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41.

Background

Multiparametric magnetic resonance imaging (mpMRI) undoubtedly affects the diagnosis and treatment of localized prostate cancer (CaP). However, clinicians need a better understanding of its accuracy and limitations in detecting individual CaP foci to optimize management.

Objective

To determine the per-lesion detection rate for CaP foci by mpMRI and identify predictors of tumor detection.

Design, setting, and participants

We carried out a retrospective analysis of a prospectively managed database correlating lesion-specific results from mpMRI co-registered with whole-mount pathology (WMP) prostatectomy specimens from June 2010 to February 2018. Participants include 588 consecutive patients with biopsy-proven CaP undergoing 3-T mpMRI before radical prostatectomy at a single tertiary institution.

Outcome measurements and statistical analysis

We measured mpMRI sensitivity in detecting individual CaP and clinically significant (any Gleason score ≥7) CaP foci and predictors of tumor detection using multivariate analysis.

Results and limitations

The final analysis included 1213 pathologically confirmed tumor foci in 588 patients with primarily intermediate- (75%) or high-risk (12%) CaP. mpMRI detected 45% of all lesions (95% confidence interval [CI] 42–47%), including 65% of clinically significant lesions (95% CI 61–69%) and nearly 80% of high-grade tumors. Some 74% and 31% of missed solitary and multifocal tumors, respectively, were clinically significant. The majority of missed lesions were small (61.1% ≤1 cm); 28.3% were between 1 and 2 cm, and 10.4% were >2 cm. mpMRI missed at least one clinically significant focus in 34% of patients overall, and in 45% of men with multifocal lesions. On multivariate analysis, smaller, low-grade, multifocal, nonindex tumors with lower prostate-specific antigen density were more likely to be missed. Limitations include selection bias in a prostatectomy cohort, lack of specificity data, an imperfect co-registration process, and uncertain clinical significance for undetected lesions.

Conclusions

mpMRI detects less than half of all and less than two-thirds of clinically significant CaP foci. The moderate per-lesion sensitivity and significant proportion of men with undetected tumor foci demonstrate the current limitations of mpMRI.

Patient summary

Magnetic resonance imaging of the prostate before surgical removal for prostate cancer finds less than half of all individual prostate cancer tumors. Large, solitary, aggressive tumors are more likely to be visualized on imaging.  相似文献   
42.

Objective

Although endovascular repair of abdominal aortic aneurysms (AAAs) has been demonstrated to have favorable outcomes, not all cohorts of patients with AAA fare equally well. Our goal was to investigate perioperative and 1-year outcomes in patients with end-stage renal disease (ESRD) on dialysis, who have traditionally fared worse after vascular interventions, to assess how ESRD affects outcomes in a large modern cohort of endovascular aneurysm repair (EVAR) patients.

Methods

The Vascular Quality Initiative database was queried for all patients undergoing EVAR from 2010 to 2017. ESRD patients were compared with patients not on dialysis. Propensity-matched scoring and multivariable analysis were used to isolate the effects of ESRD.

Results

Of 28,683 EVARs identified, there were 321 (1.12%) patients with ESRD on dialysis. Patients with ESRD had no difference in presenting AAA size (57.5 ± 12.7 mm vs 56.7 ± 17.2 mm; P = .44); however, they had more urgent/emergent repairs (20.6% vs 13.6%; P = .002) than those without ESRD. ESRD patients were more often younger, nonwhite, and nonobese and less likely to have commercial insurance (P < .05). ESRD patients more often had hypertension, coronary artery disease, congestive heart failure, previous lower extremity bypass, aneurysm repair, and carotid interventions (P < .05). There was no difference in the rate of concomitant procedures. Matching based on demographics, comorbidities, and operative details showed that ESRD patients had longer hospital length of stay (4.8 ± 9.4 days vs 4.1 ± 12.6 days; P = .026) and higher 30-day mortality (7% vs 2.4%; P < .001). There was no difference in cardiac, pulmonary, lower extremity, bowel, and stroke complications or return to the operating room. On multivariable analysis, ESRD was associated with 30-day mortality (odds ratio, 4.1; 95% confidence interval, 2.6-6.7; P < .001). Of the 24,750 elective EVARs, 1.04% had ESRD on dialysis. Matched data for elective EVAR show increased postoperative length of stay, hospital mortality, and 30-day mortality for ESRD patients on dialysis compared with those who are not. There was no association with postoperative myocardial infarction or pulmonary complications. At 1 year, patients with ESRD on dialysis had worse survival (78% vs 94%; P < .001), and ESRD was associated with higher mortality (hazard ratio, 3.3; 95% confidence interval, 2.5-4.2; P < .001).

