Univariate Kaplan-Meier Research Articles

Efficacy of root canal treatment for autotransplanted third molars: a 6-Year cohort study of 167 teeth in southern China.

Autogenous tooth transplantation offers significant advantages and promising success rates for replacing non-retainable teeth. This study aimed to investigate the prognostic factors, especially the impact of root canal treatment (RCT), of autotransplanted teeth in an up-to-6-year follow-up cohort of 167 teeth in Southern China. We enrolled adult patients from the Southern Medical University-Shenzhen Stomatology Hospital between 2017 and 2023. Patients underwent autogenous tooth transplantation to replace non-retainable molars with upper or lower third molars with Moorrees tooth development stage ≥5. All surgical procedures were performed by an experienced surgeon. The included patients were followed up for 6~72 (median 28.5) months. Success, failure, and survival rate and prognostic factors were evaluated using univariable Kaplan-Meier, multivariable generalized linear regression, and multivariable COX regression analyses. The overall success rate is 97.6% with four unsuccessful cases. Herein, two of them were removed, leading to an overall survival rate of 98.8%. A total of 159 cases (95%) received RCT in 3 months. Univariable log-rank analysis showed that RCT (RR 0.109, 95%CI 0.010 to 1.202, P = 0.028) and site relationship between donor and receipt sites (RR 3.359, 95% CI [1.210-9.329], P = 0.020) were two significant prognostic factors of autotransplanted teeth. Multivariable generalized linear regression revealed that RCT is the only significant factor protecting the success rate of autotransplanted teeth (HR 0.003, 95% CI [0.000-0.249], P = 0.010). However, in the Cox regression model, the effects of RCT (HR 0.009, 95% CI [0.000-2.514], P = 0.101) did not reach statistical significance. Other factors did not demonstrate a significant impact in this cohort. These results supported that autogenous tooth transplantation is a viable alternative to conventional implant treatment with strict indications. Our findings underscore the importance of RCT in transplanted teeth with closed or semi-closed apices. Multi-center observational studies with larger sample size and extended follow-up duration may be needed to validate the conclusion.

Dual-specificity phosphatase 23 functions as a promising prognostic biomarker in non-small cell lung cancer.

The mechanical remodeling of tumor microenvironment is critical for non-small cell lung cancer (NSCLC) progression. Dual-specificity phosphatase 23 (DUSP23) has been previously identified as a mechano-responsive gene, but its role in NSCLC progression remains unknown. We aim to elucidate the clinical significance of DUSP23 in NSCLC progression. We analyzed the expression of DUSP23 in cancer using polyacrylamide hydrogels designed to mimic the stiffness of normal (soft; ~0.5kPa) and cancerous (stiff; ~40kPa) tissues. The prognostic significance of DUSP23 expression in patients was examined using public databases. Additionally, we conducted various cell-based assays and transcriptomic analyses in DUSP23-silenced NSCLC cell lines. A risk score prognosis model was constructed using univariate Cox regression and Kaplan-Meier analysis. Our findings show that DUSP23 is upregulated in stiff matrices and is highly associated with poor prognosis in patients with solid cancers such as NSCLC and breast cancer. Silencing of DUSP23 resulted in decreased cell proliferation and invasion. Transcriptomic profiling revealed that 182 genes were downregulated, and 230 genes upregulated following DUSP23-depletion. Notably, 182 downregulated genes were enriched in cancer-related pathways, including cell cycle progression and cytoskeleton organization. Through KEGG pathway analysis, we identified 11 cancer-related genes and developed a prognostic risk model. In this model, the high-risk group of NSCLC patients exhibited significantly shorter overall survival compared to low-risk group, based on public datasets. Our study demonstrates the clinical significance of DUSP23 as a prognostic marker in NSCLC and highlights its potential role of DUSP23 in promoting NSCLC progression.

