ADC mapping of chronic cerebral hypoperfusion induced by carotid artery stenosis.

BACKGROUND: Carotid artery stenosis is associated with the occurrence of acute and chronic ischemic lesions that increase with age in the elderly population. Diffusion Imaging and ADC mapping may be an appropriate method to investigate patients with chronic hypoperfusion consecutive to carotid stenosis. This non-invasive technique allows to investigate brain integrity and structure, in particular hypoperfusion induced by carotid stenosis diseases. The aim of this study was to evaluate the impact of a carotid stenosis on the parenchyma using ADC mapping. METHODS: Fifty-nine patients with symptomatic (33) and asymptomatic (26) carotid stenosis were recruited from our multidisciplinary consultation. Both groups demonstrated a similar degree of stenosis. All patients underwent MRI of the brain including diffusion-weighted MR imaging with ADC mapping. Regions of interest were defined in the anterior and posterior paraventricular regions both ipsilateral and contralateral to the stenosis (anterior circulation). The same analysis was performed for the thalamic and occipital regions (posterior circulation). RESULTS: ADC values of the affected vascular territory were significantly higher on the side of the stenosis in the periventricular anterior (P<0.001) and posterior (P<0.01) area. There was no difference between ipsilateral and contralateral ADC values in the thalamic and occipital regions. CONCLUSIONS: We have shown that carotid stenosis is associated with significantly higher ADC values in the anterior circulation, probably reflecting an impact of chronic hypoperfusion on the brain parenchyma in symptomatic and asymptomatic patients. This is consistent with previous data in the literature.

Pulmonary hypertension associated to sarcoidosis in Switzerland

Introduction: L'hypertension pulmonaire est une complication rare de la sarcoïdose. Elle se rencontre surtout lors d'atteinte pulmonaire associée, particulièrement lorsque celle-ci est avancée. Objectif: Étudier l'épidémiologie et l'évolution clinique des patients souffrant d'hypertension pulmonaire et de sarcoïdose (SAPH) en Suisse. Méthode: Le registre suisse de l'hypertension pulmonaire a été analysé rétrospectivement pour identifier les cas SAPH de 2000 à 2011. Les paramètres cliniques, tels que le sexe, l'âge, le stade radiographique pulmonaire et l'hémodynamique sont étudiés lors de l'inscription des patients dans le registre. La classe fonctionnelle NYHA, la capacité à l'exercice (TM6M), les traitements introduits (oxygénothérapie, traitements spécifiques pour la sarcoïdose et traitements spécifiques pour l'hypertension pulmonaire), la survie et le nombre de transplantations pulmonaires effectués sont étudiés lors du suivi. Résultats: Parmi plus de 977 patients inscrits, 22 répondent aux critères d'inclusion pour la SAPH. La majorité de patients est de sexe féminin et l'âge moyen est de 59,5 +/-29,7. Le stade pulmonaire le plus souvent rencontré est de degré 4. La mPAP au diagnostic est de 44 ± 12.6 mmHg et la saturation veineuse d'oxygène est de 60%. La plupart des patients présentent une classe NYHA de 3 et le TM6M est de 368.6 ± 124.2 m à l'inclusion dans le registre. La durée moyenne du suivi des patients dans le registre est de 19.4 mois (0-57). La médiane est de 14 mois. La classe fonctionnelle NYHA et les moyennes des mètres parcourus ne montrent pas de changements significatifs lors du suivi. Au début de l'étude, comme à la fin, moins de la moitié des patients sont sous oxygénothérapie ; le traitement le plus utilisé pour l'hypertension pulmonaire est la classe des antagonistes de l'endothéline et pour la sarcoïdose les corticostéroïdes. La survie à un an est de 65 % et de 55 % à 3 ans. Pendant la période d'observation 5 patients nécessitent une transplantation pulmonaire, dont 2 sont décédés. La démarche médicamenteuse varie au cours du temps : la tendance récente est de donner plus de médicaments pour l'hypertension pulmonaire et la sarcoïdose et de favoriser les associations. Conclusion: La SAPH est une maladie rare ou tout au moins rarement diagnostiquée avec un sombre pronostic. Le degré d'hypertension est de modéré à sévère avec une limitation à l'effort importante. En cas de symptômes suggestifs chez un patient souffrant de sarcoïdose, un dépistage échocardiographique systématique devrait être proposé.

