Chronic Cerebrospinal Venous Insufficiency Research Articles

Clinical Classification and Collateral Circulation in Chronic Cerebrospinal Venous Insufficiency.

Background: As an indispensable part of the cerebral venous system, the extracranial cerebrospinal venous system is not fully recognized. This study aimed to analyze the clinical classification and imaging characteristics of chronic cerebrospinal venous insufficiency (CCSVI) quantitatively.Methods: A total of 128 patients, who were diagnosed as CCSVI by jugular ultrasound and contrast-enhanced magnetic resonance venography (CE-MRV), were enrolled from May 2018 through May 2019. For the patients with possible extraluminal compression, computed tomography venography (CTV) was applied to estimate the degree of internal jugular venous stenosis (IJVS) and rank the vertebral venous collateral circulation.Results: The causes of extraluminal compression induced IJVS included osseous compression (78.95%), carotid artery (24.21%), sternocleidomastoid muscle (5.79%), swollen lymph node (1.05%), and unknown reasons (5.26%). The subtypes of non-compression CCSVI included the high jugular bulb (77.27%), fenestration of the internal jugular vein (IJV) (7.27%), internal jugular phlebectasia (2.73%), tortuous IJV (0.91%), IJV thrombosis (14.55%), and elongated venous valves with/without erythrocyte aggregation (13.64%). For extraluminal compression induced IJVS, the ratio of severe vertebral venous expansion was higher in the severe IJVS group than that in the mild IJVS group (p < 0.001). The IJVS degree was higher in the severe vertebral venous expansion group than in the mild vertebral venous expansion group (p < 0.001).Conclusions: A multimodal diagnostic system is necessary to improve the diagnostic accuracy of CCSVI. The vertebral venous system is an important collateral circulation for CCSVI, which may be a promising indicator for evaluating IJVS degree.

Neural correlates of subjective arousal and valence in health and panic disorder

Aberrant emotion processing is a core characteristic of panic disorder (PD). Findings concerning the underlying neural pathways remain inconsistent. We applied functional magnetic resonance imaging (fMRI) in the context of a task based on the circumplex model of affect. This model links affective states to two underlying neurophysiological systems: arousal and valence. Twenty-two healthy participants and 20 participants with PD rated arousal and valence in response to affective faces during fMRI. In healthy controls, we found that arousal modulated the hemodynamic response in the parahippocampus, the ventromedial prefrontal cortex and the cuneus during face perception. Valence and extreme ratings of valence modulated the hemodynamic response in temporal, parietal, somatosensory, premotor and cerebellar regions. Comparing healthy controls to participants with PD, we found that healthy controls showed a stronger modulation of the hemodynamic response during face perception associated with extreme ratings of valence in the parahippocampus and the supplementary motor area. This suggests parahippocampal dysfunction in the processing of highly valenced affective faces in PD, which may underlie aberrant contextualization of strong affective stimuli. Our findings need to be interpreted with care as they were adjusted for multiple comparisons using a liberal correction procedure.

Chronic cerebrospinal venous insufficiency, ten years after. New headlights on a venous disease that enriched the vascular world

Two very recent scientific papers have re-opened a debate on a vascular issue, chronic cerebrospinal venous insufficiency (CCSVI), that apparently was sent in a corner by other trials and some Editorial hasty conclusions. The never-ending debate is still open and, perhaps, a one-year truce helped to calm waters and sort out, as by means of a sandbox, the situation from the vascular point of view. Before discussing why these recent papers have widened the path for CCSVI, some mind refreshing is mandatory, since the opinions are spread in all directions and a concise summary may help for those that are newcomers in this issue...