Abstract B027: Combining total cell-free DNA (cfDNA) and circulating tumor (ctDNA) to enhance the clinical sensitivity of ddPCR assays to detect minimal residual disease (MRD) in stage IIIB/C/IV melanoma patients on adjuvant immunotherapy in CheckMate 238

Abstract Background: In patients (pts) with resected, stage III/IV melanoma receiving adjuvant immunotherapy, pre-treatment (pre-Tx) and on-treatment (on-Tx) ctDNA measurements are associated with relapse free survival; however, clinical adoption has been hindered by suboptimal assay sensitivity. Methods: We used analytically validated, mutation-specific ddPCR assays to measure ctDNA and cfDNA in pre- and on-Tx plasma samples from pts with resected stage IIIB/C/IV melanoma enrolled in CheckMate 238 (NCT02388906) receiving either adjuvant Nivolumab (NIVO) or Ipilimumab (IPI). Assay choice was personalized based on detection of one of the 7 melanoma hot-spot mutations in pt tumors: BRAF V600E/K, NRAS Q61R/L/K, or TERT promotor C228T or C250T. We evaluated associations between ctDNA detection, or high cfDNA based on cutpoint analysis (>6,000 copies/ml of plasma) and recurrence-free survival (RFS), pre-Tx tumor biomarkers including tumor cell PD-L1 expression, IFNg gene signature, CD8 infiltration, and tumor mutational burden. Survival analysis was performed using univariable and multivariable Kaplan-Meier and Cox regression models. Results: Assay mutations were identified in 87% of resected tumors. In the pre-Tx samples, ctDNA alone was detected in 94/753 (12%) pts. The detection rate increased to 20% when assay positivity was defined as either detectable ctDNA or high cfDNA. The sensitivity of ctDNA detection to predict recurrence ≤6 months(m) from pre-Tx samples increased from 25% (ctDNA alone) to 33% when high cfDNA was added to detectable ctDNA; specificity decreased to 84% from 91% (ctDNA alone). The patient subgroup defined by the combined metric of ctDNA+ or high cfDNA in pre- Tx samples was significantly enriched with higher stage of disease, elevated LDH, tumor cell PD-L1 expression < 5%, and tumor IFNg-RNA signature < median. Pts with detectable pre-Tx ctDNA or high cfDNA was associated with shorter RFS in both NIVO (median RFS 20.5 m [95%CI, 2.88, 59.15]) and IPI (median RFS 7.75 m [95%CI, 2.76, 24.08]) arms compared to those with undetectable ctDNA and low cfDNA (NIVO (median RFS 47.95 m [95%CI, 11.09, 59.89]) and IPI (median RFS 24.15 m [95%CI, 5.78, 58.38])). In a multivariable model that included sex, age, treatment, and IFNg gene signature, ctDNA+ or cfDNA high was an independent predictor of shorter RFS [HR 1.624 (95%CI, 1.275, 2.068), p<0.001]. When combining pre-Tx and on-Tx measurements at week 3 (w3) and w7, the assay performance generally increased compared to pre-Tx alone. For example, pre-Tx assay positivity had a 38% positive predictive value (PPV) and 81% negative predictive value (NPV) to predict recurrence at <6 m. In pts who were undetectable at pre-Tx but became positive at w3 and remained positive at w7, PPV increased to 62% and NPV increased to 90%. Conclusions: Incorporating quantitative measurements of cfDNA with ctDNA detection in the evaluation of pre-Tx and on- Tx plasma samples improves the clinical performance of mutation-specific ddPCR assays to detect MRD in patients with resected stage III and stage IV melanoma. Citation Format: Mahrukh M Syeda, Jennifer M Wiggins, Josephine Alegun, Saim Ali, Soutrik Mandal, Tracy (Hao) Tang, Keyur Desai, Sonia Dolfi, Daniel J Tenney, Paolo A Ascierto, James Larkin, Michele Del Vecchio, Jeffrey S Weber, David Polsky. Combining total cell-free DNA (cfDNA) and circulating tumor (ctDNA) to enhance the clinical sensitivity of ddPCR assays to detect minimal residual disease (MRD) in stage IIIB/C/IV melanoma patients on adjuvant immunotherapy in CheckMate 238 [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B027.

The potential of ESCO2 as a prognostic and immunotherapeutic marker of pan-cancer and its role in anti-PD1 treatment of bladder cancer.

