Time-varying association of second primary malignancy and long-term survival outcomes in patients with head and neck cancer

A high risk of developing second primary malignancy (SPM) has been reported among head and neck cancer patients. Here, we aimed to statistically quantify the impact of SPM development on the survival of head and neck cancer patients. Our study was conducted using the Surveillance, Epidemiology and End Results database to collect the data of 48 316 patients who received curative surgical resection for initial primary head and neck squamous cell carcinoma (IP-HNSCC) in 1975 to 2019. SPM diagnosis was treated as a time-varying covariate and multivariable Cox regression analysis was conducted to estimate the association between SPM development and survival, overall or by the subsite of IP-HNSCC. Of the included patients, 11 238 patients (23.3%) developed SPM during the follow-up period. A significant reduction in survival was observed among patients with SPM (hazard ratio [HR] for overall survival, 3.30; 95% confidence interval [CI]: 3.20-3.41). The impact of SPM development on reduced survival was more significant in patients with localized IP-HNSCC vs regional IP-HNSCC (HR_OS, 3.41; 95% CI: 3.24-3.6 vs HR_OS, 3.18; 95% CI: 3.05-3.31; P for interaction <.001). The survival impact of SPM development was more evident in younger patients than in older patients. SPM in lung and bronchus was associated with the most pronounced reduction in survival, overall and across all subsites of HNSCC. Our results indicated that SPM development led to a significant reduction in survival. A greater survival benefit may be achieved through intensive surveillance for SPM in lung and bronchus targeting younger patients and those with localized HNSCC.     

原发性闭角型青光眼合并视网膜色素变性的临床特征分析

目的 分析原发性闭角型青光眼合并视网膜色素变性患者的临床特征。 方法 本研究纳入2013年4月至2017年4月于首都医科大学附属北京同仁医院眼科中心住院治疗的原发性闭角型青光眼(primary angle closure glaucoma ,PACG)合并视网膜色素变性(retinitis pigmentosa,RP)患者32例,和同期入院的不合并RP的PACG患者229例。根据青光眼类型将其分为4组,急性闭角型青光眼合并RP组(acute angle closure glaucoma with retinitis pigmentosa, AACG-RP)12例、慢性闭角型青光眼合并RP组(chronic angle closure glaucoma with retinitis pigmentosa, CACG-RP)20例、急性闭角型青光眼不合并RP组(AACG-non RP)94例、慢性闭角型青光眼不合并RP组(CACG-non RP)135例,比较4组患者的发病年龄和眼轴长度等参数。 结果 患者平均发病年龄AACG-RP组(39.00±12.07)岁、CACG-RP组(43.85±12.79)岁、AACG-non RP组(66.44±9.40)岁、CACG-non RP组(63.95±10.42)岁,4组之间差异有统计学意义(F=47.70,P<0.05)。患者平均眼轴长度AACG-RP组(21.31±1.37)mm、CACG-RP组(22.33±1.09)mm、AACG-non RP组(22.31±1.03)mm、CACG-non RP组(22.47±1.01)mm,4组之间差异有统计学意义(F=19.09,P<0.05)。 结论 原发性闭角型青光眼患者合并视网膜色素变性患者中,急性闭角型青光眼患者较慢性闭角型青光眼患者发病更早,眼轴更短。原发性闭角型青光眼合并视网膜色素变性患者,尤其是急性闭角型青光眼合并视网膜色素变性患者较无视网膜色素变性者发病年龄更早,且眼轴更短。     

Tumor Mutation Burden,Immune Cell Infiltration,and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors.Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model.Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis.Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635.Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.     

Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM.Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1, rs35767 in IGF1, and rs4376068, rs4402960, and rs6769511 in IGF2BP2) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population.Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346).Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.     

Influence Factors and Prediction Model of Bond Strength of Tunnel Fireproof Coating under Freeze–Thaw Cycles

The freeze–thaw resistant performance of a tunnel fireproof coating (TFC) has an important impact on bonding property and durability. The influence of redispersible emulsion powder, polypropylene fiber and air-entraining agent on TFCs was studied. Transverse fundamental frequency and ultrasonic sound velocity were used to evaluate the damage degree of TFC, and the mechanism was revealed by SEM and pore structure. The results show that the most beneficial effect on bond strength of TFC is redispersible emulsion powder, followed by air-entraining agent, and then polypropylene fiber. After freeze–thaw cycles, the cumulative pore volume of micropores in the TFC increases obviously, while the porosity of macropores does not change significantly. A prediction model was proposed, which can calculate the bond strength from the damage degree of TFC under freeze–thaw cycles. The achievement can promote the application of TFC in cold regions.     

