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101.

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   
102.
A case of persistent thoracic cerebrospinal fluid cutaneous fistula in a toddler following radiographically confirmed epidural catheter placement is reported. Treatment of the fistula with a thoracic epidural blood patch was successful.  相似文献   
103.
We present a case of a woman diagnosed several years previously with thoracic outlet syndrome who had a 2-3 month history of worsening wrist pain. After an intraosseous ganglion was discovered, curettage and bone grafting successfully relieved her symptoms.  相似文献   
104.
Recovery from anesthesia is ideally routine and uneventful. After extubation, the recovering postoperative patient ought to breathe without supportive care or additional oxygenation. It has been demonstrated in previous studies that postoperative pulmonary complications are clinically relevant in terms of mortality, morbidity, and length of hospital stay. Compromised postoperative ventilation can be described as the condition in which the postoperative patient does not have satisfactory spontaneous ventilation support and adequate oxygenation. Causes of impaired ventilation, oxygenation, and airway maintenance can be mechanical, hemodynamic, and pharmacologic. This review describes prevalence and differential diagnosis, including co-morbidities of postoperative apnea. The physiological mechanisms of breathing and prolonged postoperative apnea are also reviewed; these mechanisms include influences from the brainstem, the cerebral cortex, and chemoreceptors in the carotid and aortic body. Causes of prolonged postoperative apnea and management are also discussed.  相似文献   
105.
An automated radiosynthesis of carbon-11 positron emission tomography radiotracer [11C]UCB-J for imaging the synaptic density biomarker synaptic vesicle glycoprotein SV2A was established using Synthra RNPlus synthesizer. Commercially available trifluoroborate UCB-J analogue was used as a radiolabelling precursor, and the desired radiolabelled product was isolated in 11 ± 2% (n = 7) nondecay corrected radiochemical yield and formulated as a 10% EtOH solution in saline with molar activities of 20 to 100 GBq/μmol. The method was based upon the palladium(0)-mediated Suzuki cross-coupling reaction and [11C]CH3I as a radiolabelling synthon. The isolated product was cGMP compliant as demonstrated by the results of quality control analysis.  相似文献   
106.
Solution-focused brief therapy (SFBT) is a resource-based, future-oriented therapeutic approach that focuses on finding exceptions to problems and identifying coping strategies to build solutions. SFBT has been efficacious with individuals with alcohol use disorders. Chile experiences high levels of alcohol consumption and alcohol-related health consequences. Despite the international dissemination of SFBT, this is the first study to attempt a linguistic adaptation of SFBT in a Latin American country. We conducted 9 cognitive interviews to examine 13 translated main SFBT tools and 3 focus groups to gather information on cultural aspects of alcohol use in primary care. Results suggest that Chileans understood most SFBT tools, albeit with some linguistic modifications of original translations, and that family, gender, and meaningful issues should be considered when working with individuals with alcohol use disorders.  相似文献   
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109.
Background: Individuals with co-occurring disorders tend to avoid interaction with others. To instill hope, legacy intervention aims to highlight past experiences while managing life stressors for a positive outlook. Participants take part in legacy activities—crafting tangible projects and recording one's life events—in order to actualize a personal sense of legacy. Objectives: This pre-posttest research tested whether legacy intervention in a partial hospital program (PHP) on reframing past experiences through creative activities could increase life satisfaction and self-efficacy among adults with co-occurring substance misuse and mental health symptoms. Method: Eighty consented patients with co-occurring disorders were randomly assigned to two groups with 62 participants continuing: 37 in legacy intervention (LI) and 25 in partial hospital program only (PHP-only). LI participants were engaged in both PHP and legacy activities. Ten group sessions were held over the course of five weeks for cohorts of 10–15 adult patients in each intervention. Sense of legacy was measured to ensure that LI patients received the appropriate legacy dosage. Results: With RANOVA analyses between and among three time points, life satisfaction was significantly higher in the LI group with group interaction effect over time. In terms of self-efficacy, both groups showed positive changes but no significant difference could be found between the two groups over time and the interaction (time X group) effect was not significant. Importance: The legacy definitions gathered from the LI group were consistent with existing literature and showed three additional themes: children's involvement, concreteness, and life continuation after death.  相似文献   
110.
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