Background Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2), a member of the EFO2 family, is implicated in the pathogenesis and progression of various cancers. However, there has been limited comprehensive pan-cancer analysis conducted on ESCO2 thus far. Methods Publicly available databases, such as the UCSC Xena database, were utilized to examine differential expression patterns across various cancer types. In addition, variations in expression levels were investigated across distinct clinical stages. Univariate Cox regression and Kaplan-Meier survival analyses were conducted to evaluate the impact on overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) at a pan-cancer level. The correlation between ESCO2 expression and immune cell infiltration was examined to gain insight into the tumor microenvironment in different cancers. The results of the bioinformatic analysis were validated using immunotherapy clinical trials and pathological specimens. CCK-8 and transwell assay experiments were performed to investigate the biological function of ESCO2. Results ESCO2 expression was found to be up-regulated in most cancers, with a correlation to TNM stages. Prognostic analysis indicated that overexpression of ESCO2 was associated with poor prognosis in various cancers. Furthermore, the correlation between ESCO2 expression and immune cell infiltration suggested its potential as a predictor for immunotherapy efficacy. Notably, ESCO2 expression showed positive associations with immunoinhibitor, immnostimulator, MHC molecule, chemokine receptor, tumor mutation burden (TMB) and microsatellite instability (MSI) levels in bladder cancer (BLCA). The validation cohort for immunotherapy corroborated these findings and substantiated that ESCO2 could function as an autonomous prognostic biomarker and a promising target for cancer treatment via immunotherapy. In addition, in vitro experiments confirmed the role of ESCO2 in influcing the proliferation, invasion and migration of BLCA cells. Conclusion ESCO2 participates in regulating the immune infiltration and affecting the prognosis of patients in many cancers, especially in BLCA. ESCO2 may serve as a prognostic and immunotherapy biomarker in future treatment of human cancer.

Machine Vision–Detected Peritumoral Lymphocytic Aggregates Are Associated With Disease-Free Survival in Patients With Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer, with a disease recurrence rate of around 20%. Lymphoid formations, which occur in nonlymphoid tissues during chronic inflammatory, infectious, and immune responses, have been linked with tumor suppression. Lymphoid aggregates potentially enhance the body’s antitumor response, offering an avenue for attracting tumor-infiltrating lymphocytes and fostering their coordination. Increasing evidence highlights the role of lymphoid aggregate density in managing tumor invasion and metastasis, with a favorable impact noted on overall and disease-free survival (DFS) across various cancer types. In this study, we present a machine vision model to predict recurrence in different histologic subtypes of PTC using measurements related to peritumoral lymphoid aggregate density. We demonstrated that quantifying peritumoral lymphocytic presence not only is associated with better prognosis but also, along with tumor-infiltrating lymphocytes within the tumor, adds additional prognostic value in the absence of well-known second mutations including TERT. Annotations of peritumoral lymphoid aggregates on 171 well-differentiated PTCs in the Cancer Genome Atlas Thyroid Carcinoma (TCGA-THCA) data set were used to train a deep-learning model to predict regions of lymphoid aggregates across the entire tissue. The fractional area of the tissue regions covered by these lymphocytes was dichotomized to determine the following 2 risk groups: a significant and low density of peritumoral lymphocytes. DFS prognosticated using these risk groups via the Kaplan-Meier analysis revealed a hazard ratio (HR) of 2.51 (95% CI: 2.36, 2.66), tested on 170 new patients also from the TCGA-THCA data set. The prognostic performance of peritumoral lymphocyte aggregate density was compared against the univariate Kaplan-Meier analysis of DFS using the fractional area of intratumoral lymphocytes within the primary tumor with an HR of 2.04 (95% CI: 1.89, 2.19). Combining the lymphocyte features in and around the tumor yielded a statistically significant improvement in prognostic performance (HR, 3.17 [95% CI: 3.02, 3.32]) on training and were independently evaluated against 62 patients outside TCGA-THCA with an HR of 2.44 (95% CI: 2.19, 2.69). Multivariable Cox regression analysis on the validation set revealed that the density of peritumoral and intratumoral lymphocytes was prognostic independent of histologic subtype with a concordance index of 0.815.

Predicting 30-Day Outcomes in Primary Intracerebral Hemorrhage Using the Intracerebral Hemorrhage Score: A Study in Bangladesh.

