Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Immediate impact of Mindfulness-Based Cognitive Therapy (MBCT) among women with breast cancer: a systematic review and meta-analysis.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) may have positive physiological and psychological benefits for breast cancer survivors. However, few studies involved a combination of the relevant literatures to confirm the effects. METHODS: Our study included randomized controlled trials (RCTs) and non-RCTs comparing interventions of MBCT and control protocols for alleviation of symptoms among breast cancer survivors. We calculated pooled mean differences (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) by using random effects models to estimate summary effect sizes. RESULTS: Thirteen trials with 20-245 participants were considered in our studies; for the meta-analysis, 11 of these studies were eligible for assessment. The pooled meta-analysis results revealed that at the end of the MBCT intervention, participants' anxiety (SMD, - 0.70; 95% CI, - 1.26 to - 0.13; I2 = 69%), pain (SMD, - 0.64; 95% CI, - 0.92 to - 0.37; I2 = 0%), and depression (SMD, - 0.65; 95% CI, - 1.14 to - 0.17; I2 = 75%) levels significantly decreased, and their mindfulness (MD, 8.83; 95% CI, 3.88 to 13.78; I2 = 68%) levels significantly increased. CONCLUSION: The MBCT may be associated with improved pain, anxiety, depression, and mindfulness. However, the quantitative analysis pointed to an inconclusive result due to moderate to high levels of heterogeneity among indicator of anxiety, depression, and mindfulness. Future work requires more studies to better elucidate the clinical significance of this possible association. The results suggest that MBCT is highly beneficial as an intervention for patients who have received treatment for breast cancer.

The Experience of Mindfulness-Based Stress Reduction on Menopausal Symptoms, Sleep Disturbance, and Body Image among Patients with Breast Cancer-A Qualitative Study.

BACKGROUND AND AIM: The objective was to decrease patient menopausal symptoms, sleep disturbance, and body image using a nonpharmacological therapy for cultivating key healthy lifestyle habits in patients with breast cancer. MATERIALS AND METHODS: The participants were 26 women with breast cancer who had recently received structured mindfulness-based stress reduction (MBSR) training in a clinical trial. Focus groups and interviews were conducted, during which the participants were asked semistructured, open-ended questions regarding the experiences of MBSR. RESULTS: The participants indicated that MBSR helped them to alleviate hot flashes and night sweats, and improve sleep quality and be more at ease with the external aspect of their body. On the other hand, during MBSR intervention in a group manner, the participants felt more psychological support and an outlet for sharing negative emotional experiences. CONCLUSION: This study identified the short-term benefits associated with group-based MBSR for women with breast cancer. In addition, our research identified the difficulties of intervention measures and coping methods. The study described the benefits of MBSR for patients with breast cancer. The findings of this study will help nursing staff identify the main coping menopausal symptoms and control negative mental health.

Impact of mindfulness-based stress reduction on female sexual function and mental health in patients with breast cancer.

PURPOSE: There have been few studies using mindfulness-based stress reduction (MBSR) to improve sexual function in Asian women with breast cancer. This study aimed to evaluate the impact of mindfulness intervention on female sexual function, mental health, and quality of life in patients with breast cancer. METHODS: Fifty-one women with breast cancer were allocated into 6-week MBSR (n=26) sessions or usual care (n=25), without differences in group characteristics. The research tools included the Female Sexual Function Index (FSFI), the Depression Anxiety Stress Scales-21 (DASS-21), and the EuroQol instrument (EQ-5D). The Greene Climacteric Scale (GCS) was used to verify the foregoing scale. The effects of MBSR were evaluated by the differences between the post- and pre-intervention scores in each scale. Statistical analyses consisted of the descriptive dataset and Mann-Whitney ranked-pairs test. RESULTS: Although MBSR did not significantly improve sexual desire and depression in patients with breast cancer, MBSR could improve parts of female sexual function [i.e., Δarousal: 5.73 vs. -5.96, Δlubrication: 3.35 vs. -3.48, and Δsatisfaction: 8.48 vs. 1.76; all p <.005], with a range from small to medium effect sizes. A significantly benefits were found on mental health [Δanxiety: -10.92 vs.11.36 and Δstress: -10.96 vs.11.40; both p <.001], with large effect sizes, ranging from 0.75 to 0.87. CONCLUSION: Our study revealed that MBSR can improve female sexual function and mental health except for sexual desire and depression in women with breast cancer. Medical staff can incorporate MBSR into clinical health education for patients with breast cancer to promote their overall quality of life.

KRAS G12C mutations in Asia: a landscape analysis of 11,951 Chinese tumor samples.

