New insights regarding the incidence, presentation and treatment options of aorto-oesophageal fistulation after thoracic endovascular aortic repair: the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To review the incidence, clinical presentation, definite management and 1-year outcome in patients with aorto-oesophageal fistulation (AOF) following thoracic endovascular aortic repair (TEVAR). METHODS International multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2011 with a total caseload of 2387 TEVAR procedures (17 centres). RESULTS Thirty-six patients with a median age of 69 years (IQR 56-75), 25% females and 9 patients (19%) following previous aortic surgery were identified. The incidence of AOF in the entire cohort after TEVAR in the study period was 1.5%. The primary underlying aortic pathology for TEVAR was atherosclerotic aneurysm formation in 53% of patients and the median time to development of AOF was 90 days (IQR 30-150). Leading clinical symptoms were fever of unknown origin in 29 (81%), haematemesis in 19 (53%) and shock in 8 (22%) patients. Diagnosis could be confirmed via computed tomography in 92% of the cases with the leading sign of a new mediastinal mass in 28 (78%) patients. A conservative approach resulted in a 100% 1-year mortality, and 1-year survival for an oesophageal stenting-only approach was 17%. Survival after isolated oesophagectomy was 43%. The highest 1-year survival rate (46%) could be achieved via an aggressive treatment including radical oesophagectomy and aortic replacement [relative risk increase 1.73 95% confidence interval (CI) 1.03-2.92]. The survival advantage of this aggressive treatment modality could be confirmed in bootstrap analysis (95% CI 1.11-3.33). CONCLUSIONS The development of AOF is a rare but lethal complication after TEVAR, being associated with the need for emergency TEVAR as well as mediastinal haematoma formation. The only durable and successful approach to cure the disease is radical oesophagectomy and extensive aortic reconstruction. These findings may serve as a decision-making tool for physicians treating these complex patients.

Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To learn upon incidence, underlying mechanisms and effectiveness of treatment strategies in patients with central airway and pulmonary parenchymal aorto-bronchial fistulation after thoracic endovascular aortic repair (TEVAR). METHODS Analysis of an international multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2012 with a total caseload of 4680 TEVAR procedures (14 centres). RESULTS Twenty-six patients with a median age of 70 years (interquartile range: 60-77) (35% female) were identified. The incidence of either central airway (aorto-bronchial) or pulmonary parenchymal (aorto-pulmonary) fistulation (ABPF) in the entire cohort after TEVAR in the study period was 0.56% (central airway 58%, peripheral parenchymal 42%). Atherosclerotic aneurysm formation was the leading indication for TEVAR in 15 patients (58%). The incidence of primary endoleaks after initial TEVAR was n = 10 (38%), of these 80% were either type I or type III endoleaks. Fourteen patients (54%) developed central left bronchial tree lesions, 11 patients (42%) pulmonary parenchymal lesions and 1 patient (4%) developed a tracheal lesion. The recognized mechanism of ABPF was external compression of the bronchial tree in 13 patients (50%), the majority being due to endoleak formation, further ischaemia due to extensive coverage of bronchial feeding arteries in 3 patients (12%). Inflammation and graft erosion accounted for 4 patients (30%) each. Cumulative survival during the entire study period was 39%. Among deaths, 71% were attributed to ABPF. There was no difference in survival in patients having either central airway or pulmonary parenchymal ABPF (33 vs 45%, log-rank P = 0.55). Survival with a radical surgical approach was significantly better when compared with any other treatment strategy in terms of overall survival (63 vs 32% and 63 vs 21% at 1 and 2 years, respectively), as well as in terms of fistula-related survival (63 vs 43% and 63 vs 43% at 1 and 2 years, respectively). CONCLUSIONS ABPF is a rare but highly lethal complication after TEVAR. The leading mechanism behind ABPF seems to be a continuing external compression of either the bronchial tree or left upper lobe parenchyma. In this setting, persisting or newly developing endoleak formation seems to play a crucial role. Prognosis does not differ in patients with central airway or pulmonary parenchymal fistulation. Radical bronchial or pulmonary parenchymal repair in combination with stent graft removal and aortic reconstruction seems to be the most durable treatment strategy.

The ARCH Projects: design and rationale (IAASSG 001).

