Univariate Cox Regression Analysis Research Articles

Short- and Long-Term Outcomes of Patients Who Underwent the Arterial Switch Operation at Siriraj Hospital-Thailand's Largest National Tertiary Referral Center.

The aim of this study was to assess the short- and long-term outcomes of patients who underwent the arterial switch operation (ASO) at Siriraj Hospital in Thailand, and to identify postoperative complications and factors that significantly affect patient survival. We retrospectively studied all patients with dextro-transposition of the great arteries and anatomic variants who underwent the ASO from January 1995 to December 2020. Twenty-year overall survival and 15-year freedom from reoperation/reintervention were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to identify factors independently associated with 30-day mortality. Of the 171 patients included, there were 116 males (67.84%). The median (minimum, maximum) age at operation was 33.5 (3-4,499) days, and the median (minimum, maximum) bodyweight was 3.4 (2.2-44.9) kg. Most patients (115/171, 67.25%) had an intact ventricular septum, whereas 48/171 (28.07%), had ventricular septal defects. The typical coronary anatomic pattern (1LCx-2R) was found in 120 patients (70.1%). Early mortality was 8.7% ± 4.4%, and there was no late death up to 20 years postoperatively with a median follow-up of five years. Fifteen-year freedom from reoperation or reintervention was 85.7%. Atypical coronary pattern was an independent factor for survival with an adjusted hazard ratio of 5.1 (95% confidence interval: 1.22-21.4; P = .026). The results of this study revealed excellent short- and long-term outcomes of the ASO at our center. Atypical coronary anatomy was found to be the only factor that independently predicted 30-day mortality.

Soluble PD-L1 and Serum Vascular Endothelial Growth Factor-B May Independently Predict Prognosis in Patients with Advanced Non-Small Cell Lung Cancer Treated with Pembrolizumab

Background: Previous preclinical data have shown that the dynamic cross-talk between abnormal tumor vasculature and immune cell factors in the tumor microenvironment may exert a critical role in the progression and treatment resistance of non-small cell lung cancer (NSCLC). In the clinical setting, a variety of blood-based angiogenesis- and immune-related factors are being increasingly investigated as potential biomarkers of prognosis or treatment response in immunotherapy-treated NSCLC. We herein aimed to evaluate the clinical relevance of the peripheral blood levels of vascular endothelial growth factor-A and -B (VEGF-A and VEGF-B, respectively), soluble programmed cell death-1 (sPD-1), and programmed cell death-ligand 1 (sPD-L1) in patients with advanced NSCLC treated with immune checkpoint inhibitors (ICIs). Methods: Consecutive patients with advanced-stage, non-oncogene-addicted NSCLC, eligible to receive ICIs at the Oncology Unit of Sotiria Athens General Hospital, were prospectively recruited. A group of sex- and age-matched healthy controls was also enrolled for the evaluation of the potential diagnostic significance of the examined biomarkers. Serum levels of all biomarkers were measured using ELISA, both before and after treatment, and were correlated with standard clinicopathological features of patients, treatment response, progression-free survival (PFS), and overall survival (OS). Results: A total of 55 patients and 16 healthy controls were included in the final analysis. The mean age of patients and controls was 66.5 years (SD = 8.0 years) and 65.4 years (SD = 9.1 years), respectively. The majority of patients (65.5%) received pembrolizumab in combination with chemotherapy, while the remaining patients received pembrolizumab monotherapy. ROC curve analysis showed that VEGFB and sPD-1 were the only markers with a significant diagnostic value. Higher pre-treatment values of sPD-L1 (HR = 1.68; p = 0.040) and sPD-1 (HR = 10.96; p = 0.037) as well as higher post-treatment values of VEGF-B (HR = 2.99; p = 0.049) were all significantly associated with a reduced OS in univariate Cox regression analysis. The adverse prognostic significance of higher pre-treatment values of sPD-L1 (HR = 2.10; p = 0.014) and higher post-treatment values of VEGFB (HR = 3.37; p = 0.032) was further confirmed in multivariate analysis. Conclusions: Our study results suggest that serum levels of sPD-L1 and VEGF-B may independently predict prognosis in ICI-treated advanced-stage NSCLC.

