Validation of the German Revised Addenbrooke's Cognitive Examination for Detecting Mild Cognitive Impairment, Mild Dementia in Alzheimer's Disease and Frontotemporal Lobar Degeneration

Background/Aims: The diagnostic accuracy of the German version of the revised Addenbrooke's Cognitive Examination (ACE-R) in identifying mild cognitive impairment (MCI), mild dementia in Alzheimer's disease (AD) and mild dementia in frontotemporal lobar degeneration (FTLD) in comparison with the conventional Mini Mental State Examination (MMSE) was assessed. Methods: The study encompasses 76 cognitively healthy elderly individuals, 75 patients with MCI, 56 with AD and 22 with FTLD. ACE-R and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic procedure. Statistical analysis was performed using the receiver operating characteristic method and regression analyses. Results: The optimal cut-off score for the ACE-R for detecting MCI, AD, and FTLD was 86/87, 82/83 and 83/84, respectively. ACE-R was superior to MMSE only in the detection of patients with FTLD {[}area under the curve (AUC): 0.97 vs. 0.92], whilst the accuracy of the two instruments did not differ in identifying MCI and AD. The ratio of the scores of the memory ACE-R subtest to verbal fluency subtest contributed significantly to the discrimination between AD and FTLD (optimal cut-off score: 2.30/2.31, AUC: 0.77), whereas the MMSE and ACE-R total scores did not. Conclusion: The German ACE-R is superior to the most commonly employed MMSE in detecting mild dementia in FTLD and in the differential diagnosis between AD and FTLD. Thus it might serve as a valuable instrument as part of a comprehensive diagnostic workup in specialist centres/clinics contributing to the diagnosis and differential diagnosis of the cause of dementia. Copyright (C) 2010 S. Karger AG, Base

Relapsed and/or Refractory Mantle Cell Lymphoma: What Role for Temsirolimus?

Mantle Cell Lymphoma (MCL) is associated with a dismal prognosis. Recently, along with the improved understanding of the pathophysiology of this disease, new first line regimens have been established and in addition novel treatment options have entered the clinical arena. In consequence, prognosis of the disease has fortunately improved. We here focus on the rationale, current clinical knowledge and future concepts of Temsirolimus, an inhibitor of mTOR, in the treatment of MCL. At this time this drug has been shown to be effective as single agent for relapsed disease and early combination data show promising results. In addition, with a brief outline of other treatment options, we aim to guide at which place in the current treatment algorithms Temsirolimus can be integrated into the treatment of MCL patients

Safety and efficacy of advanced atrial pacing therapies for atrial tachyarrhythmias in patients with a new implantable dual chamber cardioverter-defibrillator

AbstractObjectivesThis study evaluated the safety and efficacy of atrial pacing therapies for the treatment and prevention of atrial tachycardia (AT) or atrial fibrillation (AF) in a new dual chamber implantable cardioverter defibrillator (ICD).BackgroundPatients with an ICD may also experience AT or AF that is amenable to pace termination.MethodsThe efficacy of atrial antitachycardia pacing (ATP) therapies for atrial tachycardia or atrial fibrillation (AT/AF) was determined in 151 patients after implantation of a GEM III AT ICD (Medtronic Inc., Minneapolis, Minnesota). The percentage of episodes successfully terminated was adjusted for multiple episodes per patient.ResultsA total of 717 of 728 (96%) episodes classified as AT or AF were judged to be appropriate detections. By device classification, atrial ATP terminated 187 of 383 (40% adjusted) episodes classified as AT compared with 65 of 240 episodes classified as AF (26% adjusted, p = 0.013). Atrial Ramp or Burst+ ATP terminated 184 of 378 episodes of AT (39% adjusted), whereas 50-Hz Burst pacing therapy terminated only 12 of 109 episodes of AT (12% adjusted) and 65 of 240 episodes of AF (26% adjusted). If efficacy was defined as termination of AT/AF within 20 s of delivery of the pacing therapy, ATP therapies terminated 139 of 383 (32% adjusted) episodes of AT compared with 34 of 240 episodes of AF (15% adjusted, p = 0.003). Efficacy was dependent on AT cycle length. Frequent transitions between AT and AF predicted inefficacy of atrial ATP (p < 0.001). Ventricular proarrhythmia secondary to atrial ATP was not observed.ConclusionsAtrial ATP therapies terminate many episodes of AT without ventricular proarrhythmia. The addition of 50-Hz Burst pacing has minimal efficacy for AT/AF

Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses fr symptomatic heart failure

