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Introduction: At present, clinical factors and hematological indicators have been proved to have great potential in predicting the prognosis of cancer patients, and no one has combined these two valuable indicators to establish a prognostic model for esophageal squamous cell carcinoma (ESCC) patients with stage T1-3N0M0 after R0 resection. To verify, we aimed to combine these potential indicators to establish a prognostic model. Methods: Stage T1-3N0M0 ESCC patients from two cancer centers (including training cohort: N = 819, and an external validation cohort: N = 177)—who had undergone esophagectomy in 1995–2015 were included. We integrated significant risk factors for death events by multivariable logistic regression methods and applied them to the training cohort to build Esorisk. The parsimonious aggregate Esorisk score was calculated for each patient; the training set was divided into three prognostic risk classes according to the 33rd and 66th percentiles of the Esorisk score. The association of Esorisk with cancer-specific survival (CSS) was assessed using Cox regression analyses. Results: The Esorisk model was: [10 + 0.023 × age + 0.517 × drinking history − 0.012 × hemoglobin–0.042 × albumin − 0.032 × lymph nodes]. Patients were grouped into three classes—Class A (5.14–7.26, low risk), Class B (7.27–7.70, middle risk), and Class C (7.71–9.29, high risk). In the training group, five-year CSS decreased across the categories (A: 63%; B: 52%; C: 30%, Log-rank P < 0.001). Similar findings were observed in the validation group. Additionally, Cox regression analysis showed that Esorisk aggregate score remained significantly associated with CSS in the training cohort and validation cohort after adjusting for other confounders. Conclusions: We combined the data of two large clinical centers, and comprehensively considered their valuable clinical factors and hematological indicators, established and verified a new prognostic risk classification that can predict CSS of stage T1-3N0M0 ESCC patients. [ABSTRACT FROM AUTHOR]

Background: The study on skip-N2 metastasis in small-cell lung cancer (SCLC) is lacking. Therefore, this study aimed to explore the prognostic significance of skip-N2 metastasis based on a multicenter cohort. Methods: We collected 176 SCLC patients with pathological categories T1-4N1-2M0 from four hospitals in China. Survival curves were drawn through the Kaplan–Meier method and compared by the log-rank test. The Cox regression method was used to calculate the hazard ratio (HR) and 95% confidence interval of the characteristics for cancer-specific survival (CSS). Two propensity-score methods were used to reduce the bias, including the inverse probability of treatment weighting (IPTW) and propensity-score matching (PSM). Results: This multicenter database included 64 pN1 patients, 63 non-skip-N2 cases, and 49 skip-N2 cases. Skip-N2 and the non-skip-N2 patients had gap CSS rates (skip-N2 no versus yes: 41.0% versus 62.0% for 1-year CSS, 32.0% versus 46.0% for 2-year CSS, and 20.0% versus 32.0% for 3-year CSS). After PSM, there were 32 pairs of patients to compare survival differences between N2 and skip-N2 diseases, and 34 pairs of patients to compare prognostic gaps between N1 and skip-N2 diseases, respectively. The results of IPTW and PSM both suggested that skip-N2 cases had better survival outcomes than the non-skip-N2 cases (IPTW-adjusted HR = 0.578; PSM-adjusted HR = 0.510; all log-rank p < 0.05). Besides, the above two analytic methods showed no difference in prognoses between pN1 and skip-N2 diseases (all log-rank p > 0.05). Conclusions: Skip-N2 patients were confirmed to have a better prognosis than non-skip-N2 patients. Besides, there was no survival difference between pN1 and skip-N2 cases. Therefore, we propose that the next tumor-node-metastasis staging system needs to consider the situation of skip metastasis with lymph nodes in SCLC. [ABSTRACT FROM AUTHOR]