Plasma IL-17A is increased in patients with critical MIS-C and associated to in-hospital mortality

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a rare and severe post-COVID-19 complication with multiple phenotypes.ObjectivesThe aim of this study is to study inflammatory biomarkers (cytokines and oxidative stress) in critical MIS-C patients and to observe if there is association between these biomarkers and mortality.MethodsA single-center prospective study enrolled patients with MIS-C (with positive molecular test), aged between 1 month and 18 years of age. Data was collected from 20 pediatric intensive care unit (PICU)’s bed. Inflammatory biomarkers (cytokines and oxidative stress markers) were performed on day 1 and 3 after hospitalization. Survival rate was calculated, and Kaplan-Meier curves were plotted. Univariate and multivariate Cox regression analyses were conducted. The ROC (Receiver Operating Characteristic) curve analysis was performed.Results and conclusionsA total of 41 patients out of 109 patients admitted at PICU with suspected MIS-C during the study period were included, of which 33 (80.5%) were male, 9 (22%) were under one year old, and 30 (73.2%) presented comorbidities. Among them, 16 (39%) did not survive. The mean survival time was shorter in patients with higher levels of IL-17A (≥ 19.71 pg/mL) on day 1 (115 vs 323 days, p = 0.004). Higher levels of IL-17A on day 1 were associated with mortality in both the crude model (HR 1.03, CI95% 1.004-1.057, p = 0.022) and the adjusted model (HR 1.043, CI95% 1.013-1.075, p = 0.012). ROC analysis revealed a cut-off value for the IL-17A of 14.32 pg/ml. The other immunological and inflammatory markers did not demonstrate an association with survival (p>0.05). Our findings suggest that patients with high levels of IL-17A are at greater risk for death.

Association between exposure to 35 environmental pollutants and mortality from cerebrovascular diseases: A long-term prospective study.

Environmental pollutants have been implicated in various detrimental health effects. However, the specific relationship between environmental pollutant exposure and the risk of cerebrovascular disease mortality remains uncertain. This study aimed to comprehensively explore the potential relationship between environmental pollutant exposure and risk of cerebrovascular disease mortality in the U.S. population. Data on 35 types of environmental pollutant exposure were extracted from the National Health and Nutrition Examination Survey (NHANES). Cerebrovascular disease-related deaths were ascertained from the National Center for Health Statistics, with mortality follow-up data available until December 31, 2019. Weighted univariable and multivariable Cox regression analyses were employed to evaluate the association between environmental pollutants and mortality from cerebrovascular diseases. A total of 11,643 participants were included for organochlorine pesticides, 11,912 for brominated flame retardants, 13,797 for per- and polyfluoroalkyl substances, and 14,560 for phthalates, with a median follow-up of 8.6 years. The average age of participants was approximately 46 years, with male participants comprising around 48 % of the cohort. Four types of organochlorine pesticides (hexachlorobenzene, oxychlordane, 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene, and trans-nonachlor), perfluorooctanoic acid, and mono-n-butyl phthalate were found to be associated with an increased risk of cerebrovascular disease mortality. Furthermore, the composite environmental index derived from these six pollutants also demonstrated a significant correlation with elevated cerebrovascular disease mortality risk. This prospective study provides evidence of an association between certain environmental pollutant exposure (especially for organochlorine pesticides) and risk of cerebrovascular disease mortality. These findings provide new insights into potential prevention strategies for this disease mortality from the perspective of environmental pollutant exposure.

Predictors of Arrhythmia Recurrence After Cryoballoon Ablation for Persistent Atrial Fibrillation: A Sub-Analysis of the Cryo Global Registry.

Freedom from recurrences of atrial tachyarrhythmia (ATA) is suboptimal after pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (PsAF). This sub-analysis from the Cryo Global Registry sought to investigate predictors of ablation success after PVI using cryoballoon ablation (CBA) for PsAF. ATA recurrence was defined as ≥ 30 s recurrence of atrial fibrillation, atrial flutter or atrial tachycardia after a 90-day blanking period and through 12-months. Univariate and multivariable Cox regression analysis (with ATA recurrence as an endpoint) was performed to identify CBA responders. PsAF patients (N = 882) were on average 63.9 ± 11.3 years old (69.2% male), and freedom from ATA recurrence was 79.7% (76.8%-82.2%). Longer elapsed time from PsAF diagnosis to ablation (hazard ratio [HR] 1.07 (95% confidence interval [CI]: 1.03-1.11); p = 0.002) and a larger number of previously failed antiarrhythmic drugs (HR 1.39 (95% CI: 1.13-1.70); p < 0.002) were shown to be independent predictors of ATA recurrence in a multivariate model which included 703 evaluated patients. These real-world results provide important insights to guide referral of PsAF patients, including the benefits of earlier treatment via CBA.

