Should intentional endovascular stent-graft coverage of the left subclavian artery be preceded by prophylactic revascularisation?

Thoracic endovascular aortic repair (TEVAR) has emerged as a promising therapeutic alternative to conventional open aortic replacement but it requires suitable proximal and distal landing zones for stent-graft anchoring. Many aortic pathologies affect in the immediate proximity of the left subclavian artery (LSA) limiting the proximal landing zone site without proximal vessel coverage. In patients in whom the distance between the LSA and aortic lesion is too short, extension of the landing zone can be obtained by covering the LSA's origin with the endovascular stent graft (ESG). This manoeuvre has the potential for immediate and delayed neurological and vascular symptoms. Some authors, therefore, propose prophylactic revascularisation of the LSA by transposition or bypass, while others suggest prophylactic revascularisation only under certain conditions, and still others see no requirement for prophylactic revascularisation in anticipation of LSA ostium coverage. In this review about LSA revascularisation in TEVAR patients with coverage of the LSA, we searched the electronic databases MEDLINE and EMBASE historically until the end date of May 2010 with the search terms left subclavian artery, covering, endovascular, revascularisation and thoracic aorta. We have gathered the most complete scientific evidence available used to support the various concepts to deal with this issue. After a review of the current available literature, 23 relevant articles were found, where we have identified and analysed three basic treatment concepts for LSA revascularisation in TEVAR patients (prophylactic, conditional prophylactic and no prophylactic LSA revascularisation). The available evidence supports prophylactic revascularisation of the LSA before ESG LSA coverage when preoperative imaging reveals abnormal supra-aortic vascular anatomy or pathology. We further conclude that elective patients undergoing planned coverage of the LSA during TEVAR should receive prophylactic LSA transposition or LSA-to-left-common-carotid-artery (LCCA) bypass surgery to prevent severe neurological complications, such as paraplegia or brain stem infarction.

Impact of admission glucose and diabetes on recanalization and outcome after intra-arterial thrombolysis for ischaemic stroke

BACKGROUND: Stroke patients with diabetes and admission hyperglycaemia have worse outcomes than non-diabetics, with or without intravenous thrombolysis. Poor vessel recanalization was reported in diabetics treated with intravenous thrombolysis. AIMS: This study aimed to determine the impact of admission glucose and diabetes on recanalization and outcome after intra-arterial thrombolysis. METHODS: We analysed 389 patients (213 men, 176 women) treated with intra-arterial thrombolysis. The association of diabetes and admission glucose value with recanalization, outcome, mortality, and symptomatic intracranial haemorrhage was determined. Recanalization was classified according to thrombolysis in myocardial infarction grades. Outcome was measured using the modified Rankin Scale at three-months and categorized as favourable (modified Rankin Scale 0-2) or poor (modified Rankin Scale 3-6). RESULTS: The rate of partial or complete recanalization (thrombolysis in myocardial infarction 2-3) did not differ between patients with and without diabetes (67% vs. 66%; P = 1·000). Mean admission glucose values were similar in patients with poor recanalization (thrombolysis in myocardial infarction 0-1) and patients with partial or complete recanalization (thrombolysis in myocardial infarction 2-3; 7·3 vs. 7·3 mmol/l; P = 0·746). Follow-up at three-months was obtained in 388 of 389 patients. Clinical outcome was favourable (modified Rankin Scale 0-2) in 189 patients (49%) and poor (modified Rankin Scale 3-6) in 199 patients (51%). Mortality at three-months was 20%. Diabetics were more likely to have poor outcome (72% vs. 48%; P = 0·001) and to be dead (30% vs. 19%; P = 0·044) at three-months. After multivariable analysis, there remained an independent relationship between diabetes and outcome (P = 0·003; odds ratio 3·033, 95% confidence interval 1·452-6·336), but not with mortality (P = 0·310; odds ratio 1·436; 95% confidence interval 0·714-2·888). Moreover, higher age (P = 0·001; odds ratio 1·039; 95% confidence interval 1·017-1·061), higher baseline National Institutes of Health Stroke Scale score (P < 0·0001; odds ratio 1·130; 95% confidence interval 1·079-1·182), location of vessel occlusion as categorical variable (P < 0·0001), poor collaterals (P = 0·02; odds ratio 1·587; 95% confidence interval 1·076-2·341), poor vessel recanalization (P < 0·0001; odds ratio 4·713; 95% confidence interval 2·627-8·454), and higher leucocyte count (P = 0·032; odds ratio 1·094; 95% confidence interval 1·008-1·188) were independent baseline predictors of poor outcome. Higher admission glucose was associated with poor outcome (P = 0·006) and mortality (P < 0·0001). After multivariate analyses, glucose remained independently associated with poor outcome (P = 0·019; odds ratio 1·150; 95% confidence interval 1·023-1-292) and mortality (P = 0·005; odds ratio 1·183; 95% confidence interval 1052-1·331). The rate of symptomatic intracranial haemorrhage was similar in diabetics and non-diabetics (6·7% vs. 4·6%; P = 0·512). Mean admission glucose was higher in patients with symptomatic intracranial haemorrhage than without (8·58 vs. 7·26 mmol/l; P = 0·010). Multivariable analysis confirmed an independent association between admission glucose and symptomatic intracranial haemorrhage (P = 0·027; odds ratio 1·187; 95% confidence interval 1·020-1·381). CONCLUSIONS: Diabetes and glucose value on admission did not influence recanalization after intra-arterial thrombolysis; nevertheless, they were independent predictors of poor outcome after intra-arterial thrombolysis and a higher admission glucose value was an independent predictor of symptomatic intracranial haemorrhage. This indicates that factors on the capillary, cellular, or metabolic level may account for the worse outcome in patients with elevated glucose value and diabetes.

Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo

The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

The metabolomic window into hepatobiliary disease

The emergent discipline of metabolomics has attracted considerable research effort in hepatology. Here we review the metabolomic data for non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), alcoholic liver disease (ALD), hepatitis B and C, cholecystitis, cholestasis, liver transplantation, and acute hepatotoxicity in animal models. A metabolomic window has permitted a view into the changing biochemistry occurring in the transitional phases between a healthy liver and hepatocellular carcinoma or cholangiocarcinoma. Whether provoked by obesity and diabetes, alcohol use or oncogenic viruses, the liver develops a core metabolomic phenotype (CMP) that involves dysregulation of bile acid and phospholipid homeostasis. The CMP commences at the transition between the healthy liver (Phase 0) and NAFLD/NASH, ALD or viral hepatitis (Phase 1). This CMP is maintained in the presence or absence of cirrhosis (Phase 2) and whether or not either HCC or CCA (Phase 3) develops. Inflammatory signalling in the liver triggers the appearance of the CMP. Many other metabolomic markers distinguish between Phases 0, 1, 2 and 3. A metabolic remodelling in HCC has been described but metabolomic data from all four Phases demonstrate that the Warburg shift from mitochondrial respiration to cytosolic glycolysis foreshadows HCC and may occur as early as Phase 1. The metabolic remodelling also involves an upregulation of fatty acid β-oxidation, also beginning in Phase 1. The storage of triglycerides in fatty liver provides high energy-yielding substrates for Phases 2 and 3 of liver pathology. The metabolomic window into hepatobiliary disease sheds new light on the systems pathology of the liver.

Neural correlates of a 'pessimistic' attitude when anticipating events of unknown emotional valence

Since we do not know what future holds for us, we prepare for expected emotional events in order to deal with a pleasant or threatening environment. From an evolutionary perspective, it makes sense to be particularly prepared for the worst-case scenario. We were interested to evaluate whether this assumption is reflected in the central nervous information processing associated with expecting visual stimuli of unknown emotional valence. While being scanned with functional magnetic resonance imaging, healthy subjects were cued to expect and then perceive visual stimuli with a known emotional valence as pleasant, unpleasant, and neutral, as well as stimuli of unknown valence that could have been either pleasant or unpleasant. While anticipating pictures of unknown valence, the activity of emotion processing brain areas was similar to activity associated with expecting unpleasant pictures, but there were no areas in which the activity was similar to the activity when expecting pleasant pictures. The activity of the revealed regions, including bilateral insula, right inferior frontal gyrus, medial thalamus, and red nucleus, further correlated with the individual ratings of mood: the worse the mood, the higher the activity. These areas are supposedly involved in a network for internal adaptation and preparation processes in order to act according to potential or certain unpleasant events. Their activity appears to reflect a 'pessimistic' bias by anticipating the events of unknown valence to be unpleasant.