Introduction : Tumor markers have been shown to be closely related to the long-term survival of patients with cancer and the recurrence of various malignant tumors. However, their role in thymic epithelial tumors (TETs) remains to be elucidated. We aimed to investigate whether the preoperative tumor biomarkers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) could serve as independent predictors of postoperative prognosis in patients with TETs. Materials and Methods: We retrospectively included a total of 111 patients with TETs who underwent thymectomy at our hospital. Cox regression analysis was used to evaluate the statistical significance of CEA and NSE as independent predictors of overall survival (OS) and recurrence-free survival (RFS). Kaplan–Meier curves were used to present the results of our survival analyses. Results: Cox regression analysis showed that T stage, World Health Organization (WHO) histologic type, tumor size, and CEA levels served as independent prognostic factors for OS (P <.05). Whereas for RFS, multivariate analysis showed that only T stage, WHO histologic type, and drinking history were independently associated with it (P <.05). Conclusion: Our study found that preoperative serum CEA levels and tumor size may be strong predictors of postoperative OS in patients with TETs. [ABSTRACT FROM AUTHOR]

We designed magneto-electro-elastic piezoelectric, electromagnetic (EM) metamaterials (MEEPEM) by using a square lattice of the periodic arrays of conducting wires, piezoelectric photonic crystal (PPC), and split-ring resonators (SRRs). We analyzed the mechanism for multi-field coupling in MEEPEM. The magnetic field of the EM wave excites an attractive Ampère force in SRRs, which periodically compress MEEPEM, and this can create electric polarization due to the piezoelectric effect. The electric field of the EM wave can excite a longitudinal superlattice vibration in the PPC, which can also create electric polarization. The electric polarization can couple to the electric field of the periodic arrays of conducting wires. The coupled electric field will couple to the EM wave. These interactions result in multi-field coupling in MEEPEM. The coupling creates a type of polariton, called multi-field coupling polaritons, corresponding to a photonic band gap, namely, the multi-field coupling photonic band gap. We calculated the dielectric functions, the reflection coefficients, and the effective magnetic permeability of MEEPEM. By using them, we analyzed the transmission properties of EM waves in the MEEPEM. We analyzed the possibility of MEEPEM as left-handed metamaterials and zero refractive index material. [ABSTRACT FROM AUTHOR]

Background: Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder. Methods: Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke–Fahn–Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared). Results: A total of 20 DRD patients were included (11 with GCH1 variants, 9 with TH variants). During long-term levodopa treatment, three patients with TH variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG. Conclusions: Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with TH variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of a novel computerized quantitative analysis based on histopathological and computed tomography (CT) images for predicting the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients. Methods: We retrospectively reviewed the medical records of 153 ESCC patients who underwent esophagectomy alone and quantitatively analyzed digital histological specimens and diagnostic CT images. We cut pathological images (6000 × 6000) into 50 × 50 patches; each patient had 14,400 patches. Cluster analysis was used to process these patches. We used the pathological clusters to all patches ratio (PCPR) of each case for pathological features and we obtained 20 PCPR quantitative features. Totally, 125 computerized quantitative (20 PCPR and 105 CT) features were extracted. We used a recursive feature elimination approach to select features. A Cox hazard model with L1 penalization was used for prognostic indexing. We compared the following prognostic models: Model A: clinical features; Model B: quantitative CT and clinical features; Model C: quantitative histopathological and clinical features; and Model D: combined information of clinical, CT, and histopathology. Indices of concordance (C-index) and leave-one-out cross-validation (LOOCV) were used to assess prognostic model accuracy. Results: Five PCPR and eight CT features were treated as significant indicators in ESCC prognosis. C-indices adjusted for LOOCV were comparable among four models, 0.596 (Model A) vs. 0.658 (Model B) vs. 0.651 (Model C), and improved to 0.711with Model D combining information of clinical, CT, and histopathology (all p<0.05). Using Model D, we stratified patients into low- and high-risk groups. The 3-year overall survival rates of low- and high-risk patients were 38.0% and 25.0%, respectively (p<0.001). Conclusion: Quantitative prognostic modeling using a combination of clinical data, histopathological, and CT images can stratify ESCC patients with surgery alone into high-risk and low-risk groups. [ABSTRACT FROM AUTHOR]

