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41.

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   
42.

Background

Cannabis is one of the most abused drugs worldwide, with more than 20 million users in the United States (US). As access to cannabis products increases with expanding US legislation and decriminalization of marijuana, emergency physicians must be adept in recognizing unintentional cannabis toxicity in young children, which can range from altered mental status to encephalopathy and coma.

Case Report

We report the case of a 13-month-old female presenting with self-limiting altered mental status and lethargy, with a subsequent diagnosis of tetrahydrocannabinol exposure on confirmatory urine gas chromatography-mass spectrometry.

Why Should an Emergency Physician Be Aware of This?

Considering caretakers rarely report possible cannabis exposure, history-taking must review caretakers’ medicinal and recreational drug exposures to prevent inadvertently missing the diagnosis. In the young child with altered mental status, prompt urine screening for cannabinoid detection can prevent further invasive and costly diagnostic investigations, such as brain imaging and lumbar puncture.  相似文献   
43.

Background

Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)–related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients.

Methods

We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients.

Results

A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17–26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab,?cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications.

Conclusion

In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population.Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk.  相似文献   
44.
Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology. Immune cells respond to acute signals from damaged cells, initiate neuroinflammation, and drive the pathological consequences over time. Importantly, the mechanism(s) of injury, the location of the immune cells within the brain, and the animal species all contribute to immune cell behavior following traumatic brain injury. Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration.Within this paper, we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury.  相似文献   
45.

Background

Catheter ablation of ventricular tachycardia (VT) can reduce the burden of ventricular arrhythmia (VA) but its effect on health care utilization and costs after such therapy is poorly known. We sought to compare the rates of cardiovascular (CV)-related hospitalizations, survival, and health care costs in patients with recurrent VT treated either with VT ablation or with medical therapy.

Methods

One-hundred implantable cardioverter-defibrillator patients with structural heart disease who underwent VT ablation were included. Propensity score-matched patients with recurrent VT treated with medical therapy were identified from a prospective registry of approximately 7000 de novo implantable cardioverter-defibrillator patients. Outcomes and costs were ascertained using health administrative databases.

Results

Among patients who underwent VT ablation, the cumulative rates of VA-related hospitalizations were lower in the 2 years after their ablation procedure compared with the year before (rate ratio, 0.3; 95% confidence interval [CI], 0.22-0.43). Rates of CV-related hospitalization and hospitalization because of VA post index date were similar between the VT ablation and medical therapy groups (hazard ratio [HR], 0.94; 95% CI, 0.57-1.54 and HR, 1.04; 95% CI, 0.57-1.91, respectively). Health care costs in the VT ablation patients were not increased post-ablation compared with the medical management group. The risk of all-cause mortality was lower among patients in the VT ablation group relative to the medical therapy group (HR, 0.64; 95% CI, 0.4-0.99).

Conclusions

Patients who underwent VT ablation experienced a significant reduction in their rate of VA-related hospitalizations. Patients treated with VT ablation had similar rates of CV-related hospitalization compared with those treated with medical therapy without increased health care-related costs.  相似文献   
46.

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   
47.

Context

Goals-of-care discussions are associated with improved end-of-life care for patients and therefore may be used as a process measure in quality improvement, research, and reimbursement programs.

Objectives

To examine three methods to assess occurrence of a goals-of-care discussion—patient report, clinician report, and documentation in the electronic health record (EHR)—at a clinic visit for seriously ill patients and determine whether each method is associated with patient-reported receipt of goal-concordant care.

Methods

We conducted a secondary analysis of a multicenter cluster-randomized trial, with 494 patients and 124 clinicians caring for them. Self-reported surveys collected from patients and clinicians two weeks after a clinic visit assessed occurrence of a goals-of-care discussion. Documentation of a goals-of-care discussion was abstracted from the EHR. Patient-reported receipt of goal-concordant care was assessed by survey two weeks after the visit.

Results

Fifty-two percent of patients reported occurrence of a goals-of-care discussion at the clinic visit; clinicians reported occurrence of a discussion at 66% of visits. EHR documentation occurred in 42% of visits (P < 0.001 for each compared with other two). Patients who reported occurrence of a goals-of-care discussion at the visit were more likely to report receipt of goal-concordant care than patients who reported no discussion (β 0.441, 95% CI 0.190–0.692; P = 0.001). Neither occurrence of a discussion by clinician report nor by EHR documentation was associated with goal-concordant care.

Conclusion

Different approaches to assess goals-of-care discussions give differing results, yet each may have advantages. Patient report is most likely to correlate with patient-reported receipt of goal-concordant care.  相似文献   
48.

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   
49.

Introduction

There are limited randomized data comparing radical cystectomy (RC) with bladder-sparing tri-modality therapy (TMT) in the treatment of muscle-invasive bladder cancer (MIBC). Both strategies are thought to have similar survival outcomes with different morbidity profiles. We compare the effectiveness of TMT and RC using decision-analytic modeling and the endpoint of quality-adjusted life years (QALYs).

Patients and Methods

Using a Markov model, we simulated the lifetime outcomes after TMT versus RC ± neoadjuvant chemotherapy for 67-year-old patients with clinical stage T2-T4aN0M0 MIBC. Model probabilities and utilities were extracted from the literature. The incremental effectiveness was reported in QALYs and sensitivity analyses were performed.

Results

For all patients with MIBC, although the model showed identical survival, TMT was the most effective strategy with an incremental gain of 0.59 QALYs over RC (7.83 vs. 7.24 QALYs, respectively). When limiting the model to favorable, contemporary cohorts in both the TMT and RC strategies, TMT remained more effective with an incremental gain of 1.61 QALYs (9.37 vs. 7.76 QALYs, respectively). One-way sensitivity analyses demonstrated the model was sensitive to the quality of life parameters (ie, the utilities) for RC and TMT. When testing the 95% confidence interval of the RC utility parameter the model demonstrated an incremental gain with TMT from ?0.54 to 4.23 QALYs. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 63% of model iterations.

Conclusions

This modeling study found that treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of QALYs relative to RC.  相似文献   
50.

Objective

To assess the impact of focality and location of positive surgical margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate cancer (PCa), including biochemical recurrence (BCR), metastasis and overall mortality.

Patients and Methods

From a total of 2796 cases of RP between 1993 and 2007 in our single hospital, 476 cases with PSMs were identified and included in this study. PSM location was categorized into apex, peripheral, and bladder neck. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze the impact of PSM focality and location status on oncologic survival.

Results

Of these 476 cases with PSMs, 335 (70.4%) cases were with single focal (sF) PSMs and 141 (29.6%) cases were with multifocal (mF) PSMs. Furthermore, 406 (85.3%) cases were found to have single location (sL) PSMs, and 70 (14.7%) cases were with multilocation (mL) PSMs. The median follow-up was 12.9 years. mF-PSMs and mL-PSMs showed significant impact on increased BCR risk on univariate analysis, and mL-PSMs remained significant on multivariate analysis (P = .048). Furthermore, the combination of multifocality and multilocation showed added prognostic value on predicting BCR-free survival, but not on metastasis-free survival or overall survival.

Conclusion

The presence of mF-PSMs and mL-PSMs, and especially the combination of both, demonstrated significant impact on BCR prognosis. Patients with apex sLsF-PSMs were less likely to have BCR when compared with all those with non-apex sLsF-PSMs. These results should be considered when evaluating patients for adjuvant therapy.  相似文献   
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