99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy

Purpose The purpose of this study was to determine the value of ^99mTc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. Methods TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6–8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (ΔU). Results In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean ΔU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. ΔU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum ΔU in primary tumour and in the lymph nodes. Conclusions Within the dose range of 0–8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic response.     

泛昔洛韦等3种药物抗乙型肝炎病毒的体外实验研究

 目的评价泛昔洛韦、膦甲酸钠及氧化苦参碱的体外抗HBV作用.方法采用MTT法检测3种药物对HepG2.2.15细胞的半数毒性浓度(TC5o),并在此基础上观察不同浓度药物作用于HepG2.2.15细胞后第3、5、7和9天培养上清中HBsAg、HBeAg及HBV DNA含量的变化,比较不同药物抗HBV的效果.结果泛昔洛韦和氧化苦参碱对HepG2.2.15细胞有明显的抗HBV活性,在实验浓度范围内,随着药物浓度增加和作用时间延长,其抗HBV活性增强;膦甲酸钠对HBV无明显抑制作用.结论泛昔洛韦和氧化苦参碱具有明显体外抗HBV活性,而膦甲酸钠体外对HBV无明显抑制作用.     

Prophylactic mesh placement of permanent stomas at index operation for colorectal cancer

INTRODUCTION

Parastomal herniation occurs in 30–50% of colostomy formations. The aim of this study was to radiologically evaluate the mechanical defects at stoma sites in patients who had previously undergone a permanent colostomy with or without mesh at the index operation for colorectal cancer.

METHODS

A study was performed of all colorectal cancer patients (n=41) having an end colostomy between 2002 and 2010, with or without Prolene® mesh plication, with blinded evaluation of the annual follow-up staging computed tomography (CT) for stomal characteristics. The presence of parastomal hernias, volume, dimensions, grade of the parastomal hernia and abdominal wall defect size were measured by two independent radiologists, and compared with demographic and operative variables.

RESULTS

In those patients with radiological evidence of a parastomal hernia, Prolene® mesh plication significantly reduced the incidence of bowel containing parastomal hernias at one year following the procedure (p<0.05) and also reduced the diameter of the abdominal wall defect (p=0.006).

CONCLUSIONS

Prophylactic mesh placement at the time of the index procedure reduces the diameter of abdominal wall aperture and the incidence of parastomal hernias containing bowel. Future studies should use both objective radiological as well as clinical endpoints when assessing parastomal hernia development with and without prophylactic mesh.     

Predictive value of plasma glucose level on admission for short and long term mortality in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention

Published reports describe a strong association between plasma glucose levels on admission and mortality in patients who undergo primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. The aim of this study was to assess the predictive value of admission glucose levels for early and late mortality. From 2005 to 2007, 1,646 patients underwent primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and were stratified according to admission plasma glucose level in category 1 (<7.8 mmol/L; n = 747), category 2 (7.8 to 11.0 mmol/L; n = 620), or category 3 (>11 mmol/L; n = 279). Event rates were estimated using the Kaplan-Meier method. A landmark survival analysis to 3-year follow-up was performed, with a landmark set at 30 days. Time-extended Cox regression was used to assess the predictive value of admission glucose levels. Furthermore, a stratified analysis was performed for known diabetes mellitus status at admission. Thirty-day mortality was 2.4% in category 1, 6% in category 2, and 22% in category 3 (p <0.01). Three-year mortality in 30-day survivors was 5.9% in category 1, 8.2% in category 2, and 7.1% in category 3 (p = 0.27). Glucose level on admission was a strong predictor of 30-day mortality: for every 1 mmol/L increase, the hazard increased by 14% (hazard ratio 1.14, 95% confidence interval 1.09 to 1.19, p <0.01) in patients without diabetes, by 12% (hazard ratio 1.12, 95% confidence interval 1.05 to 1.19, p <0.01) in those with diabetes, and by 13% (hazard ratio 1.13, 95% confidence interval 1.09 to 1.17, p <0.01) in the total cohort. After 30 days, glucose level at admission lost its predictive value. In conclusion, in patients with and those without diabetes, glucose level at admission is an independent predictor of early but not late mortality.     

Clinical applications of two detection systems for HIV using saliva

The purpose of this research was to determine if the accuracy of HIV saliva and serum test results were influenced by changes in collection sites. In order to do so, serum and saliva samples were collected from 615 subjects in eight different geographic settings. The oral fluid collection/testing systems utilized were the Orapette SalivaCard HIV-1/HIV-2 antibody test (Trinity Biotech, Ireland) and the Omni-SAI/Immuno Comb II HIV 1 & 2 Saliva Test (Orgenics Ltd, Israel). For comparison, serum samples were tested by ELISA (Ortho) with reactive results confirmed via HIV-1 and HIV-2 Western blots (Biotech/Dupont, Institute Pasteur). The HIV serum and oral fluid collections were conducted in numerous test sites, which provided a great diversity in temperature, lighting and physical layout. The tests proved to be 99.8% and 100% specific, and both were 100% sensitive, regardless of the physical setting of the collections. While these systems are not currently available in the US, this study clearly demonstrates they can accurately be utilized in a variety of clinical settings, providing great promise for future applications.     

Self-reflection in nursing teacher education

The reality of health care is continuously changing. Therefore, nursing teachers have to encourage and promote a critical, inquiry-oriented approach to work. This demands self-reflection during the teacher education. Teaching training crystallizes the objectives of teacher education; the process of self-reflection should be seen especially there.     

