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Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.
© 2016 American Heart Association, Inc.
Image-guided percutaneous biopsy of abdominal masses is a safe, minimally invasive procedure with a high diagnostic yield for a variety of pathologic processes. This article describes the basic technique of percutaneous biopsy, including the different modalities available for imaging guidance. Patient selection and preparation for safe performance of the procedure is emphasized, and the periprocedural management of coagulation status as well as basic indications and contraindications of the procedure are briefly discussed. In particular, the role of biopsy in the diagnosis of liver and renal masses is highlighted.
Copyright © 2015 Elsevier Inc. All rights reserved.
BACKGROUND - Younger individuals with hyperparathyroidism may experience severe disease with a higher incidence of multigland disease (MGD) and operative failure, thereby requiring subtotal parathyroidectomy. This study examines the characteristics and surgical outcome of younger compared with older patients with sporadic primary hyperparathyroidism (SPHPT).
METHODS - Prospectively collected data of 1101 patients with SPHPT who underwent parathyroidectomy at a single institution were retrospectively reviewed. Patients with multiple endocrine neoplasia (MEN), familial, secondary, or tertiary hyperparathyroidism, parathyroid carcinoma, rickets, or lithium induced disease were excluded. Patients were subdivided into two groups: (1) younger individuals < or = 40 y of age (n = 110) and (2) older individuals > 40 y of age (n = 991). Both age groups were compared for gender, clinical manifestations, pre- and postoperative laboratory values, MGD, operative success, and recurrent disease.
RESULTS - There was greater male predominance in younger compared with older patients treated for SPHPT (41% versus 25%, P = 0.0004). Of the clinical manifestations of SPHPT, kidney stones were more common in younger compared with older individuals (45% versus 29%, P = 0.0006). Conversely, bone pain was more common in older compared with younger patients (32% versus 14%, P = 0.0002). There was no statistical difference in biochemical values, MGD, and outcome between both groups.
CONCLUSIONS - Despite male predominance and few differences in symptoms, SPHPT is a similar disease entity in both younger and older individuals. Patients from both age groups can be similarly treated for SPHPT with a high rate of operative success. Routine BNE and subtotal parathyroidectomy is not necessary in younger individuals.
Caveat arthroplasty is arthroplasty undertaken to treat a presumed nonneoplastic disorder, which is later determined to be secondary to an extraarticular tumor. We identified 6 patients who had caveat arthroplasty before referral to our orthopedic oncology center. Three patients had completed arthroplasties at an average of 29 weeks before discovery of a neoplasm. Three arthroplasties were aborted after a neoplasm was discovered intraoperatively. Prearthroplasty radiographs of 4 patients were reviewed, all demonstrating evidence of malignancy. Caveat arthroplasty may be avoided if malignancy is considered preoperatively, particularly in patients with atypical symptoms, histories of cancer, and rapid periarticular bone loss. If a neoplasm is discovered intraoperatively, the arthroplasty should be aborted. Patients in whom malignancy is suspected should be referred to a musculoskeletal oncologist.
Thoracotomy is associated with significant acute postoperative pain and a high incidence of development of chronic pain. Thoracic epidural analgesia has long been standard treatment for postthoracotomy pain, but recently there has been increased interest in alternative regional techniques, particularly paravertebral analgesia. This article compares the analgesic efficacy, side effects, complications of, and contraindications for thoracic epidural and paravertebral analgesia techniques and discusses their effects on the development of chronic postthoracotomy pain. This information will allow a more considered choice of analgesic technique after thoracotomy.
We conducted a survey of 132 US kidney transplant programs to examine how they evaluate and select potential living kidney donors, focusing on donor-recipient relationships, psychosocial criteria, and consent processes. There is heterogeneity in donor-recipient relationships that are considered acceptable, although most programs (70%) will not consider publicly solicited donors. Most programs (75%) require a psychosocial evaluation for all potential living donors. Most programs agree that knowledge of financial reward (90%), active substance abuse (86%), and active mental health problems (76%) are absolute contraindications to donation. However, there is greater variability in how other psychosocial issues are considered in the selection process. Consent processes are highly variable across programs: donor and recipient consent for the donor evaluation is presumed in 57% and 76% of programs, respectively. The use of 13 different informed consent elements varied from 65% (alternative donation procedures) to 86% (description of evaluation, surgery and recuperative period) of programs. Forty-three percent use a 'cooling off' period. Findings demonstrate high variability in current practice regarding acceptable donor-recipient relationships, psychosocial criteria, and consent processes. Whether greater consensus should be reached on these donor evaluation practices, especially in the context of more expansive use of living donor kidney transplantation, is discussed.
BACKGROUND - Abacavir hypersensitivity is strongly associated with the human leukocyte antigen (HLA)-B*5701 allele; however, the cost of routine high-resolution HLA typing before initiation of therapy remains prohibitive. We propose a simple approach to reduce B*5701-associated abacavir hypersensitivity based on the screening of human immunodeficiency virus (HIV) reverse transcriptase (RT) for a signature B*5701-associated cytotoxic T lymphocyte escape mutation at RT codon 245.
METHODS - The correlation between HLA-B*5701 and RT codon 245 variation was investigated in 392 HIV-infected, antiretroviral-naive adults who were initiating highly active antiretroviral therapy. The relationship between codon 245 variation and premature abacavir discontinuation was investigated in a larger cohort of treated individuals (n=982). Associations between HLA-B*5701 and codon 245 variants were determined using Fisher's exact test or the chi (2) test.
RESULTS - A very strong association between HLA-B*5701 and RT codon 245 variation was observed. Only 1 (4.2%) of 24 subjects with B*5701 harbored virus with the clade B "wild-type" amino acid 245V, compared with 278 (75.5%) of 368 who did not have B*5701 (P<.001). The sensitivity and specificity of codon 245 substitutions for predicting HLA-B*5701 were 96% and 75%, respectively, and the positive and negative predictive values were 20% and 99.6%, respectively. This association remained robust even after antiretroviral treatment was administered (negative predictive value, 100%; n=269). In abacavir-treated individuals (n=982), codon 245 substitutions were predictive of premature abacavir discontinuation (P=.02).
CONCLUSIONS - As HIV RT sequence is incidentally obtained as a part of routine drug-resistance testing, the examination of sequence variation at RT codon 245 could be adopted as a simple, low-cost screening method to identify individuals who could be safely treated with abacavir and/or who could benefit from HLA characterization.
Spherix Inc (formerly Biospherics) is developing tagatose, an orally active lactose derivative for the potential treatment of obesity and type 2 diabetes. The compound is also under investigation for the potential treatment of anemia, hemophilia and medical problems related to infertility, birth weight and excessive maternal food intake. Phase I and II clinical trials have been completed.