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51.

Purpose

To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men.

Patients and Methods

Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c).

Results

A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P = .003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m2 (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c.

Conclusion

Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations.  相似文献   
52.
53.
Introduction: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory syncytial virus (RSV) and human rhinovirus (RV). How respiratory viral infections lead to wheeze and/or asthma is an area of active research.

Areas covered: This review provides an updated summary of the published information on the development of post-viral induced atopy and asthma and the mechanisms involved. We focus on the contribution of animal models in identifying pathways that may contribute to atopy and asthma following respiratory virus infection, different polymorphisms that have been associated with asthma development, and current options for disease management and potential future interventions.

Expert commentary: Currently there are no prophylactic therapies that prevent infants infected with respiratory viruses from developing asthma or atopy. Neither are there curative therapies for patients with asthma. Therefore, a better understanding of genetic factors and other associated biomarkers in respiratory viral induced pathogenesis is important for developing effective personalized therapies.  相似文献   

54.

Background

Liver transplantation from donors after either controlled or uncontrolled cardiac death (DCD) is associated with considerable rates of primary nonfunction (PNF) and ischemic cholangiopathy (IC). Normothermic regional perfusion (NRP) could significantly reduce such rates.

Methods

Retrospective study to analyze short-term (mortality, PNF, vascular complications) and long-term (IC, survival) complications in 11 liver transplants from controlled DCDs using NRP with extracorporeal membrane oxygenation (ECMO) (group 1). They were compared with 51 patients transplanted with grafts from donors after brain death (DBD) (group 2). Mean recipient age, sex, and Model for End-stage Liver Disease (MELD) score were not significantly different.

Results

In group 1, mean functional warm ischemia time was 15.8 (range, 7–40) minutes and 94.1 (range, 20–150) minutes on NRP. The ischemic damage was minimal, as shown by the slight alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rises in the donor serum after 1 hour on NRP and similar rises 24 hours after transplantation in both groups. No patient had IC or acute renal failure. No significant difference was found between the groups for vascular or biliary complications. One group 1 patient had PNF (9.1%), resulting in death. Overall retransplantation and in-hospital death rates were 8.1% and 4.8%, respectively, with no significant difference between groups. Estimated mean survival was 24.6 (95% confidence interval [CI], 20.2–29.1) months in group 1 and 32.3 (95% CI, 30.4–34.2) months in group 2 (not a statistically significant difference).

Conclusion

In our experience, liver transplants from controlled DCDs using NRP with ECMO is associated with a low risk of PNF and IC, with short- and long-term results comparable to those in DBD transplants.  相似文献   
55.

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Methods

We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male).

Results

Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians.

Conclusions

Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation.  相似文献   
56.

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

Methods and results

As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.

Conclusions

In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.  相似文献   
57.
BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)  相似文献   
58.

Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.

Methods

Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis was studied in the hollow-fiber infection model system in log-phase growth under neutral pH and slow growth in an acidic environment. Doses that achieved maximum bacterial kill while suppressing the emergence of drug resistance were determined. Through Monte Carlo simulations the quantitative output of this in vitro study was bridged to the human patient population to inform optimal dosage regimens while accounting for clinical minimum inhibitory concentration (MIC) distributions.

Results and Discussion

Moxifloxacin activity was significantly decreased in an acidified environment. The loss of activity was compensated by accumulation of the drug in TB lung lesions; therefore, moderate efficacy can be expected. Moxifloxacin 800 mg/day is the dose that most likely leads to resistance suppression while exerting maximum bacterial kill. Linezolid demonstrated very good activity even at a reduced pH. Linezolid 900 mg once-daily (QD) is likely to achieve a maximum killing effect and prevent the emergence of drug resistance; 600 mg QD in a robust drug regimen may have similar potential.  相似文献   
59.
Background and purpose — 1 in 5 patients are dissatisfied following unicompartmental or total knee arthroplasty (UKA or TKA). This may be partly explained by failing to return to desired activity post-arthroplasty. To facilitate return to desired activity, a greater understanding of predictors of return to desired activity in UKA and TKA patients is needed. We compared rates of return to desired activity 12 months following UKA vs. TKA, and identified and compared predictors of return to desired activity 12 months following UKA vs. TKA.