Qualitative grading of severity of lumbar spinal stenosis based on the morphology of the dural sac on magnetic resonance images.

STUDY DESIGN.: Retrospective radiologic study on a prospective patient cohort. OBJECTIVE.: To devise a qualitative grading of lumbar spinal stenosis (LSS), study its reliability and clinical relevance. SUMMARY OF BACKGROUND DATA.: Radiologic stenosis is assessed commonly by measuring dural sac cross-sectional area (DSCA). Great variation is observed though in surfaces recorded between symptomatic and asymptomatic individuals. METHODS.: We describe a 7-grade classification based on the morphology of the dural sac as observed on T2 axial magnetic resonance images based on the rootlet/cerebrospinal fluid ratio. Grades A and B show cerebrospinal fluid presence while grades C and D show none at all. The grading was applied to magnetic resonance images of 95 subjects divided in 3 groups as follows: 37 symptomatic LSS surgically treated patients; 31 symptomatic LSS conservatively treated patients (average follow-up, 2.5 and 3.1 years); and 27 low back pain (LBP) sufferers. DSCA was also digitally measured. We studied intra- and interobserver reliability, distribution of grades, relation between morphologic grading and DSCA, as well relation between grades, DSCA, and Oswestry Disability Index. RESULTS.: Average intra- and interobserver agreement was substantial and moderate, respectively (k = 0.65 and 0.44), whereas they were substantial for physicians working in the study originating unit. Surgical patients had the smallest DSCA. A larger proportion of C and D grades was observed in the surgical group. Surface measurementsresulted in overdiagnosis of stenosis in 35 patients and under diagnosis in 12. No relation could be found between stenosis grade or DSCA and baseline Oswestry Disability Index or surgical result. C and D grade patients were more likely to fail conservative treatment, whereas grades A and B were less likely to warrant surgery. CONCLUSION.: The grading defines stenosis in different subjects than surface measurements alone. Since it mainly considers impingement of neural tissue it might be a more appropriate clinical and research tool as well as carrying a prognostic value.

Initial experience with hybrid surgery in congenital heart disease in a single center : P171

Introduction: A hybrid intervention is a joint procedure involving the interventional cardiologist and the cardiac surgeon. At our institution we have opted for this type of approach in congenital heart disease since 2005. We report here our initial experience. Cases: 1. A 3 year old boy with double aortic arch and multiple muscular ventricular septal defects (VSD),was readdressed for pulmonary band (PAB) removal and residual VSD closure after previous palliation. After surgical removal of the PAB, the surgeon provided a minimal transventricular access for placement of a 6mm Amplatzer® muscular VSD occluder by the cardiologist under transoesophageal guidance. The patient was extubated the same day and discharged after 5 days. 2. An 8 year old girl with Williams syndrome was followed for two large VSDs and severe peripheral pulmonary arteries (PA) stenosis. The membranous VSD was closed surgically, the muscular VSD during the same operation by direct placement of a 12 mm Amplatzer® muscular VSD occluder. During rewarming, balloon angioplasty of peripheral PA stenosis was achieved under fluoroscopy. Patient was extubated the following day and discharged after 8 days. 3. A 9 year old boy post tetralogy of Fallot repair had severe distal stenosis of the right ventricular to PA conduit.With patient on partial cardiopulmonary bypass, an incision was made on the conduit and a CP 8 Zig 16 stent placed on the stenosis. The child passed on full bypass and the definitive placement of the stent achieved. The child was extubated at the end of the intervention and discharged after 6 days. 4. A newborn presented at 2 days life with complex aortic arch anatomy: left aortic arch and right descending thoracic aorta perfused directly from a right arterial duct and left PA atresia. The arterial duct was stented with a Genesis XD stent dilated at 7mm. Two days later the cardiac surgeon made banded the right PA. The child was extubated after the operation and discharged a week later. Conclusion: Hybrid approach opens new ways of correction or palliation in congenital heart disease with encouraging results and less morbidity.

