Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry

<p>Abstract</p> <p>Background</p> <p>The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.</p> <p>Methods</p> <p>Fifty-nine patients with biliary SOD (14% type I, 51% type II, 35% type III) were prospectively enrolled. All patients with a dilated common bile duct were offered endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy whereas all others were offered medical treatment alone. Patients were followed up for a median of 15 months and were assessed clinically for response to treatment.</p> <p>Results</p> <p>At follow-up 15.3% of patients reported complete symptom resolution, 59.3% improvement, 22% unchanged symptoms, and 3.4% deterioration. Fifty-one percent experienced symptom resolution/improvement on medical treatment only, 12% after sphincterotomy, and 10% after both medical treatment/sphincterotomy. Twenty percent experienced at least one recurrence of symptoms after initial response to medical and/or endoscopic treatment. Fifty ERCP procedures were performed in 24 patients with an 18% complication rate (16% post-ERCP pancreatitis). The majority of complications occurred in the first ERCP these patients had. Most complications were mild and treated conservatively. Age, gender, comorbidity, SOD type, dilated common bile duct, presence of intact gallbladder, or opiate use were not related to the effect of treatment at the end of follow-up (p > 0.05 for all).</p> <p>Conclusions</p> <p>Patients with biliary SOD may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without manometry. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those previously published in the literature in cohorts of patients assessed by manometry.</p

Sex and Gender Differences in Ischemic Heart Disease: Endocrine Vascular Disease Approach (EVA) Study Design

Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions

Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods: The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p&nbsp;=&nbsp;0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p&nbsp;=&nbsp;0.049). Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation

Off–label long acting injectable antipsychotics in real–world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction: Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p&nbsp;= 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p&nbsp;= 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

On the emergence of whole-body strategies from humanoid robot push-recovery learning

none7Balancing and push-recovery are essential capabilities enabling humanoid robots to solve complex locomotion tasks. In this context, classical control systems tend to be based on simplified physical models and hard-coded strategies. Although successful in specific scenarios, this approach requires demanding tuning of parameters and switching logic between specifically-designed controllers for handling more general perturbations. We apply model-free Deep Reinforcement Learning for training a general and robust humanoid push-recovery policy in a simulation environment. Our method targets high-dimensional whole-body humanoid control and is validated on the iCub humanoid. Reward components incorporating expert knowledge on humanoid control enable fast learning of several robust behaviors by the same policy, spanning the entire body. We validate our method with extensive quantitative analyses in simulation, including out-of-sample tasks which demonstrate policy robustness and generalization, both key requirements towards real-world robot deployment.openFerigo D.; Camoriano R.; Viceconte P.M.; Calandriello D.; Traversaro S.; Rosasco L.; Pucci D.Ferigo, D.; Camoriano, R.; Viceconte, P. M.; Calandriello, D.; Traversaro, S.; Rosasco, L.; Pucci, D

Endometriosis: A Retrospective Analysis of Clinical Data from a Cohort of 4,083 Patients, With Focus on Symptoms

Background: Endometriosis is an estrogen-dependent and chronic inflammatory gynecological disease due to the presence of ectopic endometrial tissue outside the uterine cavity. This disease affects approximately 10% of the female population. In spite of its relatively high prevalence, information about its pathogenesis, diagnosis, and therapy is not complete. Patients and Methods: We present a retrospective study performed on 4,083 patients with endometriosis, with a focus on symptoms. The archived data were analyzed investigating the distribution of symptoms among patients, the correlation of symptoms with the occupation of the patients, and finally the correlation with the other anamnestic data. Statistical associations between the data for all cases were then considered separately. Results: Chronic fatigue syndrome and dyspareunia were confirmed as being among the main symptoms of endometriosis, together with bowel disorders. On the other hand, we registered a low occurrence of urinary disorders and even of chronic pelvic pain, which is usually considered among the main symptoms of endometriosis. We found an increase in incidence of symptoms starting from the age group 25-29 years up to 40-44 years and, subsequently, a significant decrease in the group aged 55-59 years. For all the symptoms analyzed, we found a higher incidence in employers, graduates and freelancers. Finally, we found a protective effect of the number of gestations on chronic fatigue syndrome. Conclusion: This in-depth study on such a vast cohort of affected patients clarifies some important aspects on the complex symptomatology of this still enigmatic disease. In particular, the study highlights the symptoms most closely related to endometriosis which will help speed up the diagnostic process of patients suffering from this pathology

Endometriosis: A Retrospective Analysis on Diagnostic Data in a Cohort of 4,401 Patients

Background/Aim: Endometriosis is a gynecological estrogen-dependent inflammatory disease due to ectopic endometrial tissue and often associated with pelvic pain. Despite its high prevalence, there are still uncertainties about its pathogenesis, diagnosis, and therapy. Patients and Methods: This study presents a retrospective study conducted on 4,401 endometriosis patients, 584 of which underwent laparoscopic procedures. The archived data about clinical signs, magnetic resonance imaging (MRI) results, topography of the endometriosis lesions (obtained via laparoscopy) associated diseases, sample analysis and histological findings were analyzed. Next, the statistical associations between the information for each case, provided by these diagnostic tools were determined. Results: MRI is the most sensitive and specific diagnostic system for ovarian lesions, but poor in sensitivity and specificity for deep endometriosis lesions and not indicated for peritoneal lesions which remain the exclusive prerogative of laparoscopy. Clinical signs are essential for diagnosing deep lesions. The Ca125 and Ca19.9 markers have a poor reliability and their negativity in symptomatic patients has no clinical value, while in positive cases it could probably be used as a monitoring parameter. Conclusion: The results generated will help provide an accurate picture of the topography and distribution of endometriotic lesions. Correlation analyses between the data generated by the clinical-instrumental examinations and those on the site of the disease identified by laparoscopy, allow to define the predictive value of the clinical-instrumental signs in the diagnosis and localization of endometriotic disease

Polyamines: fundamental characters in chemistry and biology

Polyamines are small cationic molecules required for cellular proliferation and are detected at higher concentrations in most tumour tissues, compared to normal tissues. Agmatine (AGM), a biogenic amine, is able to arrest proliferation in cell lines by depleting intracellular polyamine levels. It enters mammalian cells via the polyamine transport system. Agmatine is able to induce oxidative stress in mitochondria at low concentrations (10 or 100 microM), while at higher concentrations (e.g. 1-2 mM) it does not affect mitochondrial respiration and is ineffective in inducing any oxidative stress. As this effect is strictly correlated with the mitochondrial permeability transition induction and the triggering of the pro-apoptotic pathway, AGM may be considered as a regulator of this type of cell death. Furthermore, polyamine transport is positively correlated with the rate of cellular proliferation. By increasing the expression of antizyme, a protein that inhibits polyamine biosynthesis and transport, AGM also exhibits a regulatory effect on cell proliferation. Methylglyoxal bis(guanylhydrazone) (MGBG), a competitive inhibitor of S-adenosyl-L: -methionine decarboxylase, displaying anticancer activity, is a structural analogue of the natural polyamine spermidine. MGBG has been extensively studied, preclinically as well as clinically, and its anticancer activity has been attributed to the inhibition of polyamine biosynthesis and also to its effect on mitochondrial function. Numerous findings have suggested that MGBG might be used as a chemotherapeutic agent against cancer