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Background: Cardiometabolic Index (CMI) was associated with several risk factors for stroke; however, few studies assessed the role of CMI in stroke risk. Objective: This study aimed to assess the association between CMI and stroke in a population- based cross-sectional study. Methods: This study included 4445 general residents aged ≥40 years selected by multistage stratified random cluster sampling. CMI was calculated as the product of the ratio of waist circumference to height (WHtR) and the ratio of triglyceride levels to high-density lipoprotein cholesterol levels (TG/HDL-C). Participants were categorized according to CMI quartiles: quartile 1 (Q1), quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4). Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to assess the association between CMI and stroke. Results: A total of 4052 participants were included in the study, with an overall stroke prevalence of 7.2%. The prevalence of stroke increased with CMI quartiles, ranging from 4.4% to 9.2% (p for trend Conclusion: Although there was a strong and independent association between CMI and stroke in the general population, CMI had limited discriminating ability for stroke. Thus, new parameters should be developed.

Breast cancer is a kind of malignant tumor that occurs in breast tissue, which is the most common cancer in women. Cellular metabolism is a critical determinant of the viability and function of cancer cells in tumor microenvironment. In this study, based on the gene expression profile of metabolism-related genes, the prognostic value of 20 metabolic pathways in patients with breast cancer was identified. A universal risk stratification signature that relies on 20 metabolic pathways was established and validated in training cohort, two testing cohorts and The Cancer Genome Atlas pan cancer cohort. Then, the relationship between metabolic risk score subtype, prognosis, immune infiltration level, cancer genotypes and their impact on therapeutic benefit were characterized. Results demonstrated that the patients with the low metabolic risk score subtype displayed good prognosis, high level of immune infiltration and exhibited a favorable response to neoadjuvant chemotherapy and immunotherapy. Taken together, the work presented in this study may deepen the understanding of metabolic hallmarks of breast cancer, and may provide some valuable information for personalized therapies in patients with breast cancer.

Regressive changes in epithelial stem cells underlie mammalian skin aging, but the driving mechanisms are not well understood. Here, we report that mouse skin hair follicle stem cell (HFSC) aging is initiated by their intrinsic upregulation of miR-31, a microRNA that can be induced by physical injury or genotoxic stress and is also strongly upregulated in aged human skin epithelium. Using transgenic and conditional knockout mouse models plus a lineage-tracing technique, we show that miR-31 acts as a key driver of HFSC aging by directly targeting Clock, a core circadian clock gene whose deregulation activates a MAPK/ERK cascade to induce HFSC depletion via transepidermal elimination. Notably, blocking this pathway by either conditional miR-31 ablation or clinically approved MAPK/ERK inhibitors provides safe and effective protection against skin aging, enlightening a promising therapeutic avenue for treating skin aging and other genotoxic stress-induced skin conditions such as radiodermatitis. Changes in hair and skin can be the most obvious and earliest signs of aging. The authors report that skin and hair follicle stem cell (HFSC) aging is driven by stress-induced upregulation of miR-31, which targets Clock to activate MAPK/ERK and deplete HFSCs via transepidermal elimination. Blocking the pathway with MAPK/ERK inhibitors protects against skin aging.

The purpose of this study was to explore the correlations between patients’ opioid-taking self-efficacy, social support, and their pain management satisfaction, and to evaluate the effect of social support and opioid-taking self-efficacy in explaining the variance in pain management satisfaction. We used a cross-sectional and correlational research design and recruited 123 cancer patients via convenience sampling. We used the following instruments: the Opioid-Taking Self-Efficacy Scale, the Inventory of Socially Supportive Behavior, and the Chinese version of the Pain Treatment Satisfaction Scale. There were significant and negative correlations between opioid-taking self-efficacy and pain management satisfaction (r = − .43, p

Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery.This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 μg kgThe median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010).Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.

