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1.
Drug Safety - Analgesics are among the most widely used drugs worldwide. This study describes the population treated with narcotic analgesics, their therapeutic indications and how the data have...  相似文献   
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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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Background

Biomechanics after total knee arthroplasty (TKA) often remain abnormal and may lead to prolonged postoperative recovery. The purpose of this study is to assess a biomechanical therapy after TKA.

Methods

This is a randomized controlled trial of 50 patients after unilateral TKA. One group underwent a biomechanical therapy in which participants followed a walking protocol while wearing a foot-worn biomechanical device that modifies knee biomechanics and the control group followed a similar walking protocol while wearing a foot-worn sham device. All patients had standard physical therapy postoperatively as well. Patients were evaluated throughout the first postoperative year with clinical measures and gait analysis.

Results

Improved outcomes were seen in the biomechanical therapy group compared to the control group in pain scores (88% vs 38%, P = .011), function (86% vs 21%, P = .001), knee scores (83% vs 38%, P = .001), and walking distance (109% vs 47%, P = .001) at 1 year. The therapy group showed healthier biomechanical gait patterns in both the sagittal and coronal planes at 1 year.

Conclusion

A postoperative biomechanical therapy improves outcomes following TKA and should be considered as an additional therapy postoperatively.  相似文献   
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Alkaline phosphatase (AP), a non-toxic natural compound (enzyme) has a great potential to replace or avoid the use of various drugs, in particular anti-inflammatory drugs (e.g. used during surgery and to reduce arthritis) and antibiotics applied to farm animals, which both have serious negative effects on the environment. Promising studies are being performed to demonstrate the possibility to avoid complications after major surgery (thereby eliminating the need to use harmful drugs for many years) and the reduction of antibiotics use in piglets.  相似文献   
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