Identification and validation of prognostic biomarkers in ccRCC: immune-stromal score and survival prediction

BackgroundThe tumor microenvironment (TME) is integral to tumor progression. However, its prognostic implications and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) are not yet fully elucidated. This study aims to examine the prognostic significance of genes associated with immune-stromal scores and to explore their underlying mechanisms in ccRCC.MethodsData from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) were subjected to analysis to compute immune and stromal scores utilizing the ESTIMATE algorithm. The weighted gene co-expression network analysis (WGCNA) was employed to identify gene modules associated with these scores. Differentially expressed genes were assessed using the limma package. Prognostic biomarkers were subsequently identified through univariate, LASSO, and multivariate Cox regression analyses, culminating in the development of a risk score model. Gene expression was confirmed in ccRCC cell lines (786-O, Caki-1) and tumor tissues. Functional assays, such as wound healing and Transwell assays, were employed to evaluate tumor invasion and migration. The prognostic accuracy was assessed through ROC curve analysis, and a nomogram integrating risk scores with clinical variables was constructed. Analyses of immune infiltration, human leukocyte antigen (HLA) expression, immune checkpoint expression, immunophenoscore (IPS), tumor immune dysfunction and exclusion (TIDE) scores, and responses to six targeted therapies were conducted across different risk groups.ResultsTwelve critical prognostic markers, including CAPRIN1, CXCR3, FERMT3, HAPLN3, HBP1, MACF1, MPEG1, OSCAR, STAT1, UBA7, VAMP1, and VSIG4, were identified. The risk score model exhibited a high degree of predictive accuracy for survival outcomes in ccRCC. Immune profiling revealed significant differences in the TME between risk groups, with high-risk patients displaying elevated expression of HLA and immune checkpoints. Drug sensitivity analyses suggested that high-risk patients had a better response to erlotinib, temsirolimus, axitinib, and sunitinib, whereas low-risk patients demonstrated greater sensitivity to pazopanib. Variability in immunotherapy responsiveness between groups was observed based on IPS and TIDE analyses.ConclusionThis study highlights the prognostic value and TME-related mechanisms of immune-stromal score signatures in ccRCC, developing a risk score model and nomogram for predicting patient prognosis.

Predicting survival rates: the power of prognostic nomograms in distal cholangiocarcinoma

ObjectiveThe purpose of this research is to establish a prognostic nomogram for patients with distal cholangiocarcinoma (dCCA).MethodsWe obtained clinical data from 2401 patients diagnosed with distal cholangiocarcinoma (dCCA) between 2010 and 2020 from the Surveillance, Epidemiology, and End Results database. These patients were randomly assigned to either the training or validation group in a ratio of 6:4. 228 patients were enrolled from 9 hospitals in China as the external validation cohort. Univariate and multifactorial Cox regression analyses were conducted to ascertain prognostic factors and prognostic nomograms were developed utilizing LASSO logistic regression analysis. We used the calibration curve, and area under the curve to validate the nomograms. Decision curve analysis was used to evaluate the model and its clinical applicability.ResultsThe findings demonstrated that Grade, M stages, Surgery, and Chemotherapy emerged as autonomous prognostic factors for the survival of individuals with dCCA. The developed nomograms exhibited satisfactory accuracy in forecasting 1-year, 3-year, and 5-year survival probabilities. Furthermore, the calibration curves indicated a strong concordance between the anticipated and observed outcomes. The AUC of the nomogram for 1-year, 3-year, 5 year overall survival (OS) predication were 0.809 (95%CI 78.5-83.3), 0.79 (95%CI 75.8-82.2) and 0.761 ((95%CI 72.3-80.0) in the training cohort, 0.79 (95%CI 75.9-82.0), 0.73 (95%CI 68.5-77.5), and 0.732(95%CI 68.0-78.3) in internal test cohort, 0.862 (95%CI 81.7-90.7),0.83 (95%CI 76.4-89.6),and 0.819(95%CI 74.6-89.2) in external test cohort.ConclusionThe nomograms that have been suggested demonstrate strong predictive capability. These tools can assist medical professionals in assessing the prognosis of patients with dCCA and in devising more accurate treatment strategies for them.

A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma

ObjectiveOsteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.MethodsThe data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.ResultsBased on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.ConclusionA telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.

Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p &lt; 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p &lt; 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p &lt; 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p &lt; 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p &lt; 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p &lt; 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p &lt; 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p &lt; 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p &lt; 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p &lt; 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p &lt; 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p &lt; 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p &lt; 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p &lt; 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p &lt; 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p &lt; 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p &lt; 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p &lt; 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p &lt; 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.

