factors for HNC were 42.6% (I2 = 98.8%; 95% CI: 25.2–61.0; n = 4374; k = 15) and 35.8% (I2 = 98.9%; 95% CI: 21.7–51.4; n = 4110; k = 11) respectively. The pooled current prevalence for advanced HNC (clinical stages III-IV) was 80.0% (I2 = 99.2%; 95% CI: 68.6–89.5; n = 7624; k = 18) compared to 12.2% (I2 = 96.4%; 95% CI: 6.2–19.8; n = 7624; k = 18) in early disease (clinical stages I-II). Interpretation: The results showed significantly high prevalence of cancer recurrence, poor 5-year overall survival and very high prevalence of advanced cancers at time of diagnosis. This study provides robust evidence for strategies towards prompt diagnosis and appropriate management of HNC to improve patients’ outcome in the African continent. Funding: This study was not supported by any funding.

Objective: We investigated the effects of different treatment modalities and clinical stage for hypopharyngeal carcinoma (HPC) patients. Methods: Between February 2004 and December 2012, 167 HPC patients were reviewed. We calculated overall survival (OS), progression-free survival (PFS), local failure-free survival (LFFS), regional failure-free survival (RFFS), and distant metastasis failure-free survival (DMFFS) using the Kaplan-Meier method and compared various survival outcomes between definitive chemoradiotherapy (CRT) and surgery-based therapy (SBT). Results: There were no significant differences in baseline characteristics between SBT (n = 102) and definitive CRT (n = 65) groups. The 5-year rates of OS (59.7% vs. 24.0%, p < 0.0001) and PFS (49.9% vs. 22.6%, p = 0.0002) were significantly better in patients who received SBT than in those who received definitive CRT. The SBT group also obtained better LFFS (p < 0.0001), RFFS (p = 0.0479), and DMFFS (p = 0.0110). We did similar analyses by different T-classification (T1-2, T3, and T4) and found that SBT had better OS (p < 0.0001 and p = 0.0020), PFS (p < 0.0001 and p = 0.0513), LFFS (p = 0.0002 and p = 0.0075), RFFS (p = 0.1949 and p = 0.0826), and DMFFS (p = 0.0248 and p = 0.0436) in the T4 and T1-2 subgroups but similar OS (p = 0.9598), PFS (p = 0.5052), RFFS (p = 0.9648), and DMFFS (p = 0.8239) in T3 patients. Analyses by different overall stages revealed no differences between definitive CRT and SBT for stage III patients but significantly better results for stage IV patients who received SBT. Conclusions: SBT can obtain significant survival benefits when compared with definitive CRT for the whole cohort of patients. Definitive CRT has similar survival outcomes compared with SBT only for T3 tumors or overall stage III disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between clinicopathological findings and tumor stage according to AJCC 2018 guidelines in patients suffering from Oral squamous cell carcinoma (OSCC). Methods: A descriptive study was conducted from January 2019 to January 2020 at King Edward Medical University and University of Health Sciences on a total of 49 patients enrolled after obtaining written informed consent. Clinical and radiographic findings were recorded. Pathological reporting was done using AJCC 2018 cancer staging guidelines. Association between clinicopathological features with tumor stage and grade was assessed using Chi-square and Kruskal-Wallis test. Results: Mean age of the patients was 46.1 ± 10.6 years. Most of the tumors were of well differentiated type (49%) and moderately differentiated (40.8%) with predominant clinical stage III in 42.9% & IV in 44.9 % and primary tumor stage pT2 28.6% & pT3 36.7%. Significant difference was seen for primary tumor stage in relation to age, gender, depth of invasion, primary site, and size of tumor (p < 0.01). For clinical stages, significant difference was observed in the age, gender, size of tumor, nodal metastasis, and anatomical tumor site (p < 0.01). Conclusion: Application of 8th Edition AJCC guidelines identifies the importance of the latest classification with strong association of latest stage criteria with age, gender, site of primary tumor, tumor thickness, depth of invasion, nodal metastasis and size of largest lymph node involved, and Level of Lymph node involved (level III & V) in a subset of patients from a developing country. [ABSTRACT FROM AUTHOR]

