Ventricular septal defect and bivalvular endocarditis

A 63-year-old man presented with generalized fatigue, chills, malaise, dyspnea, intermittent fevers, and 50-pound weight loss of 4 months′ duration. Blood cultures were positive for pan-sensitive Streptococcus anginosus. Transesophageal echocardiography showed an 11 mm × 3 mm mobile mass attached to the mitral valve, a 16 mm × 16 mm mobile mass attached to the pulmonary valve, and a small membranous ventricular septal defect. The patient received 12 weeks of intravenous (IV) antibiotics with eventual resolution of the masses. Multi-valve endocarditis involving both the left and right chambers is rarely reported without prior history of IV drug use or infective endocarditis. Our case emphasizes the importance of careful assessment for ventricular septal defects or extra-cardiac shunts in individuals who present with simultaneous right and left-sided endocarditis

Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis

<div><h3>Background</h3><p>Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.</p> <h3>Methods and Findings:</h3><p>We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800–1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to$467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to$44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of$15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.</p> <h3>Conclusions</h3><p>Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is “very cost effective” per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease.</p> <h3></h3><p> <em>Please see later in the article for the Editors' Summary.</em></p> </div

Estimated clinical outcomes by cryptococcal meningitis induction treatment regimen.

<p>5FC dosed at 100 mg/kg/d; amphotericin B deoxycholate dosed at 0.7–1.0 mg/kg/d. <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001316#pmed.1001316.s007" target="_blank">Figure S2</a> displays the data.</p>a<p>Mayanja-Kizza et al. used fluconazole doses of 200 mg/d and 5FC doses of 150 mg/kg/d <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001316#pmed.1001316-MayanjaKizza1" target="_blank">[30]</a>.</p>b<p>Muzoora et al. <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001316#pmed.1001316-Muzoora1" target="_blank">[13]</a> used 5 d of amphotericin and Jackson et al. <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001316#pmed.1001316-Jackson1" target="_blank">[15]</a> used 7 d of amphotericin at 1.0 mg/kg/d with fluconazole at 1,200 mg/d, whereas 7 d of amphotericin was used by Bicanic et al. <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001316#pmed.1001316-Bicanic1" target="_blank">[9]</a> (1.0 mg/kg/d) and Tansuphaswadikul et al. <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001316#pmed.1001316-Tansuphaswadikul1" target="_blank">[31]</a> (0.7 mg/kg/d).</p

Input costs of cryptococcal meningitis induction therapy and medical care.

<p>LP includes initial diagnostic CSF analysis; 5FC dosed at 100 mg/kg/d; amphotericin B deoxycholate dosed at 0.7–1.0 mg/kg/d. Cost components displayed in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001316#pmed.1001316.s006" target="_blank">Figure S1</a>.</p>a<p>Assumes 7 d of hospitalization, with additional phlebotomy for 5FC monitoring.</p

Molecular Dynamics Simulation of Ozonation of p-Nitrophenol at Room Temperature with ReaxFF Force Field

Understanding the reaction mechanism of phenol ozonation in coking wastewater is very important for industrial applications of the ozonation process. Ozonation of p-nitrophenol in water at 300 K was simulated by ReaxFF force field molecular dynamics (ReaxFF MD) employing the GPU-enabled high-performance code of GMD-Reax and a unique code of VARxMD developed in authors&#39; group. Evolution trends of aromatic ring opening, CO2 generation, dominant radicals (center dot OH, center dot O2, center dot O), and H2O clusters were obtained. The simulated CO2 generation and reduction of aromatic ring could be described with pseudo-first-order kinetics. Moreover, the reaction pathways for the ozonation of p-nitrophenol can be divided into three stages: hydrogen abstraction, opening of the six-membered-ring structure, and the breaking of C-C bonds. The simulations revealed the important role of radicals and water clusters in the ozonation of p-nitrophenol. This work is an attempt to investigate the ozonation mechanism of phenols in aqueous solutions at room temperature using ReaxFF MD, which should be helpful for further experimental or theoretical investigation of the mechanism.</p

hTERT expression in colorectal adenocarcinoma: correlations with p21, p53 expressions and clinicopathological features

Background: The clinicopathological roles and relationships of hTERT, p21 and p53 proteins have not been studied in depth in colorectal cancer. The aim of the present study is to investigate the clinicopathological roles of expression of hTERT protein expression and its relationship with the expression of p21 and p53 proteins in a large cohort of patients with colorectal adenocarcinoma.\ud Materials and methods: Expressions of hTERT, p21 and p53 proteins were investigated in 188 patients with colorectal adenocarcinomas by immunohistochemistry. The findings were correlated with the clinicopathological features and survival data of colorectal adenocarcinomas.\ud Results hTERT, p53 and p21 proteins were detected in 63%, 100% and 62% of the patients with colorectal carcinoma. High level of hTERT protein expression was noted in patients with metastases (p = 0.038) and in patients with rectal cancer (p  = 0.046). Loss or low level of p21 protein was often noted in non-mucinous colorectal adenocarcinoma when compared with mucinous adenocarcinoma (p = 0.001). Furthermore, p53 expression was more frequently noted in non-mucinous adenocarcinoma (p = 0.001). The level of expression of p21 protein was positively correlated with expression of level of hTERT protein (p = 0.00001). The survival of the patients was related to staging (p = 0.001) and p53 protein expression (p = 0.038) of the tumours.\ud Conclusions: hTERT protein expression is an indicator of the biological aggressiveness of the cancer. The level of expression of the protein was also related to the distal location and level of p21 expression of the tumours