Adjuvant radiation therapy improves outcome of patients with surgical resected adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of recurrence and poor prognosis. Previous studies revealed controversial roles of adjuvant radiation therapy (RT) in patient management. This study aimed to investigate the role of adjuvant RT in postoperative ACC patients. Patients with histologically confirmed ACC who underwent surgical resection in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020 were enrolled. Propensity score matching (PSM) was used to balance baseline characteristics between patients receiving adjuvant RT and patients who did not receive RT. Overall survival (OS) and recurrence-free survival (RFS) was analyzed using the Kaplan-Meir method. Risk factors associated with survival outcome was analyzed by univariate and multivariate Cox regression analyses. Subgroup analyses were stratified by European Network for the Study of Adrenal Tumors (ENSAT) disease stage or chemotherapy. A joint retrospective analysis of stage III patients was performed based on data obtained from Ruijin Hospital and MD Anderson Cancer Center. Among the 700 patients enrolled, 137 patients undergoing postoperative RT were matched with 137 patients who did not receive RT. Overall survival for patients with adjuvant RT was better than patients without RT (log-rank P = 0.015). The 3-year and 5-year OS were 55.2 and 47.1% for patients with RT, vs 42.6 and 34.0% for patients without RT. Multivariate analysis showed adjuvant RT was independently associated with lower mortality (hazard ratio [HR] 0.63, P = 0.007). Subgroup analysis stratified by disease stage demonstrated that adjuvant RT showed the most favorable effect in stage III patients (HR 0.53, P = 0.013). Furthermore, joint analysis of two centers showed a tendency of better OS and local control rate for stage III patients with mitotane plus RT than those with mitotane alone. Our study indicated that adjuvant RT was associated with improved prognosis for ACC patients, especially for patients with ENSAT stage III diseases. Integrating adjuvant RT into standard care of ACC may be considered.

Clinical characteristics and prognosis of ovarian juvenile granulosa cell tumors

Objective: To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT). Methods: Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients' clinical and pathological characteristics, treatments, and prognosis. Propensity score matching (PSM) was used to match the JGCT cases with adult granulosa cell tumor (AGCT) cases in SEER database. A total of 96 patients with ovarian granulosa cell tumor (OGCT), including 32 cases of JGCT and 64 cases of AGCT, were enrolled in a matched cohort analysis. Univariate and multivariate Cox regression analysis were performed on the matched cohort to explore the risk factors for overall survival. Kaplan-Meier curves and the log-rank test were used to compare the survival outcomes between JGCT and AGCT. Results: (1) The median age at diagnosis for the 34 JGCT patients was 19.5 years (ranged: 1-48 years), with 3 patients aged ≤10 years, 16 patients aged 11-20 years, 11 patients aged 21-30 years, and 4 patients aged >30 years. Tumors originated unilaterally in 33 patients, with only 1 case originating bilaterally. The maximum tumor diameter was recorded in 26 patients, with a median size of 12.4 cm (ranged: 3.5-40.0 cm). According to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 patients were diagnosed with stage Ⅰ (including 10 cases with stage Ⅰa and 9 cases with stage Ⅰc), 4 patients with stage Ⅱ, 8 patients with stage Ⅲ, and 3 patients with stage Ⅳ. Two patients did not undergo surgery for the resection of lesions. Stage Ⅰ patients (15/19) underwent fertility-sparing surgery, while stage Ⅱ-Ⅲ patients underwent either fertility-sparing surgery or cytoreductive surgery (6 cases each). Stage Ⅳ patients underwent cytoreductive surgery (2 cases). Lymph node dissection was performed in 10 patients, among which only 1 patient with positive lymph nodes metastasis. None of the 34 patients received radiotherapy, while 18 patients received adjuvant chemotherapy (included neoadjuvant chemotherapy and postoperative adjuvant chemotherapy). The proportion of stage Ⅰ patients receiving adjuvant chemotherapy was relatively low, with only 4 out of 19 patients (including 2 out of 10 cases for stage Ⅰa and 2 out of 9 cases for stage Ⅰc). The proportions of patients receiving adjuvant chemotherapy for stages Ⅱ, Ⅲ and Ⅳ were 3 out of 4 cases, 8 out of 8 cases, and 3 out of 3 cases, respectively. The follow-up ended in December 2021, with 20 patients alive and 14 dead. The survival rate for ovarian JGCT patients was 59% (20/34). Among them, the survival rate for stage Ⅰ patients was 16/19, while for stage Ⅱ-Ⅳ patients, it was 4/15; there was a statistically significant difference (P=0.002). Among stage Ⅱ-Ⅲ patients, the survival rate at the end of follow-up was 1/6 for those who underwent fertility-sparing surgery, compared to 3/6 for those who underwent cytoreductive surgery (P=0.546). (2) For the 96 OGCT patients after matching using the PSM method, 64 ovarian AGCT patients had 5 deaths and 59 survivors during the follow-up period, the survival rate was 92% (59/64) at the end of follow-up. In contrast, among the 32 ovarian JGCT patients, 13 died and 19 survived, resulting in a survival rate of 59% (19/32) at the end of follow-up, which was statistically significant difference for the AGCT group (P<0.001). Univariate Cox analysis revealed that histology, extent of surgery, chemotherapy, postoperative tumor residual status, and stage all significantly affected the survival outcomes of OGCT patients (all P<0.05). Multivariate Cox analysis revealed that variables with significant statistical differences were histology and stage. The median survival time for JGCT patients was 126 months, while AGCT patients median survival time was not reached with a statistically significant between the two groups (P<0.001). Conclusions: Ovarian JGCT predominantly occur in adolescents and young women. Lymph node metastasis is relatively rare, and treatment primarily involves surgery and adjuvant chemotherapy. Most ovarian JGCT patients are diagnosed at stage Ⅰ, with a favorable prognosis. Fertility-preserving surgery is recommended, involving salpingo-oophorectomy on the affected side plus comprehensive staging surgery, or a second surgery to achieve comprehensive staging. For stage Ⅱ-Ⅳ ovarian JGCT patients, the prognosis is relatively poor, and fertility-preserving surgery should be considered with caution. The prognosis of ovarian JGCT patients is worse than that of ovarian AGCT patients.