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Bader Alshamsan,1,2 Kausar Suleman,1 Naela Agha,1,3 Marwa I Abdelgawad,1,4 Mashari J Alzahrani,1,5 Tusneem Elhassan,1 Taher Al-Tweigeri,1 Dahish Ajarim,1 Adher Alsayed1 1Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 2Department of Medicine, College of Medicine, Qassim University, Qassim, Saudi Arabia; 3Northern Ireland Cancer Centre, Belfast City Hospital, Belfast, UK; 4Clinical Oncology Department, Assiut University, Assiut, Egypt; 5Department of Medicine, Medical Oncology, University of Ottawa, Ottawa, ONT, CanadaCorrespondence: Bader Alshamsan, Tel +9660506123866, Email bshmsan@qu.edu.saPurpose: Obesity is prevalent in Saudi Arabia and is associated with adverse clinical features and poor breast cancer (BC) outcomes. We determined the distribution of body mass index (BMI) and evaluated its association with disease characteristics and outcomes in women with non-metastatic BC.Patients and Methods: We conducted a retrospective analysis of a prospectively collected database of consecutive patients treated for non-metastatic BC between 2002 and 2014. Patients were categorized into the following groups: underweight/normal weight (BMI < 25 kg/m2), overweight (BMI 25– 29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). Regression analysis was used to evaluate clinicopathological factors associated with BMI and clinical stage.Results: A total of 2212 patients were enrolled. The median age was 45 years (interquartile range [IQR], 39– 52 years), and the median BMI was 30 kg/m2 (IQR, 26– 34 kg/m2). Most patients were premenopausal (63.6%), nearly half of the patients had stage III disease, and 11.2% were screen-detected. The prevalence of obesity was 53.4%, with a significant difference between the peri/premenopausal (49.4%) and postmenopausal (61.7%) groups (p < 0.001). Obese patients were more likely to be aged > 40 years, be postmenopausal, have a history of oral contraceptive pills, have advanced-stage disease, and have undergone radiation therapy, and were less likely to have human epithelial growth factor 2 (HER2)+ disease than non-obese patients. Premenopausal obese women had fewer hormone receptor-positive and more triple-negative cancers than postmenopausal obese women did. Obesity, non-screening-detected BC, and HER+ status were independent prognostic factors for advanced-stage presentation.Conclusion: The prevalence of obesity and its significant association with advanced BC justify the upscaling of screening services and instituting weight-reduction strategies.Keywords: obesity, body mass index, non-metastatic breast cancer, clinical stage, Saudi Arabia

Elderly patients with oral squamous cell carcinoma (OSCC) have difficulty undergoing curative surgical treatment due to various factors besides age. The purpose of the present study was to study the factors determining surgery in elderly patients with OSCC. We designed and implemented a retrospective cohort study. The study sample included elderly patients aged ≥ 70 years with OSCC and they were statistically compared between the surgery and non-surgery groups. The primary outcome variable was selecting surgery as the treatment plan, while the secondary outcome was the prognosis of each group. The sample comprised 76 patients aged ≥ 70 years with OSCC, of whom 52 treated with surgery and 24 patients treated with non-surgery. As decision factors, performance status (PS), clinical stage, serum Alb level, body mass index (BMI), and Geriatric Nutritional Risk Index (GNRI) were significantly associated with the selection of surgery. Logistic multivariate analysis identified three independent predictive factors for selecting surgery: Alb (≥3.5 vs. <3.5), PS (0, 1, 2, 3), and clinical stage. According to the decision tree analysis, curative surgery is the recommended treatment strategy for elderly patients with Alb ≥ 3.5 g/dL, PS 0, and stage I, II. In conclusion, Alb, PS, and clinical stage may be the criteria for selecting surgery in elderly patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of Traditional Chinese Medicine (TCM) syndrome type, gut microbiome distribution, and host immunity function in predicting the early and advanced clinical stages of colorectal cancer (CRC). Methods: A cross-sectional case-control study was performed which included 48 early stage and 48 advanced patients with CRC enrolled from March 2018 to December 2020. 16S rRNA gene sequencing was performed to analyze the gut microbiomes of the patients, while T and B lymphocyte subsets in peripheral blood were assessed using flow cytometry. TCM syndrome type was measured using the spleen deficiency syndrome (SDS) scale. Results: The abundance levels of Prevotella, Escherichia-Shigella, and Faecalibacterium in the gut microbiota were significantly increased in the advanced group, while Bacteroides was significantly decreased. Phascolarctobacterium was detectable only in the early metaphase group, whereas Alistipes was detectable only in the advanced group. The lymphocyte (P = .006), T helper cell (TH) (P = .002), cytotoxic T cell (TC) (P = .003), double positive T cell (DPT) (P = .02), and total T counts (P = .001) were significantly higher in the early metaphase group than in the advanced metaphase group. Compared with patients with early stage CRC, the advanced group had a higher SDS score. After adjusting for clinical stage, Spearman's correlation analysis showed interactions among gut microbiome abundance, T cell level, and SDS score. Multivariate logistic analysis showed that after controlling for the SDS score, abundance of Alistipes and Faecalibacterium, and double negative T cell (DNT) level, DPT was significantly associated with a lower risk of advanced-stage disease (hazard ratio, 0.918; P = .022). Conclusion: Our study suggested associations between clinical stage, SDS, gut microbiota, and T lymphocytes, which provided insights for a potential prediction model for the disease progression of CRC. [ABSTRACT FROM AUTHOR]

