Quality of life of patients with locally advanced head and neck cancer treated with induction chemotherapy followed by cisplatin-containing chemoradiotherapy in the Dutch CONDOR study: a randomized controlled trial.

PURPOSE: The CONDOR study showed that docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100 + RT; n = 27)) versus accelerated radiotherapy with cisplatin weekly 40 mg/m2 (cis40 + ART; n = 29) in locally advanced head and neck cancer (LAHNC) patients was not feasible. Here, we report the analysis of health-related quality of life (HRQOL) of the patients entered in this study. METHODS: HRQOL was assessed at baseline, after two TPF, before start of chemoradiotherapy, and 1, 4, 8, 12, and 24 months after completion of chemoradiotherapy using the EORTC-QLQ-C30 and QLQ-H&N35 in 62 patients. RESULTS: Compliance with the QOL questionnaires was 94% (59/62) at baseline and 61% (30/49) at 12 months, respectively. HRQOL decreased after TPF and further decreased during chemoradiohteray in both arms equally. Pain and swallowing dysfunction improved significantly during TPF but deteriorated below baseline levels during chemoradiotherapy, cis40 + ART > cis100 + RT (p < 0.05). HRQOL and symptoms restored to baseline within 12 months in both arms and remained at that level until 24 months. CONCLUSIONS: After TPF, cis40 + ART had a larger negative impact on symptoms than cis100 + RT, probably due to the ART. HRQOL and symptoms restored to baseline levels within 12 months after end of treatment in both arms, which is an important perspective for patients during the phase of most serious acute side effects of treatment. TRIAL REGISTRATION: NCT00774319.

Effectiveness of heparin solution versus normal saline in maintaining patency of intravenous locks in neonates: a double blind randomized controlled study.

AIM: The aim of this study was to evaluate the effect of heparin versus saline as flush solution for maintaining patency in peripheral intravenous locks in neonates and to investigate whether other variables influence the longevity of intravenous locks. BACKGROUND: Heparin is usually used as a regular flush solution to prevent occlusion of peripheral intravenous locks in neonates. There is no clear recommendation using heparin or saline flushing peripheral intravenous locks in neonates. The disadvantage of heparin cannot be ignored, especially in this patient group. METHODS: In a double blind prospective randomized study, neonates (gestational age >27 weeks) with intravenous locks were randomly assigned to receive heparin or saline as a flush solution in a 21-month period (2002-2004). The main outcome was the duration of patency. RESULTS: Eighty-eight neonates were included. No statistically significant difference was found in patency of peripheral intravenous locks flushed with 0.7 mL heparin (10 units/mL) (N = 42, median 56 hours) or 0.7 mL saline (N = 46, median 61 hours). When the analysis was confined to removed locks because of non-elective events, no statistically significant difference was found in duration of patency (P = 0.27). CONCLUSION: As no difference in patency could be established, using saline as a flush solution is preferable to heparin in peripheral intravenous locks in neonates, given the greater likelihood of complications associated with heparin. Although these data are more than 5 years old, the relevance of the outcome is still important for the clinical practice because of the potential adverse effects of heparin in these vulnerable infants.

Correlation of Morphology and Function of Flecks Using Short-Wave Fundus Autofluorescence and Microperimetry in Patients With Stargardt Disease.