Introduction Intracerebral hemorrhage (ICH) is a severe subtype of stroke associated with high rates of mortality and morbidity. Accurate early prognostication is essential for optimizing treatment strategies and improving patient outcomes. The ICH score, which includes clinical and imaging variables, is widely used to predict mortality and functional outcomes in ICH patients. However, limited data on the applicability of this scoring system are available from low-income countries. This study aims to evaluate the ICH score as a predictor of 30-day mortality and functional outcome, as measured by the modified Rankin Scale (mRS), in ICH patients at a tertiary care hospital in Bangladesh. Methods We conducted a prospective cohort study over one year at the National Institute of Neurosciences and Hospital in Dhaka, Bangladesh. One hundred patients aged over 18 years with confirmed primary ICH were enrolled. We collected data on demographics, clinical presentation, risk factors, and imaging findings, including the Glasgow Coma Scale (GCS), ICH score components, and hematoma volume. Patients were followed up for 30 days, and outcomes were assessed using the mRS. Statistical analyses included univariate and multivariate logistic regression and Kaplan-Meier survival estimates. Results A total of 100 participants were enrolled for the study. The mean age of participants was 59.2 ± 14.5 years, and 57 were men, and 43 were women. The overall 30-day mortality rate was 44%. Mortality rates increased significantly with higher ICH scores (p < 0.001), with all patients scoring 4 or 5 on the ICH score dying within 30 days. Lower GCS scores, larger hematoma volumes, the presence of intraventricular hemorrhage (IVH), and increasing age were associated with higher mortality. Multivariate analysis identified increasing age (p = 0.023), lower GCS score (p = 0.003), and higher ICH score (p = 0.025) as independent predictors of 30-day mortality. Higher ICH scores were also significantly associated with poor functional outcomes (mRS ≥ 4) at both discharge and 30 days (p < 0.001). GCS score emerged as an independent predictor of poor functional outcomes at 30 days (p = 0.012). Conclusions The ICH score is an effective tool for predicting 30-day mortality and functional outcomes in patients with primary ICH. Incorporating the ICH score and GCS assessment into routine clinical practice can aid healthcare providers in early risk stratification, optimizing treatment plans, and improving resource allocation.

Fat necrosis after accelerated partial breast irradiation or hypofractionated whole breast irradiation: A case-control study.

This study aimed to compare the incidence of fat necrosis after accelerated partial breast irradiation (APBI) vs hypofractionated whole breast irradiation (WBI) in patients with early-stage breast cancer. Data from early-stage breast cancer patients who underwent breast-conserving surgery and adjuvant radiotherapy between 2009 and 2022 were retrospectively collected. Radiation therapy consisted of APBI of 30 Gy in 5 daily fractions (Fx) (delivered in one week, consecutively) to the tumour bed or WBI (42.4 Gy in 16 Fx). Reports on fat necrosis were extracted from yearly mammograms and breast ultrasound imaging. The primary endpoint was the incidence of radiologically detected fat necrosis. A total of 536 patients were included among the APBI and WBI cohorts, with 268 and 268 patients respectively. The three-year Kaplan-Meier actuarial rate of fat necrosis was 32.8% (95% CI: 30.0% - 35.6%) for APBI and 22.3% (95% CI: 19.7% - 24.9%) for WBI patients. Univariate Kaplan-Meier survival analysis revealed a Hazard Ratio of 1.6 [95% CI: 1.1 - 2.2; p = 0.0055] for the fat necrosis rate within the APBI group compared to WBI. Multivariate Cox proportional hazard regression confirmed significant associations between fat necrosis and APBI (HR = 2.2 95% CI: 1.2 - 4.0; p = 0.01). The occurrence of radiologically diagnosed fat necrosis was higher in the APBI group compared to the WBI. Further investigations aiming to identify a lower-dose schedule with comparable efficacy to 30 Gy in 5 Fx but fewer toxicities, particularly for high-risk patients, are warranted.

