Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced oesophageal squamous cell carcinoma: a systematic review and economic evaluation.

Background: Recently, several novel programmed cell death protein 1 (PD-1) inhibitors have been approved for second-line treating advanced or metastatic oesophageal squamous cell carcinoma (OSCC), including camrelizumab, nivolumab, pembrolizumab, sintilimab and tislelizumab. However, the optimal treatment regimen remained ambiguous. Objectives: The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective. Design: A systematic review and economic evaluation. Data sources and methods: A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase and Scopus databases to identify eligible studies until 31 August 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS) and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on five clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios for various treatment options. Direct medical costs and utility values were obtained from public drug bidding databases, clinical trials or published literature. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. Results: Five randomized controlled trials involving 2837 patients were included in the analysis. Compared with other treatments examined, camrelizumab provided the best PFS benefits [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.56-0.86], and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2 and 3 times GDP per capita in 2022, sintilimab, tislelizumab and camrelizumab were the most cost-effective treatment options, respectively. Conclusion: Sintilimab might be the optimal treatment alternative for second-line therapy of advanced OSCC in China, followed by tislelizumab and camrelizumab. Trial registration: This study has been registered on the PROSPERO database with the registration number CRD42023495204.

METHODS: A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases to identify eligible studies until August 31, 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on 5 clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) for various treatment options. Direct medical costs and utility values were obtained from public drug bidding database, clinical trials or published literatures. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. RESULTS: Compared with other treatments examined, camrelizumab provided the best PFS benefits (HR: 0.69, 95% CI: 0.56-0.86), and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2, and 3 times GDP per capita in 2022, sintilimab, tislelizumab, and camrelizumab were the most cost-effective treatment options, respectively. CONCLUSION: Sintilimab might be the optimal treatment alternative for second-line therapy of advanced ESCC in China, followed by tislelizumab and camrelizumab.

Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced esophageal squamous cell carcinoma: a systematic review and economic evaluation Background: The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective.

Safety and efficacy of protective stent insertion to prevent carotid blowout syndrome at the distal internal carotid artery in nasopharyngeal carcinoma patients: a comparison with endovascular occlusion.

Background: Carotid blowout syndrome (CBS) frequently occurs at the distal internal carotid artery (distal-ICA) in patients with nasopharyngeal carcinoma (NPC), and remedial treatments run a high risk for neurologic complications. A case-control study was conducted to evaluate the safety and efficacy of protective stent insertion at the distal-ICA to prevent CBS in NPC patients, with a comparison to endovascular coil occlusion. Methods: A total of 28 consecutive NPC patients at high risk of CBS from June 2019 to December 2021 in Shanghai Sixth People's Hospital (a tertiary institution) were retrospectively included and divided into a stent protection group and occlusion group. Technique feasibility, treatment outcomes and neurological deficiency were compared between the two groups by two-sample test. Kaplan-Meier analysis compared patients' survival rates at mid-term follow-up. Results: Stent insertion was performed in 15 patients and ICA occlusion in 13 patients. The technical success rate was 100% in both groups. Procedure-related ischemic stroke was identified in 2 patients (15.4%) in the occlusion group, compared with none in the stent protection group. Bleeding was encountered in one patient in the stent protection group and one patient in the occlusion group, each. During a median follow-up of 10.5 (range, 2-31) months, 3 patients (20%) showed asymptomatic in-stent occlusion in the stent protection group. Notably, the median survival time was significantly longer in the stent protection group than in the occlusion group (23.3 vs. 15.8 months, P=0.04). Conclusions: Protective stenting the distal-ICA was similarly effective in preventing CBS in NPC patients but was safer than endovascular occlusion of ICA.

Caspase-3/GSDME mediated pyroptosis: A potential pathway for sepsis.