Background: Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care. Methods: Demographic and clinical information of 2901 young people who accessed mental health care at age 12–25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: 'non-specific anxious or depressive symptoms', 1b: 'attenuated mood or psychotic syndromes', 2+: 'full-threshold mood or psychotic syndromes'). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care. Results: Of the entire cohort, 2093 young people aged 12–25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60–4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36–3.28), develop suicidal ideations (OR=1.92; CI 1.30–2.84) and circadian disturbances (OR=1.94, CI 1.31–2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity. Conclusions: The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) has a high prevalence and poor prognosis. This study aimed to identify biomarkers related to the clinical stage (I-IV) of CRC. Methods: The LinkedOmics database was used as the discovery cohort, and two Gene Expression Omnibus (GEO) databases (GSE41258 and GSE422848) served as validation cohorts. The trend test of genes related to clinical stage (I-IV) of CRC patients was identified by the Jonckheere-Terpstra test. The cBioPortal database, Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan databases were used to explore the expression change and prognostic value of clinical stage-related genes in CRC patients. CRC cells overexpressed AGPAT5 were constructed and used for cell counting kit-8 (CCK-8), flow cytometric, and wound healing assays in vitro. Results: We identified four clinical stage-related genes, GSR, AGPAT5, CRLF1, and NPR3, in CRC. The CNA frequencies of GSR, CRLF1, AGPAT5, and NPR3 occurred in 11%, 2.4%, 13%, and 3% of patients, respectively. The expression of GSR and AGPAT5 tended to decrease with CRC stage (I-IV) progression, and the expression of CRLF1 and NPR3 tended to increase with CRC stage (I-IV) progression. Compared with the normal group, AGPAT5 expression was markedly decreased in stage IV CRC. Higher GSR and AGPAT5 expression levels were associated with better overall survival (OS) and disease-free survival (DFS) in CRC patients. Lower CRLF1 and NPR3 expression levels were associated with better OS and DFS in CRC. GSR, CRLF1, AGPAT5, and NPR3 expression were related to CRC progression, microsatellite instability, and tumour purity in CRC. Furthermore, AGPAT5 was downregulated in CRC cell lines, and overexpression of AGPAT5 inhibited cell proliferation and migration and promoted cell apoptosis in CRC cells. Conclusion: Low AGPAT5 expression may serve as a poor prognostic factor and clinical stage biomarker in CRC. In addition, AGPAT5 acts as a tumour suppressor in CRC progression. [ABSTRACT FROM AUTHOR]

