Risk factors for reduced function in women with a history of breast cancer.

PURPOSE: People with a history of breast cancer are at risk of losing function during and after treatment. Unfortunately, little is known about the individual and additive effects of specific treatment, disease-related, and demographic factors that may contribute to functional decline. This manuscript reports the results of a multi-center study to evaluate the effects of these factors on function. METHODS: In this cross-sectional study, women with a history of breast cancer referred to physical medicine and rehabilitation cancer rehabilitation clinics were administered the PROMIS® Cancer Function Brief 3D Profile to evaluate function in the domains of physical function, fatigue, and social participation. Clinical and demographic information, including treatment history and disease status, was recorded by clinicians. Patients were analyzed in two groups: those with active disease on antineoplastic treatment, and those with no evidence of disease (NED). A multivariable model was constructed to detect associations between clinical and demographic factors. RESULTS: In patients with NED, the presence of chemotherapy-induced peripheral neuropathy (CIPN) was strongly associated with reduced function in all three domains. In those with active disease, having brain metastases was significantly associated with reduced function in all domains and CIPN with reduced physical function. Radiation was associated with improved function in both cohorts. CONCLUSIONS: Among women seeking rehabilitative care, CIPN and the presence of brain metastases were most strongly associated with a decline in function. The effects of radiation on function were unexpected and may be partially explained by the treatment\u27s role in symptom management. Clinicians who treat breast cancer should consider a patient\u27s functional status when providing supportive care

Xenoantigenicity of porcine decellularized valves

Abstract Background The xenoantigenicity of porcine bioprosthetic valves is implicated as an etiology leading to calcification and subsequent valve failure. Decellularization of porcine valves theoretically could erase the antigenicity of the tissue leading to more durable prosthetic valves, but the effectiveness of decellularization protocols in regard to completely removing antigens has yet to be verified. Our hypothesis was that decellularization would remove the more abundant α-gal antigens but not remove all the non α-gal antigens, which could mount a response. Methods Porcine aortic valves were decellularized with 1% sodium dodecyl sulfate for 4 days. Decellularized cusps were evaluated for α-gal epitopes by ELISA. To test for non α-gal antigens, valves were implanted into sheep. Serum was obtained from the sheep preoperatively and 1 week, 1 month, and 2 months postoperatively. This serum was utilized for anti-porcine antibody staining and for quantification of anti-pig IgM and IgG antibodies and complement. Results Decellularized porcine cusps had 2.8 ± 2.0% relative α-gal epitope as compared to fresh porcine aortic valve cusps and was not statistically significantly different (p = 0.4) from the human aortic valve cusp which had a 2.0 ± 0.4% relative concentration. Anti-pig IgM and IgG increased postoperatively from baseline levels. Preoperatively anti-pig IgM was 27.7 ± 1.7 μg/mL and it increased to 71.9 ± 12.1 μg/mL average of all time points postoperatively (p = 0.04). Preoperatively anti-pig IgG in sheep serum was 44.9 ± 1.5 μg/mL and it increased to 72.6 ± 6.0 μg/mL average of all time points postoperatively (p = 0.01). There was a statistically significant difference (p = 0.00007) in the serum C1q concentration before valve implantation (2.5 ± 0.2 IU/mL) and at averaged time points after valve implantation (5.3 ± 0.3 IU/mL). Conclusions Decellularization with 1% sodium dodecyl sulfate does not fully eliminate non α-gal antigens; however, significant reduction in α-gal presence on decellularized cusps was observed. Clinical implications of the non α-gal antigenic response are yet to be determined. As such, evaluation of any novel decellularized xenografts must include rigorous antigen testing prior to human trials

Supercritical Carbon DioxideâBased Sterilization of Decellularized Heart Valves

Summary: Sterilization of grafts is essential. Supercritical carbon dioxide, electrolyzed water, gamma radiation, ethanol-peracetic acid, and hydrogen peroxide techniques were compared for impact on sterility and mechanical integrity of porcine decellularized aortic valves. Ethanol-peracetic acidâ and supercritical carbon dioxideâtreated valves were found to be sterile using histology, microbe culture, and electron microscopy assays. The cusp tensile properties of supercritical carbon dioxideâtreated valves were higher compared with valves treated with other techniques. Superior sterility and integrity was found in the decellularized valves treated with supercritical carbon dioxide sterilization. This sterilization technique may hold promise for other decellularized soft tissues. Key Words: decellularized, decontamination, heart valve, tensile properties, tissue engineerin

Additional file 1: of Xenoantigenicity of porcine decellularized valves

Methods Supplement (DOCX 19 kb

Recellularization of a novel off-the-shelf valve following xenogenic implantation into the right ventricular outflow tract.