Backgrounds. The prevalence of diabetes has increased with the increase of obesity, and finding indicators to predict diabetes risk has become an urgent need. The purpose of this study is to compare the correlation between four anthropometric indices and the prevalence of diabetes. Methods. A total of 4052 participants aged 40 years and above were selected in Dehui City, Jilin Province, using a multistage stratified whole group sampling method. Face-to-face interviews and physical examinations were conducted. Multivariate logistic analysis was used. The values of BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were divided into quartiles (Q1: study participants ≥ 40 years of age, especially in females.

Introduction Withholding the malignant bone tumors disclosure from patients is common in China. The purpose of the study was to explore the perceptions of patients, families, doctors, and nurses regarding the disclosure of malignant bone tumors in China. Method Semistructured interviews were conducted with 25 cases, consisting of 69 participants (14 patients, 25 family members, 17 doctors, and 13 nurses), and the transcripts were analysed using Colaizzi’s (1978) descriptive phenomenological analysis process. Results Five themes were identified: (1) doctors preferred to inform the family members first, (2) family members’ decisions depended on different situations, (3) the patients agreed that disclosure should be different for each person/personally, (4) care from nurses reduced the overreaction of patients, and (5) key points improve the informing quality. Discussion Family participatory cancer disclosure and multidisciplinary teams could improve the quality of cancer disclosure. Culturally congruent health care and culturally sensitive interventions in cancer disclosure are suggested.

Objective The aim of this study was to determine the clinical outcomes and long-term stability of individualized titanium mesh combined with free flap for orbital floor reconstruction after maxillectomy and to identify the risk factors for titanium mesh exposure. Material and methods The data of 66 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2011 and 2019 were retrospectively reviewed. Postoperative ophthalmic function and success of aesthetic restoration were assessed. Titanium mesh exposure was recorded and the risk factors were identified. Results Mean follow-up was for 24.8 months (range, 6-92 months). Ophthalmic function was successfully restored in 63/66 patients. Aesthetic restoration was not considered satisfactory by 10 patients. Titanium mesh exposure occurred in six patients (exposure rate, 9.1%). Preoperative radiotherapy was identified as an independent risk factor for mesh exposure (OR = 28.8, P = 0.006). Previous surgery, postoperative radiotherapy, pathological type of the primary lesion, the type of tissue flap applied, and the use of intraoperative navigation were not significant risk factors. Six patients with titanium mesh exposure underwent second surgery, but mesh exposure recurred in two patients due to insufficient soft tissue coverage. Conclusion Individualized titanium mesh with free flap can effectively restore maxilla-orbital defects. Preoperative radiotherapy is an independent predictor of postoperative titanium mesh exposure. Adequate soft tissue coverage of the mesh may reduce the risk of mesh exposure. Level of evidence Level 4 (case-control study) Laryngoscope, 2021.

Pavement maintenance and rehabilitation (M&R) records are important as they provide documentation that M&R treatment is being performed and completed appropriately. Moreover, the development of pavement performance models relies heavily on the quality of the condition data collected and on the M&R records. However, the history of pavement M&R activities is often missing or unavailable to highway agencies for many reasons. Without accurate M&R records, it is difficult to determine if a condition change between two consecutive inspections is the result of M&R intervention, deterioration, or measurement errors. In this paper, we employed deep-learning networks of a convolutional neural network (CNN) model, a long short-term memory (LSTM) model, and a CNN-LSTM combination model to automatically detect if an M&R treatment was applied to a pavement section during a given time period. Unlike conventional analysis methods so far followed, deep-learning techniques do not require any feature extraction. The maximum accuracy obtained for test data is 87.5% using CNN-LSTM.