The inflammatory response is one of the host's mechanisms to combat pathogens. Normal and controlled inflammation can accelerate the clearance of pathogens. However, in sepsis, the host often exhibits an excessive inflammatory response to infection, leading to tissue and organ damage. Therefore, studying the mechanisms underlying the occurrence and development of sepsis is of significant importance. Pyroptosis is a form of programmed cell death (PCD) executed by the gasdermins (GSDMs) family, and its pro-inflammatory characteristics are considered a crucial component of the sepsis mechanism. Previous research on pyroptosis in sepsis has mainly focused on the caspase-1/4/5/11-GSDMD pathway, which has made significant progress. However, there is a lack of research on the roles of other GSDMs family members in sepsis. New research has revealed that the caspase-3/GSDME pathway can also mediate pyroptosis, playing important roles in cancer, other inflammatory diseases, and even some sepsis-related conditions. This discovery suggests the potential value of investigating caspase-3/GSDME in sepsis research. This review provides an overview of the role of the GSDMs family in infectious diseases, summarizes current research on the caspase-1/4/5/11-GSDMD pathway, describes the role of caspase-3 in sepsis, and discusses the research findings related to pyroptosis mediated by the caspase-3/GSDME pathway in cancer, inflammatory diseases, and sepsis-related conditions. The aim of this article is to propose the concept of caspase-3/GSDME as a potential target in sepsis research. Considering the role of this pathway in other diseases, including inflammatory conditions, and given the unique nature of sepsis as an inflammatory disease, the article suggests that this pathway may also play a role in sepsis. This hypothesis provides new insights and options for future sepsis research, although direct experiments are needed to validate this hypothesis.

µPADs on Centrifugal Microfluidic Discs for Rapid Sample-to-Answer Salivary Diagnostics.

A fully integrated device for salivary detection with a sample-in-answer-out fashion is critical for noninvasive point-of-care testing (POCT), especially for the screening of contagious disease infection. Microfluidic paper-based analytical devices (µPADs) have demonstrated their huge potential in POCT due to their low cost and easy adaptation with other components. This study developed a generic POCT platform by integrating a centrifugal microfluidic disc with µPADs to realize sample-to-answer salivary diagnostics. Specifically, a custom centrifugal microfluidic disc integrated with µPADs is fabricated, which demonstrated a high efficiency in saliva treatment. To demonstrate the capability of the integrated device for salivary analysis, the SARS-CoV-2 Nucleocapsid (N) protein, a reliable biomarker for SARS-CoV-2 acute infection, is used as the model analyte. By the chemical treatment of the µPAD surface, and by optimizing the protein immobilization conditions, the on-disc µPADs were able to detect the SARS-CoV-2 N protein down to 10 pg mL-1 with a dynamic range of 10-1000 pg mL-1 and an assay time of 8 min. The integrated device was successfully used for the quantification of the N protein of pseudovirus in saliva with high specificity and demonstrated a comparable performance to the commercial paper lateral flow assay test strips.

Biomaterials-enhanced bioactive agents to efficiently block spinal metastases of cancers.

The spine is the most common site of bone metastases, as 20%-40% of cancer patients suffer from spinal metastases. Treatments for spinal metastases are scarce and palliative, primarily aiming at relieving bone pain and preserving neurological function. The bioactive agents-mediated therapies are the most effective modalities for treating spinal metastases because they achieve systematic and specific tumor regression. However, the clinical applications of some bioactive agents are limited due to the lack of targeting capabilities, severe side effects, and vulnerability of drug resistance. Fortunately, advanced biomaterials have been developed as excipients to enhance these treatments, including chemotherapy, phototherapy, magnetic hyperthermia therapy, and combination therapy, by improving tumor targeting and enabling sustaining and stimuli-responsive release of various therapeutic agents. Herein, the review summarizes the development of biomaterials-mediated bioactive agents for enhanced treatments of spinal metastases and predicts future research trends.

Effects of plastic contamination on carbon fluxes in a subtropical coastal wetland of East China.

