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.

New Strategy for Rapid Diagnosis and Characterization of Fungal Infections: The Example of Corneal Scrapings

PURPOSE: The prognosis of people infected with Fungi especially immunocompromised depends on rapid and accurate diagnosis to capitalize on time administration of specific treatments. However, cultures produce false negative results and nucleic-acid amplification techniques require complex post-amplification procedures to differentiate relevant fungal types. The objective of this work was to develop a new diagnostic strategy based on real-time polymerase-chain reaction high-resolution melting analysis (PCR-HRM) that a) detects yeasts and filamentous Fungi, b) differentiates yeasts from filamentous Fungi, and c) discriminates among relevant species of yeasts. METHODS: PCR-HRM detection limits and specificity were assessed with a) isolated strains; b) human blood samples experimentally infected with Fungi; c) blood experimentally infected with other infectious agents; d) corneal scrapings from patients with suspected fungal keratitis (culture positive and negative) and e) scrapings from patients with suspected bacterial, viral or Acanthamoeba infections. The DNAs were extracted and mixed with primers diluted in the MeltDoctor® HRM Master Mix in 2 tubes, the first for yeasts, containing the forward primer CandUn (5'CATGCCTGTTTGAGCGTC) and the reverse primer FungUn (5'TCCTCCGCTT ATTGATATGCT) and the second for filamentous Fungi, containing the forward primer FilamUn (5'TGCCTGTCCGAGCGTCAT) and FungUn. Molecular probes were not necessary. The yields of DNA extraction and the PCR inhibitors were systematically monitored. RESULTS: PCR-HRM detected 0.1 Colony Forming Units (CFU)/µl of yeasts and filamentous Fungi, differentiated filamentous Fungi from yeasts and discriminated among relevant species of yeasts. PCR-HRM performances were higher than haemoculture and sensitivity and specificity was 100% for culture positive samples, detecting and characterizing Fungi in 7 out 10 culture negative suspected fungal keratitis. CONCLUSIONS: PCR-HRM appears as a new, sensitive, specific and inexpensive test that detects Fungi and differentiates filamentous Fungi from yeasts. It allows direct fungal detection from clinical samples and experimentally infected blood in less than 2.30 h after DNA extraction

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Internuclear Ophthalmoplegia in a Child With Deficiency of Adenosine Deaminase 2

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease resulting in a syndrome which includes small-sized and medium-sized vessel vasculitis, immunodeficiency, and hematological disease (1,2). Loss-offunction; mutations in ADA2 are responsible for the disease (1)

Traumatic retinal detachment caused by a Nerf gun shot in a pediatric patient

PURPOSE: To present a case of retinal detachment caused by a Nerf-gun shot in a pediatric patient. METHODS: Single case report. RESULTS: A 16-year-old white man presented with a nasal visual field deficit and floaters in his left eye for 1 month after being shot with a foam-ball Nerf gun by a friend. Fundus examination revealed a midperipheral retinal dialysis extending from 1 to 4:30 clock hours with a macula-on retinal detachment and superficial proliferative vitreoretinopathy. He underwent successful 25-gauge pars plana vitrectomy with membrane peel, retinectomy, injection of perfluoron, endolaser, and use of 1,000 centistoke silicone oil for tamponade. CONCLUSION: This is the first reported case of traumatic retinal detachment secondary to a Nerf-gun shot

The Invisibility of Power: A Cultural Ecology of Development in the Contemporary United States

This article highlights the invisible power those in racial and gendered privilege continue to hold in the contemporary United States and the harmful psychological effects of this power on both those it oppresses and, importantly, those who wield it. A lack of empathy and an inability for compassion arise in individuals holding sociopolitical and cultural power, and we highlight how this psychological condition is qualifiable as psychosis and question why it has not been discussed as such in the literature until now. We also, however, bring attention to the invisible psychological power that marginalized populations in the United States hold, invisible because it has been left largely unrecognized by mainstream cultural forces. By centering the ways American cultural minorities successfully navigate multiply oppressive structural systems, we conclude with a reflection on how intersectional feminism can offer a philosophical lens through which to mitigate the unhealthy developmental outcomes and effects of White heteronormative male power. </jats:p

The forbidden touch: mechanical clearing of gas-induced crystalline lens feathering during vitrectomy surgery

Abstract Background and objective Lens feathering due to intraocular gas may cause significant challenges with intraoperative visualization during posterior segment surgery. Herein, we describe an intraoperative technique for improving posterior segment visualization impacted by lens feathering. Methods New technique to improve visualization in vitrectomy from gas-induced cataract. Results The light pipe is used to gently massage posterior subcapsular lens vacuoles to improve the surgical view intraoperatively. Conclusion We report an effective and efficient technique to improve lens feathering during vitreoretinal surgery without need for cataract extraction

Progression to stage 3 and 4 chronic kidney disease and risk factor stratification following endovascular aortic aneurysm repair

Background Risk of progression to various stages of chronic kidney disease (CKD) after endovascular aortic aneurysm repair (EVAR) is unknown. This study estimates progression rates to stage 3 and 4 CKD after EVAR and identifies potential predictors for progression. Methods EVAR cases (2006–2012) were retrospectively reviewed. Freedom of progression to CKD was estimated using Kaplan–Meier analysis, and predictors for progression were identified using Cox proportional hazards model. Results Two hundred and twelve consecutive patients at a single academic institution underwent EVAR for infrarenal aneurysms. Estimated freedom from progression to stage 3 CKD was 80%, 76%, and 63% at 6, 12, and 18 months, respectively, and for stage 4, 97%, 96%, and 93% at 6, 12, and 18 months, respectively. Stage 3 CKD predictors of progression included age (odds ratio (OR): 1.106, p = 0.001), diabetes (OR: 3.052, p = 0.04), perioperative use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers (OR: 3.249, p = 0.02), and operative blood loss (OR: 1.002, p &lt; 0.01). Stage 4 predictors included preoperative hemoglobin (OR: 0.473, p = 0.04) and baseline renal function (OR: 0.928, p = 0.001). Intraoperative contrast administration did not impact CKD development. Conclusions Progression to stage 3 CKD after EVAR occurs more frequently and at a higher rate compared with progression to stage 4. Different risk factors are associated with progression to each of those stages of CKD. </jats:sec