BACKGROUND: Kirsten rat sarcoma vial oncogene (KRAS) is one of the most prevalent oncogenes in multiple cancer types, but the incidence is different between the Asian and non-Asian populations. The recent development of KRAS G12C targeting drug has shown great promise. It is thus important to understand the genomic landscape of KRAS G12C in a specific population. METHODS: Sequencing data of 11,951 tumor samples collected from 11/2016 to 7/2019 from multiple centres in China were analyzed for KRAS mutation status. Concomitant genomic aberrations were further analyzed in tumors with KRAS G12C mutations, which were sequenced with comprehensive cancer panel including over 450 cancer-related genes. Smoking status and its correlation with KRAS were analyzed in 2,235 lung cancer cases within this cohort. RESULTS: KRAS mutations were identified in 1978 (16.6%) patient samples. Specifically, KRAS G12C accounted for 14.5% (n=286) of all KRAS mutations. G12C was most commonly seen in lung cancer (4.3%), followed by colorectal cancer (2.5%) and biliary cancer (2.3%). Almost all patients (99.6%) with G12C mutations had concomitant genomic aberrations. These were most commonly associated with the RAS/RTK pathway including BRAF and PI3KCA mutations. Moreover, KRAS mutation was positively correlated with smoking status in lung adenocarcinomas. CONCLUSIONS: The overall incidence of KRAS G12C mutations remains low in the Chinese population. The most common tumor types harboring KRAS G12C mutations are in patients suffering from lung, colorectal and biliary cancers.

Effects of Combined Far-Infrared Radiation and Acupuncture at ST36 on Peripheral Blood Perfusion and Autonomic Activities.

Using four-channel photoplethysmography (PPG) for acquiring peripheral arterial waveforms, this study investigated vascular and autonomic impacts of combined acupuncture-far infrared radiation (FIR) in improving peripheral circulation. Twenty healthy young adults aged 25.5 ± 4.6 were enrolled for 30-minute measurement. Each subject underwent four treatment strategies, including acupuncture at ST36 (Zusanli), pseudoacupuncture, FIR, and combined acupuncture-FIR at different time points. Response was assessed at 5-minute intervals. Area under arterial waveform at baseline was defined as AreaBaseline, whereas AreaStim referred to area at each 5-minute substage during and after treatment. AreaStim/AreaBaseline was compared at different stages and among different strategies. Autonomic activity at different stages was assessed using low-to-high frequency power ratio (LHR). The results demonstrated increased perfusion for each therapeutic strategy from stage 1 to stage 2 (all p < 0.02). Elevated perfusion was noted for all treatment strategies at stage 3 compared to stage 1 except pseudoacupuncture. Increased LHR was noted only in subjects undergoing pseudoacupuncture at stage 3 compared to stage 1 (p = 0.045). Reduced LHR at stage 2 compared to stage 1 was found only in combined treatment group (p = 0.041). In conclusion, the results support clinical benefits of combined acupuncture-FIR treatment in enhancing peripheral perfusion and parasympathetic activity.

Therapeutic modification of arterial stiffness: An update and comprehensive review.

Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids (fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as renin-angiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision.

An analysis on the direct economic loss and its influencing factors of pneumoconiosis in Zhejiang province / 预防医学

Objective To explore the characteristics and their influencing factors of economic burden for pneumoconiosis disease,and to provide a baseline to develop the prevention measures and to reduce the economic burden of pneumoconiosis. Methods The retrospective epidemiological method was used to investigate the general information of pneumoconiosis cases,frequency of outpatient and hospitalization per year,medical expenditure. Direct economic loss and its influencing factors of pneumoconiosis patients were analyzed. Results A total of 421 pneumoconiosis cases were investigated. All subjects were male,including 306 inpatients. The average medical expenditures of outpatient and inpatient were 594. 53 ± 336. 23 and 32 266. 06 ± 28 130. 67 Yuan,respectively. The annual average expenditures of outpatient and inpatient were 2 907. 25 and 48 721. 75 Yuan,respectively. In terms of health care costs,the highest proportion of western medicine was 44. 08% ,followed by traditional Chinese medicine(12. 62% ). With an increase in pneumoconiosis stage,the annual frequency of outpatient and hospitalization,as well as total expenditure increased accordingly. The average annual cost of pneumoconiosis inpatient with complications and non - complication inpatient were 55 822. 20 and 23 532. 21 Yuan,respectively. The annual average cost of outpatient with complications and without complications were 4 236. 41 and 882. 31 Yuan, respectively. The expenditures for pneumoconiosis disease with complications among outpatient and inpatient were significantly higher than those of pneumoconiosis patients without complications(P < 0. 05). Conclusion Direct economic loss of pneumoconiosis disease is relatively high. The disease stage and complications of pneumoconiosis are the main factors influencing the direct economic loss of pneumoconiosis.