Background Chemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas (LGGs), but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors with TMZ-induced hypermutation. We aimed to determine the prevalence of TMZ-induced hypermutation at recurrence and prognostic implications. Methods We sequenced recurrent tumors from 82 patients with initially low-grade IDH-mutant gliomas who underwent reoperation and correlated hypermutation status with grade at recurrence and subsequent clinical outcomes. Results Hypermutation was associated with high-grade disease at the time of reoperation (OR 12.0 95% CI 2.5-115.5, P = .002) and was identified at transformation in 57% of recurrent LGGs previously exposed to TMZ. After anaplastic (grade III) transformation, hypermutation was associated with shorter survival on univariate and multivariate analysis (HR 3.4, 95% CI 1.2-9.9, P = .024), controlling for tumor grade, subtype, age, and prior radiotherapy. The effect of hypermutation on survival after transformation was validated in an independent, published dataset. Hypermutated (HM) tumors were more likely to develop discontiguous foci of disease in the brain and spine (P = .003). To estimate the overall incidence of high-grade transformation among low-grade IDH-mutant tumors, data from a phase II trial of TMZ for LGG were analyzed. Eight-year transformation-free survival was 53.8% (95% CI 42.8-69.2), and 61% of analyzed transformed cases were HM. Conclusions TMZ-induced hypermutation is a common event in transformed LGG previously treated with TMZ and is associated with worse prognosis and development of discontiguous disease after recurrence. These findings impact tumor classification at recurrence, prognostication, and clinical trial design.

Background We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT). Methods We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest. Results The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656–0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478–0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high‐risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p, This relatively large cohort reports a comparative result: pretreatment high neutrophil‐to‐lymphocyte ratio (NLR) was an independent unfavorable risk factor for both overall survival and distant metastasis in patients with oral cavity squamous cell carcinoma (OSCC) who underwent surgery and postoperative radiotherapy. Lymphocyte‐to‐monocyte ratio (LMR) and platelet‐to‐lymphocyte ratio (PLR) were not significant.

In the past two decades, three coronaviruses with ancestral origins in bats have emerged and caused widespread outbreaks in humans, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS epidemic in 2002–2003, the appreciation of bats as key hosts of zoonotic coronaviruses has advanced rapidly. More than 4,000 coronavirus sequences from 14 bat families have been identified, yet the true diversity of bat coronaviruses is probably much greater. Given that bats are the likely evolutionary source for several human coronaviruses, including strains that cause mild upper respiratory tract disease, their role in historic and future pandemics requires ongoing investigation. We review and integrate information on bat–coronavirus interactions at the molecular, tissue, host and population levels. We identify critical gaps in knowledge of bat coronaviruses, which relate to spillover and pandemic risk, including the pathways to zoonotic spillover, the infection dynamics within bat reservoir hosts, the role of prior adaptation in intermediate hosts for zoonotic transmission and the viral genotypes or traits that predict zoonotic capacity and pandemic potential. Filling these knowledge gaps may help prevent the next pandemic., Bats harbour a multitude of coronaviruses and owing to their diversity and wide distribution are prime reservoir hosts of emerging viruses. Ruiz-Aravena, McKee and colleagues analyse the currently available information on bat coronaviruses and discuss their role in recent and potential future spillovers.

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

Background Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs). Methods Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed. Results Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively. Conclusion In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.

BackgroundAlthough postoperative delirium is a frequent complication of surgery, little is known about risk factors for delirium occurring in the post-anaesthesia care unit (PACU). The aim of this study was to determine pre- and intraoperative risk factors for the development of recovery room delirium (RRD) in patients undergoing elective non-cardiovascular surgery.MethodsRRD was diagnosed according to the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). We collected perioperative data in 228 patients undergoing elective non-cardiovascular surgery under general anaesthesia and performed univariate and multivariate logistic regression to identify risk factors related to RRD. PACU and postoperative events were recorded to assess the outcome of RRD.ResultsFifty-seven patients (25%) developed RRD. On multivariate analysis, maintenance of anaesthesia with inhalation anaesthetic agents (OR = 6.294, 95% CI 1.4–28.8, corrected p= 0.03), malignant primary disease (OR = 3.464, 95% CI = 1.396–8.592, corrected p= 0.018), American Society of Anaesthesiologists Physical Status (ASA-PS) III–V (OR = 3.389, 95% CI = 1.401–8.201, corrected p= 0.018), elevated serum total or direct bilirubin (OR = 2.535, 95% CI = 1.006–6.388, corrected p= 0.049), and invasive surgery (OR = 2.431, 95% CI = 1.103–5.357, corrected p= 0.035) were identified as independent risk factors for RRD. RRD was associated with higher healthcare costs (31,428 yuan [17,872–43,674] versus 16,555 yuan [12,618–27,788], corrected p= 0.002), a longer median hospital stay (17 days [12–23.5] versus 11 days [9–17], corrected p= 0.002), and a longer postoperative stay (11 days [7–15] versus 7 days [5–10], corrected p= 0.002]).ConclusionsIdentifying patients at high odds for RRD preoperatively would enable the formation of more timely postoperative delirium management programmes.

