In Vitro and Computational Thrombosis on Artificial Surfaces With Shear Stress

Implantable devices in direct contact with flowing blood are associated with the risk of thromboembolic events. This study addresses the need to improve our understanding of the thrombosis mechanism and to identify areas on artificial surfaces susceptible to thrombus deposition. Thrombus deposits on artificial blood step transitions are quantified experimentally and compared with shear stress and shear rate distributions using computational fluid dynamics (CFD) models. Larger steps, and negative (expanding) steps result in larger thrombus deposits. Fitting CFD results to experimental deposit locations reveals a specific shear stress threshold of 0.41 Pa or a shear rate threshold of 54 s^?1 using a shear thinning blood viscosity model. Thrombosis will occur below this threshold, which is specific to solvent‐polished polycarbonate surfaces under in vitro coagulation conditions with activated clotting time levels of 200–220 s. The experimental and computational models are valuable tools for thrombosis prediction and assessment that may be used before proceeding to clinical trials and to better understand existing clinical problems with thrombosis.     

Prospective Evaluation of the Change of Predialysis Protein‐Bound Uremic Solute Concentration With Postdilution Online Hemodiafiltration

Although protein‐bound uremic compounds have been related to outcome in observational studies, few current dialysis strategies provide more removal of those compounds than standard hemodialysis. We evaluated the evolution of protein‐bound uremic solutes after a switch from high‐flux hemodialysis to postdilution hemodiafiltration (n = 13). We compared predialysis solute concentration at 4, 5, and 9 weeks versus baseline for several protein‐bound compounds and water‐soluble solutes, as well as for β₂‐microglobulin. After 9 weeks of postdilution hemodiafiltration, a significant decrease versus baseline could be detected for total concentration of protein‐bound solutes: p‐cresylsulfate (3.98 ± 1.51–3.17 ± 1.77 mg/dL, ?20%, P < 0.01) and 3‐carboxyl‐4‐methyl‐5‐propyl‐2‐furanpropionic acid (0.72 ± 0.52–0.64 ± 0.46 mg/dL, ?11%, P < 0.01). For the other protein‐bound solutes, hippuric acid, indoleacetic acid, and indoxylsulfate, no change in total concentration could be detected. The concentration of the middle molecule, β₂‐microglobulin, decreased as well after 9 weeks of postdilution hemodiafiltration (24.7 ± 9.3–18.1 ± 6.7 mg/L, ?27%, P < 0.01). For water‐soluble compounds, no significant change of concentration was found. Postdilution hemodiafiltration in comparison to high‐flux hemodialysis provided significant reduction of predialysis concentration of protein‐bound compounds, especially those with the highest protein binding, and of β₂‐microglobulin, by ?11 to ?27% in 9 weeks.     

Hypothesis: Thyroid Hormone Abnormalities and Frailty in Elderly Patients with Chronic Kidney Disease: A Hypothesis

Thyroid hormones play a crucial role in the metabolic activities of adults, affecting almost every organ system. All types of thyroid diseases are encountered in the elderly. As symptoms and signs of thyroid diseases may overlap with what is considered to be “normal aging,” the presence of a thyroid disorder may go undiagnosed in the elderly. This potential problem is further compounded in elderly patients with chronic kidney disease (CKD), where the presence of an underlying hormonal problem such as hypothyroidism may be erroneously attributed to multiple comorbidities, the aging process, or the kidney disease. Frailty is being recognized as a contributing factor to the poor outcomes (hospitalization and high mortality) in elderly patients with CKD. Predisposing factors leading to frailty in elderly with CKD such as increased inflammatory markers, anemia, low testosterone, sarcopenia, and depression are associated with thyroid hormonal abnormalities. These associations are remarkable and raise the question of whether routine monitoring and screening for thyroid hormone changes in elderly CKD patients might be helpful in identifying reversible causes of frailty. In this review, we will focus on the associations between thyroid hormone abnormalities and the predisposing factors of frailty in elderly patients with CKD. If a cause–effect relationship of thyroid hormone abnormalities and factors predisposing to frailty in CKD patients is established, identification and treatment of thyroid abnormalities in this population would assume increased importance.     

Role of Fusion of Prone FDG‐PET and Magnetic Resonance Imaging of the Breasts in the Evaluation of Breast Cancer

Abstract: The purpose of this study is to report further about the statistically significant results from a prospective study, which suggests that fusion of prone F‐18 Fluoro‐deoxy‐glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) breast scans increases the positive predictive value (PPV) and specificity for patients in whom the MR outcome alone would be nonspecific. Thirty‐six women (mean age, 43 years; range, 24–65 years) with 90 lesions detected on MR consented to undergo a FDG‐PET scan. Two blinded readers evaluated the MR and the computer tomography (CT) attenuation‐corrected prone FDG‐PET scans side‐by‐side, then after the volumes were superimposed (fused). A semiautomatic, landmark‐based program was used to perform nonrigid fusion. Pathology and radiologic follow‐up were used as the reference standard. The sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy (with 95% confidence intervals) for MR alone, FDG‐PET alone, and fused MR and FDG‐PET were calculated. The median lesion size measured from the MR was 2.5 cm (range, 0.5–10 cm). Histologically, 56 lesions were malignant, and 15 were benign. Nineteen lesions were benign after 20–47 months of clinical and radiologic surveillance. The sensitivity of MR alone was 95%, FDG‐PET alone was 57%, and fusion was 83%. The increase in PPV from 77% in MR alone to 98% when fused and the increase in specificity from 53% to 97% were statistically significant (p < 0.05). The false‐negative rate on FDG‐PET alone was 26.7%, and after fusion this number was reduced to 9%. FDG‐PET and MR fusions were helpful in selecting which lesion to biopsy, especially in women with multiple suspicious MR breast lesions.     

