Early assessment of vestibular function after unilateral cochlear implant surgery

Introduction : Cochlear implantation (CI) has been reported to negatively effect on the vestibular function. The study of the vestibular function has variably been conducted by different types of diagnostic tools. The combined use of modern, rapidly performable diagnostic tools could reveal useful for standardizing the evaluation protocol. Methods: In a group of 28 subjects undergoing CI, the video Head Impulse Test (vHIT), the cervical Vestibular Evoked Myogenic Potentials (cVEMPS) and the short-form of Dizziness Handicap Inventory (DHI) questionnaire were investigated pre-operatively and post-operatively (implant on and off) in both the implanted and the contralateral, non-implanted ear. All surgeries were performed with a round window approach (RWA), except for three otosclerosis cases were the extended RWA (eRWA) was used. Results: The vHIT of the lateral semicircular canal showed a pre-operative vestibular involvement in nearly 50% of the cases, whilst the three canals were contemporarily affected in only 14% of them. In all the hypo-functional subjects, cVEMPs were absent. A low VOR gain in all the investigated SSCC was found in 4 subjects (14%). In those subjects, (21.7%) in whom cVEMPs were pre-operatively present and normal in the operated side, absence of response was post-operatives recorded. Discussion/Conclusion: The vestibular protocol applied for the study showed to be appropriate for distinguishing between the CI operated and the non-operated ear. In this regard, cVEMPs showed to be more sensitive than vHIT for revealing a vestibular sufferance after CI, although without statistical significance. Finally, the use of the RWA surgery was apparently not avoiding signs of vestibular impairment to occur

Predicting Early Mild Cognitive Impairment With Free Recall: The Primacy of Primacy.

OBJECTIVES: Serial position effects have been found to discriminate between normal and pathological aging, and to predict conversion from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD). Different scoring methods have been used to estimate the accuracy of these predictions. In the current study, we investigated delayed primacy as predictor of progression to early MCI over established diagnostic memory methods. We also compared three serial position methods (regional, standard and delayed scores) to determine which measure is the most sensitive in differentiating between individuals who develop early MCI from a baseline of cognitively intact older adults. METHOD: Data were analyzed with binary logistic regression and with receiver-operating characteristic (ROC). Baseline serial position scores were collected using the Rey's Auditory Verbal Learning Test and used to predict conversion to early MCI. The diagnosis of early MCI was obtained through statistical algorithm and consequent consensus conference. One hundred and ninety-one participants were included in the analyses. All participants were aged 60 or above and cognitively intact at baseline. RESULTS: The binary logistic regression showed that delayed primacy was the only predictor of conversion to early MCI, when compared to total and delayed recall. ROC curves showed that delayed primacy was still the most sensitive predictor of progression to early MCI when compared to other serial position measures. CONCLUSIONS: These findings are consistent with previous studies and support the hypothesis that delayed primacy may be a useful cognitive marker of early detection of neurodegeneration

Temporal contiguity and ageing: The role of memory organization in cognitive decline

The temporal contiguity effect is the tendency to form associations between items presented in nearby study positions. In the present study, we explored whether temporal contiguity predicted conversion to cognitively unimpaired‐declining (CUD) status from a baseline of unimpaired older adults. Data from 419 participants were drawn from the Wisconsin Registry of Alzheimer’s Prevention (WRAP) data set and analysed with binary logistic regressions. Temporal contiguity was calculated using the Rey Auditory Verbal Learning Test. Other predictors included age, years of education, sex, APOE‐ε4 status, and other measures of memory recall. Lower temporal contiguity predicted conversion to CUD after accounting for covariates. These findings support the hypothesis that temporal organization in memory is related to cognitive decline and suggest that temporal contiguity may be used for studies of early detection

Long-term ustekinumab therapy of psoriasis in patients with coexisting rheumatoid arthritis and Sjögren syndrome. Report of two cases and review of literature