Coastal wetlands are recognized as carbon sinks that play an important role in mitigating global climate change because of the strong carbon uptake by vegetation and high carbon sequestration in the soil. Over the last few decades, plastic waste pollution in coastal zones has become increasingly serious owing to high-intensity anthropogenic activities. However, the influence of plastic waste (including foam waste) accumulation in coastal wetlands on carbon flux remains unclear. In the Yangtze Estuary, we investigated the variabilities of vegetation growth, carbon dioxide (CO2) and methane (CH4) fluxes, and soil properties in a clean Phragmites australis marsh and mudflat and a plastic-polluted marsh during summer and autumn. The clean marsh showed a strong CO2 uptake capacity (a carbon sink), and the clean mudflat showed a weak CO2 sink during the measurement period. However, polluted marshes are a significant source of CO2 emissions. Regardless of the season, the gross primary production and vegetation biomass of the polluted marshes were on average 9.5 and 1.1 times lower than those in the clean marshes, respectively. Ecosystem respiration and CH4 emissions in polluted marshes were significantly higher than those in clean marshes and mudflats. Generally, the soil bulk density and salinity in polluted marshes were lower, whereas the median particle size was higher at the polluted sites than at the clean sites. Increased soil porosity and decreased salinity may favor CO2 and CH4 emissions through gas diffusion pathways and microbiological behavior. Moreover, the concentrations of heavy metals in the soil of plastic-polluted marshes were 1.24-1.49 times higher than those in the clean marshes, which probably limited vegetation growth and CO2 uptake. Our study highlights the adverse effects of plastic pollution on the carbon sink functions of coastal ecosystems, which should receive global attention in coastal environmental management.

Corrigendum to "SEC11A contributes to tumour progression of head and neck squamous cell carcinoma" [Heliyon 9(4) (April 2023) e14958].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14958.].

Cost-effectiveness analysis of serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive esophageal squamous cell carcinoma in China.

Objective: The ASTRUM-007 trial (NCT03958890) demonstrated that serplulimab plus chemotherapy administered every 2-week significantly improved progression-free and overall survival in patients with previously untreated, programmed death-ligand 1 (PD-L1) positive advanced esophageal squamous-cell carcinoma (ESCC). This study was aimed to investigate the cost-effectiveness of serplulimab plus chemotherapy in the first-line treatment of PD-L1-positive advanced ESCC. Methods: A partitioned survival model with a 2-week cycle and a 10-year time horizon was constructed from the Chinese healthcare system perspective. The survival data, direct medical costs and utilities were derived from the ASTRUM-007 trial, YAOZHI database and published sources. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Scenario, one-way and probabilistic sensitivity analyses were performed to assess the uncertainty around model parameters. Results: Compared with chemotherapy, serplulimab plus chemotherapy provided additional 0.27 QALYs with an incremental cost of $33,460.86, which had an ICER of $124,483.07 per QALY. The subgroup analyses revealed that the ICERs of serplulimab plus chemotherapy were $134,637.42 and $105,589.71 in advanced ESCC patients with 1 ≤ CPS < 10 and CPS ≥ 10, respectively. The price of serplulimab, patient weight, utility values and discount rate were the most influential parameters on base-case results. At a willingness-to-pay threshold of three times per capita GDP ($40,587.59) in 2022, the probability of serplulimab plus chemotherapy being cost-effective was 0% compared with chemotherapy. When the price of serplulimab decreased by 70%, the probabilities of serplulimab plus chemotherapy being cost-effective were 81.42%, 67.74% and 96.75% in advanced ESCC patients with PD-L1-positive, PD-L1 1≤CPS<10 and CPS≥10, respectively. Conclusion: Serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive advanced ESCC might not be cost-effective in China.

Biomaterials That Induce Immunogenic Cell Death.

