Accuracy of MRI-guided Versus Systematic Prostate Biopsy in Patients Under Active Surveillance: A Systematic Review and Meta-analysis

This meta-analysis focuses on the accuracy of upgrading to clinically significant prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsy (MRI-TB) versus systematic biopsy (SB). We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Literatura Latino Americana em Ciências da Saúde databases through January 2020 for comparative, retrospective/prospective, paired-cohort, and randomized clinical trials with paired comparisons. The population consisted of patients with low-risk PCa in active surveillance with at least 1 index lesion on imaging. We evaluated the quality of evidence by using the Quality Assessment of Diagnostic Accuracy Studies-2 score. Group comparisons considered the differences between the area under the curve summary receiver operating characteristic curve in a 2-tailed method. We also compared the positive predictive value of the best single method (MRI-TB or SB) and the referral study test (combined biopsy, a combination of MRI-TB and SB). The meta-analysis included 6 studies enrolling 741 patients. The pooled sensitivity for the 2 groups was 0.79 (95% confidence interval, 0.74-0.83; I² = 75%) and 0.67 (95% confidence interval, 0.63-0.74; I² = 55.4%), respectively. The area under the curve for the MRI-TB and SB groups were 0.99 and 0.92 (P < .001), respectively. The positive predictive value for the MRI-TB and combined biopsy groups were similar. The accumulated evidence suggests better results for MRI-TB compared with SB. Therefore, use of MRI-TB alone may be preferable in patients in active surveillance harboring low-risk PCa.     

Report of a National Conference on Donation after Cardiac Death

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Adverse hemodynamic and clinical effects of encainide in severe chronic heart failure

STUDY OBJECTIVE: To evaluate the hemodynamic effects of the antiarrhythmic drug, encainide, in patients with severe chronic heart failure. DESIGN: Unblinded, before-after study. SETTING: Referral center for patients with heart failure. PATIENTS: Thirty patients with severe chronic heart failure and a left ventricular ejection fraction less than 40%. INTERVENTIONS: Invasive hemodynamic measurements were done (using a balloon-tipped thermodilution catheter) before and for 3 hours after a single oral dose of 50 mg of encainide. MEASUREMENTS AND MAIN RESULTS: Ninety to one hundred and twenty minutes after its administration, encainide produced a significant deterioration in cardiac performance, as reflected by a fall in cardiac index from 2.3 to 1.8 L/min.m2 body surface (mean change 0.5 +/- 0.1; P less than 0.001), a fall in stroke work index from 26 to 18 g.m/m2 (mean change 8 +/- 2; P less than 0.001), and an increase in left ventricular filling pressure from 19 to 22 mm Hg (mean change 3 +/- 2; P less than 0.05). These deleterious hemodynamic effects were accompanied by worsening symptoms of heart failure in 8 of the 30 patients. Serum levels of encainide and its metabolites, O-desmethylencainide and 3-methoxy-O-desmethylencainide, were within the therapeutic range in most patients. CONCLUSIONS: Encainide can cause adverse hemodynamic and clinical effects in patients with severe chronic heart failure.     

Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure

Renal function was evaluated in 104 patients with severe chronic heart failure whom we treated with captopril or enalapril. Seventy patients showed no change or an improvement in renal function (group A), and 34 patients developed functional renal insufficiency (group B). Before converting-enzyme inhibition, group B patients received higher doses of furosemide (p less than 0.02) and had lower central venous pressures (p less than 0.05) than group A patients. After 1 to 3 months of converting-enzyme inhibition, an excessive reduction in left ventricular filling pressure (to less than 15 mm Hg) or mean arterial pressure (to less than 60 mm Hg) was noted in 28 of 34 (82%) patients in group B but in only 22 of 70 patients in group A (31%) (p less than 0.001). At the end of the study, drug-induced azotemia resolved after a reduction in the dosage of diuretics, despite unaltered treatment with captopril and enalapril. Hence, the deterioration of renal function after converting-enzyme inhibition in heart failure is not a toxic or immunologic reaction to therapy but results from specific hemodynamic events that can be ameliorated by sodium repletion.