OBJECTIVE A number of factors limit the effectiveness of current aortic arch studies in assessing optimal neuroprotection strategies, including insufficient patient numbers, heterogenous definitions of clinical variables, multiple technical strategies, inadequate reporting of surgical outcomes and a lack of collaborative effort. We have formed an international coalition of centres to provide more robust investigations into this topic. METHODS High-volume aortic arch centres were identified from the literature and contacted for recruitment. A Research Steering Committee of expert arch surgeons was convened to oversee the direction of the research. RESULTS The International Aortic Arch Surgery Study Group has been formed by 41 arch surgeons from 10 countries to better evaluate patient outcomes after aortic arch surgery. Several projects, including the establishment of a multi-institutional retrospective database, randomized controlled trials and a prospectively collected database, are currently underway. CONCLUSIONS Such a collaborative effort will herald a turning point in the surgical management of aortic arch pathologies and will provide better powered analyses to assess the impact of varying surgical techniques on mortality and morbidity, identify predictors for neurological and operative risk, formulate and validate risk predictor models and review long-term survival outcomes and quality-of-life after arch surgery.

Taste acceptability of pulverized brand-name and generic drugs containing amlodipine or candesartan.

Trials with pulverized brand-name antihypertensive drugs suggest that, from the perspective of taste acceptability, crushed candesartan, chlortalidon, hydrochlorothiazide, lercanidipine and lisinopril should be preferred to pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan, ramipril, telmisartan and valsartan. Brand-name antihypertensive drugs and the corresponding generic medicines have never been compared with respect to their taste acceptability. We therefore investigated among healthy health care workers the taste acceptability of a pulverized 1 mg-test dose of the brand-name and two generics containing either the dihydropyridine calcium-channel blocker amlodipine (Norvasc(®), Amlodipin-Mepha(®) and Amlodipin Pfizer(®)) or the angiotensin receptor antagonist candesartan (Atacand(®), Cansartan-Mepha(®) and Pemzek(®)). For this purpose, a smiley-face scale depicting four degrees of pleasure was used. Between November and December 2013, the taste test was performed among 19 nurses (15 female and 4 male subjects) and 12 physicians (5 female and 7 male subjects) aged between 25 and 49 years. Pulverized brand-names and generics containing either amlodipine or candesartan did not differ with respect to their taste acceptability.

Modified natural cycle in vitro fertilization an alternative in vitro fertilization treatment with lower costs per achieved pregnancy but longer treatment time

OBJECTIVE To analyze the cost and time requirement per achieved pregnancy in optimized modified natural cycle in vitro fertilization (mNC-IVF) based on a treatment protocol with very few consultations and to compare those with conventional gonadotropin-stimulated aVF (clVF) cycles. STUDY DESIGN Mono centric prospective trial. Eighty infertile patients each received 1 modified mNC-IVF cycle using low doses of the clomiphene citrate. Based on the number of consultations and the clinical pregnancy rate per cycle, the total costs and required time to achieve a pregnancy were analyzed and compared with cIVF. Calculations for cIVF were based on standard therapy protocols and outcomes of European registries. RESULTS Patients (21-42 years old, 35.4 +/- 4.7 years) undergoing mNC-IVF required on average 1.2 consultations before follicle aspiration. Pregnancy rate per transfer and per initiated cycle were 25% and 13.6%, respectively. Multiple pregnancies did not occur. According to the calculations, total costs per pregnancy rate were around 15% lower with mNC-IVF as compared to cIVF. In contrast, time to achieve an equal pregnancy rate was calculated to take around 30% longer with mNC-IVF as compared to cIVF. CONCLUSION mNC-IVF using very low dosages of clomiphene citrate avoids multiple pregnancies and is less expensive but more time consuming per achieved pregnancy when compared to clVF.

Arterial hypertension in children

PURPOSE OF REVIEW Although arterial hypertension is less common in children than in adults, there is growing concern about elevated blood pressure (BP) in children and adolescents not only because of the association of elevated values with the overweight epidemic, but also as cardiovascular functions are determined in childhood and track into adulthood. The purpose of the review is to discuss new aspects of childhood hypertension. RECENT FINDINGS Guidelines advocate determining BP in children as part of routine health maintenance. This recommendation was recently subject to review by the US Preventive Services Task Force. It was concluded that evidence is insufficient to assess the benefits of this screening. In our opinion, however, assessing BP is part of any thorough physical examination.Sophisticated approaches demonstrate the role of sympathetic nervous system overdrive in the field of sympathetic cardiovascular modulation of childhood arterial hypertension. SUMMARY Elevated BP in children is increasing in frequency and is now recognized as having relevant short-term and long-term consequences. Although efforts to address the childhood overweight epidemic may eventually reduce the number of young patients with hypertension, improved therapies for childhood hypertension also offer the potential for preventing or ameliorating early cardiovascular disease.