Effects of immunosuppressive therapy on renal prognosis in primary membranous nephropathy

BackgroundImmunosuppressive therapy plays a crucial role in treating membranous nephropathy, with previous studies highlighting its benefits for patients with primary membranous nephropathy (PMN). Guidelines suggest that the management of membranous nephropathy should be tailored to individual risk levels. However, there is a lack of real-world studies examining the effects of immunosuppressive therapy on renal outcomes in PMN patients. This study aimed to investigate the relationship between immunosuppressive therapy and renal prognosis in PMN patients.MethodsThis was a real-world retrospective study including patients diagnosed with PMN in Shenzhen Second People’s Hospital and Hechi People’s Hospital. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival analysis were used.ResultsAfter propensity score-matching, 464 PMN patients were included and they were assigned to conservative and immunosuppressive group in a 1:1 ratio. Immunosuppressive therapy was the protective factor of renal composite outcome (HR = 0.65, p < 0.01). Separately, the effect was significant in moderate- and high-risk but not in low-risk patients. Key influencing factors including age, blood pressure, albumin and total cholesterol levels, with slight differences among patients at different risk.ConclusionsThis study demonstrates the efficacy of immunosuppressive therapy in non-low-risk PMN patients. The key factors affecting renal prognosis in patients with different risk levels are emphasized to help provide individualized treatment.

Scoring System Assessing Risks of Growth in Sporadic Vestibular Schwannoma.

Surveillance studies offer sparse knowledge of predictors of future growth in sporadic vestibular schwannomas (VS).Our aim was identification of these risk factors. We propose a scoring system to estimate the risk of growth in sporadic vestibular schwannoma. This retrospective study is based on the demographic and radiological data of 615 adult patients under the surveillance for single VS in our center. Univariate analysis, multivariate regression, and Kaplan-Meier analysis were used when appropriate. The regression coefficient-based "VS score" was calculated based on Cox proportional-hazards regression. During surveillance, 285 tumors (46%) remained stable, 314 tumors (51%) grew, and 16 tumors (3%) shrank. The significant risks factors for future growth identified both in univariate and multivariate analyses were younger age at onset, cystic morphology, larger tumor volume, and cisternal location (as per Hannover grade). The proportion of growing tumors was 40%, 75%, and 96% among the homogeneous VS, primary cystic, and VS transformed to cystic, respectively. Moreover, tumor growth during the 1st year was significant predictor of continuous growth. Our "VS score" includes variables such as age, sex, morphology, and Hannover grade. The score extends between -3 and 6 points. Kaplan-Meier, confusion matrix, and receiver operating characteristic analysis proved high accuracy of our scoring model. Our retrospective study revealed that younger age, cystic morphology, cisternal extent, larger volume, and growth during 1st year were strong predictors of future growth. Moreover, we propose a scoring system that accurately estimates the risks of future tumor growth.

Prognostic significance of pretreatment PET parameters in inoperable, node-positive NSCLC patients with poor prognostic factors undergoing hypofractionated radiotherapy: a single-institution retrospective study

BackgroundNode-positive non-small cell lung cancers (NSCLCs) present a challenge for treatment decisions, particularly in patients ineligible for concurrent chemoradiotherapy (CRT) due to poor performance status and compromised lung function. We aimed to investigate the prognostic value of pretreatment positron emission tomography (PET) parameters in high-risk patients undergoing hypofractionated radiotherapy.MethodsA retrospective analysis was conducted on 42 consecutive patients with inoperable node-positive NSCLC, who underwent hypofractionated radiotherapy between 2014 and 2021 at a single institution. Clinical, treatment-related, and [18F]FDG PET-based parameters were correlated with progression-free survival (PFS) and overall survival (OS). Median dichotomisation was performed to establish risk groups. Statistical analyses included univariable and multivariable Cox regression and Kaplan-Meier survival analyses.ResultsAfter a median follow-up of 47.1 months (range: 0.5-101.7), the median PFS and OS were 11.5 months (95% CI: 7.4-22.0), and 24.3 months (95% CI: 14.1-31.8). In univariable Cox regression analysis, significant predictors of PFS included receipt of salvage systemic treatment (p=0.007), SUVmax (p=0.032), and tMTV (p=0.038). Similarly, ECOG-PS (p=0.014), Histology (p=0.046), and tMTV (p=0.028) were significant predictors of OS. Multivariable Cox regression analysis (MVA) identified SUVmax as a significant predictor for PFS [HR: 2.29 (95% CI: 1.02-5.15); p=0.044]. For OS, ECOG-PS remained a significant prognosticator [HR: 3.53 (95% CI: 1.49-8.39); p=0.004], and tMTV approached significance [HR: 2.24 (95% CI: 0.95-5.26); p=0.065]. Furthermore, the high tMTV group exhibited a median PFS of 5.3 months [95% CI: 2.8-10.4], while the low tMTV group had a PFS of 15.2 months [95% CI: 10.1-33.5] (p=0.038, log-rank test). Median OS was 33.5 months [95% CI: 18.3-56.8] for tMTV ≤ 36.6 ml vs. 14.1 months [95% CI: 8.1-27.2] for tMTV > 36.6 ml (p=0.028, log-rank test).ConclusionPretreatment PET parameters, especially tMTV, hold promise as prognostic indicators in NSCLC patients undergoing hypofractionated radiotherapy. The study highlights the potential of PET metrics as biomarkers for patient stratification.