The immune system takes part in most physiological and pathological processes of the body, including the occurrence and development of cancer. Immunotherapy provides a promising modality for inhibition and even the cure of cancer. During immunotherapy, the immunogenic cell death (ICD) of tumor cells induced by chemotherapy, radiotherapy, phototherapy, bioactive materials, and so forth, triggers a series of cellular responses by causing the release of tumor-associated antigens and damage-associated molecular patterns, which ultimately activate innate and adaptive immune responses. Among them, the ICD-induced biomaterials attract increasing conditions as a benefit of biosafety and multifunctional modifications. This Review summarizes the research progress in biomaterials for inducing ICD via triggering endoplasmic reticulum oxidative stress, mitochondrial dysfunction, and cell membrane rupture and discusses the application prospects of ICD-inducing biomaterials in clinical practice for cancer immunotherapy.

SEC11A contributes to tumour progression of head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent disease that has a low survival rate and high recurrence risk. Our study aims to investigate the expression and role of SEC11A in HNSCC. Methods: The expression of SEC11A was assessed in 18 pairs of cancerous and adjacent tissues by qRT-PCR and western blotting. Immunohistochemistry was performed in clinical specimen sections to evaluate the expression of SEC11A and its association with outcomes. Furthermore, the functional role of SEC11A in HNSCC tumor proliferation and progression was investigated using the in vitro cell model with lentivirus-mediated SEC11A knockdown. Colony formation and CCK8 assays were conducted to assess cell proliferation potential, while in vitro migration and invasion were examined using wound healing and transwell assays. To determine the tumor formation potential in vivo, a tumor xenograft assay was used. Results: In contrast to adjacent normal tissues, SEC11A expression was significantly elevated in HNSCC tissues. SEC11A was mainly localized in the cytoplasm, and its expression was significantly associated with patient prognosis. SEC11A was silenced using shRNA lentivirus in TU212 and TU686 cell lines, and the gene knockdown was confirmed. A series of functional assays demonstrated that SEC11A knockdown reduced cell proliferation, migration and invasion ability in vitro. In addition, the xenograft assay demonstrated that SEC11A knockdown significantly inhibited tumor growth in vivo. Tumor tissue sections of mice showed decreased proliferation potential in the shSEC11A xenografts cells by immunohistochemistry. Conclusion: SEC11A knockdown decreased cell proliferation, migration and invasion in vitro and subcutaneous tumorigenesis in vivo. SEC11A is crucial to HNSCC proliferation and progression, and may serve as a new therapeutic target.

Cost-effectiveness analysis of PD-1 inhibitors combined with chemotherapy as first-line therapy for advanced esophageal squamous-cell carcinoma in China.

Objective: This study was aimed to investigate the cost-effectiveness of all available programmed death 1 (PD-1) inhibitors combined with chemotherapy in the first-line treatment of advanced esophageal squamous-cell carcinoma (ESCC) from the Chinese healthcare system perspective. Methods: A partitioned survival model with a 3-week cycle and a 10-year time horizon was constructed based on a network meta-analysis. The survival data and utility values were derived from clinical trials, and the direct medical costs were collected from public drug bidding database and published literature. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Scenario, one-way and probabilistic sensitivity analyses were performed to assess the uncertainty around model parameters. Results: Compared with mono-chemotherapy, toripalimab, sintilimab and camrelizumab plus chemotherapy were cost-effective treatment regimens, while serplulimab, pembrolizumab and nivolumab plus chemotherapy were not cost-effective options. Toripalimab plus chemotherapy provided the highest QALYs of 0.95 with the lower cost of $8,110.53 compared to other competing alternatives. The robustness of the base-case results was confirmed by scenario and one-way sensitivity analysis. At a willingness-to-pay threshold of three times per capita gross domestic product ($38,351.20) in 2021, the probability of toripalimab plus chemotherapy being the optimal option was 74.25% compared with other six competing alternatives. Conclusion: Toripalimab plus chemotherapy represented the most cost-effective option as the first-line therapy for advanced ESCC patients in China.

