Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

BackgroundAlthough recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient''s physical rehabilitation and assess their cardiovascular prognosis.DesignWe aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection.MethodsPatients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta.ResultsAmong the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.ConclusionCPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.     

Metabolic syndrome in Zambian adults with human immunodeficiency virus on antiretroviral therapy: Prevalence and associated factors

Metabolic syndrome (MetS) is a constellation of factors including hypertension, abdominal obesity, dyslipidemia, and insulin resistance that separately and together significantly increase risk for cardiovascular disease (CVD) and diabetes. In sub-Saharan Africa, with a substantial burden of human immunodeficiency virus (HIV) and increasing prevalence of CVD and diabetes, there is a paucity of epidemiological data on demographic, laboratory, and clinical characteristics associated with MetS among people with HIV (people with human [PWH]). Therefore, this study aimed to determine the burden and factors influencing MetS in antiretroviral therapy (ART)-experienced individuals in Zambia.We collected cross-sectional demographic, lifestyle, anthropometric, clinical, and laboratory data in a cohort of ART-experienced (on ART for ≥6 months) adults in 24 urban HIV treatment clinics of Zambia between August, 2016 and May, 2020. MetS was defined as having ≥3 of the following characteristics: low high density lipoprotein cholesterol (HDL-c) (<1.0 mmol/L for men, <1.3 for women), elevated waist circumference (≥94 cm for men, ≥80 cm for women), elevated triglycerides (≥1.7 mmol/L), elevated fasting blood glucose (≥5.6 mmol/L), and elevated blood pressure (BP) (systolic BP ≥130 or diastolic BP ≥85 mm Hg). Virological failure (VF) was defined as HIV viral load ≥1000 copies/mL. The following statistical methods were used: Chi-square test, Wilcoxon rank-sum test, and multivariable logistic regression.Among 1108 participants, the median age (interquartile range [IQR]) was 41 years (34, 49); 666 (60.1%) were females. The prevalence of MetS was 26.3% (95% confidence interval [CI] 23.9–29.1). Age (adjusted odds ratio [OR] 1.07; 95% CI 1.04–1.11), female sex (OR 3.02; 95% CI 1.55–5.91), VF (OR 1.98; 95% CI 1.01–3.87), dolutegravir (DTG)-based regimen (OR 2.10; 95% CI 1.05–4.20), hip-circumference (OR 1.03; 95% CI 1.01–1.05), T-lymphocyte count (OR 2.23; 95% CI 1.44–3.43), high-sensitivity C-reactive protein (hsCRP) (OR 1.14; 95% CI 1.01–1.29), and fasting insulin (OR 1.02; 95% CI 1.01–1.04) were significantly associated with MetS.Metabolic syndrome was highly prevalent among HIV+ adults receiving ART in Zambia and associated with demographic, clinical, anthropometric, and inflammatory characteristics. The association between MetS and dolutegravir requires further investigation, as does elucidation of the impact of MetS on ART outcomes in sub-Saharan African PWH.     

Enhancement of MHC-I Antigen Presentation via Architectural Control of pH-Responsive,Endosomolytic Polymer Nanoparticles

Protein-based vaccines offer a number of important advantages over organism-based vaccines but generally elicit poor CD8⁺ T cell responses. We have previously demonstrated that pH-responsive, endosomolytic polymers can enhance protein antigen delivery to major histocompatibility complex class I (MHC-I) antigen presentation pathways thereby augmenting CD8⁺ T cell responses following immunization. Here, we describe a new family of nanocarriers for protein antigen delivery assembled using architecturally distinct pH-responsive polymers. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize linear, hyperbranched, and core-crosslinked copolymers of 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) that were subsequently chain extended with a hydrophilic N,N-dimethylacrylamide (DMA) segment copolymerized with thiol-reactive pyridyl disulfide (PDS) groups. In aqueous solution, polymer chains assembled into 25 nm micellar nanoparticles and enabled efficient and reducible conjugation of a thiolated protein antigen, ovalbumin. Polymers demonstrated pH-dependent membrane-destabilizing activity in an erythrocyte lysis assay, with the hyperbranched and cross-linked polymer architectures exhibiting significantly higher hemolysis at pH ≤ 7.0 than the linear diblock. Antigen delivery with the hyperbranched and cross-linked polymer architecture enhanced in vitro MHC-I antigen presentation relative to free antigen, whereas the linear construct did not have a discernible effect. The hyperbranched system elicited a four- to fivefold increase in MHC-I presentation relative to the cross-linked architecture, demonstrating the superior capacity of the hyperbranched architecture in enhancing MHC-I presentation. This work demonstrates that the architecture of pH-responsive, endosomolytic polymers can have dramatic effects on intracellular antigen delivery, and offers a promising strategy for enhancing CD8⁺ T cell responses to protein-based vaccines.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9697-1) contains supplementary material, which is available to authorized users.KEY WORDS: MHC-I antigen presentation, pH-responsive nanoparticle, polymer architecture, RAFT polymerization, vaccine     

Renal Replacement Therapy for Acute Kidney Injury in Severe Alcohol-Associated Hepatitis as a Bridge to Transplant or Recovery

Digestive Diseases and Sciences - Acute kidney injury is seen in approximately 30% of patients with severe alcohol-associated hepatitis (AH) and is associated with increased mortality. Controversy...     

Successful Liver Transplantation in a Patient with a Thrombosed Portomesenteric System after Multiple Failed Shunts

Combined portal and mesenteric vein thrombosis preventing restoration of adequate portal venous flow has been considered a contraindication to liver transplantation. We report a patient with failed splenorenal (SR), portocaval (PC), and mesocaval (MC) shunts, who despite the absence of any obvious means for supplying portal venous inflow to a hepatic graft, successfully underwent orthotopic liver transplantation. A method of reconstruction of the portal vein with the use of vein grafts anastomosed to a large splanchnic venous collateral is described. This technique can be used in selected patients in whom orthotopic liver transplantation might otherwise be considered technically impossible.     

