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Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...  相似文献   
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Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Patients and Methods

We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.

Results

Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.

Conclusions

FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.  相似文献   
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Objective: To examine (i) the associations between physical activity dimensions, cardiorespiratory fitness and body composition and, (ii) the associations between physical activity dimensions, cardiorespiratory fitness, body composition and biomarkers of cardiometabolic health in persons with spinal cord injury (SCI).

Methods: A cross-sectional prospective cohort study with 7-day follow-up was conducted. Body composition, cardiorespiratory fitness and biomarkers of cardiometabolic health were measured in thirty-three participants with SCI (> 1 year post injury). Physical activity dimensions were objectively assessed over 7-days.

Results: Activity energy expenditure (r =.43), physical activity level (r =.39), and moderate-to-vigorous physical activity (MVPA) (r =.48) were significantly (P < 0.001) associated with absolute (L/min) peak oxygen uptake (?O2 peak). ?O2 peak was significantly higher in persons performing ≥150 MVPA minutes/week compared to <40 minutes/week (P?=?0.003). Individual physical activity dimensions were not significantly associated with biomarkers of cardiometabolic health. However, body composition characteristics (BMI, waist and hip circumference) showed significant (P < 0.04), moderate (r >.30) associations with parameters of metabolic regulation, lipid profiles and inflammatory biomarkers. Relative ?O2 peak (ml/kg/min) was moderately associated with only insulin sensitivity (r?=?0.37, P?=?0.03).

Conclusions: Physical activity dimensions are associated with cardiorespiratory fitness; however, stronger and more consistent associations suggest that poor cardiometabolic health is associated with higher body fat content. Given these findings, the regulation of energy balance should be an important consideration for researchers and clinicians looking to improve cardiometabolic health in persons with SCI.  相似文献   

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OBJECTIVE: To investigate whether cardiovascular mortality related to obesity could be modified by physical activity. DESIGN: Mortality follow-up. SETTING: Population study. PARTICIPANTS: Participants in a health survey: 34 868 women and 32 872 men free from known cardiovascular disease or diabetes at baseline. MAIN OUTCOME MEASURES: Total cardiovascular mortality. MAIN RESULTS: During 16 years of follow-up, 3026 women and 3526 men had died from cardiovascular causes. In middle age, obesity [body mass index (BMI) of 30 or higher] was associated with increased risk of cardiovascular death, but the association weakened with age. After 70, there was no association between BMI and cardiovascular death. At all ages, a lower level of physical activity was associated with a higher cardiovascular mortality. In women with high physical activity, indicated by at least 30 min of moderate to vigorous activity more than once a week, cardiovascular mortality was only slightly higher in the obese compared to lean women (adjusted relative risk, 1.27; 95% confidence interval, 0.80-2.00). In men with high physical activity, cardiovascular mortality was, however, significantly higher among the obese (relative risk, 1.62; 95% confidence interval, 1.09-2.40). In both genders cardiovascular mortality was substantially higher in obese people who reported no regular physical activity compared to obese people with a high level of physical activity. CONCLUSION: In obese women, being highly active may, to a large extent, compensate for the risk-increasing effect of being obese, whereas in obese men who engage in a high level of physical activity, the risk of cardiovascular death may be higher than in lean and equally active men.  相似文献   
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