Screening and therapeutic programs for colorectal cancer (CRC) are invasive or not effective and unable to meet patient needs. Major advances in immunogenomics may change this status but need more exploration. Differentially expressed genes and immune-related genes (IRGs) were identified by computational methods. A prognostic model was established and validated based on survival-related IRGs via stepwise multivariate Cox regression analysis. Nine IRGs were selected and identified as survival-related genes. A 7-gene prognostic model could offer a preliminary and valid determination of risk in CRC patients. The area under the curve of the receiver operating characteristic was 0.672. The 7-gene prognostic model might be used as a novel prognostic tool in CRC patients.

Background Shear wave elastography (SWE) directly quantifies the local arterial wall stiffness by calculating the elastic modulus. However, whether carotid wall elastic modulus can predict obstructive coronary artery disease (CAD) is not well known. We aimed to investigate the value of carotid wall elastic modulus measured using SWE in identifying obstructive CAD. Materials and methods We prospectively enrolled 61 patients without carotid plaque referred for clinically indicated coronary angiography. Twenty-seven (44.3%) patients were diagnosed with obstructive CAD (≥50% coronary stenosis). The elastic modulus of common carotid artery was quantified using SWE. Ankle--brachial index (ABI) and echocardiographic global cardiac calcium score (GCCS) were measured. Results Patients with obstructive CAD had significantly higher elastic modulus than those without obstructive CAD. The maximum elastic modulus (EMmax) was independently associated with obstructive CAD after adjusting for the Framingham risk score, ABI, and GCCS. EMmax had the highest area under the curve (AUC) to identify obstructive CAD (AUC 0.70; P = 0.003). In the nested models, the model based on the Framingham risk score and ABI (χ2 = 3.74) improved by adding GCCS (χ2 = 9.95) and further improved by adding EMmax (χ2 = 15.86). Adding EMmax to the combined ABI and GCCS model increased integrated discrimination index from 0.10 to 0.19. Conclusion Carotid wall elastic modulus measured using SWE is a useful predictor of obstructive CAD in patients without carotid plaque. We demonstrated the incremental and independent value of carotid wall elastic modulus in identifying obstructive CAD compared with clinical risk factors and other imaging predictors, including ABI and GCCS. Video abstract Please see the video, in Supplemental Digital Content 1, http://links.lww.com/HJH/B551 for more insights from the authors.

A nerve stimulation-guided lumbar plexus block is a well-established technique. It is not clear whether ultrasound guidance has additional value for this deep block technique. This study aimed to examine whether ultrasound guidance using a paramedian transverse scan through the intertransverse space (PMTS-ITS) approach in combination with nerve stimulation reduces the onset time of a complete sensory block. Forty-four patients who were scheduled to undergo arthroscopic knee surgery with an ultrasound visibility score (UVS) of ≥10 for the lumbar plexus were enrolled and randomly allocated to the ultrasound guidance with nerve stimulation group (group U-N) or nerve stimulation group (group N) in this prospective, randomized, parallel-group, active-controlled study. The primary outcome was the onset time of a complete sensory block. The results showed that the onset time of a complete sensory block to pinprick and cold was 10 (10-40) min and 10 (10-40) min in group U-N, respectively, and 30 (10-40) min and 20 (10-40) min in group N (P=0.005, P=0.004), respectively. The performance time was 658±87 s in group U-N and 528±97 s in group N (P 0.05). In conclusion, ultrasound guidance using the PMTS-ITS approach in combination with nerve stimulation led to a faster onset of a complete sensory block than nerve stimulation alone for a lumbar plexus block in patients with a UVS ≥10. Ultrasound guidance with nerve stimulation significantly decreased the number of patients who required 5 or more needle passes.