An overview of randomized controlled trials on endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis patients

AbstractAbout ten years ago it was hoped that venous angioplasty for abnormal veins, primarily the internal jugular veins, will be a much awaited treatment for multiple sclerosis. Yet, a majority of randomized clinical trials on endovascular treatment for chronic cerebrospinal venous insufficiency did not reveal clinical efficacy of these procedures in multiple sclerosis patients. Still, a detailed analysis of these trials suggests that they were poorly designed, underpowered and endovascular techniques used were often far from being optimal. Nonetheless, even considering weak points of these trials, it can be concluded that venous angioplasty should not be used as a routine treatment modality in multiple sclerosis patients. Still, a possibility that some patients may benefit from endovascular treatment cannot be ruled out. This may concern patients at early stage of the disease and presenting with lesions that can easily be managed with balloon angioplasty. Therefore, we need more studies evaluating clinical efficacy of venous angioplasty in selected subgroups of multiple sclerosis patients. Importantly, it has already been demonstrated that venous angioplasty in multiple sclerosis patients is a safe procedure. Thus, also from an ethical point of view, such trials seem justifiable.

Three patterns of chronic cerebrospinal venous insufficiency in Ménière syndrome patients: Diagnosis and treatment options

Identification techniques of the three different chronic cerebrospinal venous insufficiency patterns and related treatment options are in an initial phase of evaluation and analysis. Our purpose is to describe the appropriate management, proposing a tailored approach for each one. We identified three different Ménière syndrome patients in our Audiology Department, diagnosing the corresponding chronic cerebrospinal venous insufficiency pattern by Echo-color Doppler ultrasound evaluation and treating by venous angioplasty or rehabilitative treatment according to the internal jugular and vertebral veins anomalies found in each patient. According to the pattern, after specific treatment, echo-color-Doppler control analysis revealed a normalized venous outflow correlated to Ménière symptoms reduction and/or progressive disappearance during one year follow up. An adequate analysis of venous cerebral and ear outflow and a tailored treatment may represent an effective option when chronic cerebrospinal venous insufficiency is correctly diagnosed.

Commentary: “Brave Dreams” Reanalysis Sheds New Light on Angioplasty for Venous Anomalies in Some Multiple Sclerosis Patients With Chronic Cerebrospinal Venous Insufficiency

Commentary: “Brave Dreams” Reanalysis Sheds New Light on Angioplasty for Venous Anomalies in Some Multiple Sclerosis Patients With Chronic Cerebrospinal Venous Insufficiency

Exploring the Mediascape from the Epistemologies of the South

Dominant literature on media and communication studies has insistently equated mediascape and high technology media as interchangeable concepts and realities instead of high technological media as part of a broader and more dynamic media pallet. By subscribing to this “technology- driven Darwinism”, we argue that existing dominant literature explicitly and implicitly excludes forms of mass communication that go beyond the media in its Western liberal form and procedures and, consequently, other voices, knowledge and messages. This article analyses the modern conception of media by exploring the “abyssal exclusions” (Santos, 2007) it creates. To illustrate this further, we have selected the top five 2018 SCOPUS-indexed journals, from which we gathered a sample of 116 research articles that were published between 2016-2018, to shed light on some of the most recent research trends in media studies. The definition of media used by the articles contained in our sample shows that there is a technological and modernity-driven spectrum which is fundamental in defining what is and what progressively is no longer labelled, and hence considered, media. This understanding of the media fails to include forms of mass communication that go beyond the media in its western liberal form and, consequently, exclude subaltern voices, knowledges and messages.

Justicia popular: el castigo de la comunidad en España, 1895-1923

El artículo analiza las numerosas tentativas de linchamiento popular que tuvieron lugar en la España de la Restauración. El principal objetivo reside en esclarecer las causas, lógicas y procesos históricos de este fenómeno de violencia colectiva. Para ello, se examinan los comportamientos sociales que suscitaron este tipo de reacción popular, las prácticas sociales, significados culturales y usos políticos que se manifestaban en estas expresiones de violencia y su relación con los procesos y estructuras políticas del Estado. Consideradas en el pasado como estallidos de ira y venganza propios de una sociedad atrasada, estas formas de violencia revelan el propósito de castigar una infracción que rebasaba los límites de lo tolerado por la comunidad, formas propias de entender la justicia y una preocupación compartida por mantener normas de conducta que preservasen ciertos modos de convivencia e integridad de la población. A su vez, estas acciones descubren la existencia de otras prácticas de castigo en la sociedad muy diferentes a los procedimientos liberales, que pudieron persistir o alimentarse en un contexto de desconfianza y descrédito de los representantes públicos e instituciones del Estado. La investigación se funda en la exploración de la prensa nacional y provincial, las fuentes gubernamentales, judiciales y bibliográficas