Background: Inteleukin (IL)12 and IL23 are two main cytokines involved in the pathogenesis of immune-mediated disease. IL12 is produced by macrophages and B lymphocytes and mediates differentiation of Th1 lymphocytes, while IL23 is a pro-inflammatory cytokine essential for the differentiation of Th17 cells. Ustekinumab is a human monoclonal antibody directed against the p40 protein subunit shared by IL12 and IL23, therefore it blocks the signal transmission of both cytokines. Main observations: We present two cases and discuss the long-term efficacy of ustekinumab as a treatment of psoriasis in patients affected by autoimmune diseases, rheumatoid arthritis and Sjögren’s syndrome, who presented with severe psoriasis after anti-TNF treatment. Conclusions: To the best of our knowledge, these are the first cases reported in the literature describing the long-term good efficacy of ustekinumab not only on paradoxical forms of psoriasis induced by anti-TNF-α drugs, but also on the articular involvement in a patient affected by RA and in a patient affected by Sjögren syndrome

Evaluation of Clinical and Ultrasonographic Parameters in Psoriatic Arthritis Patients Treated with Adalimumab: A Retrospective Study

Objectives. The aim of this study was to evaluate clinical and US-PD parameters in PsA during adalimumab treatment. Methods. A retrospective study has been conducted in forty patients affected by moderate-to-severe peripheral PsA. Clinical, laboratory, and US-PD evaluations were performed at baseline, after 4, 12, and 24 weeks of treatment. They included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), Health Assessment Questionnaire (HAQ) modified for Spondyloarthritis, Psoriasis Area Severity Index (PASI) score, the 28-joint Disease Activity Score (DAS 28), and US-PD assessment. US-PD findings were scored according to a semiquantitative scale (ranging 0–3) for synovial proliferation (SP), joint effusion (SE), bone erosions (BE), and PD. Results. Data obtained for clinical, laboratory findings and US-PD evaluation showed statistical significant improvement in all the measures performed except for BE. A significant parallel decrease in SE, SP, and PD values were demonstrated. Conclusion. This study demonstrated that US-PD is a valid technique in monitoring the response to adalimumab in moderate-to-severe PsA

Novel transglutaminase 1 mutations in patients affected by lamellar ichthyosis

Lamellar Ichthyosis (LI) is a form of congenital ichthyosis that is caused by mutations in the TGM1 gene that encodes for the transglutaminase 1 (TG1) enzyme. Functional inactivation of TG1 could be due to mutations, deletion or insertions. In this study, we have screened 16 patients affected by LI and found six new mutations: two transition/transversion (R37G, V112A), two nonsense mutations and two putative splice site both leading to a premature stop codon. The mutations are localized in exons 2 (N-terminal domain), 5, 11 (central catalytic domain), and none is located in the two beta-barrel C-terminal domains. In conclusion, this study expands the current knowledge on TGM1 mutation spectrum, increasing the characterization of mutations would provide more accurate prenatal genetic counselling for parents at-risk individuals

Impairment of DHA synthesis alters the expression of neuronal plasticity markers and the brain inflammatory status in mice

Docosahexaenoic acid (DHA) is a ω-3 fatty acid typically obtained from the diet or endogenously synthesized through the action of elongases (ELOVLs) and desaturases. DHA is a key central nervous system constituent and the precursor of several molecules that regulate the resolution of inflammation. In the present study, we questioned whether the impaired synthesis of DHA affected neural plasticity and inflammatory status in the adult brain. To address this question, we investigated neural and inflammatory markers from mice deficient for ELOVL2 (Elovl2−/−), the key enzyme in DHA synthesis. From our findings, Elovl2−/− mice showed an altered expression of markers involved in synaptic plasticity, learning, and memory formation such as Egr-1, Arc1, and BDNF specifically in the cerebral cortex, impacting behavioral functions only marginally. In parallel, we also found that DHA-deficient mice were characterized by an increased expression of pro-inflammatory molecules, namely TNF, IL-1β, iNOS, caspase-1 as well as the activation and morphologic changes of microglia in the absence of any brain injury or disease. Reintroducing DHA in the diet of Elovl2−/− mice reversed such alterations in brain plasticity and inflammation. Hence, impairment of systemic DHA synthesis can modify the brain inflammatory and neural plasticity status, supporting the view that DHA is an essential fatty acid with an important role in keeping inflammation within its physiologic boundary and in shaping neuronal functions in the central nervous system

Integrated Clinical-Molecular Classification of Colorectal Liver Metastases: A Biomarker Analysis of the Phase 3 New EPOC Randomized Clinical Trial

