IqYmune® is an effective maintenance treatment for multifocal motor neuropathy: A randomised,double‐blind,multi‐center cross‐over non‐inferiority study vs Kiovig®—The LIME Study

Intravenous immunoglobulin (IVIg) is the gold‐standard for maintenance treatment of multifocal motor neuropathy (MMN). This phase III, randomised, double‐blind, multi‐centre, active‐control, crossover study, aimed to evaluate the non‐inferiority of IqYmune® relative to Kiovig®, primarily based on efficacy criteria. Twenty‐two adult MMN patients, treated with any brand of IVIg (except Kiovig® or IqYmune®) at a stable maintenance dose within the range of 1 to 2 g/kg every 4 to 8 weeks, were randomised to receive either Kiovig® followed by IqYmune®, or IqYmune® followed by Kiovig®. Each product was administered for 24 weeks. The primary endpoint was the difference between IqYmune® and Kiovig® in mean assessments of modified Medical Research Council (MMRC) 10 sum score (strength of 5 upper‐limb and 5 lower‐limb muscle groups, on both sides, giving a score from 0 to 100) during the evaluation period (non‐inferiority margin of Δ = 2). A linear mixed model analysis demonstrated the non‐inferiority of IqYmune® relative to Kiovig®, independently of the covariates (value at baseline, treatment period, and treatment sequence). The estimated “IqYmune® ? Kiovig®” difference was ?0.01, with a 95% confidence interval (CI) ?0.51 to 0.48. The number of adverse reactions (ARs) and the percentage of patients affected were similar for the two products: 39 ARs in 10 patients with IqYmune® vs 32 ARs in 11 patients with Kiovig®. No thromboembolic events nor haemolysis nor renal impairment were observed. In this first clinical trial comparing two IVIg brands for maintenance treatment of MMN, efficacy and tolerability of both brands were similar.     

Accumulation of Environmental Contaminants in Wood Duck (<Emphasis Type="Italic">Aix sponsa</Emphasis>) Eggs,with Emphasis on Polychlorinated Dibenzo-<Emphasis Type="Italic">p</Emphasis>-Dioxins and Polychlorinated Dibenzofurans

We measured polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), organochlorine pesticides, and mercury in wood duck (Aix sponsa) eggs collected near a North Carolina (USA) bleached kraft paper mill. Samples were taken a decade after the mill stopped using molecular chlorine. Using avian toxic equivalency factors, 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations were 1–30 pg/g fresh wet weight in eggs (n = 48) collected near the mill in 2002–2005 and were significantly higher than those from a reference site (<1 pg/g) 25 km away. Geometric mean wood duck egg TEQs (6 pg/g) were one-fifth those measured at this site prior to the cessation of molecular chlorine bleaching. Concentrations of mercury in wood duck eggs from nests of the Roanoke River sites ranged from 0.01 to 0.14 μg/g (geometric mean, 0.04 μg/g) and were significantly higher than those from the reference site, where concentrations did not exceed 0.04 μg/g (geometric mean, 0.02 μg/g). All concentrations were lower than those associated with adverse effects in birds. The congener profiles, lack of contamination in reference site eggs, and decline in contaminant concentrations after process changes at the mill provide strong evidence that mill discharges influenced contamination of local wood duck eggs. Collectively, the results indicate that the wood duck is an effective sentinel of the spatial and temporal extent of PCDD, PCDF, and mercury contamination.     

Improvement of Stance Control and Muscle Performance Induced by Focal Muscle Vibration in Young-Elderly Women: A Randomized Controlled Trial

Filippi GM, Brunetti O, Botti FM, Panichi R, Roscini M, Camerota F, Cesari M, Pettorossi VE. Improvement of stance control and muscle performance induced by focal muscle vibration in young-elderly women: a randomized controlled trial.

Objective

To determine the effect of a particular protocol of mechanical vibration, applied focally and repeatedly (repeated muscle vibration [rMV]) on the quadriceps muscles, on stance and lower-extremity muscle power of young-elderly women.

Design

Double-blind randomized controlled trial; 3-month follow-up after intervention.

Setting

Human Physiology Laboratories, University of Perugia, Italy.

Participants

Sedentary women volunteers (N=60), randomized in 3 groups (mean age ± SD, 65.3±4.2y; range, 60–72).

Intervention

rMV (100Hz, 300–500μm, in three 10-minute sessions a day for 3 consecutive days) was applied to voluntary contracted quadriceps (vibrated and contracted group) and relaxed quadriceps (vibrated and relaxed group). A third group received placebo stimulation (nonvibrated group).

Main Outcome Measures

Area of sway of the center of pressure, vertical jump height, and leg power.

Results

Twenty-four hours after the end of the complete series of applications, the area of sway of the center of pressure decreased significantly by approximately 20%, vertical jump increased by approximately 55%, and leg power increased by approximately 35%. These effects were maintained for at least 90 days after treatment.

Conclusions

rMV is a short-lasting and noninvasive protocol that can significantly and persistently improve muscle performance in sedentary young-elderly women.     

