Long-Term Incidence And Timing Of Intraocular Hypertension After Intravitreal Triamcinolone Acetonide Injection

Purpose: To describe the long-term incidence and timing of steroid-induced ocular hypertension after intravitreal triamcinolone acetonide (IVTA) therapy. Design: Retrospective case series of 929 eyes of 841 patients. Participants: Patients with a variety of posterior segment disorders in a single group practice. Intervention: Pars plana injection of IVTA. Main Outcome Measures: Intraocular pressure (IOP) and requirement for glaucoma surgery. Results: Overall, 929 eyes received ≥1 injections (mean, 1.6) of 4 mg of IVTA. During a mean follow-up period of 14±6.9 months, the Kaplan-Meier cumulative incidences of IOP elevations \u3e21 mmHg at 6, 12, 18, and 24 months post-injection were 28.2%, 34.6%, 41.2%, and 44.6%, respectively; similarly, the incidences of eyes with IOP measurements \u3e25 mmHg were 14.6%, 19.1%, 24.1%, and 28.2%, respectively. At the same time points, lOP-lowering medications were required byl3.0%, 16.9%, 20.7%, and 24.2% of eyes, respectively. Only 3 eyes (0.3%) required lOP-lowering surgery. Preexisting glaucoma, younger age, and a history of an IOP elevation after a previous IVTA injection were risk factors for IOP elevations after IVTA injection. The minimum and maximum follow-up were 3 weeks and 37 months. The mean rate of attrition in this study was 3% per month. Conclusions: Elevations in IOP after IVTA injection are common. Younger patients and eyes with preexisting glaucoma or a history of a steroid response should be monitored more closely for IOP elevations after IVTA therapy

Outcome of elective endovascular abdominal aortic aneurysm repair in nonagenarians

ObjectiveCompared with open repair of abdominal aortic aneurysms (AAA), endovascular repair (EVAR) is associated with decreased perioperative morbidity and mortality in a standard patient population. This study sought to determine if the advantage of EVAR extends to patients aged ≥90 years.MethodsThis was a retrospective review from a prospectively maintained computerized database. Of the 322 patients aged ≥80 treated with EVAR from January 1997 to November 2007, 24 (1.9%) were aged ≥90. Mean age was 91.5 ± 1.5 years (range, 90-95 years), and 83.3% were men. Mean aneurysm size was 6.8 cm (range, 5.2-8.7 cm).ResultsMean procedural blood loss was 490 mL (range, 100-4150 mL), and 20.8% required an intraoperative transfusion. Mean postoperative length of stay was 6.0 days, (median, 4 days; mode, 1 day; range, 1-42 days), with 33.3% of patients discharged on the first postoperative day. Amongst the 24 patients, there were 6 (25.0%) perioperative major adverse events, and 2 patients died, for a perioperative mortality rate of 8.3%. Mean follow-up was 20.5 months (range, 1-49 months). Overall, three patients (12.5%) required a secondary intervention, comprising thrombectomy, angioplasty, and proximal cuff extension. No patients required conversion to open repair. Two patients (8.3%) died of AAA rupture at 507 and 1254 days. Freedom from all-cause mortality was 83.3% at 1 year and 19.3% at 5 years. Freedom from aneurysm-related mortality was 87.5% at 1 year and 73.2% at 5 years. Endoleak occurred in five patients (20.8%), with three type I and two of indeterminate type; of these, two patients with type I endoleak underwent secondary intervention at 153 and 489 days after EVAR, of which one case was successful.ConclusionOur study supports that EVAR in nonagenarians is associated with acceptable procedural success and perioperative morbidity and mortality. The medium-term results suggest that EVAR may be of limited benefit in very carefully selected patients who are aged ≥90 years

Peripheral Determinants of Oxygen Utilization in Heart Failure With Preserved Ejection Fraction

The aim of this study was to determine the arteriovenous oxygen content difference (ΔAVO2) in adult subjects with and without heart failure with preserved ejection fraction (HFpEF) during systemic and forearm exercise. Subjects with HFpEF had reduced ΔAVO2. Forearm diffusional conductance for oxygen, a lumped conductance parameter that incorporates all impediments to the movement of oxygen from red blood cells in skeletal muscle capillaries into the mitochondria within myocytes, was estimated. Forearm diffusional conductance for oxygen was not different among adults with HFpEF, those with hypertension, and healthy control subjects; therefore, diffusional conductance cannot explain the reduced forearm ΔAVO2. Instead, adiposity was strongly associated with ΔAVO2, suggesting an active role for adipose tissue in reducing exercise capacity in patients with HFpEF

Parameters affecting water-hammer wave attenuation, shape and timing. Part 2: Case studies

This two-part paper investigates parameters that may significantly affect water-hammer wave attenuation, shape and timing. Possible sources that may affect the waveform predicted by classical water-hammer theory include unsteady friction, cavitation (including column separation and trapped air pockets), a number of fluid–structure interaction effects, viscoelastic behaviour of the pipe-wall material, leakages and blockages. Part 1 of this two-part paper presents the mathematical tools needed to model these sources. Part 2 of the paper presents a number of case studies showing how these modelled sources affect pressure traces in a simple reservoir-pipeline-valve system. Each case study compares the obtained results with the standard (classical) water-hammer model, from which conclusions are drawn concerning the transient behaviour of real systems.Anton Bergant, Arris S. Tijsseling, John P. Vítkovský, Dídia I. C. Covas, Angus R. Simpson and Martin F. Lamber

Supreme activity of gramicidin S against resistant, persistent and biofilm cells of staphylococci and enterococci.

Three promising antibacterial peptides were studied with regard to their ability to inhibit the growth and kill the cells of clinical strains of Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium. The multifunctional gramicidin S (GS) was the most potent, compared to the membranotropic temporin L (TL), being more effective than the innate-defence regulator IDR-1018 (IDR). These activities, compared across 16 strains as minimal bactericidal and minimal inhibitory concentrations (MIC), are independent of bacterial resistance pattern, phenotype variations and/or biofilm-forming potency. For S. aureus strains, complete killing is accomplished by all peptides at 5 × MIC. For E. faecalis strains, only GS exhibits a rapid bactericidal effect at 5 × MIC, while TL and IDR require higher concentrations. The biofilm-preventing activities of all peptides against the six strains with the largest biofilm biomass were compared. GS demonstrates the lowest minimal biofilm inhibiting concentrations, whereas TL and IDR are consistently less effective. In mature biofilms, only GS completely kills the cells of all studied strains. We compare the physicochemical properties, membranolytic activities, model pharmacokinetics and eukaryotic toxicities of the peptides and explain the bactericidal, antipersister and antibiofilm activities of GS by its elevated stability, pronounced cell-penetration ability and effective utilization of multiple modes of antibacterial action

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

peer reviewedBackground: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non–oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non–OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction. © 202