Portal Vein Embolization before Right Hepatectomy: Improved Results Using n-Butyl-Cyanoacrylate Compared to Microparticles Plus Coils.

BACKGROUND: There is currently no consensus in the literature on which embolic agent induces the greatest degree of liver hypertrophy after portal vein embolization (PVE). Only experimental results in a pig model have demonstrated an advantage of n-butyl-cyanoacrylate (NBCA) over 3 other embolic materials (hydrophilic gel, small and large polyvinyl alcohol particles) for PVE. Therefore, the aim of this human study was to retrospectively compare the results of PVE using NBCA with those using spherical microparticles plus coils. METHODS: A total of 34 patients underwent PVE using either NBCA (n = 20), or spherical microparticles plus coils (n = 14). PVE was decided according to preoperative volumetry on the basis of contrast-enhanced CT. Groups were compared for age, sex, volume of the left lobe before PVE and future remnant liver ratio (FRL) (volume of the left lobe/total liver volume - tumor volume). The primary end point was the increase in left lobe volume 1 month after PVE. Secondary end points were procedure complications and biological tolerance. RESULTS: Both groups were similar in terms of age, sex ratio, left lobe volume, and FRL before PVE. NBCA induced a greater increase in volume after PVE than did microparticles plus coils (respectively, +74 ± 69 % and +23 ± 14 %, p < 0.05). The amount of contrast medium used for the procedure was significantly larger when microparticles and coils rather than NBCA were used (respectively, 264 ± 43 ml and 162 ± 34 ml, p < 0.01). The rate of PVE complications as well as the biological tolerance was similar in both groups. CONCLUSION: NBCA seems more effective than spherical microparticles plus coils to induce left-lobe hypertrophy.

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 need for combination antihypertensive therapy to reach target blood pressures: what has been learned from clinical practice and morbidity-mortality trials?

Pharmacological treatment of hypertension represents a cost-effective way for preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment blood pressure (BP) should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (&lt; 130/80 mmHg) if diabetes or renal disease co-exists. Most of the time such targets cannot be reached using monotherapies. This is especially true in patients who exhibit a high cardiovascular risk. The co-administration of two agents acting by different mechanisms considerably increases BP control. Such preparations are not only efficacious, but also well tolerated, and some fixed low-dose combinations have a tolerability profile similar to placebo. This is for instance the case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has recently been shown in controlled interventional trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving macrovascular stiffness. Fixed-dose combinations are becoming more and more popular and are even proposed by current hypertension guidelines as a first-line option to treat hypertensive patients.

Systematic surgical closure of patent foramen ovale in selected patients with cerebrovascular events due to paradoxical embolism. Early results of a preliminary study.

OBJECTIVE: To define therapeutic strategy for management of patients with ischemic stroke due to a high probability of paradoxical embolism through a Patent Foramen Ovale (PFO). METHODS: Since 1988 all consecutive patients with cerebrovascular events and PFO from the Stroke Registry of our population-based primary-care center are prospectively studied and followed. Since 1992, among 118 patients with cryptogenic embolic brain infarct or transient ischemic attack (TIA) and PFO, 32 consecutive patients younger than 60 years who presented at least two of the following criteria were admitted for surgery: history of Valsalva strain before stroke (11); multiple clinical events (13); multiple infarcts on brain Magnetic Resonance Imaging (MRI) (15); atrial septal aneurysm (ASA) (16); large right-to-left shunt (> 50 microbubbles) (12). RESULTS: Operative time 135' +/- 33'. CPB time 34' +/- 14'. Aortic crossclamping time 16' +/- 6'. Post-operative bleeding 485 +/- 170 ml. No homologous blood transfusion required. No neurological, cardiac or renal complications. All patients were followed-up corresponding to a cumulative time of 601 patient-months. This revealed no recurrent vascular events nor silent new brain lesions on brain MRI. Systematic simultaneous contrast Trans Esophageal Echocardiography (TEE)-Trans Cranial Doppler showed a small residual interatrial shunt in two patients. CONCLUSION: Surgical closure of a patent foramen ovale can be accomplished with very low morbidity and reduce efficiently the risk of stroke recurrence. It seems to be the option of choice in selected patients with a higher (> 1.5%/year) risk of stroke recurrence.

Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms.