From neuroscience to evidence based psychological treatments – The promise and the challenge,ECNP March 2016, Nice,France

This ECNP meeting was designed to build bridges between different constituencies of mental illness treatment researchers from a range of backgrounds with a specific focus on enhancing the development of novel, evidence based, psychological treatments. In particular we wished to explore the potential for basic neuroscience to support the development of more effective psychological treatments, just as this approach is starting to illuminate the actions of drugs. To fulfil this aim, a selection of clinical psychologists, psychiatrists and neuroscientists were invited to sit at the same table. The starting point of the meeting was the proposition that we know certain psychological treatments work, but we have only an approximate understanding of why they work. The first task in developing a coherent mental health science would therefore be to uncover the mechanisms (at all levels of analysis) of effective psychological treatments. Delineating these mechanisms, a task that will require input from both the clinic and the laboratory, will provide a key foundation for the rational optimisation of psychological treatments. As reviewed in this paper, the speakers at the meeting reviewed recent advances in the understanding of clinical and cognitive psychology, neuroscience, experimental psychopathology, and treatment delivery technology focussed primarily on anxiety disorders and depression. We started by asking three rhetorical questions: What has psychology done for treatment? What has technology done for psychology? What has neuroscience done for psychology? We then addressed how research in five broad research areas could inform the future development of better treatments: Attention, Conditioning, Compulsions and addiction, Emotional Memory, and Reward and emotional bias. Research in all these areas (and more) can be harnessed to neuroscience since psychological therapies are a learning process with a biological basis in the brain. Because current treatment approaches are not fully satisfactory, there is an imperative to understand why not. And when psychological therapies do work we need to understand why this is the case, and how we can improve them. We may be able to improve accessibility to treatment without understanding mechanisms. But for treatment innovation and improvement, mechanistic insights may actually help. Applying neuroscience in this way will become an additional mission for ECNP.     

Evaluation of lasersurgery and radiotherapy as treatment modalities in early stage laryngeal carcinoma: tumour outcome and quality of voice

For treatment of early stage (Tis-T2) laryngeal cancer the main choice is between microlaryngoscopy with carbon dioxide laser resection (laser surgery) and radiotherapy. Because both treatments provide excellent tumour control, secondary outcome variables such, as quality of voice may be of importance in treatment preference. In this study tumour outcomes and quality of voice were analysed for a cohort of patients with early stage (Tis-T2) laryngeal (glottic) carcinoma. The “physical subscale” of the voice handicap index questionnaire (VHI) and a validated five-item screening questionnaire were used. Analysis of 89 patients treated with laser surgery and 159 patients treated with radiotherapy revealed a 5-year local control of 75 and 86 % (p = 0.07). Larynx preservation (5-year) was, however, superior in patients treated with laser surgery, 93 vs 83 % (p < 0.05). Tumour outcomes were also analysed per tumour stage and none were of significant difference. Quality of voice was analysed in 142 patients. VHI scores were 12.4 ± 8.9 for laser surgery and 8.3 ± 7.7 for radiotherapy (p < 0.05), with a higher score reflecting a worse outcome. VHI scores per tumour stage for laser surgery and radiotherapy were, respectively, 12.0 ± 9.9 and 7.9 ± 7.5 in T1a (p = 0.06), 16.7 ± 9.0 and 4.9 ± 6.6 in T1b (p < 0.05). Outcomes of the five-item questionnaire showed voice deficiency in 33 % for laser surgery and 23 % for radiotherapy in T1a (p = 0.330) and 75 and 5 % for T1b (p = 0.001). Oncologic outcomes of laser surgery and radiotherapy were comparable. Larynx preservation is, however, preferable in patients initially treated with laser surgery. According to subjective voice analysis, outcomes were comparable in T1a lesions. Depth of laser resection is of influence on voice deficiency displayed by a significantly higher percentage of voice deficiency in patients treated with laser surgery for T1b lesions.     

Definitive radiation therapy for treatment of laryngeal carcinoma

Purpose

The purpose of this work was to evaluate outcome after radiotherapy (RT) for laryngeal carcinoma and investigate effects of local relapse on ultimate disease control, including surgical salvage procedures.

Methods and materials

In all, 435 patients with laryngeal carcinoma (cT1–cT4a) treated with primary RT were retrospectively analyzed. Uni- and multivariate analyses were performed to identify prognostic factors for local relapse-free survival and overall survival.

Results

Median follow-up was 38 months (range 1–144 months). The cumulative frequency of local recurrence was dependent on T stage: cT1 tumors 10?%, cT2 18?%, cT3 23?%, and cT4 36?% (p?<?0.001). Salvage surgery for local persistent/recurrent disease was performed in 59 of 78 patients (76?%). The ultimate local control rates at 5 years (including salvage therapy) were 98, 98, 87, and 68?% for cT1, cT2, cT3, and cT4 tumors (p?<?0.001), respectively. For the patients who developed local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and 26?% (p?<?0.001), respectively. Overall survival at 5 years was 68?% for patients without local relapse and 50?% for patients experiencing local failure (p?<?0.001). In univariate analysis, cT stage, cN stage, and tumor volume were statistically significant associated with local relapse-free survival. In multivariate analysis for the cT3–4 tumors, only tumor volume remained statistically significant (HR 1.017, p?=?0.001) for local relapse-free survival.

Conclusion

Local control rates for cT1–2 laryngeal carcinomas are favorable and in concordance with previous reports and most recurrences are salvaged. For cT3–4 tumors treated with RT alone, initial local control rates are moderate, and in 60?% of recurring cases salvage surgery is attempted, with ultimate local control being achieved in only a subset. For voluminous, locally advanced laryngeal tumors, more aggressive treatment modalities should be considered, including upfront laryngectomy or radiochemotherapy.