Experience of using vasoactive therapy in patients with stage I-II venous discirculatory encephalopathy

Introduction. We present the results of our own observational cohort study of patients with stage I-II discirculatory encephalopathy treated with a combination of dihydroergocriptine and caffeine (Vazobral®). Interest in this issue is due to the fact that cerebrospinal venous insufficiency plays a role in the pathogenesis of neurodegenerative and vascular diseases of the brain, leading to the development of cognitive impairment, the formation of secondary headaches, and reducing the quality of life of patients.The purpose of the study was to evaluate the effectiveness and safety of the drug Vazobral® in patients with stage I-II discirculatory encephalopathy due to venous discirculation in the presence of chronic cerebrospinal venous insufficiency.Material and methods: 102 outpatients (average age 63.5 ± 3.74 years, 25 (25.5%) men and 77 (74.5%) women) suffering from chronic cerebral ischemia and having signs of chronic cerebrospinal venous insufficiency . Stage I dyscirculatory encephalopathy with mild cognitive impairment was diagnosed in 58 (59.2%) patients, stage II dyscirculatory encephalopathy with mild cognitive impairment was diagnosed. All observed had a duplex scan of the branches of the aortic arch, jugular and vertebral veins, with a measurement of the linear velocity of blood flow; the intensity of headaches, cognitive status, the severity of affective syndrome using special questionnaires were evaluated. For 3 months, patients took Vazobral® 8/80 mg per day. The data obtained were analyzed using computer programs SPSS and Statistica. Significance of differences – with a 95% CI, p &lt;0.05.Results. Significant positive dynamics was observed in patients with Vazobral®: a decrease in headache intensity (from 4.11 to 0.67 points), cognitive function assessment increased by 14% from the initial level, the severity of the anxiety-depressive symptom complex, significantly decreased by 38–56%Conclusion. The drug Vazobral® can be recommended to increase the effectiveness of the treatment of patients suffering from stage I-II discirculatory encephalopathy with venous discirculation phenomena.

Effects of Venous Angioplasty on Cerebral Lesions in Multiple Sclerosis: Expanded Analysis of the Brave Dreams Double-Blind, Sham-Controlled Randomized Trial

Purpose: To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI). Materials and Methods: The Brave Dreams trial ( ClinicalTrials.gov identifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a post hoc assessment, venograms of patients who underwent venous angioplasty were graded as “favorable” (n=38) or “unfavorable” (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared. Results: Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005). Conclusion: Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Post hoc analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.

Potential Involvement of Impaired Venous Outflow from the Brain in Neurodegeneration: Lessons Learned from the Research on Chronic Cerebrospinal Venous Insufficiency.

About 10 years ago, the so-called chronic cerebrospinal venous insufficiency syndrome was discovered. This clinical entity, which is associated with extracranial venous abnormalities that impair venous outflow from the brain, was initially found exclusively in multiple sclerosis patients. Currently, we know that such venous lesions can also be revealed in other neurological pathologies, including Alzheimer's and Parkinson's diseases. Although direct causative role of chronic cerebrospinal venous insufficiency in these neurological diseases still remains elusive, in this paper, we suggest that perhaps an abnormal venous drainage of the brain affects functioning of the glymphatic system, which in turn results in the accumulation of pathological proteins in the cerebral tissue (such as β-synuclein, β-amyloid and α-synuclein) and triggers the venous outflow from the cranial cavity and circulation of the cerebrospinal fluid in the settings of neurodegenerative disease.

