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1.

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Methods

A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.

Results

The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.

Conclusions

Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.  相似文献   
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PURPOSE: To explore perceived barriers and benefits to physical activity in people with serious and persistent mental illness (SPMI) who were enrolled in community-based psychiatric rehabilitation. DESIGN AND METHODS: Four focus groups, two for men and two for women, were held with a total of 34 outpatients from two program sites. The investigators used a semistructured interview guide to facilitate the discussions. Audiotapes of the discussions were transcribed and analyzed for concepts and themes. FINDINGS: Significant barriers to physical activity were: mental illness symptoms, medications, weight gain from medications, fear of discrimination, and safety concerns. Being in a psychiatric rehabilitation program offered comfort and belonging, but it also had the effect of leaving activity initiation up to the program staff, which some participants perceived was part of required program compliance. However, participants viewed physical activity positively, and they linked being active to improved mental health. CONCLUSIONS: Outpatients in psychiatric rehabilitation valued physical activity, but mental illness symptoms, medication sedation, weight gain, fear of unsafe conditions, fear of discrimination, and interpretations of program compliance were barriers. Confronting how attitudes and barriers specific to this population can affect activity and reframing program compliance to include the independent initiation of activity as part of improving health might help clients of mental health services to become more active.  相似文献   
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We aimed to determine how menopausal transition symptoms cluster across 216 midlife women with fibromyalgia, chronic fatigue syndromes (FMS/CFS), or both and subsequently to compare symptom factor severity scores by menopausal status among these women and compare symptom reporting with prior community-based samples of women without obvious illness. We designed a cross-sectional telephone survey of 216 women aged 35 to 55, diagnosed with FMS/CFS, symptomatic in the prior 6 months, and without hysterectomy. Thirty-six of 61 symptoms loaded on five factors: aroused/anxious mood, depressed mood/withdrawal, musculoskeletal, gastrointestinal (GI), and vasomotor. Peri- and postmenopausal women had higher symptom severity scores for musculoskeletal, GI, and vasomotor factors but not mood factors. Symptoms for the women we studied who had FMS/CFS clustered similar to those in previous community-based samples of midlife women without major illness; however, the number of women experiencing symptoms was much higher among our sample.  相似文献   
6.

Purpose of Review

Preventable medical adverse events are a leading cause of death in the USA. The most common adverse events include medication errors, perioperative complications, venous thromboembolism, infection, and readmission. Patients requiring care with a gynecologic oncologist are at increased risk for all of these adverse events, which are both clinically undesirable and now also represent targets for reduced hospital reimbursement. The goal of this review is to identify areas of preventable harm that occur in the perioperative period on a gynecologic oncology service and identify mechanisms to minimize harm.

Recent Findings

Recognizing that gynecologic oncology surgical patients often present with advanced age, medical comorbidities, obesity, and diagnoses requiring radical procedures involving multi-organ resection, they are particularly at risk for perioperative complications, some preventable. Recent studies have examined evidence-based methods for minimizing many areas of preventable harm in gynecologic oncology surgical patients. Multiple studies have implemented bundles of care to successfully decrease surgical site infections. New data on risk of venous thromboembolism (VTE) specifically in gynecologic oncology patients guide recommendations for perioperative and extended VTE prophylaxis. Enhanced recovery after surgery programs explore a multitude of factors, many in a bundle format, to minimize overall perioperative complications and decrease length of stay. Additionally, new data are available on rates of hospital readmissions and risk factors for readmission.

Summary

There is already a wealth of information available regarding incidence of complications in gynecologic oncology surgical patients. Fortunately, there is a shift in the USA toward recognizing patient risk factors and implementing interventions to decrease the rate of preventable adverse events.
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Human lung carcinogenesis is accompanied by complex chromosomal changes that may be detected in interphase cells by fluorescence in situ hybridization (FISH) assay using recently developed multitarget DNA probes. Touch preparations of 20 non-small cell lung carcinomas, sputum specimens from 3 patients with lung cancer and from 11 ex-smokers without lung cancer, and cultured benign bronchial epithelium of 42 high-risk smokers, 9 of whom had concurrent invasive carcinoma, were tested using a four-color FISH probe (LAVysion) targeting centromere 6, 5p15.2, 7p12 (EGFR), and 8q24 (MYC). Significantly high frequencies of abnormal cells were found in each of the 20 NSCLC (100%) and in the 3 sputum specimens from lung cancer patients. None of the cytologically normal sputa contained FISH abnormalities. Cultured bronchial epithelial cells from 11 of 42 patients (26%) were abnormal for at least one probe. Abnormal FISH patterns had no association with gender, presence of tumor or histology. Multicolor FISH can readily detect chromosomal abnormalities in imprints and sputa from lung carcinomas. Chromosomal aneusomy is also frequent in bronchial epithelial cells from long-term smokers. The prognostic significance of the multicolor LAVysion FISH probe set should be validated in a controlled clinical trial.  相似文献   
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The purpose of this study was to examine the career trends of family nurse practitioner (FNP) graduates of one master's program. A questionnaire was mailed to all FNPs (N = 113) who graduated 1-11 years earlier; there was a response rate of 83%. The survey revealed that for both first and present jobs the majority were providing direct patient care as a primary care provider or practicing in an indirect role. The study findings indicate that for these graduates there is a long term commitment (demonstrated through continued employment) as well as opportunity to practice in the nurse practitioner role in a direct or indirect capacity.  相似文献   
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