Prognostic Factors Associated with Survival in Patients with Primary Duodenal Adenocarcinoma

Background/Aims: The prognostic factors in primary duodenal adenocarcinoma remain controversial. This study evaluated the prognostic factors associated with survival in patients with primary duodenal adenocarcinoma. Methods: From March 1996 to June 2008, the medical records of 30 patients with a final diagnosis of primary duodenal epithelial malignancy seen at two referral centers were reviewed retrospectively. The prognostic factors for survival were evaluated 6 months and 1, 2, and 5 years after the diagnosis. Results: The median survival was 5.7 months. The survival rate was 46.7 % (14/30), 16.7 % (5/30), 10 % (3/30), and 6.7 % (2/30) at 6 months and 1, 2, and 5 years, respectively. Multivariate analysis showed that cancer-direct-ed treatment, including curative surgery or chemotherapy, was a common independent risk factor at all follow-up times. Total bilirubin, cytology, and TNM stage were independent risk factors for survival at 1, 2, and 5 years. The white blood cell count was an independent risk factor at 1 year only. The actuarial probability of survival in patients undergoing cancer-directed treatment was significantly higher than in those without treatment at 6 months (71.4 vs. 25.0%, p < 0.01), 1 year (28.6 vs. 6.3%, p < 0.01), 2 years (21.4 vs. 0%, p < 0.01), and 5 years (14.3 vs. 0%, p < 0.01). Conclusions: The prognostic factors in patients with primary duodenal adenocarcinoma were total bilirubin, TNM stage, cytology, and cancer-directed treatments until the 5-year follow-up. Especially, cancer-directed treat-ments improved patient survival. (Korean J Intern Med 2011;26:34-40

Life Events, Coping, and Posttraumatic Stress Symptoms among Chinese Adolescents Exposed to 2008 Wenchuan Earthquake, China

PURPOSE: To examine the relationship between negative life events, coping styles, and symptoms of post-traumatic stress disorder (PTSD) among adolescent survivors exposed to 2008 Wenchuan Earthquake, China. METHODS: A survey was conducted in a sample of 2250 adolescent students from two schools in Dujiangyan District, a seriously damaged area, 20 kilometers away from the epicenter, 6 months after the earthquake. Participants completed a self-administered questionnaire including demographics, negative life events, coping styles, and PTSD symptoms. RESULTS: Academic pressure was the strongest predictor of adolescents' PTSD symptoms among all negative life events. Main effects of negative life events, positive coping and negative coping on PTSD symptoms were significant in both younger adolescents and older adolescents, while the moderator effects of two coping styles were found significant only within older adolescents. CONCLUSIONS: Coping may play a role to moderate the relationship between post-earthquake negative life events and PTSD symptom, but the function seems to depend on the age of participants. Psychosocial coping skills training may be important in the prevention and intervention of mental health problems in adolescent survivors of traumatic earthquake

Regulation of cell-to-cell communication mediated by astrocytic ATP in the CNS

It has become apparent that glial cells, especially astrocytes, not merely supportive but are integrative, being able to receive inputs, assimilate information and send instructive chemical signals to other neighboring cells including neurons. At first, the excitatory neurotransmitter glutamate was found to be a major extracellular messenger that mediates these communications because it can be released from astrocytes in a Ca2+-dependent manner, diffused, and can stimulate extra-synaptic glutamate receptors in adjacent neurons, leading to a dynamic modification of synaptic transmission. However, recently extracellular ATP has come into the limelight as an important extracellular messenger for these communications. Astrocytes express various neurotransmitter receptors including P2 receptors, release ATP in response to various stimuli and respond to extracellular ATP to cause various physiological responses. The intercellular communication “Ca2+ wave” in astrocytes was found to be mainly mediated by the release of ATP and the activation of P2 receptors, suggesting that ATP is a dominant “gliotransmitter” between astrocytes. Because neurons also express various P2 receptors and synapses are surrounded by astrocytes, astrocytic ATP could affect neuronal activities and even dynamically regulate synaptic transmission in adjacent neurons as if forming a “tripartite synapse” In this review, we summarize the role of astrocytic ATP, as compared with glutamate, in gliotransmission and synaptic transmission in neighboring cells, mainly focusing on the hippocampus. Dynamic communication between astrocytes and neurons mediated by ATP would be a key event in the processing or integration of information in the CNS

Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy

Fertility in adult females with congenital hypothyroidism (CH) diagnosed by neonatal screening

Background: CH interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy and perinatal outcome. However, in subjects with early treated CH, a normal pubertal development has been reported. There are no systematic studies about fertility and pregnancy outcome in affected adults. Objective and hypotheses: Fertility and pregnancy evalutation in CH adult females. Methods: Gynecologic history was evaluated in a semistructurated questionnaire carried out by expert clinicians. The results were compared with data derived from national register of births. 155 girls with permanent CH between 1978 and 1994, in 4 italian regions, were recalled. 69 (44.6%) subjects (mean age 22.1 ± 4.4 yrs; 25 (36%) athyreosis, 32 ectopic gland (47%), 12 (17%) in situ gland) agreed to participate our study. Results: 9 pts reported 10 pregnancies (15%),3 of which terminated by abortion (1 miscarriage: 6° week of GA in 28.4 yrs pt with ectopic thyroid gland; 2 elective abortion: 4° week of GA in 20.2 yrs pt with hypoplasia, 6° week of GA in 21.3 yrs pt with athyreosis). The abortion rate was 1.45% for miscarriage (0.54% in control population), 2.9% for elective abortion (0.86% in control population).In the fullterm pregnancies the mean increase of L-T4 dose needed in each trimester was 15% (10%-20%), 15%(10%-20%) and 20%(10%-30%) respectively. TSH values >2.5 mU/L were found in 7/7 cases in the 1st trimester, in 4/7 in the 2nd, in 4/7 in the 3th. All newborn showed normal results at neonatal screening and at thyroid ultrasound. The table shows the data of live births subdivided according to maternal age

Cost-effectiveness of alternative NTRK-testing strategies and histology-independent therapy entrectinib in 3 countries - supplementary material

Table S1. Test groups, proportional distribution umour type distribution before NTRK gene fusion testing, NTRK prevalence and tumour type distribution in entrectinib trials.Table S2. Sensitivity and specificity of immunohistochemistry (IHC) tests by tumour type.Table S3. Number of patients and parametric distributions with the lowest AIC for overall survival (OS) and time to treatment discontinuation (TTD)Table S4. Costs of biopsy, IHC, and RNA-NGS by tumour type and country.Table S5. Standard of care treatments by cancer typeTable S6. Costs of standard of care (SoC) treatment and adverse event treatment by tumour type and country.Table S7. Probability distributions used for probabilistic sensitivity analysis (PSA)Table S8. Incremental budget impact according to time horizon of national HTA guidelinesFigure S1. Model structureFigure S2. Results of the univariate sensitivity analysis</p

Budget impact and transferability of cost-effectiveness of DPYD testing in metastatic breast cancer in 3 health systems - supplementary material

Appendix Table 1. General (UK) model input parameters</p