Randomized Crossover Trial of Phosphate-binding Medication on Serum Phosphate Levels in Patients With Aortic Stenosis

PurposeAortic stenosis is a common cause of valvular heart disease with no means of prevention. The recognized association between aortic stenosis and serum phosphate raises the possibility of preventing progression of the disorder by using phosphate-binding drugs, but there is uncertainty whether such treatment lowers serum phosphate levels in patients without diagnosed renal failure. This pilot study was conducted to answer this question in patients with aortic stenosis.MethodsA randomized, double-blind, crossover trial of the phosphate-binding drug sevelamer was conducted in 72 patients. Patients were prescribed sevelamer 0.8 g (low-dose), sevelamer 2.4 g (high-dose), and matching placebo, 3 times daily with food; each regimen lasted 6 weeks and was allocated at random. Serum phosphate levels were measured at the end of each treatment period, and within-person levels were compared.FindingsSixty-one patients completed the 3 treatment periods. There was no significant difference in the mean end-treatment phosphate levels across all patients (3.38, 3.36, and 3.31 mg/dL with placebo, low-dose sevelamer, and high-dose sevelamer, respectively). Post hoc analysis showed a reduction in phosphate levels with increasing sevelamer dose in the highest baseline phosphate quartile group; a 0.3 mg/dL reduction (mean, 4.09 mg/dL with placebo, 3.95 mg/dL with low-dose sevelamer, and 3.79 mg/dL with high-dose sevelamer; P_trend = 0.027).ImplicationsSevelamer had no overall statistically significant effect in lowering serum phosphate levels, but a reduction was observed in patients with phosphate levels in the highest quartile group of the population distribution. This hypothesis-generating result requires confirmation in an independent study. If confirmed, a trial of sevelamer in preventing the progression of aortic stenosis may be justified in patients with high phosphate levels. ISRCTN Registry identifier: ISRCTN17365679.     

Is stenting for atherosclerotic renal stenosis an effective technique?

IntroductionOne of the treatments for renal artery stenosis is endovascular intervention, but its effectiveness is controversial. The present study aims to analyze the experience of a working group in the endovascular treatment of selected patients with severe obstructive atherosclerotic lesions of the renal arteries, and to characterize early and late results.MethodsThis is a retrospective study of symptomatic patients with atherosclerotic renal artery stenosis who underwent endoluminal therapy between May 12, 1999 and March 12, 2015 at two institutions. Statistical analysis was performed using the PASW Statistics program.ResultsA total of 99 patients were treated, mean age 66 years and 76.8% male. The mean degree of stenosis measured by renal Doppler echocardiography was 83% and 64.6% were ostial lesions. Mean preoperative creatinine level was higher than the postoperative mean: 1.3 vs. 1.2 mg/dl (p=0.014). The number of antihypertensive drugs in the preoperative period was higher than in the postoperative period: 2.0 vs. 1.3 (p=0.001). The mean follow-up was 40 months (0-164). The mean peak systolic velocity over time in the postoperative period was 77 cm/s (40-250). The restenosis rate was 8%, and 30-day mortality was 0%.ConclusionsThe results demonstrated that the endovascular technique has a beneficial effect on blood pressure and renal function in selected patients, and is a safe technique associated with a high rate of technical success and few complications.     

微创和传统开放后路腰椎椎间融合术治疗腰椎退行性疾病的远期预后

目的探讨微创后路腰椎椎间融合术(MIS-PLIF)和传统开放PLIF对腰椎退行性疾病(LDD)远期疗效及安全性的影响。方法 2011年1月-2014年12月收治LDD患者182例,其中96例采用传统开放PLIF治疗(PLIF组),86例采用MIS-PLIF治疗(MIS-PLIF组)。比较2组腰椎矢状位参数、多裂肌横截面积及萎缩率、融合率、疼痛视觉模拟量表(VAS)评分、日本骨科学会(JOA)评分、Oswestry功能障碍指数(ODI)及术后并发症发生情况,分析多裂肌萎缩率与顽固性腰背痛的相关性。结果 2组术后各随访时间点椎间隙高度恢复值和节段性前凸角恢复值差异均无统计学意义(P > 0.05)。2组术后1年腰椎前凸角恢复值差异无统计学意义(P > 0.05);但术后5年和末次随访时,MIS-PLIF组腰椎前凸角恢复值显著高于PLIF组,差异均有统计学意义(P < 0.05)。MIS-PLIF组术后各随访时间点多裂肌横截面积大于PLIF组,多裂肌萎缩率低于PLIF组,差异均有统计学意义(P < 0.05)。2组术后随访6个月融合率差异无统计学意义(P > 0.05)。2组术后各随访时间点下肢痛VAS评分差异无统计学意义(P > 0.05);MIS-PLIF组术后各随访时间点腰痛VAS评分、JOA评分及ODI均优于PLIF组,差异有统计学意义(P < 0.05)。MIS-PLIF组顽固性腰背痛发生率显著低于PLIF组,差异有统计学意义(P < 0.05)。合并顽固性腰背痛患者多裂肌萎缩率高于未合并顽固性腰背痛的患者,差异有统计学意义(P < 0.05)。结论术后多裂肌萎缩可能是导致顽固性腰背痛的重要原因,相较于传统开放PLIF,MIS-PLIF治疗LDD能够更有效地保持腰椎生理曲度,改善肢体活动功能,降低多裂肌萎缩程度,有助于避免顽固性腰背痛的发生。     