The interrater reliability of the pulmonary embolism severity index

RésuméLe PESI (Pulmonary Embolism Severity Index) est un score clinique pronostique s'appliquant à des patients présentant un diagnostic d'embolie pulmonaire. Notre objectif était de démontrer la reproductibilité de ce score entre différents médecins chez des patients présentant une embolie pulmonaire. Nous avons donc identifié, de façon prospective, des patients présentant une embolie pulmonaire nouvellement diagnostiquée aux urgences d'un Hôpital Universitaire (CHUV, Lausanne). Pour tous ces patients, le médecin assistant en charge ainsi que le chef de clinique superviseur ont individuellement collecté les différentes variables permettant d'établir le score selon le PESI. Ils ont, ensuite, de façon indépendante, classifié les patients dans 5 classes de risque (1-V) ainsi qu'en deux groupes à bas risque versus haut risque, respectivement les classes i-ll et les classes III à V.Nous avons examiné la reproductibilité des données entre deux groupes de médecins (médecins assistants vs chefs de clinique), pour chacune des variables constituant le PESI, pour le score total en points, pour l'attribution aux 5 classes de risque ainsi que pour la classification en deux groupes à haut risque versus bas risque. Cette évaluation de la reproductibilité des résultats obtenus par les différents médecins s'est basée sur le calcul du Kappa (K) ainsi sur les Coefficients de Corrélation Intra-classe (ICC).Parmi les 48 patients présentant une Embolie Pulmonaire inclus dans notre étude, les coefficients de reproductibilité entre médecins assistants et chefs de clinique étaient supérieurs à 0.60 pour 10 des 11 variables du PESI. La reproductibilité entre les 2 groupes de médecins, pour le total des points, pour l'attribution à une classe de risque I à V, ainsi que pour la classification en bas versus haut risque était presque parfaite.Nos résultats démontrent la haute reproductibilité du PESI, et appuient donc l'intérêt de son utilisation pour la stratification du risque chez des patients présentant une embolie pulmonaire.

Incidence and management of pulmonary embolism following spinal surgery occurring while under chemical thromboprophylaxis.

Patients undergoing spinal surgery are at risk of developing thromboembolic complications even though lower incidences have been reported as compared to joint arthroplasty surgery. Deep vein thrombosis (DVT) has been studied extensively in the context of spinal surgery but symptomatic pulmonary embolism (PE) has engaged less attention. We prospectively followed a consecutive cohort of 270 patients undergoing spinal surgery at a single institution. From these patients, only 26 were simple discectomies, while the largest proportion (226) was fusions. All patients received both low molecular weight heparin (LMWH) initiated after surgery and compressive stockings. PE was diagnosed with spiral chest CT. Six patients developed symptomatic PE, five during their hospital stay. In three of the six patients the embolic event occurred during the first 3 postoperative days. They were managed by the temporary insertion of an inferior vena cava (IVC) filter thus allowing for a delay in full-dose anticoagulation until removal of the filter. None of the PE patients suffered any bleeding complication as a result of the introduction of full anticoagulation. Two patients suffered postoperative haematomas, without development of neurological symptoms or signs, requiring emergency evacuation. The overall incidence of PE was 2.2% rising to 2.5% after exclusion of microdiscectomy cases. The incidence of PE was highest in anterior or combined thoracolumbar/lumbar procedures (4.2%). There is a large variation in the reported incidence of PE in the spinal literature. Results from the only study found in the literature specifically monitoring PE suggest an incidence of PE as high as 2.5%. Our study shows a similar incidence despite the use of LMWH. In the absence of randomized controlled trials (RCT) it is uncertain if this type of prophylaxis lowers the incidence of PE. However, other studies show that the morbidity of LMWH is very low. Since PE can be a life-threatening complication, LMWH may be a worthwhile option to consider for prophylaxis. RCTs are necessary in assessing the efficacy of DVT and PE prophylaxis in spinal patients.

Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β.

Nanoparticles are increasingly used in various fields, including biomedicine and electronics. One application utilizes the opacifying effect of nano-TiO(2), which is frequently used as pigment in cosmetics. Although TiO(2) is believed to be biologically inert, an emerging literature reports increased incidence of respiratory diseases in people exposed to TiO(2). Here, we show that nano-TiO(2) and nano-SiO(2), but not nano-ZnO, activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome, leading to IL-1β release and in addition, induce the regulated release of IL-1α. Unlike other particulate Nlrp3 agonists, nano-TiO(2)-dependent-Nlrp3 activity does not require cytoskeleton-dependent phagocytosis and induces IL-1α/β secretion in nonphagocytic keratinocytes. Inhalation of nano-TiO(2) provokes lung inflammation which is strongly suppressed in IL-1R- and IL-1α-deficient mice. Thus, the inflammation caused by nano-TiO(2) in vivo is largely caused by the biological effect of IL-1α. The current use of nano-TiO(2) may present a health hazard due to its capacity to induce IL-1R signaling, a situation reminiscent of inflammation provoked by asbestos exposure.

