Search

Supplemental Digital Content is available in the text., Background: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). Methods: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. Results: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2–1.7] versus 1.3 [1.2–1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, P

Objective— Smooth muscle cells (SMCs) are the most abundant cells in human atherosclerotic lesions and are suggested to contribute at least 50% of atheroma foam cells. In mice, SMCs contribute fewer total lesional cells. The purpose of this study was to determine the contribution of SMCs to total foam cells in apolipoprotein E-deficient (ApoE −/− ) mice, and the utility of these mice to model human SMC foam cell biology and interventions. Approach and Results— Using flow cytometry, foam cells in the aortic arch of ApoE −/− mice were characterized based on the expression of leukocyte-specific markers. Nonleukocyte foam cells increased from 37% of total foam cells in 27-week-old to 75% in 57-week-old male ApoE −/− mice fed a chow diet and were ≈70% in male and female ApoE −/− mice following 6 weeks of Western diet feeding. A similar contribution to total foam cells by SMCs was found using SMC-lineage tracing ApoE −/− mice fed the Western diet for 6 or 12 weeks. Nonleukocyte foam cells contributed a similar percentage of total atheroma cholesterol and exhibited lower expression of the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1) when compared with leukocyte-derived foam cells. Conclusions— Consistent with previous studies of human atheromas, we present evidence that SMCs contribute the majority of atheroma foam cells in ApoE −/− mice fed a Western diet and a chow diet for longer periods. Reduced expression of ABCA1, also seen in human intimal SMCs, suggests a common mechanism for formation of SMC foam cells across species, and represents a novel target to enhance atherosclerosis regression.

OBJECTIVE To evaluate surgical findings and hearing results for patient's undergoing the described surgical approach for congenitally absent or dysplastic oval window (OW). STUDY DESIGN The Institutional Review Board approved retrospective review of patients with conductive hearing loss (CHL) operated on from 1992 to 2016. SETTING Academic tertiary center. PATIENTS Patients with CHL, an intact tympanic membrane (TM), and without history of chronic infection underwent middle ear exploration. Eleven patients and 13 ears underwent an oval window drill-out (OWD) procedure. INTERVENTION Eleven patients presented, all with dysplastic or congenitally absent oval window (CAOW). CHL was identified using audiometry and tuning forks, many patients also had preoperative computed tomography temporal bones. A transcanal approach was used and an OWD was performed with a variety of prostheses placed. MAIN OUTCOME MEASURE Audiometric studies before and after intervention were compared with 12 month and long-term follow-up (1-22 yr). RESULTS Preoperative air-bone gaps ranged from 40 to 60 dB and averaged 55.1 dB. Postoperative air-bone gaps ranged from 0 to 60 dB and averaged 24.1 dB. The preoperative pure-tone average (PTA) ranged from 55 to 99 dB and averaged 71.3 dB. Postoperative PTA ranged from 21 to 108 dB and averaged 49.6 dB. CONCLUSION Dysplastic and CAOW are uncommon congenital major ear anomalies. OWD is a viable treatment option, though careful counseling is critical, as significant complications are possible, especially with facial nerve (FN) abnormalities. This series demonstrates successful closure of the air-bone gap for many patients with this technique.

BACKGROUND Organ donation after circulatory death (DCD) is increasingly being used as a means of addressing the organ supply/demand mismatch in solid organ transplantation. There is reluctance to use DCD hearts, due to an inability to precisely identify hearts that have suffered irreversible injury. We investigated novel biomarkers and clinically relevant endpoints across a spectrum of warm ischemic times, before and during ex vivo heart perfusion (EVHP), to identify features associated with a nonviable cardiac phenotype. METHODS Donor rats sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff periods (DCD groups). Left ventricular function, histochemical injury, and differences in left ventricular gene expression were studied before, and during, EVHP. RESULTS As warm ischemic time exposure increased in DCD groups, fewer hearts were functional during EVHP, and ventricular function was increasingly impaired. Histochemical assessment identified severely injured hearts during EVHP. A novel gene expression signature identified severely injured hearts during EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72-5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be useful in identifying high-risk hearts at the point of harvest (Hsp90). CONCLUSIONS We demonstrate that our preclinical model recapitulates the cardio-respiratory decompensation observed in humans, and that EVHP appears necessary to unmask distinguishing features of severely injured DCD hearts. Furthermore, we outline a clinically relevant multimodal approach to assessing candidate DCD hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in severely injured hearts during EVHP, and may also detect injury at the point of harvest.

The purpose of this review is to describe our experience with management of chronic tinnitus and to review the recent literature on the best treatment options available for treating patients who are troubled by their tinnitus. In addition, we want to highlight our experience and approach to this very common problem.Treatment options for patients are based on the severity of the tinnitus and any associated problems. The use of nutritional supplements has a place in the treatment of mild-to-moderate tinnitus. Ginkgo biloba and B-complex vitamins may have an impact on selected patients. Treatment of underlying or accompanying anxiety disorders especially with cognitive behavior therapy can help to reduce the distress associated with tinnitus. Surgical treatment options, such as cochlear implant, have been shown to be very effective in reducing tinnitus in patients with sudden unilateral hearing loss as the cause of tinnitus. Other surgical approaches, such as repetitive transcranial magnetic stimulation and vagal stimulator, have had some limited benefits.Treatment for subjective tinnitus can range from the conventional to the investigational modalities. Best treatment options take into account the possible cause of the tinnitus and other associated symptoms.

