Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

Background

Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.

Methods

Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.

Results

Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.

Conclusions

Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.     

Combining Self-Affirmation and Implementation Intentions: Evidence of Detrimental Effects on Behavioral Outcomes

Background

There is limited evidence that self-affirmation manipulations can promote health behavior change.

Purpose

The purpose of this study was to explore whether the efficacy of a self-affirmation manipulation at promoting exercise could be enhanced by an implementation intention intervention.

Methods

Participants (Study 1?N?=?120, Study 2?N?=?116) were allocated to one of four conditions resulting from the two (self-affirmation manipulation: no affirmation, affirmation) by two (implementation intention manipulation: no implementation intention, implementation intention) experimental design. Exercise behavior was assessed 1 week post-intervention.

Results

Contrary to prediction, those participants receiving both manipulations were significantly less likely to increase the amount they exercised compared to those receiving only the self-affirmation manipulation.

Conclusion

Incorporating an implementation intention manipulation alongside a self-affirmation manipulation had a detrimental effect on exercise behavior; participants receiving both manipulations exercised significantly less in the week following the intervention.     

Factors determining left atrial kinetic energy in patients with chronic mitral valve disease

BACKGROUND: Increased left atrial (LA) work is a major contributor to LA fatigue, LA failure and atrial fibrillation in patients with mitral stenosis (MS) and mitral valvular regurgitation (MVR). The present study was undertaken to define factors that determine LA work in patients with chronic mitral valve disease. PATIENTS AND METHODS: Peak left atrial kinetic energy (LAKE)was used as an index of LA work in 14 patients with MS, 14 with MVR, and 19 normal subjects matched for age and gender with MS and MVR patients. LA stroke volume and ejection fraction were measured from the biplane area-length method using echo techniques. Peak LAKE was obtained from the formula 1/2 mv2, where m = LA stroke volume x 1.06 (blood's specific gravity) and v = transmitral Doppler A-wave velocity. RESULTS: Stepwise regression analysis often clinical and echocardiographic parameters demonstrated that in MS, mitral valve area (r2 = 0.43) and LA maximal volume (r2 = 0.62), in MVR, only LA maximal volume (r2 = 0.42) contributed independently to LAKE. LAKE was greater in MS and MVR compared to control subjects while LA ejection fraction was similar in all groups.CONCLUSIONS: It is concluded that LA work is markedly increased in patients with chronic mitral valve disease. Increased LA work in chronic mitral valve disease may contribute to LA fatigue, LA failure, and atrial fibrillation.