Modeling the Liberation of Comminuted Scheelite Using Mineralogical Properties

In this paper, the modeling of the liberation of scheelite is presented. A pattern of concentration experiments was performed to investigate the scheelite liberation and distribution density calculation procedure. In this work, one sample from a Mittersill tungsten ore was studied. This work describes a method for determining the downstream milling energy requirements for rod mill products based on a Bond mill test performance. The grade distribution of particles at a given size fraction was calculated using a predictive liberation model. The concentration behavior of these particles in size fractions was evaluated using batch concentrate tests. The recovery of particles in size/grade classes, image analysis using mineral liberation analysis (MLA), and function calculations were implemented for the modeling of the liberation. By describing the size, grade, and recovery data of particles in size/grade classes, a technique for the measurement of distribution functions was developed that relates beta distribution, a model for the function based on the incomplete beta function, and a solution to produce liberation modeling. It was shown that the predicted results agreed well with the observed results. With a procedure for measuring the liberation, it was possible to carry out the first experimental measurement of the beta distribution. This liberation/concentrate model has wide potential applications for metallurgy and plant design, where the liberation modeling is to be determined with the distribution density solution to the predictive mineral liberation function equation, which includes the liberation of ore samples and their liberation characteristics.

Percutaneous Venous Angioplasty in Patients with Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency: A Randomized Wait List Control Study

Venous percutaneous transluminal angioplasty (vPTA) in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) have shown contradictory results. The aim of the study is to evaluate the efficacy of the procedure in a randomized wait list control study. 66 adults with neurologist-confirmed diagnosis of MS and sonographic diagnosis of CCSVI were allocated into vPTA-yes group (n=31) or vPTA-not group (n=35, control group). vPTA was performed immediately 15days after randomization in the PTA-yes group and 6months later in the control group. Evoked potentials (EPs), clinical-functional measures (CFMs), and upper limb kinematic measures (ULKMs) were measured at baseline (T0) and six months after in both groups, just before the venous angioplasty in the vPTA-not group (T1). Comparing the vPTA-yes and vPTA-not group, the CFM-derived composite functional outcome showed 11 (37%) versus 7 (20%) improved, 1 (3%) versus 3 (8%) stable, 0 versus 7 (20%) worsened, and 19 (61%) versus 18 (51%) mixed patients (χ2=8.71, df=3, P=0.03). Unadjusted and adjusted (for baseline confounding variables) odds ratio at 95% confidence interval were, respectively, 1.93 (1.3-2.8), P value 0.0007, and 1.85 (1.2-1.7), P value 0.002. EP- and ULKM-derived composite functional outcome showed no significant difference between the two groups. Venous angioplasty can positively impact a few CFMs especially for the quality of life but achieving disability improvement is unlikely.

Reader response: Safety and efficacy of venoplasty in MS: A randomized, double-blind, sham-controlled phase II trial.

It is very strange that Traboulsee et al.1 did not publish any MRI data; this does not allow a meta-analysis comparison with other trials. The Brave Dreams trial2 examined patients with relapsing-remitting MS (RRMS) undergoing percutaneous transluminal angioplasty (PTA) for chronic cerebrospinal venous insufficiency, and this Canadian study contains a mixed population of RRMS and secondary-progressive MS.1 Furthermore, a population with a mean age of 50 years and a disease duration of 17 years is not an acceptable study group for PTA

No association between variations in extracranial venous anatomy and clinical outcomes in multiple sclerosis patients over 5\u2009years