BACKGROUND AND PURPOSE The burden of cervical arterial atherosclerosis, which is an important risk factor of stroke, is huge in China. The visceral adiposity index (VAI) is a convenient index that is related to a series of metabolic abnormalities and a variety of diseases, including cerebrovascular diseases. This study aimed to explore the relationship between VAI and cervical arterial atherosclerosis. METHODS This cross-sectional study used the multistage stratified random cluster sampling method to acquire a representative sample of residents aged ≥40 in the general population of northeast China. All participants completed a detailed questionnaire and provided blood samples. Cervical vascular ultrasound was performed by experienced ultrasound doctors. VAI was calculated by a well-established formula and analyzed by quartiles (Q1-Q4). RESULTS A total of 3688 people aged ≥40 years who underwent cervical arterial ultrasound were finally included, amongst whom 3.2% had increased intima-media thickness (IMT), 48.6% had carotid plaque and 4.0% had cervical artery stenosis (CAS). After adjusting for several parameters, little statistical significance was found between VAI and increased IMT; compared with the VAI-Q1 group, the VAI-Q2, VAI-Q3 and VAI-Q4 groups were more likely to have CAS [odds ratio (OR) 2.01, 95% confidence interval (CI) 1.17-3.43; OR 1.82, 95% CI 1.05-3.15; OR 1.79, 95% CI 1.03-3.12] and the VAI-Q3 and VAI-Q4 groups were at greater risk of carotid plaque (OR 1.30, 95% CI 1.05-1.62; OR 1.34, 95% CI 1.07-1.67). CONCLUSIONS The VAI was related to carotid plaque and CAS in the general population that is older than 40 years.

Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2-6 microns (1~2 pixels) for healthy subjects and 3-10 microns (1~3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of “perfect segmentation” and “good segmentation” is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.

BackgroundWe sought to investigate the prognostic impact of missed RT sessions in patients who had undergone surgery for oral cavity squamous cell carcinoma (OCSCC).MethodsThe study sample consisted of 905 patients with surgically treated OCSCC who fulfilled criteria of RT course ≤8 weeks. The study participants were divided into three groups based on the characteristics of missed RT, as follows: 1) early missed RT, 2) late missed RT, and 3) RT as scheduled.ResultsThe 5-year overall survival (OS) rates in the early missed RT, late missed RT, and RT as scheduled groups were 53.0, 58.1, and 64.5%, respectively (p = 0.046). In multivariate analysis, early missed RT was independently associated with both OS (hazard ratio (HR) = 1.486; 95% confidence interval (CI): 1.122–1.966;p = 0.006) and the occurrence of distant metastasis (HR = 1.644; 95% CI: 1.047–2.583;p = 0.031).ConclusionEarly missed RT was independently associated with a higher occurrence of distant metastasis and less favorable OS in patients who had undergone surgery for OCSCC.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID‐19) pandemic, government‐mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in‐person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard‐of‐care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high‐volume cancer center at the domestic epicenter of the COVID‐19 crisis., Cancer care is undeniably affected by the coronavirus disease 2019 (COVID‐19) public health emergency, but quality cancer care must persist. A high‐volume cancer center from the domestic epicenter of the COVID‐19 crisis shares its multidisciplinary approach to integrating current public health restrictions and adopting telemedicine to optimize the care of patients with head and neck cancer; it is hoped that this center's experience will provide helpful insights to oncology colleagues.

