Prognostic relevance of microsatellite instability in pT3N0M0 colon cancer: a population-based study

Although surgery alone represents a curative approach for patients with pT3N0M0 colon cancer, about 15–20 % of these patients develop a relapse of disease. Microsatellite instability (MSI) is one of the most important molecular markers in colorectal cancer. The aim of this study was to investigate the prognostic relevance of MSI in all pT3N0M0 tumors recorded in the Cancer Registry of the Province of Modena—(Northern Italy) within the 2002–2006 period in patients who showed a relapse of disease during the 5-year period of follow-up (59 cases). They were compared to 59 controls similar in clinical and pathological features but with good prognosis. None of the subjects received adjuvant chemotherapy. MSI status was tested using BAT25, BAT26, NR24, and CAT25 fluorescent-labeled mononucleotide markers. The overall prevalence of MSI was 12.7 % (15 of 118 cases). MSI was detected mainly in mucinous adenocarcinoma (p < 0.003), in high-grade tumors (p < 0.008), in right-sided neoplasms (p < 0.005), and in patients with a better prognosis, though the difference was not statistically significant (11/59 patients ?18.6 % vs 4/59 patients ?6.7 %; OR 0.36 CI 95 % 0.11–1.15; p = 0.08). However, in multivariate analysis, MSI status becomes the strongest independent factor associated with relapse (OR 0.21, CI 95 % 0.06–0.81; p = 0.023), together with mucinous histological type (OR 0.40, CI 90 % 0.18–0.92). MSI is a relevant prognostic factor in stage pT3N0M0 colon cancer suitable to discriminate those patients with a high risk of relapse.     

Validation of automated blood cell counter for the determination of polymorphonuclear cell count in the ascitic fluid of cirrhotic patients with or without spontaneous bacterial peritonitis

OBJECTIVES: Polymorphonuclear (PMN) cell count in ascitic fluid is the most useful test for the diagnosis of spontaneous bacterial peritonitis (SBP). We evaluated the validity of an automated blood cell counter for the PMN determination in ascitic fluid by comparing it with the traditional hematologic method with a light microscope in a manual counting chamber. METHODS: A total of 130 ascitic fluid samples were collected from 74 consecutive cirrhotics. The agreement between the two techniques was assessed according to Bland and Altman's method. The sensitivity, specificity, and positive and negative predictive values of the automated blood cell counter were calculated by considering the diagnosis of SBP as a PMN count > or = 250 cells/mm(3), determined by the manual method as the "gold standard." RESULTS: The mean PMN counts assessed by the manual method and the automated blood cell counter were 124 +/- 301 cells/mm(3) and 130 +/- 339 cells/mm(3), respectively (p = 0.89, ns). The mean +/- SD of the difference between manual and automated measurements was 6 +/- 61 cells/mm(3), whereas the limits of agreement were +127 cells/mm(3) (95% CI = +108 to +147) and -115 cells/mm(3) (95%CI = -96 to -135). SBP was diagnosed in 11 patients. All but one were correctly identified with the automated blood cell counter, with a sensitivity of 94% and a specificity of 100%; positive and negative predictive values were 100% and 99.1%, respectively. CONCLUSIONS: The manual method and the automated blood cell counter have a good agreement in the PMN determination in ascitic fluid, and the automated blood cell counter is a reliable tool for rapid diagnosis of SBP.     

Cardiovascular impact of testosterone therapy for hypogonadism

Introduction: Since 2010 some evidence supporting the possible increased cardiovascular (CV) risk related to testosterone treatment (TTh) has created much debate in the scientific community. Based on these results, the US Food and Drug Administration agency has questioned TTh for aging men recognizing its value only for classical hypogonadism due to genetic or organic causes. To better clarify this topic, we scrutinized and summarized, also by using meta-analytic methods, the data generated during the last 7 years, as derived from the analysis of randomized controlled trials (RCTs) on TTh and CV risk.

Areas covered: Analysis included 31 RCTs published between 2010 and 2018. Retrieved trials included 2675 and 2308 patients in TTh and placebo groups, respectively. The analysis documented that TTh was not associated with an increased CV mortality or morbidity either when overall or major adverse CV events were considered.

Expert commentary: Despite present evidence it is important to recognize that the duration of the available trials is short (lower that 3 years) limiting final conclusions on this topic. In particular, the available information on possible long-term effects of TTh on CV risk is limited. Long-term safety studies are advisable to better clarify these points.     

HYPNOTIZABILITY AND PAIN MODULATION: A Body–Mind Perspective

The study investigated whether the cardiac activity and cognitive–emotional traits sustained by the behavioral inhibition/activation system (BIS/BAS) may contribute to hypnotizability-related pain modulation. Nociceptive stimulation (cold-pressor test) was administered to healthy participants with high (highs) and low (lows) hypnotizability in the presence and absence of suggestions for analgesia. Results showed that heart rate increased abruptly at the beginning of nociceptive stimulation in all participants. Then, only in highs heart rate decreased for the entire duration of hand immersion. During stimulation with suggestions of analgesia, pain threshold negatively correlated with heart rate. BIS/BAS activity partially accounted for the observed hypnotizability-related differences in the relation between cardiac interoception and pain experience.     

Risk Estimation Modeling and Feasibility Testing for a Mobile eHealth Intervention for Binge Drinking Among Young People: The D-ARIANNA (Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults) Project

Background: Binge drinking is common among young people but often relevant risk factors are not recognized. eHealth apps, attractive for young people, may be useful to enhance awareness of this problem. We aimed at developing a current risk estimation model for binge drinking, incorporated into an eHealth app—D-ARIANNA (Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults)—for young people. Methods: A longitudinal approach with phase 1 (risk estimation), phase 2 (design), and phase 3 (feasibility) was followed. Risk/protective factors identified from the literature were used to develop a current risk estimation model for binge drinking. Relevant odds ratios were subsequently pooled through meta-analytic techniques with a random-effects model, deriving weighted estimates to be introduced in a final model. A set of questions, matching identified risk factors, were nested in a questionnaire and assessed for wording, content, and acceptability in focus groups involving 110 adolescents and young adults. Results: Ten risk factors (5 modifiable) and 2 protective factors showed significant associations with binge drinking and were included in the model. Their weighted coefficients ranged between ?0.71 (school proficiency) and 1.90 (cannabis use). The model, nested in an eHealth app questionnaire, provides in percent an overall current risk score, accompanied by appropriate images. Factors that mostly contribute are shown in summary messages. Minor changes have been realized after focus groups review. Most of the subjects (74%) regarded the eHealth app as helpful to assess binge drinking risk. Conclusions: We could produce an evidence-based eHealth app for young people, evaluating current risk for binge drinking. Its effectiveness will be tested in a large trial.