BackgroundNo longitudinal, long-term, follow-up studies have explored the association between presence and severity of variations in extracranial venous anatomy, and clinical outcomes in patients with multiple sclerosis (MS).ObjectiveThis prospective 5-year follow-up study assessed the relationship of variations in extracranial venous anatomy, indicative of chronic cerebrospinal venous insufficiency (CCSVI) on Doppler sonography, according to the International Society for Neurovascular Disease (ISNVD) proposed consensus criteria, with clinical outcomes and disease progression in MS patients.Methods90 MS patients (52 relapsing-remitting, RRMS and 38 secondary-progressive, SPMS) and 38 age- and sex-matched HIs were prospectively followed for 5.5 years. Extracranial and transcranial Doppler-based venous hemodynamic assessment was conducted at baseline and follow-up to determine the extent of variations in extracranial venous anatomy. Change in Expanded Disability Status Scale (∆EDSS), development of disability progression (DP) and annualized relapse rate (ARR) were assessed.ResultsNo significant differences were observed in MS patients, based on their presence of variations in extracranial venous anatomy at baseline or at the follow-up, in ∆EDSS, development of DP or ARR. While more MS patients had ISNVD CCSVI criteria fulfilled at baseline compared to HIs (58% vs. 37%, p = 0.03), no differences were found at the 5-year follow-up (61% vs. 56%, p = 0.486).DiscussionThis is the longest follow-up study assessing the longitudinal relationship between the presence of variations in extracranial venous anatomy and clinical outcomes in MS patients. Conclusion: The presence of variations in extracranial venous anatomy does not influence clinical outcomes over the 5-year follow-up in MS patients.

Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency (CCSVI) in people with multiple sclerosis.

Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. The most widely accepted hypothesis regarding its pathogenesis is that it is an immune-mediated disease. It has been hypothesised that intraluminal defects, compression, or hypoplasia in the internal jugular or azygos veins may be important factors in the pathogenesis of MS. This condition has been named 'chronic cerebrospinal venous insufficiency' (CCSVI). It has been suggested that these intraluminal defects restrict the normal blood flow from the brain and spinal cord, causing the deposition of iron in the brain and the eventual triggering of an auto-immune response. The proposed treatment for CCSVI is venous percutaneous transluminal angioplasty (PTA), which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS. This is an update of a review first published in 2012. To assess the benefit and safety of venous PTA in people with MS and CCSVI. We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's Specialised Register up to 30 August 2018, CENTRAL (in the Cochrane Library 2018, issue 8), MEDLINE up to 30 August 2018, Embase up to 30 August 2018, metaRegister of Controlled Trials, ClinicalTrials.gov., the Australian New Zealand Clinical Trials Registry, and the World Health Organization (WHO) International Clinical Trials Registry platform. We examined the bibliographies of the included and excluded studies. We included randomised controlled trials (RCTs) in which PTA and sham interventions were compared in adults with MS and CCSVI. Two authors independently assessed study eligibility and risk of bias, and extracted data. We reported results as risk ratios (RR) with 95% confidence intervals (CI). We performed statistical analyses using the random-effects model; and we assessed the certainty of the evidence using GRADE. We included three RCTs (238 participants) in this update. One hundred and thirty-four participants were randomised to PTA and 104 to sham treatment. We attributed low risk of bias to two (67%) studies for sequence generation and two (67%) studies for performance bias. All studies were at a low risk of detection bias, attrition bias, reporting bias and other potential sources of bias.There was moderate-quality evidence to suggest that venous PTA did not increase the proportion of patients who had operative or post-operative serious adverse events compared with the sham procedure (RR 3.33, 95% CI 0.36 to 30.44; 3 studies, 238 participants); nor did it increase the proportion of patients who improved on a functional composite measure including walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity over 12-month follow-up (RR 0.84, 95% CI 0.55 to 1.30; 1 study, 110 participants); nor did it reduce the proportion of patients who experienced new relapses at six- or 12-month follow-up (RR 0.87, 95% CI 0.51 to 1.49; 3 studies, 235 participants). There was no effect of venous PTA on disability worsening measured by the Expanded Disability Status Scale, which was reported at follow-up intervals of six months (one study), 11 months (one study) and 12 months (one study). Quality of life was reported in two studies with no difference between treatment groups. Moderate or severe pain during or post venography was reported in both PTA and sham-procedure participants in all included studies. Venous PTA was not effective in restoring blood flow assessed at one-month (one study) or 12-month follow-up (one study). This systematic review identified moderate-quality evidence that, compared with sham procedure, venous PTA intervention did not provide benefit on patient-centred outcomes (disability, physical or cognitive functions, relapses, quality of life) in people with MS. Venous PTA has proven to be a safe technique but in view of the available evidence of its ineffectiveness, this intervention cannot be recommended in people with MS. All ongoing trials were withdrawn or terminated and hence this updated review is conclusive. No further randomised clinical studies are needed.