Prospective comparison of clinical prognostic scores in elderly patients with pulmonary embolism.

Background: The Geneva Prognostic Score (GPS), the Pulmonary Embolism Severity Index (PESI), and its simplified version (sPESI) are well known clinical prognostic scores for pulmonary embolism (PE).Objectives: To compare the prognostic performance of these scores in elderly patients with PE. Patients/Methods: In a multicenter Swiss cohort of elderly patients with venous thromboembolism, we prospectively studied 449 patients aged ≥65 years with symptomatic PE. The outcome was 30-day overall mortality. We dichotomized patients as low- vs. higher-risk in all three scores using the following thresholds: GPS scores ≤2 vs. >2, PESI risk classes I-II vs. III-V, and sPESI scores 0 vs. ≥1. We compared 30-day mortality in low- vs. higher-risk patients and the areas under the receiver operating characteristic curve (ROC). Results: Overall, 3.8% of patients (17/449) died within 30 days. The GPS classified a greater proportion of patients as low risk (92% [413/449]) than the PESI (36.3% [163/449]) and the sPESI (39.6% [178/449]) (P<0.001 for each comparison). Low-risk patients based on the sPESI had a mortality of 0% (95% confidence interval [CI] 0-2.1%) compared to 0.6% (95% CI 0-3.4%) for low-risk patients based on the PESI and 3.4% (95% CI 1.9-5.6%) for low-risk patients based on the GPS. The areas under the ROC curves were 0.77 (95%CI 0.72-0.81), 0.76 (95% CI 0.72-0.80), and 0.71 (95% CI 0.66-0.75), respectively (P=0.47). Conclusions: In this cohort of elderly patients with PE, the GPS identified a higher proportion of patients as low-risk but the PESI and sPESI were more accurate in predicting mortality.

Validation of a model to predict adverse outcomes in patients with pulmonary embolism.

AIMS: To validate a model for quantifying the prognosis of patients with pulmonary embolism (PE). The model was previously derived from 10 534 US patients. METHODS AND RESULTS: We validated the model in 367 patients prospectively diagnosed with PE at 117 European emergency departments. We used baseline data for the model's 11 prognostic variables to stratify patients into five risk classes (I-V). We compared 90-day mortality within each risk class and the area under the receiver operating characteristic curve between the validation and the original derivation samples. We also assessed the rate of recurrent venous thrombo-embolism and major bleeding within each risk class. Mortality was 0% in Risk Class I, 1.0% in Class II, 3.1% in Class III, 10.4% in Class IV, and 24.4% in Class V and did not differ between the validation and the original derivation samples. The area under the curve was larger in the validation sample (0.87 vs. 0.78, P=0.01). No patients in Classes I and II developed recurrent thrombo-embolism or major bleeding. CONCLUSION: The model accurately stratifies patients with PE into categories of increasing risk of mortality and other relevant complications. Patients in Risk Classes I and II are at low risk of adverse outcomes and are potential candidates for outpatient treatment.

Endovascular treatment of symptomatic intracranial arterial stenosis: six-year experience in a single-center series of 42 consecutive patients with acute and mid-term results.

BACKGROUND: The limitations of the medical management of symptomatic intracranial arterial stenosis encourage the development of new therapeutic strategies such as intracranial stenting. OBJECTIVE: To report and analyze the results of a series of 42 patients treated with 3 different endovascular techniques: isolated angioplasty, balloon-expandable coronary stents, and the Wingspan self-expandable intracranial stent system. METHODS: Forty-two patients presenting with symptomatic intracranial arterial stenosis were treated with one of these techniques. Computed tomography angiography was performed 6 months after the procedure, and the clinical neurological statuses were categorized using the modified Rankin Scale and the National Institutes of Health Stroke Scale. RESULTS: A total of 42 lesions were treated: 9 with isolated angioplasty, 14 with balloon-expandable coronary stents, and 19 with Wingspan self-expandable intracranial stents. The mean patient age was 62.9 years, and the mean arterial diameter stenosis was 73.9%. Technical success was achieved in 97.6% of the patients. The overall incidence of procedural complications was 21.4%, and the postoperative permanent morbidity/mortality rate was 7.1%. There were 3 cases of in-stent thrombosis (1 fatal) and 5 cases of asymptomatic restenosis (11.9%), 3 in the isolated angioplasty group and 2 in the Wingspan self-expandable intracranial stent group (mean follow-up 20.4 months). The rate of restenosis was higher in the angioplasty group (33%) than in the coronary (0%) and Wingspan stent (10.5%) groups. CONCLUSION: Endovascular treatment of symptomatic intracranial stenosis has significant overall morbidity and mortality rates. Nevertheless, the very critical natural history of severe refractory lesions and the relatively favorable postoperative evolution suggest that it should be considered the first alternative strategy in cases in which medical therapy has failed.