Purpose: The purpose of this study was to evaluate the functional relevance of longitudinal changes in hyperautofluorescent areas and flecks in Stargardt disease (STGD1) using short-wavelength autofluorescence (SW-AF) imaging. Methods: In this prospective, longitudinal study, 31 patients with STGD1 (56 eyes) underwent microperimetry (MP) and SW-AF imaging twice in 3 to 5 years. A total of 760 MP test points were included in the statistical analysis based on stable fixation and accurate alignment of SW-AF and MP. Autofluorescence intensity was qualitatively assessed in all MP test points. Small circumscriptive hyperautofluorescent lesions were defined as flecks. Longitudinal imaging characteristics observed on SW-AF were classified into the following categories: appearing, disappearing, and stable flecks, stable hyperautofluorescent, and stable background autofluorescence. The relationship between SW-AF intensity changes and MP changes was analyzed using a linear mixed model corrected for baseline sensitivity. Results: Retinal sensitivity declined most in locations without change in SW-AF intensity. Functional decline per year was significantly larger in flecks that disappeared (-0.72 ± 1.30 dB) compared to flecks that appeared (-0.34 ± 0.65 dB), if baseline sensitivity was high (≥10 dB; P < 0.01). The correlation between the change observed on SW-AF and the sensitivity change significantly depended on the sensitivity at baseline (P = 0.000). Conclusions: Qualitative longitudinal assessment of SW-AF poorly reflected the retinal sensitivity loss observed over the course of 3 to 5 years. Translational Relevance: When aiming to assess treatment effect on lesion level, a multimodal end point including MP focused on hyperautofluorescent lesions appears essential but needs further studies on optimizing MP grids, eye-tracking systems, and alignment software.

A quantitative assessment of costimulation and phosphatase activity on microclusters in early T cell signaling.

T cell signaling is triggered through stimulation of the T cell receptor and costimulatory receptors. Receptor activation leads to the formation of membrane-proximal protein microclusters. These clusters undergo tyrosine phosphorylation and organize multiprotein complexes thereby acting as molecular signaling platforms. Little is known about how the quantity and phosphorylation levels of microclusters are affected by costimulatory signals and the activity of specific signaling proteins. We combined micrometer-sized, microcontact printed, striped patterns of different stimuli and simultaneous analysis of different cell strains with image processing protocols to address this problem. First, we validated the stimulation protocol by showing that high expression levels CD28 result in increased cell spreading. Subsequently, we addressed the role of costimulation and a specific phosphotyrosine phosphatase in cluster formation by including a SHP2 knock-down strain in our system. Distinguishing cell strains using carboxyfluorescein succinimidyl ester enabled a comparison within single samples. SHP2 exerted its effect by lowering phosphorylation levels of individual clusters while CD28 costimulation mainly increased the number of signaling clusters and cell spreading. These effects were observed for general tyrosine phosphorylation of clusters and for phosphorylated PLCγ1. Our analysis enables a clear distinction between factors determining the number of microclusters and those that act on these signaling platforms.

Mannitol as salvage treatment for Complex Regional Pain Syndrome Type I.

INTRODUCTION: Complex Regional Pain Syndrome Type I (CRPS I) is a continuation of symptoms and signs due to a pathological exaggerated reaction in an extremity of the human body after an injury or operation. Although the clinical picture of CRPS I in the majority of patients is well known, the underlying pathophysiology remains unclear. In The Netherlands, intravenous mannitol administration used as hydroxyl radical scavenger for patients who do not respond to conservative treatment of CRPS I is advocated but little evidence supports this salvage strategy. In this study the effect of mannitol as salvage medication was evaluated in a well-defined multimodal step-up treatment protocol. PATIENTS AND METHODS: A consecutive group of 68 adult patients with persistent CRPS I was analysed, who underwent a total of 100 mannitol infusions. The effect of treatment was considered per sign and per symptom according to the Veldman et al. criteria for CRPS I. RESULTS: Overall improvement of CRPS I after mannitol treatment was successful in 24% after 1 week, and in 30% after 1 month. Mannitol treatment had some effect in patients with initially warm CRPS I in contrast to patients with cold CRPS I (OR=6.30 with CI [2.37-16.75]). Also patients with CRPS I at the upper extremity had more benefit than patients with CRPS I at the lower extremity (OR=3.26 with CI [1.34-7.93]). Poor results of mannitol treatment were associated with cold CRPS I (p<0.001), chronic CRPS I (p=0.04) and multiple mannitol treatments (p=0.04). CONCLUSION: Mannitol did not significantly contribute to the overall success of treatment in patients with CRPS I. Patients, presenting with acute, warm CRPS I in the upper extremity may have some benefit.