Evaluation of a trough-only extrapolated area under the curve vancomycin dosing method on clinical outcomes.

Background Vancomycin dosing strategies targeting trough concentrations of 15-20 mg/L are no longer supported due to lack of efficacy evidence and increased risk of nephrotoxicity. Area-under-the-curve (AUC) nomograms have demonstrated adequate attainment of AUC goals ≥ 400 mg h/L with more conservative troughs (10-15 mg/L). Objective The purpose of this study is to clinically validate a vancomycin AUC dosing nomogram compared to conventional dosing methods with regards to therapeutic failure and rates of acute kidney injury.

Relationship of Patient Self-Administered COPD Assessment Test to Physician Standard Assessment of Chronic Obstructive Pulmonary Disease in a Family Medicine Residency Training Program.

Assessing the global impact of chronic obstructive pulmonary disease (COPD) on a patient's life can be difficult to perform in the clinical setting due to time constraints and workflow challenges. The primary objective of this study was to compare disease impact ratings between patient self-administered COPD Assessment Test (CAT) and physician standard office assessment. This prospective study was conducted at a family medicine residency clinic in northeast Tennessee.

Comparison of perceived personality traits between the pharmacy residents admitted through the match or scramble process.

Introduction: The purpose of this study is to determine whether certain personality traits are as prominent in pharmacy practice residents who obtain positions through the post-Match process, previously referred to as the Scramble, as compared to residents who match directly with programs.

Methods: Pharmacy residency program directors (RPDs) across the United States were asked to complete an electronic survey that gauged RPD perceptions of 13 personality traits commonly seen in pharmacy residents. RPDs were requested to separately evaluate residents who Scrambled and Matched to their respective programs.

Comparison of Postoperative Bleeding in Total Hip and Knee Arthroplasty Patients Receiving Rivaroxaban, Enoxaparin, or Aspirin for Thromboprophylaxis.

Background: Guidelines recommend the use of multiple pharmacologic agents and/or mechanical compressive devices for prevention of venous thromboembolism, but preference for any specific agent is no longer given in regard to safety or efficacy.

Objective: To compare postoperative bleeding rates in patients receiving enoxaparin, rivaroxaban, or aspirin for thromboprophylaxis after undergoing elective total hip arthroplasty or total knee arthroplasty.

Methods: This retrospective cohort analysis evaluated patients who received thromboprophylaxis with either enoxaparin, rivaroxaban, or aspirin.

Preventing Hospitalizations From Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Chronic obstructive lung disease is among the leading causes of adult hospital admissions and readmissions in the United States. Preventing acute exacerbations is the primary approach in therapy. Combinations of smoking cessation, pulmonary rehabilitation, vaccinations and inhaled and oral medications may all reduce the overall risk of acute exacerbations.

Treatment response in the PIVENS trial is associated with decreased Hedgehog pathway activity.

Unlabelled: Hedgehog (Hh) ligand production by ballooned hepatocytes drives nonalcoholic steatohepatitis (NASH) progression in mice. The NIDDK-sponsored PIVENS trial (NCT00063622) showed that vitamin E (VitE) improved NASH. We investigated whether VitE treatment and improvement in NASH were associated with changes in Hh pathway activity.

Mutations in the gene that encodes the F-actin binding protein anillin cause FSGS.

FSGS is characterized by segmental scarring of the glomerulus and is a leading cause of kidney failure. Identification of genes causing FSGS has improved our understanding of disease mechanisms and points to defects in the glomerular epithelial cell, the podocyte, as a major factor in disease pathogenesis. Using a combination of genome-wide linkage studies and whole-exome sequencing in a kindred with familial FSGS, we identified a missense mutation R431C in anillin (ANLN), an F-actin binding cell cycle gene, as a cause of FSGS.

Histopathologic and immunohistochemical sequelae of bariatric embolization in a porcine model.

Purpose: To evaluate the histopathologic sequelae of bariatric embolization on the gastric mucosa and to correlate with immunohistochemical evaluation of the gastric fundus, antrum, and duodenum.

Materials And Methods: This study was performed on 12 swine stomach and duodenum specimens after necropsy. Of the 12 swine, 6 had previously undergone bariatric embolization of the gastric fundus, and the 6 control swine had undergone a sham procedure with saline.

Normal cardiac function in mice with supraphysiological cardiac creatine levels.

Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions.

Melanoma immunotherapy using mature DCs expressing the constitutive proteasome.

Background: Many cancers, including melanoma, exclusively express constitutive proteasomes (cPs) and are unable to express immunoproteasomes (iPs). In contrast, mature DCs used for immunotherapy exclusively express iPs. Since proteasomes generate peptides presented by HLA class I molecules, we hypothesized that mature melanoma antigen-loaded DCs engineered to process antigens through cPs would be superior inducers of antimelanoma immunity in vivo.