Tumor necrosis factor-alpha (TNFα) is an inflammatory cytokine that regulates inflammation and tumor progression in non-small cell lung cancer (NSCLC). The higher levels of TNF α are known to induce expression of several genes such as TNFα-induced protein 2 (TNFAIP2) with a largely unknown role in NSCLC. We provide the preliminary evidence for the role of TNFAIP2 in NSCLC progression and its epigenetic regulation mediated by microRNA, miR-145-5p. The expression of TNFAIP2 was confirmed using quantitative real-time PCR, immunohistochemistry, and Western blot in NSCLC tissue and paired adjacent normal tissue. All in vitro assays were undertaken in A549 and H23 cells and chemoresistance assays were undertaken in A549/Cisplatin (DDP) and H23/DDP cell types. TNFAIP2 silencing was undertaken using lipofectamine transfection of specific siRNA. Cells were co-transfected with miR-145-5p, and TNFAIP2-3' untranslated region (UTR) or TNFAIP2 with mutated 3'UTR using the luciferase vector pGL. Cell viability, transwell migration, and invasion were assessed. The role of caspase 3 proteins in cell viability was ascertained using Western blot. The tumor tissues (and cisplatin-resistant cell lines A549/DDP and H23/DDP) expressed significantly higher levels of TNAIP2 mRNA and protein. Silencing of TNFAIP2 resulted in reduced cell viability, reduced invasion, and migration in vitro. Silencing of TNFAIP2 in A549/DDP and H23/DDP had higher expression of TNFAIP2, reduced cell viability, and increased induction of caspase 3. MiR-145-5p binds to the 3'UTR of TNFAIP2. Overexpression of MiR-145-5p reduced expression of TNFAIP2, decreased cell viability, reduced cell migration and invasion, and significantly reduced expression of caspase 3 protein. TNFAIP2 mediates tumorigenesis in NSCLC through, not completely known pathways. miR-145-5p negatively regulates TNFAIP2 expression. miR-145-5p-mediated therapies may be explored in NSCLC.

Background Glioma is a common malignant tumor worldwide. Sevoflurane (Sev) has been reported to inhibit the metastasis of glioma cells, but the underlying molecular mechanism needs further exploration. Methods Cell Counting Kit-8 (CCK8) assay was used to check cell viability. Flow cytometry assay was hired to check cell apoptosis. The protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), hexokinase 2 (HK2) and magnesium transporter 1 (MAGT1) in samples were measured by Western blot. The abilities of cell migration and invasion were estimated by transwell assay. Glucose colorimetric assay kit and lactate colorimetric assay kit were used to check glucose consumption and lactate production, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circular RNA (circRNA) circ_0002755 (also known as the circRNA1656) and microRNA (miR)-628-5p in samples. The interaction between miR-628-5p and circ_0002755 or MAGT1 was predicated by starBase, which was verified by the dual-luciferase reporter assay. Xenograft tumor model was established to explore the biological role of circ_0002755 in vivo. Results Sev inhibited cell viability, migration, invasion and promoted cell apoptosis, and also reduced glucose consumption and lactate production. Circ_0002755 was significantly upregulated in glioma tissues and cells, while its level was notably declined under Sev treatment. Besides, overexpression of circ_0002755 overturned Sev-mediated inhibitory effect on glioma progression. Further research indicated that circ_0002755 targeted miR-628-5p, and miR-628-5p targeted MAGT1, and Sev modulated glioma progression via circ_0002755/miR-628-5p/MAGT1 axis. Moreover, Sev hindered tumor growth in vivo. Conclusion Sev mediated glioma progression via circ_0002755/miR-628-5p/MAGT1 axis.

Background & Aims Glecaprevir/pibrentasvir is approved for treating adults infected with HCV genotypes 1–6. In clinical trials, glecaprevir/pibrentasvir was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. A systematic review and meta-analysis of the real-world effectiveness and safety of glecaprevir/pibrentasvir were undertaken. Methods Real-world studies reporting SVR12 in adults with HCV infection (n ≥20) treated with glecaprevir/pibrentasvir were identified in journal publications from January 1, 2017, to February 25, 2019, and congress presentations through April 14, 2019. Random-effects meta-analysis was used to determine SVR12 rates using data from ≥2 cohorts; intention-to-treat (ITT) analyses included patients treated with glecaprevir/pibrentasvir who had SVR12 data available, discontinued early, or were lost to follow-up; modified ITT (mITT) analyses excluded those with non-virologic failure. Naive pooling was used to calculate adverse event (AE) rates. Results Overall, 12,531 adults were treated with glecaprevir/pibrentasvir (18 cohorts). Of patients with post-treatment week 12 data, SVR12 rates were 96.7% (95% CI 95.4–98.1) in the ITT population (n = 8,583, 15 cohorts) and 98.1% (95% CI 97.1–99.2) in the mITT population (n = 7,001, 14 cohorts). SVR12 rates were ≥95% across subgroups (HCV genotype, cirrhosis status, treatment history, treatment duration, on-label treatment, and subgroups of interest). AEs were reported in 17.7% (1,271/7,199) of patients (8 cohorts). Serious AEs were reported in 1.0% (55/5,522) of patients (6 cohorts). The most frequent AEs were pruritus, fatigue, and headache. AE-related treatment discontinuations were reported in 0.6% (33/5,595) of patients (6 cohorts). Conclusions Consistent with clinical trials, real-world evidence indicates that glecaprevir/pibrentasvir is a well-tolerated and highly effective pangenotypic treatment for a broad range of HCV-infected patients. Lay summary It is important to assess treatments for hepatitis C virus (HCV) in the real world, as patient populations tend to be more diverse and potentially less adherent to treatment compared to those in clinical trials. Results from 18 studies performed in real-world clinics were pooled and analyzed to investigate the effectiveness and safety of a direct-acting antiviral combination (glecaprevir/pibrentasvir) in routine clinical practice. This analysis showed that glecaprevir/pibrentasvir is highly effective and well tolerated across all HCV genotypes and patient groups studied. It also showed that results seen in the real world are similar to the results seen in clinical trials, even in patients historically considered more challenging to treat.

PurposeThe contribution of rare genetic variation in the development of soft-tissue sarcoma (STS) remains underexplored. To address this gap, we conducted a whole-exome case-control and somatic-germline interaction study to identify and characterise STS susceptible genes.MethodsThe study involved 219 STS cases from The Cancer Genome Atlas and 3507 controls. All cases and controls were matched genetically onEuropean ancestry based on the 1000 Genomes project. Cross-platform technological stratification was performed with XPAT and gene-based association tests with VAAST 2.ResultsNF1 exhibited the strongest genome-wide signal across the six subtypes, with p=1×10−5. We also observed nominally significant association signals for three additional genes of interest, TP53 (p=0.0025), RB1 (p=0.0281), and MSH2 (p=0.0085). BAG1, which has not previously been implicated in STS, exhibited the strongest genome-wide signal after NF1, with p=6×10−5. The association signals for NF1 and MSH2 were driven primarily by truncating variants, with ORs of 39 (95% CI: 7.1 to 220) for NF1 and 33 (95% CI: 2.4 to 460) for MSH2. In contrast, the association signals for RB1 and BAG1 were driven primarily by predicted damaging missense variants, with estimated ORs of 12 (95% CI: 2.4 to 59) for RB1 and 20 (95% CI: 1.4 to 300) for BAG1.ConclusionsOur results confirm that pathogenic variants in NF1, RB1 and TP53 confer large increases in the risk of developing multiple STS subtypes, provide support for the role of MSH2 in STS susceptibility and identify BAG1 as a novel candidate STS risk gene.

Purpose To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. Materials and Methods Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with Results Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2–69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. Conclusion The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

Purpose Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats. Methods We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy. Results Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin. Conclusion Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.