Hemodynamics of cerebral veins analyzed by 2d and 4d flow mri and ultrasound in healthy volunteers and patients with multiple sclerosis.

Hemodynamic alterations of extracranial veins are considered an etiologic factor in multiple sclerosis (MS). However, ultrasound and MRI studies could not confirm a pathophysiological link. Because of technical challenges using standard diagnostics, information about the involvement of superficial intracranial veins in proximity to the affected brain in MS is scarce. To comprehensively investigate the hemodynamics of intracranial veins and of the venous outflow tract in MS patients and controls. Prospective. Twenty-eight patients with relapsing-remitting MS (EDSS1.9 ± 1.1; range 0-3) and 41 healthy controls. 3T/2D phase-contrast and time-resolved 4D flow MRI, extra- and transcranial sonography. Hemodynamics within the superficial and deep intracranial venous system and outflow tract including the internal, basal, and great cerebral vein, straight, superior sagittal, and transverse sinuses, internal jugular and vertebral veins. Sonography adhered to the chronic cerebrospinal venous insufficiency (CCSVI) criteria. Multivariate repeated measure analysis of variance, Student's two-sample t-test, chi-square, Fisher's exact test; separate analysis of the entire cohort and 32 age- and sex-matched participants. Multi- and univariate main effects of the factor group (MS patient vs. control) and its interactions with the factor vessel position (lower flow within dorsal superior sagittal sinus in MS, 3 ± 1 ml/s vs. 3.8 ± 1 ml/s; P < 0.05) in the uncontrolled cohort were attributable to age-related differences. Age- and sex-matched pairs showed a different velocity gradient in a single segment within the deep cerebral veins (great cerebral vein, vena cerebri magna [VCM] 7.6 ± 1.7 cm/s; straight sinus [StS] 10.5 ± 2.2 cm/s vs. volunteers: VCM 9.2 ± 2.3 cm/s; StS 10.2 ± 2.3 cm/s; P = 0.01), reaching comparable velocities instantaneously downstream. Sonography was not statistically different between groups. Consistent with previous studies focusing on extracranial hemodynamics, our comprehensive analysis of intracerebral venous blood flow did not reveal relevant differences between MS patients and controls. Level of Evidence 1. Technical Efficacy Stage 3. J. Magn. Reson. Imaging 2020;51:205-217.

Consent, democracy and the future of liberalism

In this paper, I examine the ways in which liberal theory and democratic procedure have sought to address the justificatory challenge posed by the existence of coercive states, given the liberal account of individuals as naturally free and equal. In doing so, I invoke the justifications for the limited state advanced by the Austrian school of political economy, referring in particular to the work of F.A.Hayek. I argue that the scepticism this school of theory advances with regard to the effectiveness and desirability of state intervention into the affairs of free individuals, offers a better approach to understanding state legitimacy than does the ideal theory often relied upon by liberal political theorists. I further argue that the simple inclusion of majoritarian democratic procedure as the method for deciding whether, when and how states should intervene into the affairs of free individuals cannot legitimise these interventions in a manner consistent with the demands of liberalism. I finally employ the Austrian school’s scepticism about the state’s capacity to ‘do good’ to advance a proposal for reducing the degree to which any individual need be coerced by a state seeking to advance particular ends rather, than to enforce general rules.