Elevated ITGA5 facilitates hyperactivated mTORC1-mediated progression of laryngeal squamous cell carcinoma via upregulation of EFNB2.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck, and it has shown increasing incidence and mortality. The mechanistic target of rapamycin complex 1 (mTORC1) is frequently dysregulated in LSCC, but its underlying mechanisms remain unclear. Methods: Establishment of a novel LSCC cell line using primary LSCC tumor tissues with dysregulated mTORC1 activity and then stable knockdown of Raptor (an mTORC1 specific component) in this cell line. Transcriptomic sequencing, quantitative real-time PCR, western blot analysis, and immunofluorescence assays were used to identify the crucial downstream effector of mTORC1. A series of experiments were conducted to investigate the functions and underlying mechanisms of the mTORC1 target gene in LSCC progression. Clinical LSCC samples were used to evaluate the association of mTORC1 and its downstream targets with clinicopathological features and patient prognosis. Finally, the influence on cisplatin (CDDP) sensitivity upon depletion of the mTORC1 target gene was assessed using a cell culture system, a cell line-derived xenograft (CDX) model, and a patient-derived xenograft (PDX) model. Results: We successfully established a novel LSCC cell line with hyperactivated mTORC1 activity and then identified integrin subunit alpha 5 (ITGA5) as a novel functional downstream effector of mTORC1 in the progression of LSCC. Elevated ITGA5 promotes LSCC progression through augmentation of ephrin-B2 (EFNB2). Clinical data analysis indicated that the activation of the mTORC1-ITGA5-EFNB2 signaling pathway is associated with malignant progression and poor prognosis of LSCC patients. Inhibition of ITGA5 significantly sensitized LSCC cells to CDDP. Conclusions: Our findings highlight a novel molecular mechanism for the tumorigenesis driven by deregulated mTORC1 signaling in LSCC, suggesting that the ITGA5-EFNB2 axis may be a therapeutic target for the treatment of mTORC1-related LSCC.

Identification and validation of a novel tumor driver gene signature for diagnosis and prognosis of head and neck squamous cell carcinoma.

Objective: Head and neck squamous cell carcinoma (HNSCC) is a common heterogeneous cancer with complex carcinogenic factors. However, the current TNM staging criteria to judge its severity to formulate treatment plans and evaluate the prognosis are particularly weak. Therefore, a robust diagnostic model capable of accurately diagnosing and predicting HNSCC should be established. Methods: Gene expression and clinical data were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Key prognostic genes associated with HNSCC were screened with the weighted gene co-expression network analysis and least absolute shrinkage and selection operator (LASSO) Cox regression model analysis. We used the timeROC and survival R packages to conduct time-dependent receiver operating characteristic curve analyses and calculated the area under the curve at different time points of model prediction. Patients in the training and validation groups were divided into high- and low-risk subgroups, and Kaplan-Meier (K-M) survival curves were plotted for all subgroups. Subsequently, LASSO and support vector machine algorithms were used to screen genes to construct diagnostic model. Furthermore, we used the Wilcoxon signed-rank test to compare the half-maximal inhibitory concentrations of common chemotherapy drugs among patients in different risk groups. Finally, the expression levels of eight genes were measured using quantitative real-time polymerase chain reaction and immunohistochemistry. Results: Ten genes (SSB, PFKP, NAT10, PCDH9, SHANK2, PAX8, CELSR3, DCLRE1C, MAP2K7, and ODF4) with prognostic potential were identified, and a risk score was derived accordingly. Patients were divided into high- and low-risk groups based on the median risk score. The K-M survival curves confirmed that patients with high scores had significantly worse overall survival. Receiver operating characteristic curves proved that the prognostic signature had good sensitivity and specificity for predicting the prognosis of patients with HNSCC. Univariate and multivariate Cox regression analyses confirmed that the gene signature was an independent prognostic risk factor for HNSCC. Diagnostic model was built by identifying eight genes (SSB, PFKP, NAT10, PCDH9, CELSR3, DCLRE1C, MAP2K7, and ODF4). The high-risk group showed higher sensitivity to various common chemotherapeutic drugs. DCLRE1C expression was higher in normal tissues than in HNSCC tissues. Conclusion: Our study identified the important role of tumor-driver genes in HNSCC and their potential clinical diagnostic and prognostic values to facilitate individualized management of patients with HNSCC.