The prognostic value of baseline EARL standardized FDG PET indices in pediatric and adolescent high-grade osteosarcoma.

To investigate the prognostic value of baseline European Association of Nuclear Medicine Research Ltd. (EARL) standardized [18F]fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG PET-CT) quantitative values for survival and to evaluate cutoff values identified in other studies. Pediatric and adolescent patients with high-grade osteosarcoma were included. Baseline [18F]FDG PET-CT, with EARL-accredited reconstructions, was the standard diagnostic staging procedure. Cox proportional hazard analysis for event-free survival (EFS) and overall survival (OS) was performed with clinical prognostic factors. Kaplan-Meier analysis and log-rank tests were applied to investigate the prognostic performance of the [18F]FDG PET indices. In total, 66 patients were included in this study. In the univariable Cox regression analysis, peak lean-body mass corrected SUV (SULpeak) (hazard ratio (HR): 1.04), total lesion glycolysis (TLG) (HR: 1.0), and metabolic tumor volume (MTV) (HR: 1.0) were not associated with EFS or OS. Log-rank analysis showed a significant difference in EFS for all SULmax and SULpeak cutoffs. For MTVtotal the maximum Youden, and for TLGtotal, the maximum Youden and maximally selected rank cutoff resulted in a significant EFS difference. No cutoff for any measure showed a significant difference in OS between the groups. ROC curves for event status had an AUC of 0.67, 0.66, 0.64, and 0.64 for SULmax, SULpeak, MTVtotal, and TLGtotal, respectively. In this study, the baseline EARL-standardized [18F]FDG PET indices of children and adolescents with osteosarcoma were not prognostic of EFS or OS. The proposed prognostic cutoffs from earlier studies suffer from important technical and statistical issues. Question Prognostic value of baseline [18F]FDG PET-CT imaging markers have been reported for histologic response and survival in high-grade osteosarcoma but have not been validated for clinical practice. Findings Baseline SUVpeak, TLGtotal, and MTVtotal measured on EARL-accredited reconstructions were not prognostic factors for survival in pediatric and adolescent patients with high-grade osteosarcoma. Clinical relevance A wide range of values for SUVpeak and SUVmax cutoffs with similar prognostic value were identified, questioning the value of a single proposed cutoff. Lack of validation, with important technical and statistical issues of proposed prognostic cutoffs, limits clinical implementation.

LncRNAs in serum-derived extracellular vesicles are potential biomarker and correlated with immune infiltration in gastric cancer

BackgroundLong non-coding RNAs (lncRNAs) in extracellular vesicles (EVs) have been confirmed as effective non-invasive biomarkers for multiple diseases. However, their expression and clinical value in gastric cancer (GC) remain poorly understood.Materials and methodsSerum EV RNA was extracted from four patients with GC and four healthy controls, followed by high-throughput RNA sequencing. LncRNAs were further validated in training and validation sets using quantitative real-time reverse transcription polymerase chain reaction.ResultsA total of 37,684 lncRNAs were obtained, and 10 lncRNAs were selected based on the criteria (P &amp;lt; 0.05 and |log2FoldChange| ≥1). Serum EV lncRNA RMRP, RPPH1, and linc-ROR were significantly higher in patients with GC than in those with chronic gastritis, atypical hyperplasia, or healthy control (all P &amp;lt; 0.05). Three lncRNAs were also significantly correlated with tumor diameter, lymphatic metastasis, distal metastasis, and TNM stage (all P &amp;lt; 0.05). The area under the curve (AUC) values for lncRNA RMRP, RPPH1, and linc-ROR were 0.727, 0.774, and 0.811, respectively. Corresponding sensitivity and specificity were 63.4% and 85.4%, 50.7% and 89.6%, and 78.5% and 66.7%. The combination of these three lncRNAs with carcinoembryonic antigen (CEA) yielded an AUC of 0.909, with a sensitivity and specificity of 83.3% each. Furthermore, high EV linc-ROR and RMRP expression levels were associated with worse disease-free survival and overall survival (OS). Univariate and multivariate Cox regression analyses confirmed that linc-ROR was the only independent prognostic factor for GC. Finally, the lncRNA-miRNA-mRNA network showed that three lncRNAs were predicted to interact with 15 miRNAs and 69 mRNAs. In addition, lncRNA RMRP and linc-ROR were correlated with immune cell infiltration, including neutrophils, central memory CD4 T cells, macrophage, and natural kill T cells.ConclusionEV lncRNAs are prospective biomarker and correlated with immune cell infiltration in GC. It provides a foundation for the development of serum EV-targeted novel biomarkers and immunotherapy targets of GC.

Adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation and tyrosine kinase inhibitors: development and validation of a clinical prediction model based on cytogenetics, IKZF1 deletions and minimal residual disease.

The aim of this study was to develop and validate a nomogram predicting progression-free survival (PFS) for adult patients with positive acute lymphoblastic leukemia(Ph + ALL) who have undergone allogeneic hematopoietic stem cell transplantation(allo-HSCT) and tyrosine kinase inhibitor(TKI) treatment. Data were retrospectively collected from 176 adult patients diagnosed with Ph + ALL and treated with allo-HSCT and TKIs at The First Affiliated Hospital, Zhejiang University School of Medicine, between January 2015 and May 2023. 70% of the patients were randomly assigned to the training group(n = 124) and 30% of the patients were assigned to the validation group(n = 52). Univariate Cox regression analysis and Akaike Information Criterion(AIC) were utilized to identify significant predictive factors, leading to the development of a nomogram designed to forecast the probability of PFS at 6, 9, and 12 months post-transplantation. The final nomogram incorporated three key variables: presence of complex additional cytogenetic abnormalities (ACAs), minimal residual disease (MRD) status prior to allo-HSCT, and IKZF1 gene deletions. The calibration curves showed excellent consistency between the nomogram prediction and actual observation for 6-, 9- and 12-month PFS in the training set and validation set. The C-index of the training set was 0.726(95%CI: 0.635-0.816), which was no significantly different from the validation set(C-index = 0.774, 95%CI: 0.674-0.875, P > 0.05). This study may provide a simple and efficient prediction model for patients with Ph + ALL undergoing allo-HSCT and TKIs, which can accurately predict PFS subsequent to transplantation. This tool could potentially aid clinicians in decision-making processes and improve patient outcomes.

Development and external validation of a model for lung transplantation-free survival prediction of primary Sjögren's syndrome-associated interstitial lung disease: a prospective cohort study

BackgroundThe primary Sjögren's Syndrome-associated Interstitial Lung Disease (pSS-ILD) patients have a worse prognosis than pSS patients without pulmonary involvement. This study aims to establish a prediction nomogram for early prediction of lung transplantation (LTx)-free survival in pSS-ILD patients.MethodsThe training cohort comprised 260 patients from China-Japan Friendship Hospital between January 1, 2016, and June 30, 2022, while the external validation cohort consisted of 135 patients from Beijing Chaoyang Hospital between January 1, 2007, and December 31, 2012. Univariable Cox regression analysis and least absolute shrinkage and selection operator (LASSO) were employed for variable selection, and a nomogram model was developed to predict the 1 -, 3 -, 5-year LTx-free survival. Both discrimination and calibration of the nomogram were assessed using concordance index (C-index), area under the curve (AUC), calibration curve and decision curve analysis (DCA).ResultsMultivariable Cox regression demonstrated that elevated age, oxygenation index, CA125 and fibrosis score were independent risk factors for LTx-free survival in pSS-ILD patients. The C-index displayed of the training and validation cohorts were 0.812 and 0.809. The 1-, 3-, 5-year AUC values in training and validation cohorts were 0.781, 0.874, 0.909 and 0.793, 0.826, 0.863 respectively. Bias-corrected curve is close to the ideal curve and revealed a strong consistency between actual observation and prediction.