Determination of respiratory gas flow by electrical impedance tomography in an animal model of mechanical ventilation

Background A recent method determines regional gas flow of the lung by electrical impedance tomography (EIT). The aim of this study is to show the applicability of this method in a porcine model of mechanical ventilation in healthy and diseased lungs. Our primary hypothesis is that global gas flow measured by EIT can be correlated with spirometry. Our secondary hypothesis is that regional analysis of respiratory gas flow delivers physiologically meaningful results. Methods In two sets of experiments n = 7 healthy pigs and n = 6 pigs before and after induction of lavage lung injury were investigated. EIT of the lung and spirometry were registered synchronously during ongoing mechanical ventilation. In-vivo aeration of the lung was analysed in four regions-of-interest (ROI) by EIT: 1) global, 2) ventral (non-dependent), 3) middle and 4) dorsal (dependent) ROI. Respiratory gas flow was calculated by the first derivative of the regional aeration curve. Four phases of the respiratory cycle were discriminated. They delivered peak and late inspiratory and expiratory gas flow (PIF, LIF, PEF, LEF) characterizing early or late inspiration or expiration. Results Linear regression analysis of EIT and spirometry in healthy pigs revealed a very good correlation measuring peak flow and a good correlation detecting late flow. PIFEIT = 0.702 · PIFspiro + 117.4, r2 = 0.809; PEFEIT = 0.690 · PEFspiro-124.2, r2 = 0.760; LIFEIT = 0.909 · LIFspiro + 27.32, r2 = 0.572 and LEFEIT = 0.858 · LEFspiro-10.94, r2 = 0.647. EIT derived absolute gas flow was generally smaller than data from spirometry. Regional gas flow was distributed heterogeneously during different phases of the respiratory cycle. But, the regional distribution of gas flow stayed stable during different ventilator settings. Moderate lung injury changed the regional pattern of gas flow. Conclusions We conclude that the presented method is able to determine global respiratory gas flow of the lung in different phases of the respiratory cycle. Additionally, it delivers meaningful insight into regional pulmonary characteristics, i.e. the regional ability of the lung to take up and to release air.

Experimental and Calculated Spectra of π-Stacked Mild Charge-Transfer Complexes: Jet-Cooled Perylene·(Tetrachloroethene) n , n = 1,2

The S0 ↔ S1 spectra of the mild charge-transfer (CT) complexes perylene·tetrachloroethene (P·4ClE) and perylene·(tetrachloroethene)2 (P·(4ClE)2) are investigated by two-color resonant two-photon ionization (2C-R2PI) and dispersed fluorescence spectroscopy in supersonic jets. The S0 → S1 vibrationless transitions of P·4ClE and P·(4ClE)2 are shifted by δν = −451 and −858 cm–1 relative to perylene, translating to excited-state dissociation energy increases of 5.4 and 10.3 kJ/mol, respectively. The red shift is ∼30% larger than that of perylene·trans-1,2-dichloroethene; therefore, the increase in chlorination increases the excited-state stabilization and CT character of the interaction, but the electronic excitation remains largely confined to the perylene moiety. The 2C-R2PI and fluorescence spectra of P·4ClE exhibit strong progressions in the perylene intramolecular twist (1au) vibration (42 cm–1 in S0 and 55 cm–1 in S1), signaling that perylene deforms along its twist coordinate upon electronic excitation. The intermolecular stretching (Tz) and internal rotation (Rc) vibrations are weak; therefore, the P·4ClE intermolecular potential energy surface (IPES) changes little during the S0 ↔ S1 transition. The minimum-energy structures and inter- and intramolecular vibrational frequencies of P·4ClE and P·(4ClE)2 are calculated with the dispersion-corrected density functional theory (DFT) methods B97-D3, ωB97X-D, M06, and M06-2X and the spin-consistent-scaled (SCS) variant of the approximate second-order coupled-cluster method, SCS-CC2. All methods predict the global minima to be π-stacked centered coplanar structures with the long axis of tetrachloroethene rotated by τ ≈ 60° relative to the perylene long axis. The calculated binding energies are in the range of −D0 = 28–35 kJ/mol. A second minimum is predicted with τ ≈ 25°, with ∼1 kJ/mol smaller binding energy. Although both monomers are achiral, both the P·4ClE and P·(4ClE)2 complexes are chiral. The best agreement for adiabatic excitation energies and vibrational frequencies is observed for the ωB97X-D and M06-2X DFT methods.

Is Photodynamic Therapy an Effective Treatment for Periodontal and Peri-Implant Infections?

Antimicrobial photodynamic therapy (PDT) has attracted much attention for the treatment of pathogenic biofilm associated with peridontitis and peri-implantitis. However, data from randomized controlled clinical studies (RCTs) are limited and, to some extent, controversial, making it difficult to provide appropriate recommendations. Therefore, the aims of the present study were (a) to provide an overview on the current evidence from RCTs evaluating the potential clinical benefit for the additional use of PDT to subgingival mechanical debridement (ie, scaling and root planing) alone in nonsurgical periodontal therapy; and (b) to provide clinical recommendations for the use of PDT in periodontal practice.