Background: In this post hoc analysis of the PRODIGY study, we aimed to investigate factors associated with survival outcomes and provide evidence for designing optimal perioperative treatment strategies for gastric cancer patients receiving neoadjuvant chemotherapy. Patients and methods: A total of 212 patients in the neoadjuvant chemotherapy group of the PRODIGY study were included as the study population. The prognostic impact of clinicopathologic factors, including the initial radiological clinical stage (cStage) and post-neoadjuvant chemotherapy pathological stage (ypStage), was analyzed. Results: The median age was 58 years. The majority of patients (77.4%) had cStage III disease, and about 10% and 25% had ypStage 0 and I disease, respectively. According to the initial cStage, progression-free survival (PFS) and overall survival (OS) were significantly different (P < 0.01). PFS and OS were also different according to the ypStage (P < 0.01). In multivariate analyses, cStage IIIC disease (vs. cStage II) and ypStage II and III disease (vs. ypStage 0/I) were independent factors for poor survival outcomes. Based on the patterns of PFS and OS according to both cStage and ypStage, three patient groups were defined. These groups showed distinct PFS and OS (P < 0.01) with 5-year PFS rates of 95.7%, 77.9%, and 31.3% and 5-year OS rates of 95.7%, 82.4%, and 42.5%, respectively. Conclusions: Both initial cStage and ypStage were independent factors for survival outcomes of gastric cancer patients treated with neoadjuvant chemotherapy. Efforts should be made to develop optimal peri-operative treatment strategies for patients at different risks according to cStage and ypStage. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of advanced imaging technologies, it remains difficult to achieve sufficient staging accuracy to ensure a tailored treatment strategy for patients with upper tract urothelial carcinoma (UTUC). The aim of the study was to identify preoperative risk factors for tumor upstaging in patients with UTUC initially staged as clinical T2 or lower and to analyze these factors separately for renal pelvic cancer and ureteral cancer., Methods: This retrospective study included data from patients with UTUC who underwent nephroureterectomy. Among them, patients who underwent a staging evaluation using computed tomography urography within 90 days before surgery were selected. Various preoperative factors were evaluated, and multivariate logistic regression analyses were conducted to identify predictors of pathological tumor upstaging., Results: The study included 496 patients, of whom 392 were diagnosed with clinical T2 stage or lower. Among these, 125 patients (31.9%) were upstaged to pathological T3 or T4 disease. Multivariate analysis identified positive voided urine cytology [hazard ratio (HR) =2.94, P<0.001] and tumor size ≥30 mm (HR =1.90, P=0.008) as independent predictors of upstaging. Subgroup analysis showed that positive voided urine cytology (HR =2.71, P=0.004) and tumor size ≥30 mm (HR =3.39, P=0.001) were significant risk factors for renal pelvic cancer. In contrast, significant predictors for ureteral cancer included positive voided urine cytology (HR =3.11, P=0.003) and hydronephrosis (HR =2.69, P=0.03)., Conclusions: Positive voided urine cytology and larger tumor size were significant predictors of pathological upstaging in patients with UTUC. Differences in the risk factors between renal pelvic and ureteral cancers highlight the need for tailored preoperative evaluations and management strategies. Further studies are required to refine these predictive models and improve clinical decision-making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-357/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Purpose: Pre-operative evaluation identifying clinical-stage affects the decision regarding the extent of surgical resection in right colon cancer. This study was designed to predict a proper surgical resection through the prognosis of clinical Stage I right colon cancer. Patients and Methods: We included patients who were diagnosed with clinical and pathological Stage I right-sided colon cancer, including appendiceal, caecal, ascending, hepatic flexure and proximal transverse colon cancer, between August 2010 and December 2016 in two tertiary teaching hospitals. Patients who underwent open surgeries were excluded because laparoscopic surgery is the initial approach for colorectal cancer in our institutions. Results: Eighty patients with clinical Stage I and 104 patients with pathological Stage I were included in the study. The biopsy reports showed that the tumour size was larger in the clinical Stage I group than in the pathological Stage I group (3.4 vs. 2.3 cm, P < 0.001). Further, the clinical Stage I group had some pathological Stage III cases (positive lymph nodes, P = 0.023). The clinical Stage I group had a higher rate of distant metastases (P = 0.046) and a lower rate of overall (P = 0.031) and cancer-specific survival (P = 0.021) than the pathological Stage I group. Compared to pathological Stage II included in the period, some of the survival curves were located below the pathological Stage II, but there was no statistical difference. Conclusion: The study results show that even clinical Stage I cases, radical resection should be considered in accordance with T3 and T4 tumours.

Abstract Background The study aimed to appraise the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in amyotrophic lateral sclerosis (ALS), and to explore the associations between non-motor symptoms (mood changes, cognitive disturbances and sleep disturbances). Methods EQ-5D-5L descriptive scores were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ-VAS) was used for self-rating of current health status. Multiple logistic regression analysis was used to explore the factors associated with HRQoL. Results Among the 547 enrolled ALS patients who were assessed using EQ-5D-5L, the highest frequency of reported problems was with usual activities (76.7%), followed by self-care (68.8%) and anxiety/depression (62.0%). The median health utility score was 0.78 and the median EQ-VAS score was 70. Clinical factors corresponding to differences in the EQ-5D-5L health utility score included age of onset, onset region, the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and King’s College stages. Patients with depression, anxiety, and poor sleep had lower health utility scores. Patients with excessive daytime sleepiness and rapid eye movement sleep behavior disorder had lower EQ-VAS scores. Multivariate logistic analysis indicated that ALSFRS-R scores, depression, and anxiety were associated with health utility scores. After adjusting other parameters, ALSFRS-R score, stages, and depression were significantly associated with EQ-VAS scores (P

