Phase II study of sorafenib in patients with relapsed or refractory lymphoma

The safety and activity of the multikinase inhibitor sorafenib were investigated in patients with relapsed or refractory lymphoproliferative disorders who received sorafenib (400 mg) twice daily until disease progression or appearance of significant clinical toxicity. The primary endpoint was overall response rate (ORR). Biomarkers of sorafenib activity were analysed at baseline and during treatment. Thirty patients (median age, 61 years; range, 18-74) received a median of 4 months of therapy. Grade 3-4 toxicities included hand/foot skin reactions (20%), infections (12%), neutropenia (20%) and thrombocytopenia (14%). Two patients achieved complete remission (CR), and two achieved partial remission (PR) for an ORR of 13%. Stable disease (SD) and progressive disease (PD) was observed in 15 (50%) and 11 patients (37%), respectively. The median overall survival (OS) for all patients was 16 months. For patients who achieved CR, PR and SD, the median time to progression and OS was 5 and 24 months, respectively. Compared with patients with PD, responsive patients had significantly higher baseline levels of extracellular signal-regulated kinase phosphorylation and autophagy and presented a significant reduction of these parameters after 1 month of therapy. Sorafenib was well tolerated and had a clinical activity that warrants development of combination regimens.     

Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4

Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are the strongest baseline predictors of a sustained virologic response (SVR) to peg-interferon (PegIFN) and ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 patients too is unknown. The aim was to investigate the predictive power of the rs12979860 IL28B SNP for a response to Peg-IFN and Rbv in HCV-4 patients. All HCV-4 patients consecutively treated between September 2004 and June 2010 with PegIFN and Rbv at two liver centers at the Maggiore Hospital Milan (Italy) underwent TaqMan SNP Genotyping assays for testing rs12979860 genotype. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis) 103 were included in the final analysis; five discontinued treatment for nonvirologic reasons and four did not consent to genetic testing. Twenty-four (23%) were genotype CC, 65 (63%) CT, and 14 (14%) TT. Overall, 50 (49%) achieved an SVR: 21 (88%) CC patients versus 29 (37%) CT/TT (P < 0.0001). CC patients more often had a rapid virologic response (RVR) than CT/TT patients (12, 50% versus 23, 29%; P = 0.08), while also showing lower relapse rates (0% [0/21] versus 36% [16/45] P = 0.0013). In non-RVR patients, SVR rates were higher in CC than CT/TT patients (9 [75%] versus 13 [23%] P = 0.001). By logistic regression, the IL28B rs12979860 CC genotype was an independent predictor of SVR with an odds ratio of 8.0 (95% confidence interval 2.00-32.01; P = 0.003). CONCLUSION: The IL28B rs12979860 SNP may have an added value in the treatment algorithm of HCV-4 patients because it is the strongest predictor of an SVR to PegIFN/Rbv therapy.     

Paediatric traumatic brain injury: A review of pertinent issues

Children with traumatic brain injury (TBI), regardless of the severity of the injury, often face challenges when living in home, school and community. Their needs are often overlooked and recognition of the long-term consequences is not always central to the management of the child in the school or community. This article provides references to pertinent literature and suggestions for intervention from the clinical experiences of four individuals with extensive experience of the family stresses, educational, cognitive-communicative and behavioural challenges that occur after TBI in children. It provides information regarding these issues, particularly educational situations, and suggests methods that may be useful for service providers and family members.     

Professional development and leadership training opportunities for healthcare professionals

Background

Formal leadership training is a relatively recent addition to the educational armamentarium of the health care executive. Leadership training opportunities for physicians, surgeons, and scientists have gradually appeared over the past 15 to 20 years, but information about them has been scant, with few comprehensive reviews made available to the community at large. This article describes the major opportunities available to obtain formal and informal leadership training for careers in medical school administration. Programs that are specifically targeted to women are described in detail.

Data Sources

Information was obtained from the author's direct knowledge, direct communication with the leadership of each program, and the Web site of each sponsoring organization, when available.

Conclusions

Many opportunities for leadership training are now available to surgeons, with several specifically designed for women. The author strongly encourages surgeons to avail themselves of these opportunities, as both anecdotal information and published data suggest that these programs are highly effective in enhancing leadership careers.     

Laser Doppler anemometry measurements of steady flow through two bi-leaflet prosthetic heart valves

Introduction

In vitro hydrodynamic characterization of prosthetic heart valves provides important information regarding their operation, especially if performed by noninvasive techniques of anemometry. Once velocity profiles for each valve are provided, it is possible to compare them in terms of hydrodynamic performance. In this first experimental study using laser doppler anemometry with mechanical valves, the simulations were performed at a steady flow workbench.

Objective

To compare unidimensional velocity profiles at the central plane of two bi-leaflet aortic prosthesis from St. Jude (AGN 21 - 751 and 21 AJ - 501 models) exposed to a steady flow regime, on four distinct sections, three downstream and one upstream.

Methods

To provide similar conditions for the flow through each prosthesis by a steady flow workbench (water, flow rate of 17L/min. ) and, for the same sections and sweeps, to obtain the velocity profiles of each heart valve by unidimensional measurements.

Results

It was found that higher velocities correspond to the prosthesis with smaller inner diameter and instabilities of flow are larger as the section of interest is closer to the valve. Regions of recirculation, stagnation of flow, low pressure, and flow peak velocities were also found.

Conclusions

Considering the hydrodynamic aspect and for every section measured, it could be concluded that the prosthesis model AGN 21 - 751 (RegentTM) is superior to the 21 AJ - 501 model (Master Series). Based on the results, future studies can choose to focus on specific regions of the these valves.     

Exaggerated blood pressure response during exercise treadmill testing: functional and hemodynamic features, and risk factors

The factors which contribute to an exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) are not wholly understood. The association between the insertion/deletion polymorphisms of the angiotensin-converting enzyme (ACE) and M235T of the angiotensinogen with EBPR during ETT still remains unstudied. To identify and compare the risk factors for hypertension between normotensive subjects with EBPR and those who exhibit a normal curve of blood pressure (BP) during ETT. In a series of EBPR cases from a historical cohort of normotensive individuals, a univariate analysis was performed to estimate the association of the studied factors with BP behavior during ETT. Additionally, logistic multivariate regression was conducted to analyze the joint effects of the variables. P-values above 0.05 were considered statistically significant. From a total of 10,027 analyzed examinations, only 219 met the criteria employed to define EBPR, which resulted in a prevalence of 12.6%. For the systolic component of the BP, hyperreactive subjects displayed a mean age and body mass index (BMI) significantly higher than the others (P=0.002 and <0.001, respectively). No association was observed between the polymorphisms cited above and EBPR. An analysis of the joint effect of variables has indicated that only age (P< 0.001) and BMI (P=0.001) were specifically associated with systolic BP during exercise. Age and BMI were the only factors that independently influenced EBPR during ETT.