LRRC55 (leucine-rich repeat-containing protein 55) protein is an auxiliary γ subunit of BK (Big conductance potassium channel) channels, which leftward shifts GVs of BK channels around 50 mV in the absence of cytosolic Ca2+. LRRC55 protein is also the only γ subunit of BK channels that is expressed in mammalian nervous system. However, the expression pattern of LRRC55 gene in adult mammalian brain remains elusive. In this study, we investigated the distribution of LRRC55 mRNA in the adult mouse brain by using in situ hybridization. We found that LRRC55 mRNA is richly expressed in the adult mouse medial habenula nucleus (MHb), cerebellum and pons. However, the potential role of LRRC55 in MHb and cerebellum could be different based on the function of BK channels in these brain regions. [ABSTRACT FROM AUTHOR]

Cri-du-Chat syndrome (MIM 123450) is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs), diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5)(p13.3p15.33) spanning ∼26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5) (q23;p14.1p15.31),ins(21;5)(q21;p13.3p14.1),ins(21;5)(q21;p15.31p15.33),inv(7)(p22q32)dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5) identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5). Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family. [ABSTRACT FROM AUTHOR]

Background: The relationship between quality of life and survival outcomes in esophageal cancer patients following curative resection is not well established. This study aimed to longitudinally assess quality of life indicators and their association with overall survival (OS) in these patients., Methods: A total of 232 patients were included in the study, and their quality of life was prospectively assessed at different time points using the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30) and the disease-specific esophageal module (QLQ-OES18). The scores of QLQ indicators at each time point were summarized, and changes in postoperative assessment were compared with preoperative assessments. The association of deterioration in certain indicators with OS was evaluated at each time point using Cox univariable analysis. Further confirmation of independent variables was carried out using Cox multivariable analysis., Results: The study cohort comprised 62 females (26.7%), and 113 patients (48.7%) aged over 60 years. The median follow-up time was 80 months (range, 8-118 months). At 24 months after discharge, patients reported improvements in role function, fatigue, cognition function, emotional function, social function, insomnia, appetite loss, nausea and vomiting, constipation, financial status, trouble swallowing saliva, and pain related to esophageal cancer. However, physical function, dyspnea, diarrhea, global health status, choking when swallowing, trouble talking, and reflux remained compromised. Multivariable regression analysis revealed deterioration in role function, emotional function, and coughing difficulty at 6 months, and dyspnea, pain, and cognitive function at 24 months post-discharge were identified as independent prognostic factors for OS., Conclusions: Our findings underscore the importance of monitoring quality of life indicators in esophageal cancer patients as they may significantly influence survival outcomes. The identification of specific quality of life indicators as prognostic factors highlights the need for a patient-centered approach in clinical practice to enhance care and potentially improve survival., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-311/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Treatment with immune checkpoint inhibitors, widely known as immune checkpoint blockade therapy (ICBT), is now the fourth pillar in cancer treatment, offering the chance of durable remission for patients with advanced disease. However, ICBT fails to induce objective responses in most cancer patients with still others progressing after an initial response. It is necessary, therefore, to elucidate the primary and acquired resistance mechanisms to ICBT to improve its efficacy. Here, we highlight the paradoxical role of the cytokine interferon-γ (IFN-γ) in ICBT response: on the one hand induction of IFN-γ signalling in the tumour microenvironment correlates with good ICBT response as it drives the cellular immune responses required for tumour destruction; nonetheless, IFN-γ signalling is implicated in ICBT acquired resistance. We address the negative feedback and immunoregulatory effects of IFN-γ signalling that promote immune evasion and resistance to ICBT and discuss how these can be targeted pharmacologically to restore sensitivity or circumvent resistance., (© 2023 The Author(s).)