Patients and methods — Patients were prospectively recruited from 2 hospitals prior to undergoing UKA or primary TKA. Patients reported preoperatively the activity/activities that were limited due to their knee that they wished to return to after arthroplasty. At 12-months postoperatively, patients reported whether they had returned to these activities (‘return to desired activity’). Preoperative predictors evaluated were age, sex, BMI, education, comorbidities, pain expectations, Oxford Knee Score (OKS), UCLA Activity Score, and EQ-5D. Generalized linear models assessed the relationship between potential predictors and return-to-desired-activity.

Results — The response rate of all patients eligible for 12-month follow-up was 74%. TKA patients (n = 575) were older (mean (SD) 70 (9) vs. 67 (10)) with a greater BMI (31 (6) vs. 30 (5)) than patients undergoing UKA (n = 420). 75% of UKA and 59% of TKA patients returned to desired activity. TKA patients had a greater risk of non-return to desired activity than patients undergoing UKA (risk ratio (95% CI) 1.5 (1.2–1.8)). Predictors of non-return to desired activity following UKA were worse OKS (0.96 (0.93–0.99)), higher BMI (1.04 (1.01–1.08)), and worse expectations (1.9 (1.2–2.8)). Predictors of non-return to desired activity following TKA were worse EQ-5D (0.53 (0.33–0.85)) and worse OKS (0.98 (0.96–1.0)).

Interpretation — UKA patients were more likely to return to desired activity than TKA patients. Predictors of return to desired activity differed following UKA and TKA. Optimizing selection of arthroplasty procedure based on patient characteristics and targeting predictors of poor outcome may facilitate return to desired activity with potential to enhance postoperative satisfaction.  相似文献   

60.
Purpose: To investigate the impact of donor and recipient factors on graft survival in penetrating keratoplasty (PK).

Material and Methods: This retrospective study included 365 eyes that underwent PK using corneas from 231 donors between June 2010 and June 2015. Patients were divided into three groups (group 1: primary endothelial diseases; group 2: iatrogenic endothelial disorders; and group 3: other pathologies with a healthy endothelium) according to PK indications. The primary outcome measure was corneal graft survival at the last visit (clear or opaque). Graft clarity was assessed using Kaplan–Meier survival analysis.

Results: The most frequent PK indication was keratoconus (KC) (20.5%) followed by pseudophakic bullous keratopathy (PBK) (18.9%). Donor age had a negative impact on endothelial cell density (ECD) measured by an eye bank specular microscope (p < 0.001). Median best-corrected visual acuity in logarithm of the minimum angle of resolution units increased from 2.1 to 0.8 at 1 year after PK (p < 0.001). The clear graft rate was 96.7% at year 1, 88.8% at year 2, and 85.5% at year 3. Overall graft survival was 84.9% during a median of 39 months (range: 24–79 months) of follow-up. A higher graft survival rate (67.2%) was observed in KC compared to PBK during 6 years (p < 0.001). Recipients younger than 50 years of age showed a better graft survival rate than those older than 70 years of age (p = 0.037). Donor ECD, time between excision and death, and preservation time had no significant effect on graft survival. Frequent graft rejection episodes (GREs) and additional procedures during surgery had a negative impact on graft survival (p < 0.001 and p = 0.014, respectively). A worse graft survival was observed in group 2 compared to groups 1 and 3 (p = 0.042).

Conclusions: Young recipient age and KC were associated with a better graft survival. Graft endothelial density and preservation time had no impact on graft survival. PBK, low vision at baseline and year 1, frequent GREs, and additional interventions during surgery had a negative impact on graft survivals.  相似文献   

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