Xiaohang Li,1 Xu Li,1 Simei Chen,1 Yang Wu,1 Yuhan Liu,1 Tingting Hu,1 Jiayi Huang,1 Jianlin Yu,1 Zihuan Pei,1 Tingting Zeng,2 Liming Tan1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Jiangxi Province Key Laboratory of Laboratory Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Liming TanDepartment of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Jiangxi Province Key Laboratory of Laboratory Medicine, No. 1 Minde Road, Donghu District, Nanchang, Jiangxi, People’s Republic of ChinaTel +86 791-86300410Email ndefy84029@ncu.edu.cnPurpose: To explore the clinical significance of tumor necrosis factor receptor-associated protein (TRAP1), mitotic arrest deficient 2 (mad2) and anti-nuclear mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC).Patients and Methods: Serum concentrations of TRAP1 and MSA were determined by enzyme-linked immunosorbent assay (ELISA), including SCLC group (Num.=86), non-small cell lung cancer (NSCLC) group (Num.=105), pulmonary nodules (PN) group (Num.=94), and 60 healthy subjects as control group (Num.=60). Whereas fluorescence quantitative PCR (qt-PCR) method was used to detect the expression of mad2.Results: The expression of TRAP1 was low in SCLC and NSCLC compared with the other two groups, and was the lowest in SCLC, which was negatively correlated with the occurrence of the disease (P< 0.05); the sensitivity and specificity of TRAP1 for SCLC were 75.29%, 93.33%, and the area under SCLC curve was 0.903; compared with the other three groups, the level of MSA was the highest in the SCLC, and the results were significantly different (P< 0.05), while the area under the SCLC curve was 0.856, and the sensitivity and specificity were 62.78% and 95.24%, respectively. Mad2 is overexpressed in SCLC, but not in PN. The area under the SCLC curve is 0.835, and the sensitivity and specificity are 56.98% and 92.38%; TRAP1 levels are negatively correlated with SCLC tumor stage, the level of TRAP1 was significantly lower in stage III–IV than in stage I–II (P< 0.05); combined analysis of TRAP1 and MAD2 and MSA showed that the sensitivity and specificity for SCLS were 95.35% and 99.05%, respectively.Conclusion: TRAP1 is of great value in the early diagnosis of SCLC as well as differential diagnosis with NSCLC. TRAP1 combined with MAD2 and MSA improved the sensitivity and specificity and provided a new idea for the clinical diagnosis of SCLC.Keywords: TRAP1, diagnosis, small cell lung cancer, clinical stage, metastasis

This study explored the predictors of upstaging and multiple sites of extension, and constructed a predictive model based on perioperative characteristics to calculate the risk of upstaging of cT1 renal cell carcinoma to pT3. We retrospectively reviewed 1012 patients diagnosed with cT1 renal cell carcinoma who underwent surgical treatment at the Affiliated Hospital of Qingdao University between June 2016 and August 2021. The continuous and categorical variables were analyzed using the Mann–Whitney U test and Chi-square test, respectively. After randomly dividing patients into a training set and an internal validation set with a ratio of 7:3, univariate and multivariate logistic regression analyses were used to explore the predictors of upstaging and multiple sites of extension. A nomogram model was established based on the predictors of upstaging and was validated. Ninety-one cases (8.99%) of renal cell carcinoma were upstaged to pT3. In the training set, multivariate logistic regression identified the following predictors of upstaging: maximum tumor diameter, hilus involvement, tumor necrosis, tumor edge irregularity, symptoms, smoking, and platelet–lymphocyte ratio. A nomogram model was established based on the predictors. The area under the receiver operating characteristic curve was 0.810 in the training set, and 0.804 in the validation set. A 10-fold internal cross-validation conducted 200 times showed that the mean area under the curve was 0.797. The calibration curve and decision curve analysis suggested that the nomogram had robust clinical predictive power. Analyses showed higher neutrophil–lymphocyte ratio and tumor necrosis were associated with multiple sites of extrarenal extension in patients with pT3a renal cell carcinoma. We identified 7 predictors of upstaging to pT3 and 2 predictors of multiple sites of extension. A nomogram model was constructed with satisfactory accuracy for predicting upstaging to pT3. This retrospective study analyzed 1012 patients diagnosed with cT1 renal cell carcinoma who underwent surgical treatment. Using univariate and multivariate logistic regression analyses, we identified the risk factors, constructed a predictive model and validated it. Our research contributes to assessing the risk of upstaging in patients with cT1 renal cell carcinoma and offering more assistance in the selection of surgical approaches. [ABSTRACT FROM AUTHOR]

