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71.

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   
72.
Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

  相似文献   
73.
Abstract

Background: Widespread concerns about new medical graduates’ ‘work readiness’ may reflect, in part, differences in mandatory learning outcomes for medical students and new medical graduates.

Purpose: To examine differences between required medical student and PGY1 (first year resident) training program outcomes, and the nature and magnitude of these differences.

Method: Comparison, systematic identification and thematic analysis of differences between the graduate outcomes in the Australian Medical Council Standards for the Assessment and Accreditation of Primary Medical Programs and those in the New Zealand Curriculum Framework for Prevocational Training.

Results: The relationship between these outcome statements were categorized as: essentially similar; continuity; partial discontinuity; and complete discontinuity of learning trajectory. Areas requiring substantial new learning may reflect medical schools’ focus on individual student performance, and on learning and assessments based on single episodes of often uncomplicated illness. This contrasted with a post-graduate focus on integrated health care delivery by teams and management of complex illnesses over the whole patient care journey.

Conclusions: Characterizing these marked differences between pre-graduate and postgraduate standards, within a trajectory of learning, explains some of the difficulties in students’ preparation for work readiness. These could inform learning interventions to support new graduates’ professional development to ensure patient safety. Development and revision of accreditation standards should include formal review against the expectations of the preceding and succeeding phases of learning.  相似文献   
74.

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   
75.

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Methods and results

In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders.

Conclusion

SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.  相似文献   
76.

Background

There are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension.

Objectives

The purpose of this study was to evaluate the blood pressure (BP) response after RSD in sham-controlled randomized trials.

Methods

Databases were searched through June 30, 2018. Randomized trials (RCTs) with ≥50 patients comparing catheter-based RSD with a sham control were included. The authors calculated summary treatment estimates as weighted mean differences (WMD) with 95% confidence intervals (CIs) using random-effects meta-analysis.

Results

The analysis included 977 patients from 6 trials. The reduction in 24-h ambulatory systolic blood pressure (ASBP) was significantly greater for patients treated with RSD than sham procedure (WMD ?3.65 mm Hg, 95% CI: ?5.33 to ?1.98; p < 0.001). Compared with sham, RSD was also associated with a significant decrease in daytime ASBP (WMD ?4.07 mm Hg, 95% CI: ?6.46 to ?1.68; p < 0.001), office systolic BP (WMD ?5.53 mm Hg, 95% CI: ?8.18 to ?2.87; p < 0.001), 24-h ambulatory diastolic BP (WMD ?1.71 mm Hg, 95% CI: ?3.06 to ?0.35; p = 0.01), daytime ambulatory diastolic BP (WMD ?1.57 mm Hg, 95% CI: ?2.73 to ?0.42; p = 0.008), and office diastolic BP (WMD ?3.37 mm Hg, 95% CI: ?4.86 to ?1.88; p < 0.001). Compared with first-generation trials, a significantly greater reduction in daytime ASBP was observed with RSD in second-generation trials (6.12 mm Hg vs. 2.14 mm Hg; p interaction = 0.04); however, this interaction was not significant for 24-h ASBP (4.85 mm Hg vs. 2.23 mm Hg; p interaction = 0.13).

Conclusions

RSD significantly reduced blood pressure compared with sham control. Results of this meta-analysis should inform the design of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with hypertension.  相似文献   
77.

Background

Nutrition specialists are considered key members of multicomponent pediatric weight management intervention teams, but to date, their contribution has not been quantified.

Objective

The purpose of this systematic review was to estimate the effectiveness of interventions provided by treatment teams that include a nutrition specialist on pediatric weight management outcomes, including body mass index (BMI), BMI z score, and waist circumference when compared with treatment teams that do not include a nutrition specialist.