Current research on valvular heart repair has focused on tissue-engineered heart valves (TEHV) because of its potential to grow similarly to native heart valves. Decellularized xenografts are a promising solution; however, host recellularization remains challenging. In this study, decellularized porcine aortic valves were implanted into the right ventricular outflow tract (RVOT) of sheep to investigate recellularization potential. Porcine aortic valves, decellularized with sodium dodecyl sulfate (SDS), were sterilized by supercritical carbon dioxide (scCO2) and implanted into the RVOT of five juvenile polypay sheep for 5 months (n = 5). During implantation, functionality of the valves was assessed by serial echocardiography, blood tests, and right heart pulmonary artery catheterization measurements. The explanted valves were characterized through gross examination, mechanical characterization, and immunohistochemical analysis including cell viability, phenotype, proliferation, and extracellular matrix generation. Gross examination of the valve cusps demonstrated the absence of thrombosis. Bacterial and fungal stains were negative for pathogenic microbes. Immunohistochemical analysis showed the presence of myofibroblast-like cell infiltration with formation of new collagen fibrils and the existence of an endothelial layer at the surface of the explant. Analysis of cell phenotype and morphology showed no lymphoplasmacytic infiltration. Tensile mechanical testing of valve cusps revealed an increase in stiffness while strength was maintained during implantation. The increased tensile stiffness confirms the recellularization of the cusps by collagen synthesizing cells. The current study demonstrated the feasibility of the trans-species implantation of a non-fixed decellularized porcine aortic valve into the RVOT of sheep. The implantation resulted in recellularization of the valve with sufficient hemodynamic function for the 5-month study. Thus, the study supports a potential role for use of a TEHV for the treatment of valve disease in humans

Mechanical properties.

<p>(A.) Stiffness comparison of native porcine, decellularized porcine with sterilization, and recellularized porcine explant after 5 months in vivo. (B.) Ultimate tensile strength comparison of native porcine, decellularized porcine implant with sterilization, and recellularized porcine explant after 5-months in vivo.</p

Gross examination.

<p>Explanted aortic valves showing aortic cusp without evidence of thrombosis, increased thickness, or calcification. Explant taken immediately after 5-month sacrifice and cross-sectioned to show anatomical features.</p

Laboratory analysis reported in mean and standard deviation.

<p>Laboratory analysis reported in mean and standard deviation.</p

Staining of porcine aortic cusps post-explant at 5-months.

<p>H&E staining representative (A) Histology section of decellularized porcine cusp prior to implantation (scale: 1000 μm). Image shows ECM intact without presence of nuclear cellular material. (B) Recellularized Aortic cusp of sheep (scale: 400 μm). Image shows intact ECM with infiltration of host-derived cells as shown in the magnified image within stain B at (20x). (C) Alizarin Red; characterization of aortic cusps post-explant at 5-months representative images (scale: 400 μm) showing absence of calcification on tissues, (D) Von Kassa; characterization of aortic cusps post-explant at 5-months representative images (scale: 400 μm) showing absence of calcification on tissues. In the case of calcification, stains C and D would show hyderdense dark areas.</p

Determination of i<i>n vivo</i> valvular hemodynamics.

<p>(A) Representative echocardiographic image at 3-months. The aortic valve cusps were free of fibrosis or thickening arrow indicates aortic valve cusps. The Doppler flow confirms no valve stenosis, and gradient was measured. (B) Systolic gradients across the pulmonic valves over time measured using continuous wave Doppler echocardiography. The mean pressure gradient was elevated at one month but remained unchanged over the course of the study (P = 0.25 for mean gradient at 1- vs 5- months). (C) Hemodynamic measurement taken immediately prior to explant using invasive pulmonary artery catheters. mRAP, mean right atrial pressure; mPAP, mean pulmonary artery pressure; RVSP, right ventricular systolic pressure; PV, pulmonic valve peak to peak gradient; PCWP, pulmonary capillary wedge pressure.</p