Allergic rhinitis has a high prevalence and negatively impacts quality of life. Patients commonly use complementary and integrative modalities to help alleviate their symptoms of allergic rhinitis, with approximately one in five receiving acupuncture. This article reviews the evidence base on the efficacy/effectiveness, safety and cost-effectiveness of acupuncture for allergic rhinitis.Our review of the medical literature from January 2013 through December 2014 revealed that there is research demonstrating efficacy and effectiveness for acupuncture in the treatment of allergic rhinitis, as well as improvement of quality of life and quality-adjusted life-years.There are high-quality randomized controlled trials that demonstrate efficacy and effectiveness for acupuncture in the treatment of both seasonal and perennial allergic rhinitis. Smaller head-to-head studies also show some preliminary benefit of acupuncture when compared with antihistamines, but these had a variety of methodological limitations. Further studies of higher quality are needed, particularly with a focus on comparative effectiveness research.

Purpose of review Complementary and integrative medicine (CIM), formerly known as alternative medicine, is now part of the mainstream management for patients with a host of medical issues. This current opinion focuses on the use of CIM, more specifically, the use of nutritional and herbal therapies and homeopathic medications for patients with allergic symptoms. Recent findings The literature review revealed that naturally occurring substances when compared with placebo more often than not resulted in significant improvement of the allergic rhinitis symptoms. Summary Despite encouraging results, additional studies with greater rigor are needed.

Introduction: Granzyme B (GzmB) is a serine protease involved in immune cell-mediated apoptosis that is enabled through a mechanism involving the pore-forming protein, perforin that facilitates internalization. However, recent evidence suggests that GzmB contributes to matrix remodeling and fibrosis through an extracellular, perforin-independent process. Hypothesis: GzmB contributes to cardiac fibrosis through a perforin-independent pathway involving extracellular proteolysis. Methods: Using a murine model of Angiotensin II (Ang II)-induced cardiac fibrosis, wild-type, GzmB deficient and Perforin deficient mice were treated with Ang II for 4 weeks, and were examined for the presence of cardiac fibrosis. Echocardiography was performed in these mice to examine the cardiac function. The level of Inflammation and inflammatory cells infiltration were examined by immunohistochemistry and RT-PCR analysis. The in vitro endothelial barrier function was measured by electric cell-substrate impedance sensing. Results: GzmB was highly up-regulated in both murine and human cardiac fibrosis. Genetic deficiency of GzmB markedly reduced Ang II-induced cardiac dysfunction, hypertrophy and fibrosis, independently of perforin. GzmB deficiency also decreases microhemorrhage, inflammation, and fibroblast accumulation in vivo. In vitro studies identified VE-cadherin as a GzmB substrate. VE-cadherin is a key endothelial cell-cell junction protein. GzmB-mediated VE-cadherin cleavage resulted in increased endothelial permeability, and increased transcellular conductance. These results were also observed in vivo. Conclusions: GzmB contributes to the onset and progression of cardiac fibrosis through a perforin-independent process involving the cleavage of VE-cadherin.

OBJECTIVE The purpose of the study was to analyze changes in neural response telemetry using the Cochlear Nucleus 24 Contour before and after stylet removal in a human model. STUDY DESIGN Prospective study. SETTING Tertiary referral center. PATIENTS Twelve patients (23-72 years old) undergoing cochlear implantation, using the Nucleus 24 Contour implant, secondary to congenital and age-related hearing loss. INTERVENTION Cochlear implantation with Cochlear Nucleus 24 Contour implant. MAIN OUTCOME MEASURE Neural response telemetry thresholds were recorded initially with the stylet in and then with the stylet out during the implant procedure. RESULTS Stimulus levels to obtain neural response telemetry threshold after stylet removal were statistically lower after the stylet was removed. CONCLUSION The Nucleus 24 Contour achieves a perimodiolar position once the stylet is removed, and this leads to reduction in the current required to elicit a threshold neural response telemetry response.

Objective: Human adipose lies in specific anatomic depots. Peri-vascular adipose appears unique and impacts blood vessel biology, but direct human data is limited. In view of their theorized roles, we tested the hypothesis that human peri-vascular and subcutaneous adipose tissue hold distinct phenotypic signatures. We also evaluated the impact of clinical parameters on adipose phenotype. Methods: Fresh human peri-vascular and subcutaneous adipose tissues were collected intra-operatively from patients undergoing major lower extremity amputation (n=27) and assayed for protein levels of the adipose-associated mediators IL-6, IL-8, leptin, TNF-α, MCP-1, adiponectin, resistin and PAI-1. Results: Leptin (2.4 fold, p=0.045) and adiponectin (1.8 fold, p=0.007) were significantly more abundant in subcutaneous compared to peri-vascular adipose (Table I). Clinical data were used to model associations between clinical characteristics and mediator levels. Age positively correlated with peri-vascular PAI-1 expression (β=0.64, p=0.042), and hyperlipidemia negatively correlated with peri-vascular adipose adiponectin (β=-1.18, p=0.039). Conclusions: While significant similarity was observed between subcutaneous and peri-vascular adipose from leg amputation patients, the differential in adipose derived hormones leptin and adiponectin provides direct human evidence that these tissue compartments hold distinct biologic roles. Further investigation into the unique nature of peri-vascular adipose may provide meaningful guidance in managing peripheral vascular disease.