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1.
目的:通过对颈椎病患者上下终板弧形高度、椎间隙高度与椎间隙后骨赘的影像学测量,研究其相关性及其临床应用价值。方法:收集2017年9月至2018年9月颈椎病手术108例患者的临床资料,男48例,年龄30~72岁,平均52岁,女60例,年龄37~79岁,平均54岁。其中C2,3 6例,C3,4 15例,C4,5 32例,C5,6 42例,C6,7 13例。术前及术后摄颈椎X线片,利用PACS(Picture Archiving and Communication Systems)调阅影像,测量椎间隙的下上终板弧形高度(L1,L2),椎间隙高度(L3)及后方骨赘的宽度(L4)。利用Spearman分析它们之间的相关性。结果:L1与L4对比(r=-0.34,P<0.05),L3与L4对比(r=-0.36,P<0.05),存在负相关。L1与L3对比(r=0.38,P<0.05),L2与L3对比(r=0.48,P<0.05),存在正相关。L1与L2对比(P>0.05),L2与L4对比(P>0.05),差异无统计学意义。结论:下终板弧形高度与椎间隙后缘骨赘宽度呈负相关,通过其测量可明确颈椎退变程度,对颈椎病的早期防治有指导意义。  相似文献   
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Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma  相似文献   
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Background

Persistent iatrogenic atrial septal defect (iASD) is a common but poorly characterized complication after cryoballoon (CB) pulmonary vein isolation (PVI) procedures. We therefore investigate its prevalence, evolution, risk factors, and clinical outcomes in a prospective longitudinal study.

Methods

A total of 108 patients (41 women, mean age 57 ± 11.3) underwent CB PVI for AF. Serial transesophageal echocardiography (TEE) was performed 9 months and then annually until 6 years after the procedure to study the characteristics of persistent iASD.

Results

Persistent iASD occurred in 33 (30.6%) patients 9 months after CB PVI. Spontaneous closure of iASD was found in 6 (22.2%) and 3 (15.8%) patients 2 and 3 years after the procedures, respectively. No spontaneous closure was observed on 4, 5, and 6-year TEE follow-up. The projected long-term persistence rate of iASD after CB PVI was therefore 20% (30.6% × 0.778 × 0.842). Using multivariate logistic regression, a higher number of cryoapplications (≥ 2 minutes) was the only independent predictor of persistent iASD 9 months after CB PVI (odds ratio [OR] 1.207; 95% confidence interval [CI], 1.033-1.411, P = 0.018). Two (1.9%) patients with significantly larger iASD size than the others (long diameter 12.6 ± 0.8 vs 3.7 ± 1.5 mm, P < 0.001; short diameter 10.9 ± 0.2 vs 3 ± 1.1 mm, P < 0.001) required percutaneous closure because of exertional dyspnea and right ventricular enlargement. Over 129.7 patient-years follow-up, during which iASD persisted, there was no occurrence of neurologic events.

Conclusions

Approximately one fifth of patients undergoing CB PVI will have permanently persistent iASD. Patients with defect sizes of greater than 10 mm may need percutaneous closure due to significant left-to-right shunting.  相似文献   
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Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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Context

Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.

Objectives/Methods

We used multivariate hierarchical linear modeling to simultaneously evaluate associations between five distinct patterns of conjoint symptom distress and functional impairment (symptom-functional states) and subjective caregiving burden, QOL, and depressive symptoms in a convenience sample of 215 family caregiver–patient dyads. Data were collected every 2 to 4 weeks over patients' last 6 months.

Results

Caregivers of patients in the worst symptom-functional states (States 3–5) reported worse subjective caregiving burden and depressive symptoms than those in the best two states, but the three outcomes did not differ between caregivers of patients in State 3 and States 4–5. Caregivers of patients in State 5 endured worse subjective caregiving burden and QOL than those in State 4. Caregivers of patients in State 4 suffered worse subjective caregiving burden and depressive symptoms but comparable QOL to those in State 2.

Conclusion

Patients' five distinct, conjoint symptom-functional states were significantly and differentially associated with their caregivers' worse subjective caregiving burden, QOL, and depressive symptoms while caring for patients over their last 6 months.  相似文献   
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