Insults during the fetal period predispose the offspring to systemic cardiovascular disease, but little is known about the pulmonary circulation and the underlying mechanisms. Maternal undernutrition during pregnancy may represent a model to investigate underlying mechanisms, because it is associated with systemic vascular dysfunction in the offspring in animals and humans. In rats, restrictive diet during pregnancy (RDP) increases oxidative stress in the placenta. Oxygen species are known to induce epigenetic alterations and may cross the placental barrier. We hypothesized that RDP in mice induces pulmonary vascular dysfunction in the offspring that is related to an epigenetic mechanism. To test this hypothesis, we assessed pulmonary vascular function and lung DNA methylation in offspring of RDP and in control mice at the end of a 2-wk exposure to hypoxia. We found that endothelium-dependent pulmonary artery vasodilation in vitro was impaired and hypoxia-induced pulmonary hypertension and right ventricular hypertrophy in vivo were exaggerated in offspring of RDP. This pulmonary vascular dysfunction was associated with altered lung DNA methylation. Administration of the histone deacetylase inhibitors butyrate and trichostatin A to offspring of RDP normalized pulmonary DNA methylation and vascular function. Finally, administration of the nitroxide Tempol to the mother during RDP prevented vascular dysfunction and dysmethylation in the offspring. These findings demonstrate that in mice undernutrition during gestation induces pulmonary vascular dysfunction in the offspring by an epigenetic mechanism. A similar mechanism may be involved in the fetal programming of vascular dysfunction in humans.

Telmisartan: a different angiotensin II receptor blocker protecting a different population?

The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET()) showed that the angiotensin II receptor blocker (ARB) telmisartan was as protective as the reference-standard ramipril in a broad cross-section of patients at increased cardiovascular risk, but was better tolerated. Telmisartan has a unique profile among ARBs, with a high affinity for the angiotensin II type 1 receptor, a long duration of receptor binding, a high lipophilicity and a long plasma half life. This leads to sustained and powerful blood pressure lowering when compared with the first marketed ARBs, such as losartan and valsartan. Some pharmacological properties of telmisartan clearly distinguish it from other members of the ARB class and may contribute to the clinical effects seen with telmisartan. A class effect for ARBs cannot be assumed. To date, telmisartan is the only ARB that has been shown to reduce cardiovascular risk in at-risk cardiovascular patients.

Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

Psicopatología de la desinhibición: un modelo para el estudio de la psicopatía

En este artículo se hace referencia a un modelo analógico para el estudio de los síndromes de la conducta desinhibida en humanos, denominado "Psicopatología de la Desinhibición". Este modelo propone una similitud entre las manifestaciones de conducta de humanos desinhibidos y los animales con lesión septal, sugiriendo de forma hipotética qué irregularidades en el sistema límbico podrían ser el sustrato biológico de estos síndromes entre los que es prototípico la psicopatología.

Interplay between connexin40 and nitric oxide signaling during hypertension.

Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the adaptation of endothelial and smooth muscle cells to hemodynamic changes. To decipher the in vivo interplay between these proteins, we studied Cx40-null mice, a model of renin-dependent hypertension which displays an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels. These mice, which were either untreated or subjected to the 1-kidney, 1-clip (1K1C) procedure, a model of volume-dependent hypertension, were compared with control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) procedure, a model of renin-dependent hypertension. All operated mice became hypertensive and featured hypertrophy and altered Cx expression of the aorta. The combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice raised blood pressure and cardiac weight index. Under these conditions, all aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also featured decreased levels of eNOS. In these animals, the volume overload caused by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a higher NO release. The findings provide evidence that Cx40 and Cx37 play an in vivo role in the regulation of eNOS.

The role of peptidoglycan in chlamydial cell division: towards resolving the chlamydial anomaly.

Chlamydiales are obligate intracellular bacteria including some important pathogens causing trachoma, genital tract infections and pneumonia, among others. They share an atypical division mechanism, which is independent of an FtsZ homologue. However, they divide by binary fission, in a process inhibited by penicillin derivatives, causing the formation of an aberrant form of the bacteria, which is able to survive in the presence of the antibiotic. The paradox of penicillin sensitivity of chlamydial cells in the absence of detectable peptidoglycan (PG) was dubbed the chlamydial anomaly, since no PG modified by enzymes (Pbps) that are the usual target of penicillin could be detected in Chlamydiales. We review here the recent advances in this field with the first direct and indirect evidences of PG-like material in both Chlamydiaceae and Chlamydia-related bacteria. Moreover, PG biosynthesis is required for proper localization of the newly described septal proteins RodZ and NlpD. Taken together, these new results set the stage for a better understanding of the role of PG and septal proteins in the division mechanism of Chlamydiales and illuminate the long-standing chlamydial anomaly. Moreover, understanding the chlamydial division mechanism is critical for the development of new antibiotics for the treatment of chlamydial chronic infections.

