Chemoradiation for advanced hypopharyngeal carcinoma: a retrospective study on efficacy, morbidity and quality of life

Chemoradiation (CRT) is a valuable treatment option for advanced hypopharyngeal squamous cell cancer (HSCC). However, long-term toxicity and quality of life (QOL) is scarcely reported. Therefore, efficacy, acute and long-term toxic effects, and long-term QOL of CRT for advanced HSCC were evaluated,using retrospective study and post-treatment quality of life questionnaires. in a tertiary hospital setting. Analysis was performed of 73 patients that had been treated with CRT. Toxicity was rated using the CTCAE score list. QOL questionnaires EORTC QLQ-C30, QLQ-H&N35, and VHI were analyzed. The most common acute toxic effects were dysphagia and mucositis. Dysphagia and xerostomia remained problematic during long-term follow-up. After 3 years, the disease-specific survival was 41%, local disease control was 71%, and regional disease control was 97%. The results indicated that CRT for advanced HSCC is associated with high locoregional control and disease-specific survival. However, significant acute and long-term toxic effects occur, and organ preservation appears not necessarily equivalent to preservation of function and better QOL

Effects of total laryngectomy on olfactory function, health-related quality of life, and communication: a 3-year follow-up study

<p>Abstract</p> <p>Background</p> <p>As total laryngectomy results in loss of airflow through the nose, one of the adverse effects for a majority of patients is the reduced or complete loss of olfactory function. However, with the introduction of a new method, the Nasal Airflow-Inducing Maneuver (NAIM), an important technique is available for laryngectomized patients to regain the ability to smell. The purpose of the present study was to assess changes in olfaction, health-related quality of life (HRQL) and communication 3 years after NAIM rehabilitation.</p> <p>Methods</p> <p>18 patients (15 men and 3 women; mean age, 71 years) who had undergone laryngectomy and NAIM rehabilitation were followed longitudinally for 3 years. For comparison an age and gender matched control group with laryngeal cancer treated with radical radiotherapy was included. Olfactory function was assessed using the Questionnaire on Odor, Taste and Appetite and the Scandinavian Odor Identification Test. HRQL was assessed by: 1) the European Organization for Research and Treatment for cancer quality of life questionnaires; and 2) the Hospital Anxiety and Depression Scale. Communication was assessed by the Swedish Self-Evaluation of Communication Experiences after Laryngeal Cancer. Descriptive statistics with 95% confidence interval were calculated according to standard procedure. Changes over time as well as tests between pairs of study patients and control patients were analyzed with the Fisher nonparametric permutation test for matched pairs.</p> <p>Results</p> <p>Thirty-six months after rehabilitation 14 of 18 laryngectomized patients (78%) were smellers. There were, with one exception (sleep disturbances), no clinically or statistically significant differences between the study and the control group considering HRQL and mental distress. However, statistical differences (p < 0.001) were found between the study and the control group concerning changes in communication.</p> <p>Conclusion</p> <p>Olfactory training with NAIM should be integrated into the multidisciplinary rehabilitation program after total laryngectomy. Our study shows that patients who were successfully rehabilitated concerning olfaction and communication had an overall good HRQL and no mental distress. Moreover, the EORTC questionnaires should be complemented with more specific questionnaires when evaluating olfaction and communication in laryngectomized patients.</p

Dissection of the Role of PfEMP1 and ICAM-1 in the Sensing of Plasmodium falciparum-Infected Erythrocytes by Natural Killer Cells

BACKGROUND: Host innate immunity contributes to malaria clinical outcome by providing protective inflammatory cytokines such as interferon-γ, and by shaping the adaptive immune response. Plasmodium falciparum (Pf) is the etiologic agent of the most severe forms of human malaria. Natural Killer (NK) cells are lymphocytes of the innate immune system that are the first effectors to produce interferon-γ in response to Pf. However, the molecular bases of Pf-NK cell recognition events are unknown. Our study focuses on the role of Pf erythrocyte membrane protein 1 (PfEMP1), a major Pf virulence factor. PfEMP1 is expressed on parasitized-erythrocytes and participates to vascular obstruction through the binding to several host receptors. PfEMP1 is also a pivotal target for host antibody response to Pf infection. METHODOLOGY/PRINCIPAL FINDINGS: Using genetically-engineered parasite mutant strains, a human genetic deficiency, and blocking antibodies, we identified two receptor-ligand pairs involved in two uncoupled events occurring during the sensing of Pf infection by NK cells. First, PfEMP1 interaction with one of its host receptor, chondroitin sulfate A, mediates the cytoadhesion of Pf-infected erythrocytes to human NK cell lines, but is not required for primary NK cell activation. Second, intercellular adhesion molecule-1 (ICAM-1), another host receptor for PfEMP1, is mandatory for NK cell interferon-γ response. In this case, ICAM-1 acts via its engagement with its host ligand, LFA-1, and not with PfEMP1, consistent with the obligatory cross-talk of NK cells with macrophages for their production of interferon-γ. CONCLUSION/SIGNIFICANCE: PfEMP1-independent but ICAM-1/LFA-1-dependent events occurring during NK cell activation by Pf highlight the fundamental role of cellular cooperation during innate immune response to malaria

Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone

<p>Abstract</p> <p>Background</p> <p>Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN.</p> <p>Methods</p> <p>Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-β synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS).</p> <p>Results</p> <p>Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-β by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis.</p> <p>Conclusions</p> <p>Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.</p

Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES):A randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue

<p>Abstract</p> <p>Background</p> <p>Cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, and muscle strength and with an increase in fatigue. While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength, the results of studies conducted to date have not been consistent. Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised, outpatient (hospital- or physical therapy practice-based) versus home-based programs.</p> <p>Methods</p> <p>This multicenter, prospective, randomized trial will evaluate the effectiveness of a low to moderate intensity, home-based, self-management physical activity program, and a high intensity, structured, supervised exercise program, in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue and in enhancing the health-related quality of life (HRQoL). Patients receiving adjuvant chemotherapy for breast or colon cancer (n = 360) are being recruited from twelve hospitals in the Netherlands, and randomly allocated to one of the two treatment groups or to a 'usual care' control group. Performance-based and self-reported outcomes are assessed at baseline, at the end of chemotherapy and at six month follow-up.</p> <p>Discussion</p> <p>This large, multicenter, randomized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness, minimizing fatigue, and maintaining or enhancing patients' quality of life. If demonstrated to be effective, exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer receiving chemotherapy.</p> <p>Trial registration</p> <p>This study is registered at the Netherlands Trial Register (NTR 2159)</p

Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys

Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed