Summary Background MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. Methods ...We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival. Findings 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio HR 2·73, 95% CI 1·46–5·11; p=0·0019), DMFS (3·48, 1·57–7·75; p=0·0020), and overall survival (2·48, 1·24–4·96; p=0·010). We noted equivalent findings in the internal validation set for DFS (2·47, 1·32–4·61; p=0·0052), DMFS (2·28, 1·09–4·80; p=0·030), and overall survival (2·87, 1·38–5·96; p=0·0051) and in the independent set for DFS (3·16, 1·65–6·04; p=0·0011), DMFS (2·39, 1·05–5·42; p=0·037), and overall survival (3·07, 1·34–7·01; p=0·0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0·68 95% CI 0·60–0·76 vs 0·60 0·52–0·67; p=0·013), the internal validation set (0·70 0·61–0·78 vs 0·61 0·54–0·68; p=0·012), and the independent set (0·70 0·62–0·78 vs 0·63 0·56–0·69; p=0·032). Interpretation Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression. Funding Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities.
Summary Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is ...unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III–IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18–59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov , number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38–49), 3-year failure-free survival was 80% (95% CI 75–85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66–78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48–0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 42% vs 17 7%), leucopenia (98 41% vs 41 17%), and stomatitis (98 41% vs 84 35%). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. Funding Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).
Summary Background The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the ...contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. Methods We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3–4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m2 cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0–2·27 Gy per fraction with five daily fractions per week for 6–7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60–66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m2 adjuvant cisplatin and 800 mg/m2 per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov , number NCT00677118. Findings 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3–61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81–90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78–88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49–1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 21% of 205 patients treated with adjuvant chemotherapy). Interpretation Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. Funding Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010–178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).
Objective To assess the effect of a weight-loss program on improving iron status in overweight and obese school-aged children. Study design The data were analyzed in overweight and obese children ...(7-11 years of age; 114 girls and 212 boys) with body mass index-for-age z-scores (BAZ) >1 from a weight-loss program. Schools were randomly divided into 2 groups: intervention and control. Children in the intervention group underwent a 1-year, nutrition-based comprehensive intervention weight-loss program. Anthropometric, dietary intake, and physical activity data were collected at baseline and follow-up (1 year). Iron status and inflammatory markers were assessed within a month. Results In the intervention group, BAZ decreased more than that in the control group (−0.4 ± 0.7 vs −0.1 ± 0.6, P < .0001); and iron profiles and inflammation status were improved at follow-up. In multivariable linear regression models, a greater decrease of BAZ and inflammation factors predicted a better improvement of iron status. After adjustment of ΔBAZ, ΔC-reactive protein was significantly associated with Δserum ferritin (β: 1.89; 95% CI, 0.70-3.09; P = .002) and Δsoluble transferrin receptor (β: 0.88; 95% CI, 0.16-0.59; P = .017); Δinterleukin-6 was significantly associated with Δserum ferritin (β: 1.22; 95% CI, 0.64-1.79; P < .0001). Conclusions Iron status and inflammation were improved by weight reduction. The improvement in inflammatory markers during weight reduction was independently associated with improvements of iron status.
Background Although the early use of a risk stratification score in upper GI bleeding is recommended, existing risk scores are not widely used in clinical practice. Objective We sought to develop and ...validate an easily calculated bedside risk score, AIMS65, by using data routinely available at initial evaluation. Design Data from patients admitted from the emergency department with acute upper GI bleeding were extracted from a database containing information from 187 U.S. hospitals. Recursive partitioning was applied to derive a risk score for in-hospital mortality by using data from 2004 to 2005 in 29,222 patients. The score was validated by using data from 2006 to 2007 in 32,504 patients. Accuracy to predict mortality was assessed by the area under the receiver operating characteristic (AUROC) curve. Main Outcome Measurements Mortality, length of stay (LOS), and cost of admission. Results The 5 factors present at admission with the best discrimination were albumin less than 3.0 g/dL, international normalized ratio greater than 1.5, altered mental status, systolic blood pressure 90 mm Hg or lower, and age older than 65 years. For those with no risk factors, the mortality rate was 0.3% compared with 31.8% in patients with all 5 ( P < .001). The model had a high predictive accuracy (AUROC = 0.80; 95% CI, 0.78-0.81), which was confirmed in the validation cohort (AUROC = 0.77, 95% CI, 0.75-0.79). Longer LOS and increased costs were seen with higher scores ( P < .001). Limitations Database data used does not include outcomes such as rebleeding. Conclusions AIMS65 is a simple, accurate risk score that predicts in-hospital mortality, LOS, and cost in patients with acute upper GI bleeding.
Background Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood. Objective Address ...the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation. Methods IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcεRI. Results IgG autoantibodies binding to both free and FcεRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen. Conclusion Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma.
Abstract Purpose We undertook a randomized controlled trial to assess the efficacy of group-based behavioral activation with mindfulness (BAM) for treating subthreshold depression in primary care in ...Hong Kong. Methods We recruited adult patients aged 18 years or older with subthreshold depression from public primary care clinics and randomly assigned them to a BAM intervention group or a usual care group. The BAM group was provided with eight 2-hour weekly BAM sessions by trained allied health care workers. Patients in the usual care group received usual medical care with no additional psychological interventions. The primary outcome was depressive symptoms measured by the Beck Depression Inventory-II at 12 months. Secondary outcomes included incidence of major depressive disorder at 12 months. We assessed quality of life, activity and circumstances change, functional impairment, and anxiety at baseline, end of intervention, 5 months, and 12 months. Results We randomly allocated 115 patients to the BAM intervention and 116 patients to usual care. At 12 months, compared with usual care peers, BAM patients had a slightly more favorable change in levels of depressive symptoms on the Beck Depression Inventory-II (between-group mean difference in score = −3.85; 95% CI, −6.36 to −1.34; Cohen d = −0.46, 95% CI, −0.76 to −0.16). Incidence of major depressive disorder was lower with BAM (10.8% vs 26.8%, P = .01), whereas groups did not differ significantly on other secondary outcomes at 12 months. Conclusions Group BAM appears to be efficacious for decreasing depressive symptoms and reducing the incidence of major depression among patients with subthreshold depression in primary care, although generalizability of our findings may be limited.
Objective To explore the role of estrogen receptor-α36 (ER-α36) in epidermal growth factor receptor (EGFR)-related carcinogenesis in endometrial cancer. Study Design The expression of ER-α36, EGFR, ...and phospho-extracellular signal-regulated kinase was analyzed using immunohistochemistry in endometrial cancer samples. The cellular localization of ER-α36 and EGFR was determined using immunofluorescence in the endometrial cancer Hec1A cells. The level of phospho-extracellular signal-regulated kinase of Hec1A cells was determined using Western blotting after treatment with epidermal growth factor. Results Positive rate of ER-α36 was increased in high-stage ( P = .03) and high-grade ( P = .224) endometrial cancer; expression of ER-α36 and EGFR exhibited a significant positive correlation (r = 0.334, P = .025) and they showed substantial colocalization on the plasma membrane of glandular cells; phospho-extracellular signal-regulated kinase positive rate in ER-α36 positive group and EGFR positive group was higher than that of ER-α36 negative group ( P = .014) and EGFR negative group ( P = .016); finally, ER-α36 mediated epidermal growth factor-stimulated extracellular signal-regulated kinase activation in Hec1A cells. Conclusion ER-α36 mediates EGFR-related extracellular signal-regulated kinase activation in endometrial cancer.
This cross-sectional survey assessed both risk and prevention of health care workers to bloodborne virus transmission in 2 hospitals in Beijing. The identified discrepancy between the high level of ...occupational blood exposure and suboptimal compliance with standard precautions underscores the urgent need for interventions to enhance occupational safety of health care workers in China.
Objective: We assessed the efficacy and safety of transarterial chemoembolization (TACE) in combination with lenvatinib plus programmed death receptor-1 (PD-1) signaling inhibitors (camrelizumab or ...sintilimab) in unresectable hepatocellular carcinoma (uHCC). Methods: In this retrospective study, patients with uHCC were pretreated with lenvatinib for 1 to 2 weeks before TACE. Camrelizumab or sintilimab were initially administered intravenously in 1 week after TACE of a 21-day cycle. Primary objectives were objective response rate (ORR) and disease control rate (DCR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST). The secondary endpoints included the progression-free survival (PFS), overall survival (OS), and toxicity. Results: Between March 5, 2019 and February 30, 2021, 53 patients were screened for eligibility. At data cutoff, 35.8% of patients remained on treatment. Median follow-up was 15.4 months. Confirmed ORR in the 51 evaluable patients was 54.9% (95% CI 41.4%-67.7%). DCR was 84.3% (95% CI 72.0%-91.8%). Median PFS was 8.5 months (95% CI 6.4 to 10.6 months). The median OS was not estimable. Grade ≥3 treatment-related adverse events occurred in 32.1% of patients. No new safety signals were identified. Conclusion: TACE in combination with lenvatinib plus anti-PD-1 inhibitors may have promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.
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