Influenza surveillance on ‘foie gras’ duck farms in Bulgaria, 2008–2012

Objectives

Ducks can shed and spread influenza A viruses (IAVs) while showing no disease signs. Our objective was to clarify the role of ‘foie gras’ ducks in the circulation of IAVs in Bulgaria.

Methods

Monthly avian influenza surveillance was conducted on 63 ‘foie gras’ duck farms, 52 of which were surveyed throughout the study between November 2008 and April 2012. Virologic and serologic samples were collected and tested. During this time, wild bird samples were collected at major wild bird‐resting areas near the Black Sea coast and Danube River.

Results

The study showed high isolation frequency of low‐pathogenicity avian influenza viruses. In the raising population (<75 days old), subtypes H3, H4, and H6 were detected monthly and H5 LPAIV, sporadically. Different subtypes (H1, H10, H11) were isolated from the fattening premises (75‐ to 100‐day‐old ducks), suggesting different routes of introduction. Only 6 of the 52 farms that were surveyed both virologically and serologically were influenza‐free throughout the study, possibly due to higher biosecurity measures implemented. No evidence of direct transmission of IAV from wild birds was found. Wild bird surveillance showed low isolation frequency of IAV. IAV prevalence of 0·55% for migratory ducks and 0·53% for migratory geese was estimated in November–December 2011 and January–February 2012, respectively, at two ornithologically important locations near the Black Sea coast.

Conclusions

The ‘foie gras’ duck farms in Bulgaria are an optimal niche where Eurasian‐like IAVs are maintained and reassorted unapparent to farmers and veterinarians.     

Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease

Parkinson's disease (PD) is characterized by a progressive loss of midbrain dopamine neurons and the presence of cytoplasmic inclusions called Lewy bodies. Mutations in several genes including alpha-synuclein and parkin have been linked to familial PD. The loss of parkin's E3-ligase activity leads to dopaminergic neuronal degeneration in early-onset autosomal recessive juvenile parkinsonism, suggesting a key role of parkin for dopamine neuron survival. To evaluate the potential neuroprotective role of parkin in the pathogenesis of PD, we tested whether overexpression of wild-type rat parkin could protect against the toxicity of mutated human A30P alpha-synuclein in a rat lentiviral model of PD. Animals overexpressing parkin showed significant reductions in alpha-synuclein-induced neuropathology, including preservation of tyrosine hydroxylase-positive cell bodies in the substantia nigra and sparing of tyrosine hydroxylase-positive nerve terminals in the striatum. The parkin-mediated neuroprotection was associated with an increase in hyperphosphorylated alpha-synuclein inclusions, suggesting a key role for parkin in the genesis of Lewy bodies. These results indicate that parkin gene therapy may represent a promising candidate treatment for PD.     

Juvenile rhesus monkeys have lower type 2 cytokine responses than adults after primary infection with Schistosoma mansoni

Adults and children have differences in their susceptibility to schistosomiasis. The relative influences of age-dependent innate resistance and acquired immunity in the differences between susceptibility to schistosomiasis are difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. In contrast to the adult animals, the juvenile rhesus monkeys had low levels of interleukin (IL)-4 and IL-5 production by peripheral blood mononuclear cells after schistosome infection, as well as lower levels of parasite-antigen-specific antibody (IgG, IgM, and IgA) responses, and produced limited antigen-specific or total IgE. Juvenile animals had statistically nonsignificant increased worm burdens and tissue or fecal egg counts, compared with that of adults, whereas circulating schistosome antigens were significantly higher in infected juvenile monkeys. These results suggest that juvenile rhesus monkeys have reduced type 2 cytokine responses after primary schistosome infections and perhaps are more susceptible to parasite infection.     

Frequency,risk factors,and outcome of hyperlactatemia after cardiac surgery

STUDY OBJECTIVE: To determine the respective frequencies, risk factors, and outcomes of no hyperlactatemia (NHL), immediate hyperlactatemia (IHL), or late hyperlactatemia (LHL) > 3 mmol/L after cardiac surgery. DESIGN: Prospective and observational study. SETTING: Cardiac surgery ICU in a 130-bed private community nonteaching hospital. PATIENTS: Consecutive patients (n = 325) undergoing cardiopulmonary bypass (CPB) for cardiac surgery. INTERVENTION: None. MEASUREMENTS: Arterial blood gas levels and lactate concentrations were measured at ICU admission, 4 h after surgery, between 6 h and 16 h after surgery, and on day 1. MAIN RESULTS: Sixty-seven patients (20.6%) had an IHL on ICU admission, and 56 patients (17.2%) acquired LHL during their ICU stay. ICU mortality was 1.5% for NHL, 3.6% for LHL, and 14.9% for IHL groups (p < 0.0001). The three groups differed significantly for elective surgery, type of operation, CPB duration, intraoperative mean arterial pressure, and intraoperative and postoperative use of vasopressor. Independent risk factors for IHL were nonelective surgery, CPB duration, and intraoperative use of vasopressor. Logistic regression identified hyperglycemia and epinephrine therapy for LHL as postoperative risk factors. Receiver operating characteristic curves showed that IHL more accurately predicted ICU mortality than LHL. CONCLUSIONS: Hyperlactatemia is common after cardiac surgery. A lactate threshold of 3 mmol/L at ICU admission is able to identify a population at risk of morbidity and mortality after cardiac surgery.