The fate of aortic valve after rheumatic mitral valve surgery

ObjectiveDeterioration of the native aortic valve function by a late progression of rheumatic disease is not infrequent in patients who underwent rheumatic mitral valve surgery; however, this phenomenon has not been clearly quantified.MethodsA total of 1155 consecutive patients (age 52.0 ± 12.9 years; 807 female) who underwent rheumatic mitral valve surgery without concomitant aortic valve surgery from 1997 to 2015 were enrolled. The primary end point was the composite of progression to severe aortic valve dysfunction or a requirement of subsequent aortic valve replacements during follow-up. To determine the risk factors of the primary outcome, we performed the generalized linear mixed model.ResultsThe baseline severities of aortic valve were none to trivial in 880 patients (76.2%), mild in 256 patients (22.2%), and moderate in 19 patients (1.6%). The latest 1062 echocardiographic assessments (91.9%; median, 81.2 postoperative months; interquartile range, 37.3-132.1 months) demonstrated 26 cases (0.33%/patient-year) meeting the primary end point during follow-up. Cumulative incidence of the primary end point at 10 years was 0.4% ± 0.3% and 7.4% ± 2.5% depending on the presence of mild or greater aortic valve dysfunction at baseline (P < .01). In multivariable analyses, aortic valve peak pressure gradient (odds ratio, 1.14; 95% confidence interval, 1.10-1.20), aortic regurgitation degree (mild over none: odds ratio, 3.26; 95% confidence interval, 1.15-9.23), and time (odds ratio, 1.30; 95% confidence interval 1.19-1.41) were significantly associated with the occurrence of the primary end point.ConclusionsProgression of severe aortic valve dysfunction and the need for aortic valve replacement are uncommon in patients undergoing rheumatic mitral valve surgery. However, such events were relatively common among those with mild or greater aortic valve dysfunction at the time of mitral valve surgery.     

Une cause rare d’hypertension artérielle pulmonaire : l’amylose thoracique

Isolated thoracic involvement in amyloidosis is a rare and serious condition. Its association with pulmonary arterial hypertension (PAH) usually weakens the prognosis. We report the case of a 40-year-old man with a smoking history, hospitalized for chest pain, abdominal pain and acute respiratory distress. The cardiac ultrasound revealed a circumferential pericardial effusion as well as a pulmonary artery systolic pressure (PAPS) at 80 mmHg. Chest imaging (computed tomography scan and magnetic resonance imaging) showed a tissue process developed in the pericardial sheath (60 × 45 mm) sheathing the ascending aorta and infiltrating the trunk of the pulmonary artery and its right branch. Anatomopathological and immunohistochemical study of the process revealed AL amyloidosis. Note that the patient had no signs of extrathoracic amyloidosis. Blood and urine electrophoresis and immunoelectrophoresis as well as bone marrow mylogram and biopsy were normal. The patient was put on oral anticoagulant as he presented with PAH. A therapeutic protocol with thalidomide and dexamethasone has been initiated. The course of the disease was marked by total regression of the clinical signs, a marked decrease in the amyloid process on imaging and a normalization of the PAPS; our follow-up being three years.     

New advances in Amyotrophic Lateral Sclerosis genetics: Towards gene therapy opportunities for familial and young cases

Due to novel gene therapy opportunities, genetic screening is no longer restricted to familial cases of ALS (FALS) cases but also aplies to the sporadic populations (SALS). Screening of four main genes (C9orf72, SOD1, TARDBP and FUS) identified the causes in 15% of Amyotrophic Lateral Sclerosis (ALS) patients (two third of the familial cases and 8% of the sporadic ones) but their respective contribution to ALS phenotype varies according the age of disease onset. The genetic overlap between ALS and other diseases is expanding and includes frontotemporal dementia, Paget's Disease of Bone, myopathy for adult cases, HSP and CMT for young cases highlighing the importance of retrieving the exhaustive familial history for each indivdual with ALS. Incomplete disease penetrance, diversity of the possible phenotypes, as well as the lack of confidence concerning the pathogenicity of most identified variants and/or possible oligogenic inheritance are burdens of ALS genetic counseling to be delivered to patients and at risk individuals. The multitude of rare ALS genetic causes identifed seems to converge to similar cellular pathways leading to inapropriate response to stress emphacising new potential therapeutic options for the disease.     

Spatial Filtering of Electroencephalography Reduces Artifacts and Enhances Signals Related to Spinal Cord Stimulation (SCS)

ObjectivesHow spinal cord stimulation (SCS) in its different modes suppresses pain is poorly understood. Mechanisms of action may reside locally in the spinal cord, but also involve a larger network including subcortical and cortical brain structures. Tonic, burst, and high-frequency modes of SCS can, in principle, entrain distinct temporal activity patterns in this network, but finally have to yield specific effects on pain suppression. Here, we employ high-density electroencephalography (EEG) and recently developed spatial filtering techniques to reduce SCS artifacts and to enhance EEG signals specifically related to neuromodulation by SCS.Materials and MethodsWe recorded high-density resting-state EEGs in patients suffering from pain of various etiologies under different modes of SCS. We established a pipeline for the robust spectral analysis of oscillatory brain activity during SCS, which includes spatial filtering for attenuation of pulse artifacts and enhancement of brain activity potentially modulated by SCS.ResultsIn sensor regions responsive to SCS, neuromodulation strongly reduced activity in the theta and low alpha range (6–10 Hz) in all SCS modes. Results were consistent in all patients, and in accordance with thalamocortical dysrhythmia hypothesis of pain. Only in the tonic mode showing paresthesia as side effect, SCS also consistently and strongly reduced high-gamma activity (>84 Hz).ConclusionsEEG spectral analysis combined with spatial filtering allows for a spatially and temporally specific assessment of SCS-related, neuromodulatory EEG activity, and may help to disentangle therapeutic and side effects of SCS.