Methods

The results of a comprehensive literature search and a systematic and more targeted update of that search were included in the meta-analyses: a search of controlled trials published between July 2005 and April 2012, conducted during the 2015 Pediatric Weight Management Update Project of the Academy of Nutrition and Dietetics Evidence Analysis Library, and an update search of controlled trials published between May 2012 and December 2015 focusing on a more specific topic within the previous search. Studies included overweight and/or obese patients aged 6 to 18 years receiving outpatient weight management treatment. Data extraction of all studies identified was performed using a standardized tool. The resulting data from the search and the systematic update were merged. Ninety-nine studies and 209 study arms were included in the analysis. An exploratory meta-analysis using alternative meta-analytic methods designed for complex, heterogenous interventions was conducted to identify relative contributions by intervention provider category at selected time points. Meta-regression analyses were used to evaluate significant differences from the reference category for each provider category.

Results

The nutrition specialist-only condition resulted in increased reductions in BMI z score compared with behavioralist-only, combined nutrition specialist and behavioralist, and neither nutrition specialist or behavioralist category (reference) throughout the analysis. Meta-regression analysis indicated that the difference in BMI z score between the nutrition specialist-only category and the reference category was significant at 3 to <6 months, 6 months to <1 year, and 1-year to 2-year time points (P=0.01, P=0.05, and P=0.01, respectively). There were smaller increases in BMI over time for the nutrition specialist-only provider category compared with reference categories, and this difference was significant at the 3 to <6 months and 1-year to 2-years time points (P=0.001 and P=0.05, respectively). There were no significant differences among provider categories for waist circumference at any time point.

Conclusions

Indirect evidence indicated that pediatric weight management outcomes for BMI z score and BMI at selected time points appeared to be better when a nutrition specialist was involved in delivering care.  相似文献   
78.
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   
79.

Purpose

The purpose of this study was to assess the potential of a deep learning model to discriminate between benign and malignant breast lesions using magnetic resonance imaging (MRI) and characterize different histological subtypes of breast lesions.

Materials and methods

We developed a deep learning model that simultaneously learns to detect lesions and characterize them. We created a lesion-characterization model based on a single two-dimensional T1-weighted fat suppressed MR image obtained after intravenous administration of a gadolinium chelate selected by radiologists. The data included 335 MR images from 335 patients, representing 17 different histological subtypes of breast lesions grouped into four categories (mammary gland, benign lesions, invasive ductal carcinoma and other malignant lesions). Algorithm performance was evaluated on an independent test set of 168 MR images using weighted sums of the area under the curve (AUC) scores.

Results

We obtained a cross-validation score of 0.817 weighted average receiver operating characteristic (ROC)-AUC on the training set computed as the mean of three-shuffle three-fold cross-validation. Our model reached a weighted mean AUC of 0.816 on the independent challenge test set.

Conclusion

This study shows good performance of a supervised-attention model with deep learning for breast MRI. This method should be validated on a larger and independent cohort.  相似文献   
80.

Aim

We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases.

Methods & patients

The Helsinki VCA program initially required the fulfillment of legal, hospital, financial, and ethical requirements. Thereafter, the assembling of a multidisciplinary team commenced. A team of Plastic, maxillofacial and ENT surgeons comprise the facial VCA team. The protocol involves collaboration with the Solid Organ Transplant (SOT) team, transplant immunology, immunosuppression, microbiology, psychiatric evaluation, well-defined VCA indications and informed consent. Between 2011 and 2017 two patients were selected for transplantation. Both patients had a severe composite facial deformity involving the maxilla and mandible following earlier ballistic injury.

Results

Patient 1 was a 35 year-old male who underwent successful near total face transplantation in February 2016 and at 30 months he has a good aesthetic outcome with symmetrical restoration of the central face and good sensory and symmetrical motor functional outcomes. Patient 2 was a 58 year-old male who underwent full face transplantation in March 2018 and at 5 months he has recovered without major problems.

Conclusion

A successful facial VCA program requires a well-prepared research protocol, experts from multiple specialties and careful patient selection. The establishment of the Helsinki VCA program required long and thorough planning and resulted in the first two Nordic face transplantation cases. This protocol now forms the platform (as a proof of concept) for other types of vascularized composite allotransplantations.  相似文献   
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