Analysis of recurrence factors after balloon compression for trigeminal neuralgia and the relationship between pear-shaped balloon and guidewire path

BackgroundPercutaneous balloon compression (PBC) is widely used to treat trigeminal neuralgia due to its significant efficacy and low treatment cost. However, there is considerable variation in postoperative pain recurrence among patients. Currently, the factors influencing pain recurrence after PBC are under discussion. This study aims to explore the impact of individual patient parameters and surgical parameters on postoperative pain recurrence following PBC. The goal is to provide clinicians with a reference for preoperative assessment of pain recurrence risk and to offer insights for effectively intervening in controllable influencing parameters. MethodsA analysis was conducted on 114 patients who underwent PBC in the Department of Neurosurgery at Hebei General Hospital. Univariate Kaplan-Meier analysis and multivariate Cox regression analysis were performed on the general and surgical data of the patients to identify factors potentially associated with postoperative pain recurrence. ResultsThe results of the multivariate Cox regression analysis showed that a history of hypertension, MRI indicating trigeminal nerve compression and a non-ideal pear-shaped balloon were statistically significant factors for pain recurrence after PBC. Additionally, the guidewire path during the procedure had a statistically significant impact on the rate of achieving a pear-shaped balloon (P<0.05). ConclusionA history of hypertension, MRI indicating trigeminal nerve compression and a non-ideal pear-shaped balloon shape are independent risk factors for pain recurrence after PBC. Additionally, to avoid pain recurrence due to an unfavorable balloon shape, it is recommended to use 3D-slicer for preoperative guidewire path simulation and 3D reconstruction of Meckel's cavity.

The role of HGH1 in breast cancer prognosis: a study on immune response and cell cycle

BackgroundBreast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA.MethodsThe Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1’s role in BRCA.ResultsIHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells’ proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration.ConclusionBiomarkers such as HGH1 can reliably predict prognosis in BRCA patients.

Prognostic Significance of Baseline Clinical and [68Ga]Ga-PSMA PET Derived Parameters on Biochemical Response, Overall Survival, and PSA Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Undergoing [177Lu]Lu-PSMA Therapy.

In this study, we sought to identify the clinical baseline characteristics and pre-therapy 68Ga-PSMA PET derived parameters that can have impact on PSA (biochemical) response, OS and PSA PFS in patients with metastatic castration-resistant prostate cancer (mCRPC) who undergo RLT with [177Lu]Lu-PSMA-617. Various pre-treatment clinical and PSMA PET derived parameters were gathered and computed. We used PSA response as the criteria for more than a 50% decrease in PSA level, and OS and PSA PFS as endpoints. We assessed the collected parameters in relation to PSA response. Additionally, we employed univariable Cox regression and Kaplan-Meier analysis with log rank to evaluate the influence of the parameters on OS and PFS. A total of 125 mCRPC patients were included in this study. The median age was 68 years (range: 49-89). Among the cases, 77 patients (62%) showed PSARS, while 48 patients (38%) did not show PSA response. The median OS was 14 months (range: 1-60), and the median PSA-PFS was 10 months (range: 1-56). Age, prior history of chemotherapy, and SUVmax had a significant impact on PSA response (p<0.05). PSA response, RBC count, hemoglobin, hematocrit, neutrophil to lymphocyte ratio (NLR), alkaline phosphatase (ALP), number of metastases, wbPSMA-TV, and wbTL-PSMA significantly affected OS. GS, platelet count, NLR, and number of metastases were found to have a significant impact on PSA PFS. We have identified several baseline clinical and PSMA PET derived parameters that can serve as prognostic factors for predicting PSA response, OS, and PSA PFS after RLT. Based on the findings, we believe that these clinical baseline characteristics can assist nuclear medicine specialists in identifying RLT responders who have long-term survival and PFS.