Radiomics signature as a new biomarker for preoperative prediction of neoadjuvant chemoradiotherapy response in locally advanced rectal cancer

PURPOSEWhether radiomics methods are useful in prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) is unclear. This study aimed to investigate multiple magnetic resonance imaging (MRI) sequence-based radiomics methods in evaluating therapeutic response to nCRT in patients with locally advanced rectal cancer (LARC).METHODSThis retrospective study enrolled patients with LARC (06/2014–08/2017) and divided them into nCRT-sensitive and nCRT-resistant groups according to postoperative tumor regression grading results. Radiomics features from preoperative MRI were extracted, followed by dimension reduction using the minimum redundancy maximum relevance filter. Three machine-learning classifiers and an ensemble classifier were used for therapeutic response prediction. Radiomics nomogram incorporating clinical parameters were constructed using logistic regression. The receiver operating characteristic (ROC), decision curves analysis (DCA) and calibration curves were also plotted to evaluate the prediction performance.RESULTSThe machine learning classifiers showed good prediction performance for therapeutic responses in LARC patients (n=189). The ROC curve showed satisfying performance (area under the curve [AUC], 0.830; specificity, 0.794; sensitivity, 0.815) in the validation group. The radiomics signature included 30 imaging features derived from axial T1-weighted imaging with contrast and sagittal T2-weighted imaging and exhibited good predictive power for nCRT. A radiomics nomogram integrating carcinoembryonic antigen levels and tumor diameter showed excellent performance with an AUC of 0.949 (95% confidence interval, 0.892–0.997; specificity, 0.909; sensitivity, 0.879) in the validation group. DCA confirmed the clinical usefulness of the nomogram model.CONCLUSIONThe radiomics method using multiple MRI sequences can be used to achieve individualized prediction of nCRT in patients with LARC before treatment.

Colorectal cancer is one of the most common malignancies. It ranks fourth for morbidity and third for mortality among malignant tumors, among which the proportion of rectal cancer with poor prognosis is over 60% (1, 2). Neoadjuvant therapy, combined with total mesorectal excision, has become a common strategy for rectal cancer (3). Response to neoadjuvant chemoradiotherapy (nCRT) is a marker of good prognosis in patients with locally advanced rectal cancer (LARC) (4). Tumor regression grading (TRG) is a reliable biomarker for evaluating the efficacy of nCRT (5, 6). TRG reflects the treatment effect of nCRT by evaluating fibrosis and the ratio of residual tumor cells (4). The accurate nCRT evaluation can only be achieved by postoperative histopathological TRG (3, 4), and there is still no technology that can noninvasively evaluate the therapeutic response.Magnetic resonance imaging (MRI) is commonly used in the diagnosis, preoperative staging, and therapeutic efficacy evaluation of rectal cancer. Prediction of the efficacy of nCRT by MRI has been rarely reported, partly due to the heterogeneity of the tumor combined with the prevalence of fibrosis and edema of lesions and surrounding tissue after nCRT. Over the recent years, a magnetic resonance TRG system was proposed for the evaluation of nCRT efficacy by using MRI and evaluating residual tumor and fibrosis. Nevertheless, the magnetic resonance TRG method has a low predictive value for pathological TRG and poor consistency, which hinders its clinical applications (7, 8).In recent years, radiomics has drawn increasing attention in oncology. Radiomics features selected from medical images have shown to be highly associated with the diagnosis and prognosis of cancers, and even with gene expression patterns (9). Studies highlighted the value of radiomics approaches in determining tumor status, preoperative staging, and efficacy evaluation (9, 10). Nevertheless, the application of the radiomics methods in evaluating therapeutic responses to nCRT is limited (11).Accordingly, the aim of the present study was to establish an nCRT prediction model based on multiple MRI sequences combined with tumor anatomy and biological characteristics so as to achieve a comprehensive preliminary prediction of nCRT efficacy for rectal cancer before treatment, to provide an essential basis for the rational formulation of clinical diagnosis and treatment decisions, and to avoid unnecessary exposure to radiotherapy and chemotherapy and the related risks such as toxicity and delayed definitive surgery.     

Optimize the management of urological tube-related emergencies during the coronavirus disease 2019 (COVID-19) pandemic

BackgroundTo introduce and determine the value of optimized strategies for the management of urological tube-related emergencies with increased incidence, complexity and operational risk during the global spread of coronavirus disease 2019 (COVID-19).MethodsAll emergent urological patients at Tongji Hospital, Wuhan, during the period of January 23 (the beginning of lockdown in Wuhan) to March 23, 2020, and the corresponding period in 2019 were recruited to form this study’s COVID-19 group and control group, respectively. Tongji Hospital has the most concentrated and strongest Chinese medical teams to treat the largest number of severe COVID-19 patients. Patients in the control group were routinely treated, while patients in the COVID-19 group were managed following the optimized principles and strategies. The case incidence for each type of tube-related emergency was recorded. Baseline characteristics and management outcomes (surgery time, secondary complex operation rate, readmission rate, COVID-19 infection rate) were analyzed and compared across the control and COVID-19 periods.ResultsThe total emergent urological patients during the COVID-19 period was 42, whereas during the control period, it was 124. The incidence of tube-related emergencies increased from 53% to 88% (P<0.001) during the COVID-19 period. In particular, the incidence of nephrostomy tube-related (31% vs. 15%, P=0.027) and single-J stent-related problems (19% vs. 6%, P=0.009) increased significantly. The mean surgery times across the two periods were comparable. The number of secondary complex operations increased from 12 (18%) to 14 (38%) (P=0.028) during the COVID 19-period. The number of 2-week postoperative readmission decreased from 10 (15%) to 1 (3%) (P=0.049). No participants contracted during the COVID-19 period.ConclusionsUrological tube-related emergencies have been found to have a higher incidence and require more complicated and dangerous operations during the COVID-19 pandemic. However, the optimized management strategies introduced in this study are efficient, and safe for both urologists and patients.