The great fluid debate: saline or so-called "balanced" salt solutions?

BACKGROUND Intravenous fluids are commonly prescribed in childhood. 0.9 % saline is the most-used fluid in pediatrics as resuscitation or maintenance solution. Experimental studies and observations in adults suggest that 0.9 % saline is a poor candidate for fluid resuscitation. Although anesthesiologists, intensive care specialists, perioperative physicians and nephrologists have been the most active in this debate, this issue deserves some physiopathological considerations also among pediatricians. RESULTS As compared with so-called "balanced" salt crystalloids such as lactated Ringer, administration of large volumes of 0.9 % saline has been associated with following deleterious effects: tendency to hyperchloremic metabolic acidosis (called dilution acidosis); acute kidney injury with reduced urine output and salt retention; damaged vascular permeability and stiffness, increase in proinflammatory mediators; detrimental effect on coagulation with tendency to blood loss; detrimental gastrointestinal perfusion and function; possible uneasiness at the bedside resulting in unnecessary administration of more fluids. Nevertheless, there is no firm evidence that these adverse effects are clinically relevant. CONCLUSIONS Intravenous fluid therapy is a medicine like insulin, chemotherapy or antibiotics. Prescribing fluids should fit the child's history and condition, consider the right dose at the right rate as well as the electrolyte levels and other laboratory variables. It is unlikely that a single type of fluid will be suitable for all pediatric patients. "Balanced" salt crystalloids, although more expensive, should be preferred for volume resuscitation, maintenance and perioperatively. Lactated Ringer appears unsuitable for patients at risk for brain edema and for those with overt or latent chloride-deficiency. Finally, in pediatrics there is a need for new fluids to be developed on the basis of a better understanding of the physiology and to be tested in well-designed trials.

Magnesium in cystic fibrosis - Systematic review of the literature

BACKGROUND The metabolism of sodium, potassium, and chloride and the acid-base balance are sometimes altered in cystic fibrosis. Textbooks and reviews only marginally address the homeostasis of magnesium in cystic fibrosis. METHODS We performed a search of the Medical Subject Headings terms (cystic fibrosis OR mucoviscidosis) AND (magnesium OR hypomagnes[a]emia) in the US National Library of Medicine and Excerpta Medica databases. RESULTS We identified 25 reports dealing with magnesium and cystic fibrosis. The results of the review may be summarized as follows. First, hypomagnesemia affects more than half of the cystic fibrosis patients with advanced disease; second, magnesemia, which is normally age-independent, relevantly decreases with age in cystic fibrosis; third, aminoglycoside antimicrobials frequently induce both acute and chronic renal magnesium-wasting; fourth, sweat magnesium concentration was normal in cystic fibrosis patients; fifth, limited data suggest the existence of an impaired intestinal magnesium balance. Finally, stimulating observations suggest that magnesium supplements might achieve an improvement in respiratory muscle strength and mucolytic activity of both recombinant and endogenous deoxyribonuclease. CONCLUSIONS The first comprehensive review of the literature confirms that, despite being one of the most prevalent minerals in the body, the importance of magnesium in cystic fibrosis is largely overlooked. In these patients, hypomagnesemia should be sought once a year. Furthermore, the potential of supplementation with this cation deserves more attention.

Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes.

Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.