Serum inflammatory markers as prognostic marker for nasopharyngeal carcinoma with liver metastasis: a multi-center retrospective study.

This retrospective study investigated the prognostic value of serum inflammatory markers in nasopharyngeal carcinoma (NPC) patients, focusing on their association with overall survival (OS) and liver metastasis-free survival (LMFS). The study included 314 NPC patients treated between 2010 and 2020. Clinical characteristics, treatment methods, and serum inflammatory markers were assessed. Patients were categorized into two groups of with and without liver metastasis. Univariate and multivariate Cox regression and Kaplan-Meier survival analyses were performed to investigate the prognostic value of serum inflammatory markers in NPC patients with and without liver metastasis. In the whole cohort, univariate Cox regression analysis singled out tumor necrosis factor-α (TNF-α) (HR = 1.57, 95% CI 1.44-4.90, p = 0.004) and neutrophil-to-lymphocyte ratio (NLR) (HR = 2.13, 95% CI 1.33-3.99, p = 0.009), which were significantly associated with poorer OS. In patients with liver metastasis, TNF-α and NLR could not independently predict OS. However, high TNF-α levels were independently associated with worse OS in patients without liver metastasis (HR (95% CI) = 2.75 (1.67-8.68), p < 0.001). High NLR levels could independently predict poor OS in both groups with (HR (95% CI) = 1.94 (1.77-6.38), p = 0.010) and without liver metastasis (HR (95% CI) = 1.58 (1.19-7.54), p = 0.009). Ultimately, TNF-α and NLR could not significantly predict LMFS. This study highlights the prognostic significance of TNF-α and NLR in NPC patients, especially in those with liver metastasis. These inflammatory markers could serve as valuable indicators for assessing the prognosis of NPC patients. Further research is warranted to validate their clinical utility and explore potential therapeutic implications.

Comorbidities and mortality risk in COVID-19 patients with congestive heart failure: A comprehensive analysis

The COVID-19 pandemic has posed unprecedented challenges to global healthcare systems, resulting in alarming incidence and mortality rates among patients with comorbidities, including heart failure. Understanding the characteristics of heart failure and other comorbidities during the COVID-19 pandemic is crucial for effective prevention and treatment. However, the current understanding of these characteristics among different racial groups remains incomplete. In this study, we investigated a cohort of 4711 patients, classifying them into congestive heart failure (CHF) and non-CHF groups. Biomarker analysis revealed noteworthy variations in blood urea nitrogen, aspartate aminotransferase, and white blood cell levels based on the presence or absence of CHF. Stratified by three racial groups, univariate logistic regression analysis identified significant differences in multiple variables, including CHF. Subsequent univariate Cox regression and Kaplan-Meier analysis demonstrated variations in mortality factors among distinct populations, with age and comorbidity playing prominent roles. This study utilized a large-scale database to investigate the characteristics of heart failure and related variables during the COVID-19 pandemic. The findings revealed distinctive mortality risk factors among various racial groups, emphasizing the significance of customized risk assessment and management approaches for diverse populations. These findings also provide a valuable resource for the development of targeted interventions and the promotion of equitable healthcare outcomes in the context of the COVID-19 pandemic.

SPP1 could be an immunological and prognostic biomarker: From pan-cancer comprehensive analysis to osteosarcoma validation.

Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.

Development and validation of a nomogram for predicting lymph node metastasis in early gastric cancer.