Growth rate of Usnea aurantiacoatra (Jacq.) Bory on Fildes Peninsula, Antarctica and its climatic background.

The ages of a fruticose lichen of Usnea aurantiacoatra (Jacq.) Bory, from Fildes Peninsula, King George Island, Southwest Antarctic, were determined by radiocarbon (14C), and it is 1993-1996 at bottom and 2006-2007 at top of the lichen branch. The growth rates of U. aurantiacoatra calculated are 4.3 to 5.5 mm year(-1) based on its length and ages. The comparisons show that the growth rates of U. aurantiacoatra are higher than those of U. antarctica (0.4 to 1.1 mm year(-1)). The growth rates of fruticose lichens are always higher, usually >2 mm year(-1), than those of crustose ones, usually <1 mm year(-1), in polar areas. A warming trend on Fildes Peninsula is recorded in the period from 1969 to 2010 obviously: the mean annual temperature rose from -2.75 to -1.9°C and the average temperature of summer months from 0.95 to 1.4°C, as well as the average temperature of winter months from -6.75 to -5.5°C. The alteration of lichen growth rates in polar areas may respond to the climatic and environmental changes, and the lichens may act as bio-monitor of natural condition.

Gender differences in the impact of diabetes on mortality in patients with established coronary artery disease: a report from the eastern Taiwan integrated health care delivery system of Coronary Heart Disease (ET-CHD) registry, 1997-2006.

OBJECTIVES: The effect of type 2 diabetes mellitus (DM) on mortality was more pronounced in women than men with coronary artery disease (CAD) in the pre-stent era before 1996. However this relationship is controversial in the post-stent era. METHODS: We studied a cohort of 1073 patients with angiographically defined CAD from the Eastern Taiwan integrated health care delivery system of Coronary Heart Disease (ET-CHD) registry during 1997-2003 in Tzu-Chi General Hospital, Hualien, Taiwan. To evaluate gender-specific DM effect on mortality, the subjects were divided into 4 groups: diabetic women (n=147), non-diabetic women (n=127), diabetic men (n=239), and non-diabetic men (n=560). At a mean follow-up of 5.4 years, cardiac and all-cause mortality were the primary end points. RESULTS: Annual total mortality rates were 10.2%, 5.1%, 7.2%, and 4.8%; annual cardiac mortality rates were 8.2%, 3.0%, 4.3%, and 2.6% for diabetic women, non-diabetic women, diabetic men, and non-diabetic men, respectively. Multivariate Cox regression models, adjusted for possible confounders showed that gender-specific hazard ratios (HRs) of DM for total mortality were 2.02 (95% CI: 1.32-3.09), and 1.72 (95% CI: 1.32-2.25) for women and men, respectively. The HRs for total mortality associated with diabetes were not different between women and men (p=0.53). Similarly, adjusted gender-specific HRs of DM for cardiac mortality were 2.46 (95% CI: 1.45-4.19) for women, and 1.83 (95% CI: 1.28-2.62) for men, which were also not significantly different (p=0.36). CONCLUSIONS: Among patients with CAD, the impact of DM on mortality was consistently higher in women than in men, but the differences across sexes were not statistically significant after 1996 in Taiwan.

Optimization of biodiesel production catalyzed by fungus cells immobilized in fibrous supports.

A circulating packed-bed bioreactor system using fibrous nonwoven fabric as the immobilization matrix was suitable for simultaneous cell growth and immobilization of Rhizopus oryzae fungus cells, which could be used for lipase-mediated production of biodiesel by methanolysis of soybean oil. Response surface methodology and 5-level-5-factor central composite rotatable design was proved to be a powerful tool for the optimization of methanolysis conditions catalyzed by immobilized R. oryzae whole cell biocatalyst. A quadratic polynomial regression model was used to analyze the relationship between the yield and the significant reaction parameters. The analysis confirmed that water content, molar ratio of methanol to oil, cell weight, and reaction time were the significant factors affecting the yield at a 95% confidence level (p < 0.05). Under the optimum condition at 10.97% (w/w) water content, 0.64 molar ratio of methanol to oil, 2.25% (w/w) cell weight, and 23.3 h reaction time, the predicted value of yield was 72.6%. Validation experiments with yields of 70.77 +/- 2.46% verified the availability and the accuracy of the model.