La mirada de los jóvenes : Una aproximación al impacto de los cambios socioeconómicos recientes en la subjetividad de los jóvenes de clase media

Las clases medias en Argentina se han caracterizado, sobre todo desde la segunda mitad del siglo XX, por ser un sector social dinámico, por su optimismo en cuanto al progreso y por las amplias posibilidades de ascenso social que les brindaba la situación económica del país, posibilidades que el peronismo extendió luego a las clases trabajadoras. Durante los primeros años de la década del noventa, el país logró estabilizarse económicamente dejando atrás el fantasma hiperinflacionario, permitiendo un notable, si bien breve, crecimiento económico. La Convertibilidad permitió a gran parte de la población acceder a nuevos patrones de consumo; los shoppings y los barrios cerrados comenzaron a formar parte del paisaje urbano. A consecuencia se produce una mutación en las condiciones de vida y en los hábitos de consumo, sobre todo de los sectores medios. Al correr la década se advierten los costos del modelo neoliberal: el aumento veloz e inédito del desempleo, la caída en los ingresos de la mayoría de los trabajadores, el aumento de la pobreza y la marginalidad. En definitiva, la estructura social del país se vio modificada y sus efectos fueron sentidos por la gran mayoría de la población, aunque de diferente manera y en diferentes momentos. Los más afectados fueron los sectores de menores ingresos, pero en gran medida también aquellos ubicados en los sectores medio-bajo de la estructura social, que en su mayoría pasaron a conformar una nueva categoría social: los nuevos pobres. La investigación indaga acerca del impacto de la crisis económica en la subjetividad de los jóvenes de clase media, en particular en su visión acerca del país y en sus perspectivas a futuro. Al mismo tiempo, intenta delinear las nuevas prácticas, creencias y valores que adquieren las clases medias post-crisis, que debieron adaptarse a las nuevas circunstancias, y en muchos casos modificar sus hábitos de vida y patrones de consumo. Algunos hallazgos permitan afirmar que las transformaciones que ha sufrido el país en lo social y económico han sido tan profundas que impactaron en el imaginario e identidad social de los sectores medios: se desmoronan las tradicionales perspectivas de ascenso social, se desarrollan nuevas estrategias de consumo; el optimismo se revierte a consecuencia del futuro incierto, mientras que la educación parece ser uno de los pocos valores que se niegan a relegar

La mirada de los jóvenes : Una aproximación al impacto de los cambios socioeconómicos recientes en la subjetividad de los jóvenes de clase media

Las clases medias en Argentina se han caracterizado, sobre todo desde la segunda mitad del siglo XX, por ser un sector social dinámico, por su optimismo en cuanto al progreso y por las amplias posibilidades de ascenso social que les brindaba la situación económica del país, posibilidades que el peronismo extendió luego a las clases trabajadoras. Durante los primeros años de la década del noventa, el país logró estabilizarse económicamente dejando atrás el fantasma hiperinflacionario, permitiendo un notable, si bien breve, crecimiento económico. La Convertibilidad permitió a gran parte de la población acceder a nuevos patrones de consumo; los shoppings y los barrios cerrados comenzaron a formar parte del paisaje urbano. A consecuencia se produce una mutación en las condiciones de vida y en los hábitos de consumo, sobre todo de los sectores medios. Al correr la década se advierten los costos del modelo neoliberal: el aumento veloz e inédito del desempleo, la caída en los ingresos de la mayoría de los trabajadores, el aumento de la pobreza y la marginalidad. En definitiva, la estructura social del país se vio modificada y sus efectos fueron sentidos por la gran mayoría de la población, aunque de diferente manera y en diferentes momentos. Los más afectados fueron los sectores de menores ingresos, pero en gran medida también aquellos ubicados en los sectores medio-bajo de la estructura social, que en su mayoría pasaron a conformar una nueva categoría social: los nuevos pobres. La investigación indaga acerca del impacto de la crisis económica en la subjetividad de los jóvenes de clase media, en particular en su visión acerca del país y en sus perspectivas a futuro. Al mismo tiempo, intenta delinear las nuevas prácticas, creencias y valores que adquieren las clases medias post-crisis, que debieron adaptarse a las nuevas circunstancias, y en muchos casos modificar sus hábitos de vida y patrones de consumo. Algunos hallazgos permitan afirmar que las transformaciones que ha sufrido el país en lo social y económico han sido tan profundas que impactaron en el imaginario e identidad social de los sectores medios: se desmoronan las tradicionales perspectivas de ascenso social, se desarrollan nuevas estrategias de consumo; el optimismo se revierte a consecuencia del futuro incierto, mientras que la educación parece ser uno de los pocos valores que se niegan a relegar

La mirada de los jóvenes : Una aproximación al impacto de los cambios socioeconómicos recientes en la subjetividad de los jóvenes de clase media

