Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

Background: Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology.

Methods: In this single-center prospective study of 208 biopsies (median = 5.

Impact of Belatacept Conversion on Renal Function, Histology, and Gene Expression in Kidney Transplant Patients With Chronic Active Antibody-mediated Rejection.

Background: Here, we present our initial experience with a prospective protocol of belatacept conversion in patients with chronic active antibody-mediated rejection (caAMR) and a high degree of chronicity at the time of diagnosis.

Methods: We converted 19 patients (mean age, 45 ± 12 y) with biopsy-proven caAMR from tacrolimus to belatacept at a median of 44 months post-kidney transplant.

Results: At a median of 29 months (interquartile range, 16-46 mo) postconversion, death-censored graft and patient survivals were 89% and 95%, respectively.

Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series.

Background: Traditional therapies for caAbMR have unclear efficacy with significant side effects in recipients of kidney transplants (KTs). A recent single-center case series suggested tocilizumab (TCZ) could stabilize renal function and improve microvascular inflammation. Here we report our findings of the use of TCZ in patients with caAbMR.

Successful kidney transplantation in a patient with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome).

Background: Congenital thrombotic thrombocytopenic purpura (TTP) may not be recognized until organ failure related to the microvascular thrombosis occurs. Kidney failure may be the initial presenting clinical feature. Kidney transplantation has been contraindicated because of the assumption that the continuing microvascular thrombosis will cause inevitable graft failure.

Phase I study of pemetrexed with sorafenib in advanced solid tumors.

Purpose: To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors.

Results: Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cumulative toxicity, while the cohort B dose schedule was found to be more tolerable.

Pre-transplant phospholipase A2 receptor autoantibody concentration is associated with clinically significant recurrence of membranous nephropathy post-kidney transplantation.

Previous studies that have assessed the association of pre-transplant antiphospholipase A2 receptor autoantibody (PLA2R-Ab) concentration with a recurrence of membranous nephropathy (rMN) post-kidney transplant have yielded variable results. We tested 16 consecutive transplant patients with a history of iMN for pre-transplant PLA2R-Ab. Enzyme-linked immunosorbent assay titers (Euroimmun, NJ, USA) >14 RU/mL were considered positive.

High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia and Renal Failure in Nephrectomized LDL Receptor Knockout Mice: Role of Intestine Derived Lipopolysaccharide.

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD.

Comparison of effects of p53 null and gain-of-function mutations on salivary tumors in MMTV-Hras transgenic mice.

p53 is an important tumor suppressor gene which is mutated in ~50% of all human cancers. Some of these mutants appear to have acquired novel functions beyond merely losing wild-type functions. To investigate these gain-of-function effects in vivo, we generated mice of three different genotypes: MMTV-Hras/p53(+/+), MMTV-Hras/p53(-/-), and MMTV-Hras/p53R172H/R172H.

Attenuation of sepsis-induced organ injury in mice by vitamin C.

Background: Multiple organ dysfunction syndrome (MODS) is the principal cause of death in patients with sepsis. Recent work supports the notion that parenteral vitamin C (VitC) is protective in sepsis through pleiotropic mechanisms. Whether suboptimal levels of circulating VitC increase susceptibility to sepsis-induced MODS is unknown.

Small cell osteosarcoma with Ewing sarcoma breakpoint region 1 gene rearrangement detected by interphase fluorescence in situ hybridization.

Because of its characteristic morphologic appearance, small cell osteosarcoma (SCO) can be confused with other small round cell malignancies of the bone, most importantly with Ewing sarcoma, making this distinction difficult. A specific tool used in separating SCO from Ewing sarcoma has been the detection of Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements in Ewing sarcoma and their absence in SCO. However, there are rare case reports that have documented the existence of EWSR1 gene rearrangement in SCO.

A cause of unbearably painful breast, diffuse dermal angiomatosis.

Diffuse dermal angiomatosis is a rare disorder, considered to be a variant of reactive cutaneous angioendotheliomatosis. The patients commonly present with severe intractable breast pain and characteristic reticular violaceous erythematous plaques with central ulcerations. Histologically, there is infiltration of the recticular dermis by endothelial cells due to excess vascular proliferation.

hnRNP L regulates the tumorigenic capacity of lung cancer xenografts in mice via caspase-9 pre-mRNA processing.

Caspase-9 is involved in the intrinsic apoptotic pathway and suggested to play a role as a tumor suppressor. Little is known about the mechanisms governing caspase-9 expression, but post-transcriptional pre-mRNA processing generates 2 splice variants from the caspase-9 gene, pro-apoptotic caspase-9a and anti-apoptotic caspase-9b. Here we demonstrate that the ratio of caspase-9 splice variants is dysregulated in non-small cell lung cancer (NSCLC) tumors.

Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.

Objectives: We sought to determine whether gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve cardiac magnetic resonance (CMR) detection and characterization of human atherosclerosis.

Background: Gd-containing lipid-based NPs targeting macrophages have improved MR detection of murine atherosclerosis.

Methods: Gadolinium-containing untargeted NPs, anti-CD36 NPs, and nonspecific Fc-NPs were created.

Infection of spotted salamanders (Ambystoma maculatum) with Ichthyophonus-like organisms in Virginia.

Ichthyophonus-like organisms were found in two free-ranging adult spotted salamanders (Ambystoma maculatum) captured within two different vernal ponds in the Virginia Commonwealth University Rice Center for Environmental Life Sciences in Charles City County, Virginia. Histopathologic examination of necropsied specimens revealed large spores, often enclosed by granulomas. These enclosed spores resembled those caused by the fish pathogen Ichthyophonus hoeferi.

Dissecting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative.

Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma.

Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array.

Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers.

Background: Chronic allograft nephropathy (CAN) is a cause of graft loss. The multistage processes that result in CAN are poorly understood. Noninvasive assays for detecting allograft dysfunction and predicting long-term outcomes are a priority in transplantation (Tx).

Underestimation of the presence of breast carcinoma in papillary lesions initially diagnosed at core-needle biopsy.

Purpose: To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy.

Materials And Methods: Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. Mammographic database review (1994-2003) revealed core biopsy diagnoses of benign papilloma (n=38), atypical papilloma (n=15), sclerotic papilloma (n=6), and micropapilloma (n=4) in 57 women (mean age, 57 years).

Treatment of skeletal Erdheim-Chester disease with zoledronic acid: case report and proposed mechanisms of action.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by tissue infiltration of lipid-laden macrophages, multinucleated giant cells, and inflammatory infiltrate of lymphocytes and histiocytes. The disease typically involves long bone, but may also affect the central nervous system, the orbit, retroperitoneal organs, and the lungs. Patients with visceral involvement tend to have poorer outcome.

Potential pitfalls in diagnostic oral pathology: a review for the general surgical pathologist.

Oral developmental, reactive, benign neoplastic and malignant neoplastic conditions, many odontogenic in origin, may not be seen routinely by the general surgical pathologist and therefore may present a diagnostic dilemma. This article describes odontogenic and nonodontogenic conditions with little or no destructive potential along with the more aggressive conditions that resemble them clinically and histologically. The importance of clinical and radiographic correlation as an adjunct to tissue diagnosis is highlighted.

A new alloantigen-independent control for chronic allograft nephropathy rat models.

Background: Isografts are used as controls in many transplant experiments. Our laboratory and others have noticed histological changes in control isograft groups of rats similar to allograft groups, suggesting alloantigen-independent factors contributing to chronic allograft nephropathy. However, the isograft model as a nonalloantigen control is flawed because of the potential of unrecognized minor antigen differences between rats.

Intramuscular angiomatous tumors associated with periosteal changes and pain.

This case report discusses two cases in which patients present with the uncommon triad of extremity pain, focal periosteal reaction on imaging studies, and intramuscular hemangioma on pathologic examination. Both patients presented in this article were older than those previously reported in the literature. Neither patient reported complete resolution of pain following excision, although there was marked improvement.

Digital photography: a primer for pathologists.

The computer and the digital camera provide a unique means for improving hematology education, research, and patient service. High quality photographic images of gross specimens can be rapidly and conveniently acquired with a high-resolution digital camera, and specialized digital cameras have been developed for photomicroscopy. Digital cameras utilize charge-coupled devices (CCD) or Complementary Metal Oxide Semiconductor (CMOS) image sensors to measure light energy and additional circuitry to convert the measured information into a digital signal.

A pathologist's perspective on bone marrow aspiration and biopsy: I. Performing a bone marrow examination.

The bone marrow aspirate and biopsy is an important medical procedure for the diagnosis of hematologic malignancies and other diseases, and for the follow-up evaluation of patients undergoing chemotherapy, bone marrow transplantation, and other forms of medical therapy. During the procedure, liquid bone marrow is aspirated from the posterior iliac crest or sternum with a special needle, smeared on glass microscope slides by one of several techniques, and stained by the Wright-Giemsa or other techniques for micro-scopic examination. The bone marrow core biopsy is obtained from the posterior iliac crest with a Jamshidi or similar needle and processed in the same manner as other surgical specimens.