Procedure Preference and Intention-to-Treat Outcomes after Listing for Lung Transplantation among U.S. Adults. A Cohort Study.

Bilateral lung transplantation is widely used to treat chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), on the basis of an expectation of improved survival after transplantation. Yet, waiting list mortality is higher while awaiting bilateral transplantation. The net effect of procedure preference on overall survival is unknown. To determine whether an unrestricted procedure preference is associated with improved overall outcomes after listing for lung transplantation. We performed a retrospective cohort study of 12,155 adults with COPD or ILD listed for lung transplantation in the United States between May 4, 2005, and December 31, 2014. We defined a "restricted" procedure preference as listing for "bilateral transplantation only" and an "unrestricted" procedure preference as listing for any combination of bilateral or single lung transplantation. We used a composite "intention-to-treat" primary outcome that included events both before and after transplantation, defined as the number of days between listing and death, removal from the list for clinical deterioration, or retransplantation. In adjusted analyses, an unrestricted procedure preference was associated with a 3% lower rate of the primary intention-to-treat outcome in COPD (adjusted hazard ratio [aHR], 0.97; 95% confidence interval [CI], 0.89-1.07) and a 1% higher rate in ILD (aHR, 1.01; 95% CI, 0.94-1.08). There was no convincing evidence that these associations varied by age, disease severity, or the use of mechanical support. Among those with ILD and concomitant severe pulmonary hypertension, an unrestricted preference was associated with a 17% increased rate of the primary outcome (aHR, 1.17; 95% CI, 0.99-1.39). An unrestricted preference was consistently associated with lower rates of death or removal from the list for clinical deterioration and with higher rates of transplantation. Graft failure rates were similar among those listed with restricted and unrestricted preferences. When considering outcomes both before and after transplantation, we found no evidence that patients with COPD or ILD benefit from listing for bilateral lung transplantation compared with listing for a more liberal procedure preference. An unrestricted listing strategy for suitable candidates may increase the number of transplants performed without impacting overall survival.

Prospective study of clinical, neurophysiological and urodynamic findings in multiple sclerosis patients undergoing percutaneous transluminal venous angioplasty

ObjectiveVerify whether Percutaneous Transluminal Angioplasty (PTA) may affect neural conduction properties in Multiple Sclerosis (MS) patients, thereby modifying patients’ disability, with prospective neurophysiological, urodynamic, clinical and subjective well-being evaluations. MethodsIn 55 out of 72 consecutively screened MS patients, the following procedures were carried out before (T0), at 2–6 months (T1) and at 6–15 months (T2) after a diagnostic phlebography, eventually followed by the PTA intervention if chronic cerebrospinal venous insufficiency (CCSVI) was diagnosed: clinical/objective evaluation (Expanded Disability Status Scale, EDSS), ratings of subjective well-being, evaluation of urodynamic functions and multimodal EPs (visual, acoustic, upper and lower limbs somatosensory and motor evoked potentials). ResultsThe number of dropouts was relatively high, and a complete set of neurophysiological and clinical data remained available for 37 patients (19 for urological investigations). The subjective well-being score significantly increased at T1 and returned close to basal values at T2, but their degree of objective disability did not change. Nevertheless, global EP-scores (indexing the impairment in conductivity of central pathways in multiple functional domains) significantly increased from T0 (7.9 ± 6.0) to T1 (9.2 ± 6.3) and from T0 to T2 (9.8 ± 6.3), but not from T1 and T2 (p > 0.05). Neurogenic urological lower tract dysfunctions slightly increased throughout the study. ConclusionsThe PTA intervention did not induce significant changes in disability in the present cohort of MS patients, in line with recent evidence of clinical inefficacy of this procedure. SignificanceAbsence of multimodal neurophysiological and functional testing changes in the first 15 months following PTA suggests that conduction properties of neural pathways are unaffected by PTA. Current findings suggest that the short-lived (2–6 months), post-PTA, beneficial effect on subjective well-being measures experienced by MS patients is likely related to a placebo effect.