Las clases medias en Argentina se han caracterizado, sobre todo desde la segunda mitad del siglo XX, por ser un sector social dinámico, por su optimismo en cuanto al progreso y por las amplias posibilidades de ascenso social que les brindaba la situación económica del país, posibilidades que el peronismo extendió luego a las clases trabajadoras. Durante los primeros años de la década del noventa, el país logró estabilizarse económicamente dejando atrás el fantasma hiperinflacionario, permitiendo un notable, si bien breve, crecimiento económico. La Convertibilidad permitió a gran parte de la población acceder a nuevos patrones de consumo; los shoppings y los barrios cerrados comenzaron a formar parte del paisaje urbano. A consecuencia se produce una mutación en las condiciones de vida y en los hábitos de consumo, sobre todo de los sectores medios. Al correr la década se advierten los costos del modelo neoliberal: el aumento veloz e inédito del desempleo, la caída en los ingresos de la mayoría de los trabajadores, el aumento de la pobreza y la marginalidad. En definitiva, la estructura social del país se vio modificada y sus efectos fueron sentidos por la gran mayoría de la población, aunque de diferente manera y en diferentes momentos. Los más afectados fueron los sectores de menores ingresos, pero en gran medida también aquellos ubicados en los sectores medio-bajo de la estructura social, que en su mayoría pasaron a conformar una nueva categoría social: los nuevos pobres. La investigación indaga acerca del impacto de la crisis económica en la subjetividad de los jóvenes de clase media, en particular en su visión acerca del país y en sus perspectivas a futuro. Al mismo tiempo, intenta delinear las nuevas prácticas, creencias y valores que adquieren las clases medias post-crisis, que debieron adaptarse a las nuevas circunstancias, y en muchos casos modificar sus hábitos de vida y patrones de consumo. Algunos hallazgos permitan afirmar que las transformaciones que ha sufrido el país en lo social y económico han sido tan profundas que impactaron en el imaginario e identidad social de los sectores medios: se desmoronan las tradicionales perspectivas de ascenso social, se desarrollan nuevas estrategias de consumo; el optimismo se revierte a consecuencia del futuro incierto, mientras que la educación parece ser uno de los pocos valores que se niegan a relegar

Debris flow magnitudes: a global catalog

The episodic occurrence of debris flow events in response to stochastic precipitation and wildfire events makes hazard prediction challenging. Previous work has shown that frequency-magnitude distributions of non-fire-related debris flows follow a power law, but less is known about the distribution of post-fire debris flows. As a first step in parameterizing hazard models, we use frequency-magnitude distributions and cumulative distribution functions to compare volumes of post-fire debris flows to non-fire-related debris flows. Due to the large number of events required to parameterize frequency-magnitude distributions, and the relatively small number of post-fire event magnitudes recorded in the literature, we collected data on 73 recent post-fire events in the field. The resulting catalog of 988 debris flow events is presented as an appendix to this article. We found that the empirical cumulative distribution function of post-fire debris flow volumes is composed of smaller events than that of non-fire-related debris flows. In addition, the slope of the frequency-magnitude distribution of post-fire debris flows is steeper than that of non-fire-related debris flows, evidence that differences in the post-fire environment tend to produce a higher proportion of small events. We propose two possible explanations: 1) post-fire events occur on shorter return intervals than debris flows in similar basins that do not experience fire, causing their distribution to shift toward smaller events due to limitations in sediment supply, or 2) fire causes changes in resisting and driving forces on a package of sediment, such that a smaller perturbation of the system is required in order for a debris flow to occur, resulting in smaller event volumes.

FDI inflows and outflows, intellectual property rights, and productivity growth

Using panel data of 57 countries during the period of 1995-2012, this study investigates the impact of intellectual property rights (IPR) processes on productivity growth. The IPR processes are decomposed into three stages, innovation process, commercialization process, and IPR protection process. Our results suggest that better IPR protection is directly associated with productivity improvement only in developed economies. In addition, the contribution of IPR processes on growth through foreign direct investment (FDI) appears to be very limited. Only FDI inflows in developed countries which help to create a better innovative capability lead to a higher growth. And in connection with FDI outflows, only IPR protection and commercialization processes are proven to improve productivity in the case of developing countries, particularly when the country acts as the investing country.