Construction of a radiogenomic signature based on endoplasmic reticulum stress for predicting prognosis and systemic combination therapy response in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Various factors in the tumor environment (TME) can lead to the activation of endoplasmic reticulum stress (ERS), thereby affecting the occurrence and development of tumors. The objective of our study was to develop and validate a radiogenomic signature based on ERS to predict prognosis and systemic combination therapy response.MethodsUsing data from The Cancer Genome Atlas Program (TCGA) as a training cohort and data from International cancer genome consortium (ICGC) as a testing cohort. Univariate Cox regression and multivariate Cox regression analysis were used to identify prognostic-related genes and construct a model. HCC single-cell data obtained from Gene Expression Omnibus (GEO) were used to map gene signatures and explore inter-cellular signaling communications. Finally, a radiogenomic signature was used to predict the objective response rate (ORR) and overall survival (OS).ResultsA total of four gene signatures related to ERS, including Stanniocalcin-2 (STC2), Melanoma-Associated Antigen 3 (MAGEA3), BR Serine/Threonine-Protein Kinase 2 (BRSK2), DEAD/H-Box Helicase 11 (DDX11) were identified. Macrophages were significantly different between high-risk and low-risk groups. The high-risk group showed higher targeting programmed cell death-1 (PD-1) and mutated tumor protein p53 (TP53) scores. Drug sensitivity analysis found that most sensitive drugs target the phosphatidylinositol 3-kinase/ mechanistic target of rapamycin (PI3K/mTOR) signaling pathway. Further research revealed the expression of STC2 in the endothelial cells (ECs), particularly plasmalemma vesicle associated protein (PLVAP) + ECs, and may regulate the reprogramming and function of macrophages. Furthermore, we identified nine radiomic features and established a radiogenomic signature based on ERS that can predict prognosis and response to systemic combination therapy. This signature can guide systemic combination therapy for patients with unresectable HCC.ConclusionsWe established an ERS prognostic model that can predict patient prognosis. We also found that ERS is closely related to the TME and is mainly manifested in the interaction between tumor-associated endothelial cells (TAEs) and tumor-associated macrophages (TAMs). Moreover, we constructed a radiogenomic signature based on the ERS. This signature can guide subsequent combination therapy for patients with unresectable HCC.

Ten years' single surgeon experience of excision and primary anastomosis urethroplasty for traumatic urethral stricture: an analysis of risk factors for urethral stricture recurrence.

Excision and primary anastomosis (EPA) urethroplasty is the standard treatment for traumatic urethral strictures, but managingthem remains challenging for urologists. Identifying factors leading to EPA urethroplasty failure benefits both patients andsurgeons. This study aims to analyze risk factors for urethral stricture recurrence after one-year follow-up of EPA urethroplasty. Data on male patients undergoing EPA urethroplasty at the Urology Department of Saiful AnwarGeneral Hospital from January 2013 until December 2023 were prospectively recorded. Successful urethroplasty, defined as theabsence of additional treatment necessity, was assessed until 12 months follow-up. Demographic data, time to surgery, strictureetiology, comorbidities, prior urethral interventions, and operationsteps were recorded. Univariate and multivariate Cox regression analyses were performed using IBM SPSS Statisticsversion 21. Total 95 patients were observed, and 89 patients wereincluded, averaging 41.2 ± 15.59 years old. EPA urethroplasty succeeded in 91% of cases over a median follow-up of 16.3months. Pelvic fracture urethral injury (PFUI) was the predominant etiology in 74% of cases, with an average stricture lengthof 25.4 ± 16.3 mm. The average time to surgery was performed on average 6.67 ± 4.07 months after diagnosis. In univariateanalysis, body mass index (BMI), time to surgery, and stricture length were associated with urethral stricture recurrence.However, only time to surgery showed a significant association in multivariate analysis. Obesity, the length of the stricture, and delayed surgical intervention are associated with an increased risk of urethral stricture recurrence in patients following EPA. EPA urethroplasty demonstrates a high success rate in managing traumatic urethral strictures.

Survival in patients with CKD 3–5 after 12 months of exercise training – a post-hoc analysis of the RENEXC trial

