Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial.

PURPOSE: To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia. PATIENTS AND METHODS: A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events. RESULTS: The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (相似文献   

Seasonal variation in vitamin D levels in psoriatic arthritis patients from different latitudes and its association with clinical outcomes

Objective. Vitamin D insufficiency appears to be a pandemic problem and is more common in inhabitants of high latitude compared to low latitude areas. We aimed to determine the prevalence of vitamin D deficiency/insufficiency in patients with psoriatic arthritis (PsA), its seasonal and geographic variation, and the possible association with demographics and disease activity.Methods. This study was conducted in a northern geographic area and in a subtropical region from March 2009 to August 2009. Most subjects were assessed in both winter and summer. Demographics, clinical data, skin photo type, and serum 25-hydroxyvitamin D (25[OH]D) levels were determined. Multivariate linear and logistic mixed models were used to assess the relationship with serum 25(OH)D levels.Results. In total, 302 PsA patients were enrolled. Two hundred fifty-eight patients were evaluated during the winter,while 214 patients were evaluated during the summer. 25(OH)D levels in winter and summer were adequate (north: 41.3%winter and 41.4% summer, south: 42.1% winter and 35.1% summer), insufficient (north: 55.7% winter and 58.6% summer,south: 50.9% winter and 62.2% summer), and deficient (north: 3% winter and 0% summer, south: 7% winter and 2.7%summer) among patients. There was no association between 25(OH)D levels, geographic and seasonal interaction, race,employment status, and skin photo type or disease activity in both seasons. No association between disease activity in summer and vitamin D levels in winter could be found.Conclusion. A high prevalence of vitamin D insufficiency among PsA patients was found. There was no seasonal variation in 25(OH)D levels among PsA patients in the southern and northern sites. No association could be established between disease activity and vitamin D level.     

Particle formation and risk of embolization during transseptal catheterization: comparison of standard transseptal needles and a new radiofrequency transseptal needle

Objective  

Anecdotally, the Brockenbrough transseptal needle generates plastic particles through a process of skiving (shaving off particles), when advanced through the dilator and sheath. This study was performed to assess particle creation by the Brockenbrough needle during transseptal catheterization. We explore strategies that may reduce this phenomenon, including use of the Brockenbrough stylet and a radiofrequency transseptal needle.     

Quantitative dispersion microscopy

Refractive index dispersion is an intrinsic optical property and a useful source of contrast in biological imaging studies. In this report, we present the first dispersion phase imaging of living eukaryotic cells. We have developed quantitative dispersion microscopy based on the principle of quantitative phase microscopy. The dual-wavelength quantitative phase microscope makes phase measurements at 310 nm and 400 nm wavelengths to quantify dispersion (refractive index increment ratio) of live cells. The measured dispersion of living HeLa cells is found to be around 1.088, which agrees well with that measured directly for protein solutions using total internal reflection. This technique, together with the dry mass and morphology measurements provided by quantitative phase microscopy, could prove to be a useful tool for distinguishing different types of biomaterials and studying spatial inhomogeneities of biological samples.     

Increased utilization of the VH6 gene family in patients with autoimmune idiopathic thrombocytopenic purpura

The VH gene family utilization pattern among pokeweed mitogen-stimulated immunocompetent B cells (available repertoire) and naturally activated B cells (actual repertoire) from the spleen was analysed in a group of patients with autoimmune idiopathic thrombocytopenic purpura (AITP). For this purpose a non-radioactive RNA in situ hybridization technique was employed, allowing detection of VH gene family expression in single cells. The results show that the VH gene family expression pattern in patients with AITP does not correlate with genomic complexity of the VH genes. Furthermore, the pattern of VH gene family utilization in AITP patients is statistically different from that of healthy controls in the available, but not in the actual repertoire. The VH5 gene family is used at a frequency of 11.3% in patients' resting B lymphocytes, compared to 23.9% in controls. The VH6 gene family is used more frequently in patients (23.0% compared to 3.8% in controls). The increase in VH6 gene expression is not reflected in the actual repertoire, where the frequency of expression is 6.4%, and can therefore not be directly related to the presence of disease specific autoantibodies.     

ALK-Rearranged Non–Small-Cell Lung Cancer Is Associated With a High Rate of Venous Thromboembolism

Background

Patients with lung cancer are at increased risk for venous thromboembolism (VTE), particularly those receiving chemotherapy. It is estimated that 8% to 15% of patients with advanced non–small-cell lung cancer (NSCLC) experience a VTE in the course of their disease. The incidence in patients with specific molecular subtypes of NSCLC is unknown. We undertook this review to determine the incidence of VTE in patients with ALK (anaplastic lymphoma kinase)-rearranged NSCLC.

Time to viral suppression is not related to achievement of SVR12 in HCV GT1‐infected patients treated with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin

High rates of sustained virologic response at post‐treatment week 12 (SVR12) were achieved in six phase 3 trials of ombitasvir (OBV, an NS5A inhibitor), paritaprevir (an NS3/4A protease inhibitor) co‐dosed with ritonavir (PTV/r) + dasabuvir (DSV, an NS5B RNA polymerase inhibitor) (ie, 3D regimen) with or without ribavirin (RBV) in adults with chronic genotype (GT) 1 hepatitis C virus (HCV) infection. We assessed whether time to first HCV RNA value below the lower limit of quantification in patients with and without cirrhosis was associated with achievement of SVR12. Data were analysed from GT1‐infected patients enrolled in six phase 3 studies of 3D ± RBV. Patients who experienced non‐virologic failure were excluded from analysis. HCV RNA was determined using the Roche COBAS TaqMan RT‐PCR assay (lower limit of quantification, LLOQ =25 IU/mL). SVR12 was analysed by week of first HCV RNA suppression, defined as HCV RNA <LLOQ. The analysis included a total of 2027 patients. Cumulative proportions of subjects with initial HCV RNA suppression <LLOQ at weeks 1, 2, 4 and 6 were 31%, 81%, 99% and 100%, respectively. SVR12 was achieved by 98%, 97%, 98% and 92% of patients with initial suppression at Weeks 1, 2, 4 and 6, respectively (P=.42, trend test). Across six phase 3 trials of 3D ± RBV, most patients achieved viral suppression by week 2. Time to viral suppression was not associated with subsequent achievement of SVR12, suggesting that on‐treatment virologic monitoring may not be necessary with this regimen.     

Ribavirin revisited in the era of direct‐acting antiviral therapy for hepatitis C virus infection

Over the past two decades, ribavirin has been an integral component of treatment for hepatitis C virus (HCV) infection, where it has been shown to improve the efficacy of (pegylated) interferon. However, because of treatment‐limiting side effects and its additive toxicity with interferon, the search for interferon‐ and ribavirin‐free regimens has been underway. The recent approvals of all‐oral direct acting antivirals (DAAs) have revolutionized the HCV therapeutic landscape, and initially it was expected that the role of ribavirin with DAA regimens would be eliminated. On the contrary, what we have witnessed is that ribavirin retains an important role in the optimal treatment of some subgroups of patients, particularly those that historically have been considered the most difficult to cure. Fortunately, it has also been recognized that the safety profile of ribavirin is improved when co‐administered with all‐oral DAA combinations in the absence of interferon. Despite the antiviral mechanism of action of ribavirin being poorly understood, we now have a range of novel insights into the potential role of ribavirin in all‐oral DAA HCV treatment and greater insight into the antiviral mechanism by which it continues to provide clinical benefit for defined patient groups.