Conclusions

Among patients undergoing EVAR, ESRD is independently associated with higher perioperative and 1-year mortality despite not being associated with higher postoperative complications. This should be taken into account during informed consent for EVAR and risk-benefit considerations in this high-risk population, particularly for elective repair.  相似文献   
43.
ABSTRACT

Latinos are less likely to seek health care for eating disorders and more likely to drop out of treatment than members of other ethnic groups, highlighting existing challenges to engagement in traditional mental health care. This study explored the role of family in the treatment of adult Latinas with eating disorders through content analysis of family sessions adjunctive to cognitive behavioral therapy. This study yielded insight into the experiences of 10 Latinas with eating disorders (M age = 39.90 years) and 10 relatives (M age = 39.50) from the Promoviendo una Alimentación Saludable trial who were randomly selected to receive six family enhancement sessions. Data from 53 sessions were analyzed using a qualitative content analysis approach. Family intervention might serve as a valuable adjunct to conventional treatment by positively influencing social, family, and emotional support for Latinas with eating disorders.  相似文献   
44.

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Methods and results

The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.

Conclusion

The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.  相似文献   
45.

Background and aim

Given the contradictory results of previous randomized controlled trials (RCTs), we performed a systematic review and meta-analysis to quantify and summarize the effects of folic acid supplementation on C-reactive protein (CRP).

Methods and results

We performed a systematic search of all available RCTs conducted up to October 2018 in the following databases: PubMed, Scopus, and Cochrane. RCTs that investigated the effect of folate on CRP were included in the present study. Data were combined with the use of generic inverse-variance random-effects models. Statistical heterogeneity between studies was evaluated using Cochran's Q-test. Ten RCTs (1179 subjects) were included in the present meta-analysis. Pooled analysis results showed that folate supplementation significantly lowered the serum CRP level (weighted mean difference (WMD): ?0.685 mg/l, 95% CI: ?1.053, ?0.318, p < 0.001). However, heterogeneity was significant (I2 = 96.7%, p = 0.000). Stratified analyses indicated that sex, intervention period, and type of study population were sources of heterogeneity. Following analysis, results revealed that the greatest impact was observed in women (WMD: ?0.967 mg/l, 95% CI: ?1.101, ?0.833, p = 0.000), patients with type 2 diabetes mellitus (WMD: ?1.764 mg/l, 95% CI: ?2.002, ?1.526, p = 0.000), and intervention period less than 12 weeks (WMD: ?0.742 mg/l, 95% CI: ?0.834, ?0.650, p = 0.000).

Conclusion

This meta-analysis suggested that folic acid supplementation could significantly lower the serum CRP level. Folic acid leads to greater CRP lowering effect in women, patients with T2DM, and those with less than 12-week intervention.  相似文献   
46.

Background

The International Agency for Research on Cancer (IARC) has recently classified glyphosate as a Group 2A ‘probably carcinogenic to humans’. Due to this carcinogenic classification and resulting international debate, there is an increased demand for studies evaluating human health effects from glyphosate exposures. There is currently limited information on human exposures to glyphosate and a paucity of data regarding glyphosate's biological half-life in humans.

Objective

This study aims to estimate the human half-life of glyphosate from human urine samples collected from amenity horticulture workers using glyphosate based pesticide products.

Methods

Full void urine spot samples were collected over a period of approximately 24?h for eight work tasks involving seven workers. The elimination time and estimation of the half-life of glyphosate using three different measurement metrics: the unadjusted glyphosate concentrations, creatinine corrected concentrations and by using Urinary Excretion Rates (UER) (μg L?1, μmol/mol creatinine and UER μg L?1) was calculated by summary and linear interpolation using regression analysis.

Results

This study estimates the human biological half-life of glyphosate as approximately 5 ½, 10 and 7 ¼ hours for unadjusted samples, creatinine corrected concentrations and by using UER (μg L?1, μmol/mol creatinine, UER μg L?1), respectively. The approximated glyphosate half-life calculations seem to have less variability when using the UER compared to the other measuring metrics.

Conclusion

This study provides new information on the elimination rate of glyphosate and an approximate biological half-life range for humans. This information can help optimise the design of sampling strategies, as well as assisting in the interpretation of results for human biomonitoring studies involving this active ingredient. The data could also contribute to the development or refinement of Physiologically Based PharmacoKinetic (PBPK) models for glyphosate.  相似文献   
47.

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Materials and methods

The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.

Results

In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).

Conclusions

We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.  相似文献   
48.
49.
There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies  相似文献   
50.
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