Applying antagonistic activation pattern to the single-trial classification of mental arithmetic.

Background: At present, the application of fNIRS in the field of brain-computer interface (BCI) is being a hot topic. By fNIRS-BCI, the brain realizes the control of external devices. A state-of-the-art BCI system has five steps which are cerebral cortex signal acquisition, data pre-processing, feature selection and extraction, feature classification and application interface. Proper feature selection and extraction are crucial to the final fNIRS-BCI effect. This paper proposes a feature selection and extraction method for the mental arithmetic task. Specifically, we modified the antagonistic activation pattern approach and used the combination of antagonistic activation patterns to extract features for enhancement of the classification accuracy with low calculation costs. Methods: Experiments are conducted on an open-acquisition dataset including fNIRS signals of eight healthy subjects of mental arithmetic (MA) tasks and rest tasks. First, the signals are filtered using band-pass filters to remove noise. Second, channels are selected by prior knowledge about antagonistic activation patterns. We used cerebral blood volume (CBV) and cerebral oxygen exchange (COE) of selected each channel to build novel attributes. Finally, we proposed three groups of attributes which are CBV, COE and CBV + COE. Based on attributes generated by the proposed method, we calculated temporal statistical measures (average, variance, maximum, minimum and slope). Any two of five statistical measures were combined as feature sets. Main results: With the LDA, QDA, and SVM classifiers, the proposed method obtained higher classification accuracies the basic control method. The maximum classification accuracies achieved by the proposed method are 67.45 ± 14.56% with LDA classifier, 89.73 ± 5.71% with QDA classifier, and 87.04 ± 6.88% with SVM classifier. The novel method reduced the running time by 3.75 times compared with the method incorporating all channels into the feature set. Therefore, the novel method reduces the computational costs while maintaining high classification accuracy. The results are validated by another open-access dataset including MA and rest tasks of 29 healthy subjects.

Cost-effectiveness analysis of nivolumab combination therapy in the first-line treatment for advanced esophageal squamous-cell carcinoma.

Objective: We aimed to investigate the cost-effectiveness of nivolumab plus chemotherapy and nivolumab plus ipilimumab versus chemotherapy in the first-line treatment for advanced esophageal squamous-cell carcinoma (ESCC) patients from a healthcare system perspective in China. Methods: On the basis of the CheckMate 648 trial, a partitioned survival model was constructed to estimate economic costs and health outcomes among overall and PD-L1-positive advanced ESCC patients over a 10-year lifetime horizon. The health-related costs and utilities were obtained from the local charges and published literature. The lifetime costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were measured. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model. Results: In the base-case analysis, in overall and PD-L1-positive advanced ESCC patients, the ICERs were $415,163.81/QALY and $216,628.00/QALY for nivolumab plus chemotherapy, and$430,704.11/QALY and $185,483.94/QALY for nivolumab plus ipilimumab, respectively, compared with chemotherapy. One-way sensitivity analyses revealed that patients' weight was the most influential parameter on ICER. The PSA demonstrated that the probability of nivolumab combination therapy being cost-effective was 0% over chemotherapy at the current price and willingness-to-pay threshold ($38,351.20/QALY). When the price of nivolumab and ipilimumab decreased 80%, the cost-effective probability of nivolumab plus ipilimumab increased to 40.44% and 86.38% in overall and PD-L1-positive advanced ESCC patients, respectively. Conclusion: Nivolumab combination therapy could improve survival time and health benefits over chemotherapy for advanced ESCC patients, but it is unlikely to be a cost-effective treatment option in China.

Biomaterials for Interbody Fusion in Bone Tissue Engineering.