Background: The efficacy of monotherapy of AMG-510 is limited. This study explored whether the AMG-510 and cisplatin combination increases the anti-tumor effect in lung adenocarcinoma with the mutation of Kirsten rat sarcoma viral oncogene (KRAS) G12C., Methods: Patients' data were used to analyze the proportion of KRAS G12C mutation. Besides, the next-generation sequencing data was used to uncover information about co-mutations. The cell viability assay, the concentration inhibiting 50% of cell viability (IC50) determination, colony formation, and cell-derived xenografts were conducted to explore the anti-tumor effect of AMG-510, Cisplatin, and their combination in vivo. The bioinformatic analysis was conducted to reveal the potential mechanism of drug combination with improved anticancer effect., Results: The proportion of KRAS mutation was 2.2% (11/495). In this cohort with KRAS mutation, the proportion of G12D was higher than others. Besides, KRAS G12A mutated tumors had the likelihood of concurrent serine/threonine kinase 11 (STK11) and kelch-like ECH-associated protein 1 (KEAP1) mutations. KRAS G12C and tumor protein p53 (TP53) mutations could appear at the same time. In addition, KRAS G12D mutations and C-Ros oncogene 1 (ROS1) rearrangement were likely to be present in one tumor simultaneously. When the two drugs were combined, the respective IC50 values were lower than when used alone. In addition, there was a minimum number of clones among all wells in the drug combination. In in vivo experiments, the tumor size reduction in the drug combination group was more than twice that of the single drug group (p < 0.05). The differential expression genes were enriched in the pathways of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling and extracellular matrix (ECM) proteoglycans compared the combination group to the control group., Conclusions: The anticancer effect of the drug combination was confirmed to be better than monotherapy in vitro and in vivo. The results of this study may provide some information for the plan of neoadjuvant therapy and the design of clinical trials for lung adenocarcinoma patients with KRAS G12C mutation., (© 2023. The Author(s).)

Background: Thymic carcinoma (TC) is a rare malignant tumor that can have a poor prognosis, and accurate prognostication prediction remains difficult. We aimed to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) based on a large cohort of patients., Methods: The Surveillance Epidemiology and End Results (SEER) database was searched to identify TC patients (1975-2016). Univariate and multivariable Cox regression analyses were used to identify predictors of OS and CSS, which were used to construct nomograms. The nomograms were evaluated using the concordance index (C-index), calibration curve, receiver operating characteristic curve, and decision curve analysis (DCA). Subgroup analysis was performed to identify high-risk patients., Results: The analysis identified six predictors of OS (Masaoka stage, surgical method, lymph node metastasis, liver metastasis, bone metastasis, and radiotherapy) and five predictors of CSS (Masaoka stage, surgical method, lymph node metastasis, tumor size, and brain metastasis), which were used to create nomograms for predicting three-year and five-year OS and CSS. The nomograms had reasonable C-index values (OS: 0.687 [training] and 0.674 [validation], CSS: 0.712 [training] and 0.739 [validation]). The DCA curve revealed that the nomograms were better for predicting OS and CSS, relative to the Masaoka staging system., Conclusion: We developed nomograms using eight clinicopathological factors that predicted OS and CSS among TC patients. The nomograms performed better than the traditional Masaoka staging system and could identify high-risk patients. Based on the nomograms' performance, we believe they will be useful prognostication tools for TC patients.

Introduction: Systemic nutrition and immune inflammation are the key factors in cancer development and metastasis. This study aimed to compare and assess four nutritional status and immune indicators: prognostic nutritional index (PNI), nutritional risk index (NRI), neutrophil-to-lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII) as prognostic indicators for patients with thymic epithelial tumors., Materials: We retrospectively reviewed 154 patients who underwent thymic epithelial tumor resection at our hospital between 2004 and 2015. The optimal cutoff value for each nutritional and immune index was obtained using the X-tile software. Kaplan-Meier curves and Cox proportional hazards models were used for survival analysis., Results: Univariate analysis showed that PNI, NRI, NLR, SII, albumin (ALB), the albumin/globulin ratio (A/G), WHO stage, T stage, and drinking history were associated with the overall survival (OS) of patients ( P < 0.05). The NRI, NLR, A/G, ALB, T stage, and WHO stage were significant independent prognostic factors of OS in multivariate analysis ( P < 0.05). Finally, we constructed a coNRI-NLR model to predict OS and recurrence-free survival (RFS)., Conclusions: This study suggests that the preoperative NRI, NLR, and coNRI-NLR model may be important prognostic factors for patients with thymic epithelial tumors who undergo surgical resection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Liang, Hu, Liu and Ma.)

