Resting-state functional MRI in multicenter studies on multiple sclerosis: a report on raw data quality and functional connectivity features from the Italian Neuroimaging Network Initiative

The Italian Neuroimaging Network Initiative (INNI) is an expanding repository of brain MRI data from multiple sclerosis (MS) patients recruited at four Italian MRI research sites. We describe the raw data quality of resting-state functional MRI (RS-fMRI) time-series in INNI and the inter-site variability in functional connectivity (FC) features after unified automated data preprocessing. MRI datasets from 489 MS patients and 246 healthy control (HC) subjects were retrieved from the INNI database. Raw data quality metrics included temporal signal-to-noise ratio (tSNR), spatial smoothness (FWHM), framewise displacement (FD), and differential variation in signals (DVARS). Automated preprocessing integrated white-matter lesion segmentation (SAMSEG) into a standard fMRI pipeline (fMRIPrep). FC features were calculated on pre-processed data and harmonized between sites (Combat) prior to assessing general MS-related alterations. Across centers (both groups), median tSNR and FWHM ranged from 47 to 84 and from 2.0 to 2.5, and median FD and DVARS ranged from 0.08 to 0.24 and from 1.06 to 1.22. After preprocessing, only global FC-related features were significantly correlated with FD or DVARS. Across large-scale networks, age/sex/FD-adjusted and harmonized FC features exhibited both inter-site and site-specific inter-group effects. Significant general reductions were obtained for somatomotor and limbic networks in MS patients (vs. HC). The implemented procedures provide technical information on raw data quality and outcome of fully automated preprocessing that might serve as reference in future RS-fMRI studies within INNI. The unified pipeline introduced little bias across sites and appears suitable for multisite FC analyses on harmonized network estimates.

     

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression

Background

Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD.

Objectives

To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch.

Methods

Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up.

Results

A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch.

Conclusions

Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.     

Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study

Objective

Aim of our study was to evaluate the effectiveness of the association between N-Palmitoylethanolamine and transpolydatin in the management of chronic pelvic pain related to EMS.

Study design

This was a randomized, double-blind, parallel-group, placebo-controlled clinical trial involving 61 subjects, submitted to a first line laparoscopic conservative surgery, who were randomized into 3 groups receiving: group A (n = 21) the association N-Palmitoylethanolamine-transpolydatin 400 mg + 40 mg twice a day for 3 months; group B (n = 20) the placebo for 3 months; group C (n = 20) a single course of Celecoxib 200 mg twice a day for 7 consecutive days. Assessments of the severity of pelvic endometriosis (pelvic pain, dysmenorrhoea and dyspareunia) were recorded before and after treatment on a questionnaire and a 10-point VAS. Differences between groups were verified with Kruskal-Wallis ANOVA for non-parametric multiple comparisons.

Results

A marked decrease in dysmenorrhoea, dyspareunia and pelvic pain was observed in all groups, and the association between N-Palmitoylethanolamine and transpolydatin resulted to be more effective than placebo (P < .001). Additionally, the treatment with Celecoxib resulted in a decrease in pelvic pain more effective either than the association N-Palmitoylethanolamine and transpolydatin or placebo.

Conclusion

These preliminary results show that the association between micronized N-Palmitoylethanolamine and transpolydatin is effective in the management of pelvic pain related to endometriosis after laparoscopy. Additionally, this association seems to be safe, shows an optimal control of pain and can be used in patients who are unable to receive other therapies.     

Human leukocyte antigen class II genes and Helicobacter pylori infection: does genotype overwhelm environmental exposure?

OBJECTIVE: We investigated associations between human leukocyte antigen class II genes, environmental exposures, and Helicobacter pylori infection. METHODS: Sixty-eight subjects with histologically confirmed H. pylori and intestinal metaplasia (cases) and 70 healthy subjects without H. pylori (controls) matched for age, sex, and year of birth were included in this study. All patients answered a detailed questionnaire designed to collect sociodemographic characteristics, smoking, alcohol drinking, and dietary habits. Human leukocyte antigen class II genes were typed with genomic DNA. The cytotoxins CagA and VacA were investigated with serology. Odds ratios and corresponding 95% confidence intervals were estimated from multivariate conditional logistic regression. Multiple correspondence analysis was used to represent the interrelationships of a multiple contingency table. RESULTS: Human leukocyte antigen DRB1, DQA1, and DQB1 genotypes were not significantly associated with H. pylori infection and intestinal metaplasia. No significant association with blood group or Lewis antigen system was found. However, multiple correspondence analysis clearly associated H. pylori with environmental exposure: the control group largely consumed olive oil, fresh fruits, and vegetables and histories of never or formerly smoking and the case group (those positive for H. pylori and metaplasia) largely consumed eggs, meat and butter and had histories of smoking cigarettes. CONCLUSIONS: These findings suggested that H. pylori infection is not influenced by a genetic compound and confirmed the relevance of environmental exposure.     

The level of physical activity in long-term survivors of testicular cancer

The aim of this study was to estimate the level of physical activity (LPA) in a large cohort of testicular cancer survivors (TCSs) and compare these results with observations from men in the same age range in the general population (GenPop). We also wanted to identify parameters that influenced physical activity. The study populations consisted of 1276 TCSs treated with surgery, radiotherapy or chemotherapy with or without surgery (mean observation time was 12 years), and 20391 male inhabitants from a Norwegian county (GenPop). All completed a question investigating two sub-levels of physical activity. The logistic regression analysis adjusting for different covariates, showed significantly more physically active men among the TCSs compared with the GenPop (43 versus 37%) (adjusted odds ratio (aOR)=1.32 (95% Confidence Interval (CI) 1.10-1.58)). The results indicate that the experience of testicular cancer increases rather than reduces the LPA in TCSs, independent of treatment given.