Lymph node metastasis (LNM) significantly impacts the treatment and prognosis of early gastric cancer (EGC). Consequently, the precise prediction of LNM risk in EGC patients is essential to guide the selection of appropriate surgical approaches in clinical settings. To develop a novel nomogram risk model for predicting LNM in EGC patients, utilizing preoperative clinicopathological data. Univariate and multivariate logistic regression analyses were performed to examine the correlation between clinicopathological factors and LNM in EGC patients. Additionally, univariate Kaplan-Meier and multivariate Cox regression analyses were used to assess the influence of clinical factors on EGC prognosis. A predictive model in the form of a nomogram was developed, and its discrimination ability and calibration were also assessed. The incidence of LNM in the study cohort was 19.6%. Multivariate logistic regression identified tumor size, location, degree of differentiation, and pathological type as independent risk factors for LNM in EGC patients. Both tumor pathological type and LNM independently affected the prognosis of EGC. The model's performance was reflected by an area under the curve of 0.750 [95% confidence interval (CI): 0.701-0.789] for the training group and 0.763 (95%CI: 0.687-0.838) for the validation group. A clinical prediction model was constructed (using tumor size, low differentiation, location in the middle-lower region, and signet ring cell carcinoma), with its score being a significant prognosis indicator.

Identification of Cuproptosis-related Gene Lipoyltransferase 1 as a Promising Biomarker in Oral Squamous Cell Carcinoma.

To find efficient cuproptosis-related biomarkers to explore the oncogenesis and progression of oral squamous cell carcinoma (OSCC). All the original data were downloaded from the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and Kaplan-Meier survival analysis were used to identify the gene related to survival. Tumor Immune Estimation Resource 2.0 (TIMER 2.0) was used to reveal the different expression of cuproptosis-related gene lipoyltransferase 1 (LIPT1) in various kinds of tumours. LIPT1, as a cuproptosis-related gene, was found to be differentially expressed in the OSCC group and the control group. It was also found to be related to the prognosis of OSCC. Pan cancer analysis showed LIPT1 was also involved in various kinds of tumours. All the results demonstrate that the cuproptosis-related gene LIPT1 is highly involved in the oncogenesis and progression of OSCC. These findings give new insight for further research into the cuproptosis-related biomarkers in OSCC.

Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published. To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time. DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out. LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro. LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

Neck Dissection in cT3/T4 Mucoepidermoid Carcinoma of the Oral Cavity and Oropharynx

Previous research has reported high occult nodal metastases rates for T3/T4 mucoepidermoid carcinoma (MEC) of the oropharynx (OP) and oral cavity (OC). Our study evaluates if there is a benefit of neck dissection (ND) in these patients. The 2004–2016 National Cancer Database was queried for cases of adult MEC of the OC and OP. Patients with clinical T3/T4 disease were included while those with metastatic disease were excluded. Patients were divided into two cohorts: those treated with and without ND. Univariate chi-square, Kaplan-Meier, and multivariable Cox regression analyses were implemented. A total of 243 patients met inclusion criteria, of which 79 (32.5%) underwent ND. The majority of patients were less than 60 years old (60.1%), White (76.2%), and male (53.5%). 92 (37.9%) patients had clinically node-positive (cN+) disease. ND patients had higher rates of cN + disease (53.2% vs. 30.5%, p = 0.002). Of patients undergoing ND, 35 (44.3%) had cN0 disease while 42 (53.2%) had cN + disease. ND patients more commonly had grade III/IV tumors (45.1% vs. 23.4%, p = 0.002). Upon examination of dissected nodes, 20.3% of cN0 patients undergoing ND were found to have occult nodal metastases. There was no significant difference in 5-year overall survival between patients with and without ND (61.8% vs. 53.6%, p = 0.610), even on multivariable Cox analysis (hazard ratio: 1.52, 95% confidence interval: 0.73–3.18, p = 0.269). Our study found patients with cN0 MEC of the OC and OP have a high rate (20.3%) of occult nodal metastasis. In this cohort, patients with ND were not found to have improved survival, possibly due to statistical underpowering. Further research is needed to evaluate the indications and benefit of ND for this rare tumor presentation.