In recent years, interbody fusion cages have played an important role in interbody fusion surgery for treating diseases like disc protrusion and spondylolisthesis. However, traditional cages cannot achieve satisfactory results due to their unreasonable design, poor material biocompatibility, and induced osteogenesis ability, limiting their application. There are currently 3 ways to improve the fusion effect, as follows. First, the interbody fusion cage is designed to facilitate bone ingrowth through the preliminary design. Second, choose interbody fusion cages made of different materials to meet the variable needs of interbody fusion. Finally, complete post-processing steps, such as coating the designed cage, to achieve a suitable osseointegration microstructure, and add other bioactive materials to achieve the most suitable biological microenvironment of bone tissue and improve the fusion effect. The focus of this review is on the design methods of interbody fusion cages, a comparison of the advantages and disadvantages of various materials, the influence of post-processing techniques and additional materials on interbody fusion, and the prospects for the future development of interbody fusion cages.

Smartphone assisted portable biochip for non-invasive simultaneous monitoring of glucose and insulin towards precise diagnosis of prediabetes/diabetes.

Diabetes is a chronic disease with metabolic disorders. Prediabetes is a condition in which the blood glucose levels are not high enough to be diagnosed as diabetes, but insulin resistance and ß-cell dysfunction are simultaneously present. Glucose and insulin are important biomarkers for diagnosing diabetes/prediabetes. It is critical and essential to monitor glucose and insulin levels to achieve the early and precise diagnosis, timely prevention and scientific management of diabetes/prediabetes. Here, an electrochemical aptasensor on screen-printed carbon electrode (SPCE) was developed for non-invasive simultaneous real-time detection of glucose and insulin in saliva. Two thiolated aptamers specific to glucose and insulin, respectively, were fabricated onto gold nanoparticles (AuNPs) decorated SPCE through Au-S bonds to form the sensing interface terminated with redox probes methylene blue (SPCE-AuNPs-GluApt-MB and SPCE-AuNPs-InsApt-MB). With the electrochemical signal readout on SPCE, the sensing interface responded to glucose linearly in the range of 0.1-50 mM with a detection limit of 0.08 mM, and responded linearly to insulin in the range of 0.05-15 nM with a detection limit of 0.85 nM. Integration of a SPCE based sensing interface with a portable wireless biochip, the continuous real-time detection of glucose and insulin in saliva was successfully realized with smartphone signal readout in a non-invasive way, demonstrating its potential as a non-invasive and reliable tool for precise diagnosis of diabetes/prediabetes in a point of care fashion.

Clinical outcomes of coblation-assisted pediatric endoscopic endonasal skull base surgery.

BACKGROUND: Pediatric skull base surgeries are confined by developmental and anatomical issues. Radiofrequency coblation integrates the functions of ablation, suction, and coagulation with the ability to dissolve tissues with limited thermal injury, making it an ideal instrument for pediatric skull base surgery. We sought to evaluated the clinical outcomes of coblation-assisted pediatric endoscopic skull base surgery. METHODS: Medical records of patients under 15 years of age undergoing endoscopic skull base surgery were retrospectively reviewed. The estimated blood loss (EBL)/operating time (OT) and Wormald grade were used for intraoperative blood loss grading. RESULTS: Generally, 28 patients (17 males, 11 females) with an average age of 8.4 ± 4.2 years, (range, 11 months to 15 years old) were included. Coblation was applied in 20 patients for mucosa coagulation and handling, cartilage removal, tumor separation and excision. The primary diagnoses included juvenile nasopharyngeal angiofibroma (n = 5), traumatic cerebrospinal fluid (CSF) leak (n = 6), congenital meningoencephalocele (n = 6) and miscellaneous sinonasal and skull base neoplasm (n = 11). The application of coblation was related with a significant decrease in EBL/OT (34.1 ± 17.5 vs 56.3 ± 22.6 ml/h, p = 0.048) and Wormald grade (5.7 ± 1.5 vs 6.9 ± 2.0, p = 0.038), compared with the traditional techniques. All surgical procedures were uneventful. No significant difference in postoperative complications, including cranial nerve dysfunction and CSF rhinorrhea were documented during the follow-up period (average, 34.7 ± 4.4 months). CONCLUSION: We suggested the coblation be a safe and effective instrument for pediatric skull base surgery.