BackgroundPhysical performance is low and physical activity declines in people with chronic kidney disease (CKD). Both factors are associated with decreased survival. Our hypothesis was that improved physical performance after 12 months of exercise training would result in better survival in patients with CKD stages 3 to 5 not on kidney replacement therapy (KRT). Our aims in this study were to investigate the survival effects of (1) baseline physical performance and (2) physical performance after 12 months of exercise training.MethodsThis is a post-hoc analysis of the RENEXC trial, a randomized controlled study comparing 12 months of strength- and balance training both in combination with aerobic training. Both groups improved physical performance with no between group differences. Patients were categorized into five groups: improved ≥ 5%, unchanged, deteriorated ≥ 5%, non-completers, missing data. Univariate and multivariate Cox regression analyses were used and adjusted for age, sex, comorbidity, time on dialysis and time with a kidney transplant.Results151 patients participated, mean age 66 ± 14 years, 65% men, eGFR 22.5 ± 8.2 ml/min/1.73m2, average follow-up 60 months.Multivariate analysesThe baseline 6-minute walk test (6MWT) (HR 0.996; 95% CI [0.993–0.998]) and 30-second sit-to-stand (30s-STS) (HR 0.94 CI [0.89–1.0]) were positively associated with survival. After 12 months of exercise improved handgrip strength (HGS) right (HR 2.66; 95% CI [1.07–6.59]) was associated with better survival compared with deterioration. Improvement compared with noncompletion was associated with better survival (6MWT (HR 2.88; 95% CI [1.4–5.88]), HGS right (HR 4.44; 95% CI [1.79–10.98]), functional reach (HR 3.69; 95% CI [1.82–7.48]), isometric quadriceps strength right (HR 2.86; 95% CI [1.43–5.72]), 30s-STS (HR 3.44; 95% CI [1.66–7.11]).ConclusionBaseline walking distance, muscular strength and endurance in the legs were independently associated with survival in people with CKD stages 3–5 without KRT. After completing 12 months of exercise training improved walking distance, muscular strength and endurance, and balance were positively associated with survival, compared with noncompleters. Better physical performance at baseline and the ability to complete 12 months of exercise training conferred survival benefits. There are probably several factors affecting better survival. These factors require elucidation in future studies.Trial registrationClinicalTrials.gov NCT02041156. Registration date 20,240,107.

Association of the Revised Cardiac Risk Index with 1-year postoperative mortality: A single-center retrospective study.

To explore risk factors for 1-year postoperative mortality and to identify its association with the Revised Cardiac Risk Index (RCRI). This was a retrospective cohort study involving 54,933 patients aged 18years and above who were surgically treated under general or regional anesthesia in a tertiary hospital in Singapore. Independent risk factors for 1-year postoperative mortality were identified by univariate Cox regression analysis. The association between the RCRI and 1-year postoperative mortality was assessed by the Kaplan-Meier estimator and multivariate Cox regression analysis and was further validated in subgroup analyses stratified by the sex, age, and type of anesthesia. A total of 54,933 eligible patients were enrolled in this study that included 23,922 patients classified as RCRI Class I, 25,979 as Class II, 3700 as Class III, and 1332 as Class IV. Cox regression analysis demonstrated that male sex, age, higher American Society of Anesthesiologists (ASA) physical status classification level, regional anesthesia, emergency surgery, degree of anemia, and increased RCRI were significantly associated with the increased risk of 1-year postoperative mortality (HR>1, all P<0.001). The significant association between RCRI and 1-year postoperative mortality still existed after adjusting for confounding factors. An RCRI Class IV was associated with a mortality risk greater than two-fold larger than that observed at an RCRI Class I (adjusted HR 2.14, 95% CI 1.78 to 2.56, p<0.001). Subgroup analyses revealed that the 1-year postoperative mortality was significantly higher in patients with RCRI Class IV than that of Classes I-III regardless of the sex, age, and type of anesthesia. RCRI is significantly correlated with 1-year postoperative mortality regardless of sex, age, and type of anesthesia. Further studies to validate these findings are warranted.

Superior Regional Control and Laryngeal Function Preservation With Radiotherapy Versus Partial Laryngectomy: A Propensity Score-Matched Analysis of562Early Glottic Cancer Patients.

We aimed to compare the outcomes of patients with T1-T2N0M0 glottic squamous cell carcinoma who underwent either partial laryngectomy (PL) or radiotherapy (RT). A retrospective analysis of 562 patients treated with RT (n = 151) or PL (n = 411) was conducted. The Kaplan-Meier method was used to estimate outcomes. The risk factors were identified using univariate and multivariate Cox regression analyses. Propensity score matching (PSM) was used to adjust for baseline variations. Post-PSM, the 5-year overall survival (89.4% vs. 88.4%, p = 0.879), 5-year cancer-specific survival (91.9% vs. 90.1%, p = 0.554), and 5-year local relapse-free survival (87.2% vs. 89.3%, p = 0.487) rates did not differ significantly between the two groups. However, the 5-year regional relapse-free survival rate was significantly higher in the RT group than that in the PL group (99.3% vs. 93.3%, p = 0.009). Recurrence was most likely to occur in the lymph nodes at levels II and III. Supraglottic engagement has emerged as an independent prognostic factor for regional relapse in T2 stage diagnosed PL. The RT group demonstrated significantly superior speech function (mean: 6.065) compared to the PL group (mean: 10.650, p < 0.0001). RT yielded survival rates, local control, and laryngeal preservation comparable to PL. RT is associated with a higher regional control rate in T2 patients. Supraglottic involvement is an independent risk factor for regional relapse in patients with T2 disease after PL. The RT group exhibited extremely low complication rates and significantly improved speech function.