Ivabradine: Beyond heart rate control

Chronic stable angina pectoris (CSAP) usually occurs in patients with coronary artery disease (CAD) that affects one or more large epicardial arteries. It results when myocardial perfusion is insufficient to meet cardiac metabolic demand. Elevated heart rate (HR) is an important factor in the development of myocardial ischemia and angina pectoris. The pharmacologic agents most commonly administered in the treatment of CSAP are β-blockers and calcium channel blockers (CCBs). However, the use of β-blockers is limited by poor compliance related to contraindications and comorbidities, especially in elderly patients. Ivabradine is a new selective HR-lowering agent that selectively inhibits the pacemaker current I _f in the sinus atrial node. In several randomized controlled trials, ivabradine 5–10 mg twice daily has demonstrated equivalent anti-ischemic and anti-anginal activity to β-blockers and CCBs, with a good safety and tolerability profile. Although ivabradine has been shown not to improve cardiac outcomes in patients with stable CAD and left ventricular systolic dysfunction, it may be used to reduce the incidence of CAD outcomes in a subgroup of patients with HR ≥70 bpm. The aim of this short review is to summarize the use of ivabradine in the treatment of CSAP, and its potential utility in atherosclerosis, primitive and dilatative cardiomyopathy, and arrhythmias, such as postural tachycardia syndrome and inappropriate sinus tachycardia, where exclusive lowering of elevated HR may prove beneficial.     

Single-photon emission computed tomography/computed tomography in brain tumors

Anatomic imaging procedures (computed tomography [CT] and magnetic resonance imaging [MRI]) have become essential tools for brain tumor assessment. Functional images (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]) can provide additional information useful during the diagnostic workup to determine the degree of malignancy and as a substitute or guide for biopsy. After surgery and/or radiotherapy, nuclear medicine examinations are essential to assess persistence of tumor, to differentiate recurrence from radiation necrosis and gliosis, and to monitor the disease. The combination of functional images with anatomic ones is of the utmost importance for a full evaluation of these patients, which can be obtained by means of imaging fusion. Despite the fast-growing diffusion of PET, in most cases of brain tumors, SPECT studies are adequate and provide results that parallel those obtained with PET. The main limitation of SPECT imaging with brain tumor-seeking radiopharmaceuticals is the lack of precise anatomic details; this drawback is overcome by the fusion with morphological studies that provide an anatomic map to scintigraphic data. In the past, software-based fusion of independently performed SPECT and CT or MRI demonstrated usefulness for brain tumor assessment, but this process is often time consuming and not practical for everyday nuclear medicine studies. The recent development of dual-modality integrated imaging systems, which allow the acquisition of SPECT and CT images in the same scanning session, and their co-registration by means of the hardware, has facilitated this process. In SPECT studies of brain tumors with various radiopharmaceuticals, fused images are helpful in providing the precise localization of neoplastic lesions, and in excluding the disease in sites of physiologic tracer uptake. This information is useful for optimizing diagnosis, therapy monitoring, and radiotherapy treatment planning, with a positive impact on patient management.     

Evaluating the role of the genetic variations of PTPN22, NFKB1, and FcGRIIIA genes in inflammatory bowel disease: a meta-analysis

BACKGROUND: We tested several polymorphisms of genes involved in the mucosal immune system in a population of inflammatory bowel disease (IBD) patients to investigate their possible implication in disease predisposition. METHODS: Polymorphisms of 3 candidate genes (PTPN22, NFkB1, and FcGRIIIA) were investigated in 649 IBD patients (343 with Crohn's disease [CD] and 306 with ulcerative colitis [UC]), 176 unaffected relatives, and 256 healthy controls. Allele and genotype frequencies were correlated with clinical characteristics and major variants of the CARD15 gene. Our findings were pooled in a meta-analysis with the available studies in the literature. RESULTS: No significant difference for the PTPN22 and NFkB1 variants was found. In contrast, allele and genotype frequencies of the G559T allele of the FcGRIIIA gene were significantly different in CD patients compared to controls (allele T 12% versus 8%, odds ratio [OR] = 1.58, 95% confidence interval [CI] 1.06-2.35; GT genotype 23% versus 16%, OR = 1.64, 95% CI = 1.08-2.5). However, no significant overtransmission of the T allele was confirmed at the family-based analysis. For all genes, neither an interaction with CARD15 gene, nor a significant difference at genotype/phenotype analysis was demonstrated, included response to medical therapy. CONCLUSIONS: Although involved in autoimmune diseases, the PTPN22 and NFkB1 genes do not seem involved in the IBD predisposition, also according to meta-analysis results. The association with the G559T polymorphism of the FcGRIIIA gene in CD patients deserves further investigation.     

Is a Dual‐Sensor Pacemaker Appropriate in Patients with Sino‐Atrial Disease? Results from the DUSISLOG Study

BACKGROUND: Rate-responsive pacemakers (PMs) are often supplied with accelerometer (XL) and minute ventilation (MV) sensors to provide a physiologic rate response according to patient needs. No information is available about the real benefit of dual-sensor rate-responsive pacing on the daily life of patients. METHODS: DUSISLOG (Dual Sensor vs Single Sensor comparison using patient activity LOGbook) is a two-arm prospective, randomized, multicenter study that enrolled 105 patients who received a rate-responsive PM (Insignia), Guidant Corp.). After 1 month of DDD pacing at 60 ppm lower rate, a single sensor (XL or MV, randomized) was activated for 3 months at the manufacturer's suggested nominal settings, followed by a 3-month period with dual sensors optimized with automatic response. During the last month of each period, the following data concerning patient physical activity were retrieved from PM diagnostics (Activity Log): mean percentage of physical activity, mean intensity of activity. Quality of life (QoL) scores and 6-minute walk test (WT) were also recorded. RESULTS: Single-sensor rate-responsive pacing resulted in symptomatic benefit equally with XL and MV sensors while no additional benefit was found using dual sensor. In a subgroup analysis, patients (17%) with marked chronotropic incompetence and with 0% atrial sensing received benefits from single sensor with an additional advantage from sensor (QoL: +21 +/- 14% P < 0.05; WT: +17 +/- 7% P < 0.02). CONCLUSION: In most patients with rate-responsive devices, a single sensor is sufficient to achieve a satisfactory rate response. A dual sensor combination and optimization provides an additional benefit only in a selected population with an advanced atrial chronotropic disease.