Malnutrition is associated with the prognosis of malignant disease. The geriatric nutritional risk index (GNRI), based on serum albumin (ALB) levels and the present and ideal body weight, is a simple screening tool with which to predict the risk of malnutrition and mortality in patients. We hypothesised that nutritional markers could predict the prognosis of patients with oral squamous cell carcinoma (OSCC). The primary predictor variable was the GNRI score and the primary outcome variable was overall survival (OS). Univariate and multivariate analyses were performed using a Cox proportional hazard model to identify independent prognostic factors. The sample comprised 155 patients, of whom 17 presented with a low GNRI score (≤98) and 138 with a high GNRI score (≥ 98). There was a significant difference in OS when patients were stratified according to GNRI scores, with OS rates of 29.2% and 76.4% for scores of 98 and under and scores of over 98, respectively (p < 0.001). Univariate analyses showed that OS was significantly associated with GNRI score, age, T classification, N classification, stage, body mass index (BMI), prognostic nutrition index, and ALB levels. Analysis identified three independent predictive factors for OS: age (hazard ratio (HR) 2.184; 95% confidence interval (CI) 1.119 to 4.261; p = 0.022), stage (HR 2.684; 95% CI 1.457 to 5.367; p = 0.011), and GNRI score (HR 4.559; 95% CI 2.172 to 9.570; p <0.001). The results suggest that the GNRI score (>98 vs ≤98) is a good prognostic marker in patients with OSCC, along with age and stage. [ABSTRACT FROM AUTHOR]

Introduction Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in bipolar disorders(BD). The heart age of patients with BD was found to be 8.5 years higher than gender-age matched health controls. Metabolic side effects of antipsychotics, poor diet, insufficient physical activity, smoking and sedentary life style increase the risk of cardiovascular disease in bipolar patients. QRISK-3 is an approved risk classification that calculates the 10-year risk of developing a heart attack or stroke. Objectives This study aims to determine whether there is a difference between cardiovascular disease risk scores and clinical stages of bipolar disorder Methods 35 outpatients that were followed up in Selcuk University Medical Faculty were evaluated. The clinical stages and qrisk3 scores were calculated. Results 68.6% (n:24) of the patients were female. 42.9% of patients were in stage 3b (recurrent relapses, complete remission between episodes). The mean age was 36.94 ±10.46 years. The mean heart age was 50.54±17.35. The mean Q risk3 score was 5.59±8.18. There was no difference between bipolar patients at stage 2 and stage 3 in terms of age(p=0.36 and gender(p=0.73). When we compared the qrisk3 total socres and heart age of the patients in stage 2 and 3, we could not find any difference between groups (p=0.74, p=0.57 respectively). Conclusions Even though we could not find any difference of qrisk scores at different clinical stages of patients with BD, the CVD risk increases with the age. Prospective longitudinal follow-up studies are required to evaluate dual interaction of clinical stages and CVD risk in BD. Disclosure No significant relationships.

Background and Aim: Centroblastic lymphoma (CBL) is the most common morphological type of lymphoma found in dogs; it is usually identified through cytology in veterinary clinical practice. This study aimed to identify the demographic and clinical characteristics of dogs with CBL that was diagnosed with cytology and immunocytochemistry. Materials and Methods: Dogs with a suspicion of lymphoma were diagnosed by cytology supported by immunocytochemistry with the use of the updated Kiel classification adapted for dogs. During the analyzed time period, 336 lymphomas were diagnosed in dogs, including 171 cases of CBL. Epidemiological and clinical data from the dogs with CBL were provisionally collected. Results: The epidemiology analysis revealed an increased risk of CBL in Rottweilers, golden retrievers, and Bernese mountain dogs. At admission, most of the dogs displayed generalized lymphadenopathy with spleen and liver enlargement. The most common hematological abnormality was leukocytosis due to neutrophilia. The most common biochemical abnormality was elevated alanine aminotransferase and alkaline phosphatase activities and selective hypoproteinemia due to hypoalbuminemia. Conclusion: Rottweilers, Bernese mountain dogs, and golden retrievers appear to be overrepresented among dogs with CBL. CBL is usually diagnosed at an advanced clinical stage according to the World Health Organization; however, it is usually accompanied by only minor hematological and biochemical abnormalities.