Mechanisms and drug therapy of pulmonary hypertension at high altitude.

Abstract Scherrer, Urs, Yves Allemann, Emrush Rexhaj, Stefano F. Rimoldi, and Claudio Sartori. Mechanisms and drug therapy of pulmonary hypertension at high altitude. High Alt Med Biol 14:126-133, 2013.-Pulmonary vasoconstriction represents a physiological adaptive mechanism to high altitude. If exaggerated, however, it is associated with important morbidity and mortality. Recent mechanistic studies using short-term acute high altitude exposure have provided insight into the importance of defective vascular endothelial and respiratory epithelial nitric oxide (NO) synthesis, increased endothelin-1 bioavailability, and overactivation of the sympathetic nervous system in causing exaggerated hypoxic pulmonary hypertension in humans. Based on these studies, drugs that increase NO bioavailability, attenuate endothelin-1 induced pulmonary vasoconstriction, or prevent exaggerated sympathetic activation have been shown to be useful for the treatment/prevention of exaggerated pulm9onary hypertension during acute short-term high altitude exposure. The mechanisms underpinning chronic pulmonary hypertension in high altitude dwellers are less well understood, but recent evidence suggests that they differ in some aspects from those involved in short-term adaptation to high altitude. These differences have consequences for the choice of the treatment for chronic pulmonary hypertension at high altitude. Finally, recent data indicate that fetal programming of pulmonary vascular dysfunction in offspring of preeclampsia and children generated by assisted reproductive technologies represents a novel and frequent cause of pulmonary hypertension at high altitude. In animal models of fetal programming of hypoxic pulmonary hypertension, epigenetic mechanisms play a role, and targeting of these mechanisms with drugs lowers pulmonary artery pressure. If epigenetic mechanisms also are operational in the fetal programming of pulmonary vascular dysfunction in humans, such drugs may become novel tools for the treatment of hypoxic pulmonary hypertension.

Pulmonary embolism severity index and troponin testing for the selection of low-risk patients with acute symptomatic pulmonary embolism.

Summary Background: The combination of the Pulmonary Embolism Severity Index (PESI) and troponin testing could help physicians identify appropriate patients with acute pulmonary embolism (PE) for early hospital discharge. Methods: This prospective cohort study included a total of 567 patients from a single center registry with objectively confirmed acute symptomatic PE. On the basis of the PESI, each patient was classified into 1 of 5 classes (I to V). At the time of hospital admission, patients had troponin I (cTnI) levels measured. The endpoint of the study was all-cause mortality within 30 days after diagnosis. We calculated the mortality rates in 4 patient groups: group 1: PESI class I-II plus cTnI <0.1 ng mL(-1); group 2: PESI classes III-V plus cTnI <0.1 ng mL(-1); group 3: PESI classes I-II plus cTnI >/= 0.1 ng mL(-1); and group 4: PESI classes III-V plus cTnI >/= 0.1 ng mL(-1). Results: The study cohort had a 30-day mortality of 10% (95% confidence interval [CI], 7.6 to 12.5%). Mortality rates in the 4 groups were 1.3%, 14.2%, 0% and 15.4%, respectively. Compared to non-elevated cTnl, the low-risk PESI had a higher negative predictive value (NPV) (98.9% vs 90.8%) and negative likelihood ratio (NLR) (0.1 vs 0.9) for predicting mortality. The addition of non-elevated cTnI to low-risk PESI did not improve the NPV or the NLR compared to either test alone. Conclusions: Compared to cTnl testing, PESI classification more accurately identified patients with PE who are at low risk of all-cause death within 30-days of presentation.