Introduction: Thymic epithelial tumors are the most common mediastinal tumors. Despite the high survival rate after surgery, some patients still require postoperative adjuvant therapy and closer follow-up. Hematological indicators such as biochemical routines and coagulation indicators have been reported to be independently associated with the prognosis of various malignancies. Therefore, we included hematological indicators in the analysis., Methods: The data of 105 patients with thymic epithelial tumors were retrospectively collected from Sun Yat-sen University Cancer Center, and the patients with missing preoperative hematological indicators were excluded. X-tile software was used to obtain the best cutoff value of each preoperative hematological indicator, and COX regression analysis and Kaplan-Meier survival curves were used to demonstrate statistically significant results., Results: COX univariate regression analysis of all patients showed that Masaoka stage, T stage, WHO histologic types, D-dimer, albumin-fibrinogen ratio (AFR), Fibrinogen (Fbg) were associated with postoperative overall survival ( P < .05). T stage, WHO histologic types, D-dimer, and AFR were associated with postoperative recurrence-free survival ( P < .05). Finally, multivariate regression analysis showed that T stage, D-dimer levels were independently associated with postoperative overall survival (OS) and recurrence-free survival (RFS) in patients with thymic epithelial tumors., Conclusions: For thymic epithelial tumors, higher preoperative D-dimer levels predict poorer survival and shorter recurrence-free survival. This may help guide postoperative adjuvant therapy and follow-up patterns in patients with thymic epithelial tumors.

Background: In this study, we aim to establish a nomogram to predict the prognosis of non-small cell lung cancer (NSCLC) patients with stage I-IIIB disease after pneumonectomy. Methods: Patients selected from the Surveillance, Epidemiology, and End Results (SEER, N = 2,373) database were divided into two cohorts, namely a training cohort (SEER-T, N = 1,196) and an internal validation cohort (SEER-V, N = 1,177). Two cohorts were dichotomized into low- and high-risk subgroups by the optimal risk prognostic score (PS). The model was validated by indices of concordance (C-index) and calibration plots. Kaplan-Meier analysis and the log-rank tests were used to compare survival curves between the groups. The primary observational endpoint was cancer-specific survival (CSS). Results: The nomogram comprised six factors as independent prognostic indictors; it significantly distinguished between low- and high-risk groups (all P < 0.05). The unadjusted 5-year CSS rates of high-risk and low-risk groups were 33 and 60% (SEER-T), 34 and 55% (SEER-V), respectively; the C-index of this nomogram in predicting CSS was higher than that in the 8th TNM staging system (SEER-T, 0.629 vs. 0.584, P < 0.001; SEER-V, 0.609 vs. 0.576, P < 0.001). In addition, the PS might be a significant negative indictor on CSS of patients with white patients [unadjusted hazard ration (HR) 1.008, P < 0.001], black patients (unadjusted HR 1.007, P < 0.001), and Asian or Pacific Islander (unadjusted HR 1.008, P = 0.008). In cases with squamous cell carcinoma (unadjusted HR 1.008, P < 0.001) or adenocarcinoma (unadjusted HR 1.008, P < 0.001), PS also might be a significant risk factor. Conclusions: For post-pneumonectomy NSCLC patients, the nomogram may predict their survival with acceptable accuracy and further distinguish high-risk patients from low-risk patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Chen, Liu, Jiang, Huang, Lin, Long, Zhang and Ma.)