AIMS: We performed a randomized, double blind, crossover study of cardiac contractility modulation (CCM) signals in heart failure patients. METHODS AND RESULTS: One hundred and sixty-four subjects with ejection fraction (EF) < 35% and NYHA Class II (24%) or III (76%) symptoms received a CCM pulse generator. Patients were randomly assigned to Group 1 (n = 80, CCM treatment 3 months, sham treatment second 3 months) or Group 2 (n = 84, sham treatment 3 months, CCM treatment second 3 months). The co-primary endpoints were changes in peak oxygen consumption (VO2,peak) and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Baseline EF (29.3 +/- 6.7% vs. 29.8 +/- 7.8%), VO2,peak (14.1 +/- 3.0 vs. 13.6 +/- 2.7 mL/kg/min), and MLWHFQ (38.9 +/- 27.4 vs. 36.5 +/- 27.1) were similar between the groups. VO2,peak increased similarly in both groups during the first 3 months (0.40 +/- 3.0 vs. 0.37 +/- 3.3 mL/kg/min, placebo effect). During the next 3 months, VO2,peak decreased in the group switched to sham (-0.86 +/- 3.06 mL/kg/min) and increased in patients switched to active treatment (0.16 +/- 2.50 mL/kg/min). MLWHFQ trended better with treatment (-12.06 +/- 15.33 vs. -9.70 +/- 16.71) during the first 3 months, increased during the second 3 months in the group switched to sham (+4.70 +/- 16.57), and decreased further in patients switched to active treatment (-0.70 +/- 15.13). A comparison of values at the end of active treatment periods vs. end of sham treatment periods indicates statistically significantly improved VO2,peak and MLWHFQ (P = 0.03 for each parameter). CONCLUSION: In patients with heart failure and left ventricular dysfunction, CCM signals appear safe; exercise tolerance and quality of life (MLWHFQ) were significantly better while patients were receiving active treatment with CCM for a 3-month period

Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

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Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate

A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer. Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib. Results: LVEF (SD) mean change from baseline was -0.8 ($\pm$8.6) LVEF(%) after 2 cycles (n=31) and -1.2 $\pm$7.8) LVEF(%) after 4 cycles of sorafenib (n=24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations ($t_{max}$) after 1 cycle (n=31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n=31) and HR (n=30) at maximum sorafenib concentrations ($t_{max}$) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and ($C_{max}$) of sorafenib and its main metabolites and any cardiovascular parameters. Conclusions: The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment

Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients.</p> <p>Methods</p> <p>We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma.</p> <p>Results</p> <p>From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001).</p> <p>Conclusions</p> <p>This is the first time that a potential "surrogate marker" has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice.</p

Comparison of Blue Light-Filtering IOLs and UV Light-Filtering IOLs for Cataract Surgery: A Meta-Analysis

Background: A number of published randomized controlled trials have been conducted to evaluate visual performance of blue light-filtering intraocular lenses (IOL) and UV light-filtering intraocular lenses (IOL) after cataract phacoemulsification surgery. However, results have not always been consistent. Therefore, we carried out a meta-analysis to compare the effectiveness of blue light-filtering IOLs versus UV light-filtering IOLs in cataract surgery. Methods and Findings: Comprehensive searches of PubMed, Embase, Cochrane Library and the Chinese BioMedical literature databases were performed using web-based search engines. Fifteen trials (1690 eyes) were included for systematic review, and 11 of 15 studies were included in this meta-analysis. The results showed that there were no significant differences in postoperative mean best corrected visual acuity, contrast sensitivity, overall color vision, or in the blue light spectrum under photopic light conditions between blue light-filtering IOLs and UV light-filtering IOLs [WMD = 20.01, 95%CI (20.03, 0.01), P = 0.46; WMD = 0.07, 95%CI (20.04, 0.19), P = 0.20; SMD = 0.14, 95%CI (20.33, 0.60), P = 0.566; SMD = 0.20, 95%CI (20.04, 0.43), P = 0.099]. However, color vision with blue light-filtering IOLs was significantly reduced in the blue light spectrum under mesopic light conditions [SMD = 0.74, 95%CI (0.29, 1.18), P = 0.001]. Conclusion: This meta-analysis demonstrates that postoperative visual performance with blue light-filtering IOLs is approximately equal to that of UV light-filtering IOLs after cataract surgery, but color vision with blue light-filtering IOL

Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents.</p> <p>Methods</p> <p>Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment.</p> <p>Results</p> <p>Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034).</p> <p>Conclusions</p> <p>Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.</p