Scleroderma and IgG4-related disease.

IgG4-related disease is a syndrome which involves lymphoplasmacytic infiltrates and soft tissue sclerosis, elevated serum IgG4 titer, and increased IgG4-positive plasma cells in a variety of tissues. Scleroderma is also characterized by fibrosis and lymphoplasmacytic infiltrates. To our knowledge, the presence of IgG4-positive cells has not been well characterized in scleroderma.

Diagnostic and clinical considerations in concomitant bone marrow involvement by plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis: a series of 15 cases and review of literature.

Context: Plasma cell myeloma and chronic lymphocytic leukemia are both common hematologic malignancies, sharing many epidemiologic features. Concomitant detection of the 2 conditions poses special diagnostic challenges for the pathologist.

Objective: To describe the pathologic findings in cases of concomitant bone marrow involvement by myeloma and CD5(+) monoclonal B cells and to outline the differential diagnostic possibilities, suggest a workup for correct diagnosis, and examine clinical outcome.

p40 (ΔNp63) and keratin 34βE12 provide greater diagnostic accuracy than p63 in the evaluation of small cell lung carcinoma in small biopsy samples.

The use of p63 has been advocated for separating small cell lung carcinoma from poorly differentiated non-small cell lung carcinoma, in particular, squamous cell lung carcinoma. However, p63 is not entirely specific in this distinction, as several studies have demonstrated p63 immunoreactivity in a proportion of small cell lung carcinomas. p40 (ΔNp63) has recently been purported to be a highly specific marker for squamous cell lung carcinoma, but data regarding p40 (ΔNp63) in small cell lung carcinoma, a key differential diagnostic consideration in biopsy samples of squamous cell lung carcinoma, are lacking.

Follicular lymphoma with prominent Dutcher body formation: a pathologic study of 3 cases in comparison with nodal or splenic lymphoplasmacytic lymphoma and marginal zone lymphoma.

Dutcher bodies have been described in lymphoid neoplasms with plasmacytic differentiation, including plasma cell myeloma, lymphoplasmacytic lymphoma, and marginal zone lymphoma. We report a pathologic study of 3 cases of follicular lymphoma with extensive Dutcher body formation in comparison with lymphoplasmacytic lymphoma and marginal zone lymphoma. Of 3 cases, 1 showed a follicular growth pattern, whereas the other 2 cases demonstrated only a vague nodular appearance highlighted by immunohistochemical analysis.

A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension.

Rationale: Human clinical trials using type 1 angiotensin (AT(1)) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT(1) receptors may have divergent effects on target organ damage in hypertension.

Objective: We examined the role of AT(1) receptors on T lymphocytes in the pathogenesis of hypertension and its complications.

Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease.

Unlabelled: The Hedgehog (HH)-signaling pathway mediates several processes that are deregulated in patients with metabolic syndrome (e.g., fat mass regulation, vascular/endothelial remodeling, liver injury and repair, and carcinogenesis).

Molecular detection of circulating Sezary cells in patients with mycosis fungoides: could it predict future development of secondary Sezary syndrome? A single-institution experience.

While the majority of patients with early-stage mycosis fungoides (MF) have an excellent prognosis, a few cases progress to secondary Sezary syndrome (sSS), which carries a dismal clinical outcome. We retrospectively analyzed 135 cases of MF/SS and correlated molecular detection of T-cell clones in the skin and blood with other clinicopathologic findings. When stratified by the diagnoses, patients with MF demonstrated a 26.

Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of nonalcoholic fatty liver disease.

A small cell variant of ALK-positive, CD8-positive anaplastic large cell lymphoma with primary subcutaneous presentation mimicking subcutaneous panniculitis-like T-cell lymphoma.

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is an uncommon non-Hodgkin's lymphoma of T-cell origin, the majority of which express CD4 and show frequent pan-T-cell antigen loss. While most cases of ALK+ ALCL have the common pattern characterized by anaplastic morphology with hallmark cells, a less common but well-recognized variant with a small cell pattern may pose a diagnostic challenge. We report a case of ALK+ ALCL with small cell morphology and CD8 subset restriction in a 53-year-old male patient who presented primarily with multiple recurrent subcutaneous nodules with histopathologic features simulating a subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival.

A correlation between expression of the glucose-regulated protein of 78 kDa (GRP78) in malignant melanoma tumors and poor patient survival is well established. In this study, in addition to demonstrating the expression of GRP78 in tumor tissue, we investigated the immune response against GRP78 in a group of patients with different progression stages of malignant melanoma. Furthermore, we analyzed the glycosylation status of GRP78 immunoglobulin (Ig) G autoantibodies at these stages and evaluated their capacities to affect the protein B-dependent protein kinase signaling pathway and unfolded protein response signaling mechanisms, all known to promote malignant melanoma cell proliferation and survival.