Trastuzumab in Primary Inflammatory Breast Cancer (IBC): High Pathological Response Rates and Improved Outcome

Abstract: Inflammatory breast cancer (IBC) represents a rare but aggressive and lethal form of locally advanced breast cancer (LABC) and frequently with HER‐2 neu overexpressed or amplified. We retrospectively identified 16 newly diagnosed HER‐2/neu‐positive IBC patients who were treated with preoperative trastuzumab. We determined the pathological complete response rate (pCR) when trastuzumab was added to preoperative chemotherapy in patients with HER2/neu‐positive IBC. Furthermore, we assessed the expression of CXCR4 in metastatic recurrence sites. Ten patients (62.5%) achieved a pCR. Six patients (37.5%) achieved a partial response. Median follow‐up of all patients was 24.2 months. Four (25%) patients have experienced a progression, of which three were in the brain. Two‐year progression‐free survival was 59.4% (95% CI 35–100). High expression of CXCR4 was detected in the brain metastases. We conclude that in spite of high pCR rates among women with HER‐2/neu‐positive IBC treated with neoadjuvant trastuzumab‐based regimens the outcome remains dismal and brain recurrences are frequent. CXCR4 may represent a novel therapeutic target.     

Imaging of Dermatofibrosarcoma Protuberans of Breast

Abstract: Dermatofibrosarcoma protuberans (DFSP) is a rare superficial soft tissue malignancy. We report a 45‐year‐old woman diagnosed with DFSP involving the breast. Ultrasound of DFSP revealed a heteroechogenetic breast mass, which showed normal adjacent dermis. Mammography disclosed a high‐density mass without microcalcification. MRI showed an enhancing lobulated lesion with small area of cystic change and hemorrhage. The patient underwent excision biopsy and pathology revealed DFSP of the breast. DFSP involving the breast is rare and preoperative diagnosis by imaging could be a challenge for clinicians. A solitary mixed echogenicity and ill‐defined soft tissue with no microcalcification located in the subdermal region could indicate the presence of DFSP.     

Lipomatous Hypertrophy of the Interatrial Septum: A Rare Cause of Right Ventricular Impairment

Abstract We report a case of a 70‐year‐old woman admitted with symptoms of decompensated heart failure. Magnetic resonance imaging revealed lipomatous hypertrophy of the interatrial septum with partial upper right atrial inflow obstruction, partial obstruction of the right ventricular outflow tract, and excessive accumulation of adipose tissue in the pericardial space. The patient underwent excision of the septal lipomatous mass, which relieved the right ventricular outflow obstruction. (J Card Surg 2010;25:171‐174)     

Access Platform Techniques for Transcatheter Aortic Valve Replacement

Abstract Background: One of the unique variables for successful implantation of transcatheter aortic valves involves the ability to secure an access route for deployment of the aortic valve. Aim of study: A large number of the high‐risk patients with critical aortic stenosis referred for transcatheter valve implantation approach may not be candidates for the femoral approach due to peripheral vascular disease with the morbidity and mortality increased severalfold in patients who develop access related complications. Method & Results: A thorough knowledge and review of various alternate access site techniques and trouble shooting are therefore important and required by the implanting cardiac surgeons involved in transcatheter aortic valve therapy. Conclusion: The article review highlights the various percutaneous, hybrid, and surgical access techniques platforms available as well as options for implantation of these devices . (J Card Surg 2010;25:373‐380)     

Meta‐Analyses Qualify Metzincins and Related Genes as Acute Rejection Markers in Renal Transplant Patients

Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T‐cell–mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t‐ and i‐scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, ‐9, TIMP1, ‐2, thrombospondin2 (THBS2) and fibrillin1. RT‐PCR using microdissected glomeruli/tubuli confirmed MMP7, ‐9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, ‐9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/‐9 represent potential molecular AR markers.     

Liver Transplantation with Grafts from Controlled Donors after Cardiac Death: A 20‐Year Follow‐up at a Single Center

The first liver transplantation (LTx) in Sweden was performed in 1984, but brain death as a legal death criterion was not accepted until 1988. Between November 1984 and May 1988, we performed 40 consecutive LTxs in 32 patients. Twenty‐four grafts were from donors after cardiac death (DCD) and 16 grafts from heart‐beating donors (HBD). Significantly, more hepatic artery thrombosis and biliary complications occurred in the DCD group (p < 0.01 and p < 0.05, respectively). Graft and patient survival did not differ between the groups. In the total group, there was a significant difference in graft survival between first‐time LTx grafts and grafts used for retransplantation. There was better graft survival in nonmalignant than malignant patients, although this did not reach statistical significance. Multivariate analysis revealed cold ischemia time and post‐LTx peak ALT to be independent predictive factors for graft survival in the DCD group. In the 11 livers surviving 20 years or more, follow‐up biopsies were performed 18–20 years post‐LTx (n = 10) and 6 years post‐LTx (n = 1). Signs of chronic rejection were seen in three cases, with no difference between DCD and HBD. Our analysis with a 20‐year follow‐up suggests that controlled DCD liver grafts might be a feasible option to increase the donor pool.