Proximity of excitatory synapses and astroglial gap junctions in layer IV of the mouse barrel cortex.

Neurons and astrocytes, the two major cell populations in the adult brain, are characterized by their own mode of intercellular communication--the synapses and the gap junctions (GJ), respectively. In addition, there is increasing evidence for dynamic and metabolic neuroglial interactions resulting in the modulation of synaptic transmission at the so-called "tripartite synapse". Based on this, we have investigated at the ultrastructural level how excitatory synapses (ES) and astroglial GJ are spatially distributed in layer IV of the barrel cortex of the adult mouse. We used specific antibodies for connexin (Cx) 30 and 43 to identify astroglial GJ, these two proteins are known to be present in the majority of astroglial GJ in the cerebral cortex. In electron-microscopic images, we measured the distance between two ES, between two GJ and between a GJ and its nearest ES. We found a ratio of two GJ per three ES in the hollow and septal areas. Taking into account the size of an astrocyte domain, the high density of GJ suggests the occurrence of reflexive type, i.e. GJ between processes of the same astrocyte. Interestingly, the distance between an ES and an astroglial GJ was found to be significantly lower than that between either two synapses or between two GJ. These observations indicate that the two modes of cell-to-cell communication are not randomly distributed in layer IV of the barrel cortex. Consequently, this feature may provide the morphological support for the recently reported functional interactions between neuronal circuits and astroglial networks.

Significance of an isolated new right bundle branch block in a patient with chest pain.

Chest pain is a common presenting symptom in emergency departments, and a typical manifestation of acute myocardial infarction (AMI). Recognition of ECG changes in AMI is essential for timely diagnosis and treatment. Right bundle branch block (RBBB) may be an isolated sign of AMI, and was previously considered as a criterion for fibrinolytic therapy. Since the most recent European Society of Cardiology and American Heart Association guidelines in 2013, RBBB alone is no longer considered a diagnostic criterion of AMI, even if it occurs in the context of acute chest pain, as RBBB does not usually interfere with the interpretation of ST-segment alteration. Our case illustrates an acute septal myocardial infarction with an isolated RBBB, and thus the importance of recognising this pattern in order to permit timely diagnosis and treatment.

Cell wall precursors are required to organize the chlamydial division septum.

Members of the Chlamydiales order are major bacterial pathogens that divide at mid-cell, without a sequence homologue of the FtsZ cytokinetic tubulin and without a classical peptidoglycan cell wall. Moreover, the spatiotemporal mechanisms directing constriction in Chlamydia are not known. Here we show that the MreB actin homologue and its conserved regulator RodZ localize to the division furrow in Waddlia chondrophila, a member of the Chlamydiales order implicated in human miscarriage. RodZ is recruited to the septal site earlier than MreB and in a manner that depends on biosynthesis of the peptidoglycan precursor lipid II by the MurA enzyme. By contrast, crosslinking of lipid II peptides by the Pbp3 transpeptidase disperses RodZ from the septum. Altogether, these findings provide a cytological framework for understanding chlamydial cytokinesis driven by septal cell wall synthesis.

Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke.

OBJECTIVE: We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation. METHODS: The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) "high-risk" echocardiographic features, and (3) neuroradiologic findings. RESULTS: A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use. CONCLUSION: Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.

HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease.

Fructose is a major component of dietary sugar and its overconsumption exacerbates key pathological features of metabolic syndrome. The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs. KHK-C displays superior affinity for fructose compared with KHK-A and is produced primarily in the liver, thus restricting fructose metabolism almost exclusively to this organ. Here we show that myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1α (HIF1α) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C. Heart-specific depletion of SF3B1 or genetic ablation of Khk, but not Khk-A alone, in mice, suppresses pathological stress-induced fructose metabolism, growth and contractile dysfunction, thus defining signalling components and molecular underpinnings of a fructose metabolism regulatory system crucial for pathological growth.