IMPORTANCE: Personalized treatment approaches for patients with oligometastatic colorectal liver metastases are critically needed. We previously defined 3 biologically distinct molecular subtypes of colorectal liver metastases: (1) canonical, (2) immune, and (3) stromal. OBJECTIVE: To independently validate these molecular subtypes in the phase 3 New EPOC randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: This retrospective secondary analysis of the phase 3 New EPOC randomized clinical trial included a bi-institutional discovery cohort and multi-institutional validation cohort. The discovery cohort comprised patients who underwent hepatic resection for limited colorectal liver metastases (98% received perioperative chemotherapy) from May 31, 1994, to August 14, 2012. The validation cohort comprised patients who underwent hepatic resection for liver metastases with perioperative chemotherapy (fluorouracil, oxaliplatin, and irinotecan based) with or without cetuximab from February 26, 2007, to November 1, 2012. Data were analyzed from January 18 to December 10, 2021. INTERVENTIONS: Resected metastases underwent RNA sequencing and microRNA (miRNA) profiling in the discovery cohort and messenger RNA and miRNA profiling with microarray in the validation cohort. MAIN OUTCOMES AND MEASURES: A 31-feature (24 messenger RNAs and 7 miRNAs) neural network classifier was trained to predict molecular subtypes in the discovery cohort and applied to the validation cohort. Integrated clinical-molecular risk groups were designated based on molecular subtypes and the clinical risk score. The unique biological phenotype of each molecular subtype was validated using gene set enrichment analyses and immune deconvolution. The primary clinical end points were progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 240 patients were included (mean [range] age, 63.0 [56.3-68.0] years; 151 [63%] male), with 93 in the discovery cohort and 147 in the validation cohort. In the validation cohort, 73 (50%), 28 (19%), and 46 (31%) patients were classified as having canonical, immune, and stromal metastases, respectively. The biological phenotype of each subtype was concordant with the discovery cohort. The immune subtype (best prognosis) demonstrated 5-year PFS of 43% (95% CI, 25%-60%; hazard ratio [HR], 0.37; 95% CI, 0.20-0.68) and OS of 63% (95% CI, 40%-79%; HR, 0.38; 95% CI, 0.17-0.86), which was statistically significantly higher than the canonical subtype (worst prognosis) at 14% (95% CI, 7%-23%) and 43% (95% CI, 32%-55%), respectively. Adding molecular subtypes to the clinical risk score improved prediction (the Gönen and Heller K for discrimination) from 0.55 (95% CI, 0.49-0.61) to 0.62 (95% CI, 0.57-0.67) for PFS and 0.59 (95% CI, 0.52-0.66) to 0.63 (95% CI, 0.56-0.70) for OS. The low-risk integrated group demonstrated 5-year PFS of 44% (95% CI, 20%-66%; HR, 0.38; 95% CI, 0.19-0.76) and OS of 78% (95% CI, 44%-93%; HR, 0.26; 95% CI, 0.08-0.84), superior to the high-risk group at 16% (95% CI, 10%-24%) and 43% (95% CI, 32%-52%), respectively. CONCLUSIONS AND RELEVANCE: In this prognostic study, biologically derived colorectal liver metastasis molecular subtypes and integrated clinical-molecular risk groups were highly prognostic. This novel molecular classification warrants further study as a possible predictive biomarker for personalized systemic treatment for colorectal liver metastases. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN22944367

Tildrakizumab in moderate-to-severe plaque psoriasis: A multicenter, retrospective, real-life study

New biologic agents targeting interleukin (IL)23/T-helper17 axis, such as tildrakizumab, have been developed for the treatment of plaque psoriasis. To analyze the efficacy and safety of tildrakizumab in a real life setting of patients affected by moderate-to-severe psoriasis over a 28-week treatment period. A multicentric retrospective study was conducted in patients who initiated tildrakizumab between February 2020 and March 2021. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16 and 28 weeks. The percentage change in PASI value from baseline to the considered time-points, proportion of patients with absolute PASI <3 at week 28 and the percentages of achieving a PASI75 or PASI90 response were assessed. Data about potential safety issues and adverse events (AEs) were collected. Statistical analysis were performed for establish clinical efficacy and for variables predicting clinical response. Fifty nine patients with psoriasis were included. Overall mean PASI percentage reduction was of 88% from baseline to week 28 and 47 out of 59 patients (79.7%) at week 28 had an absolute PASI <3. PASI75 and PASI90 responses at week 28 were achieved by 48 (81.40%) patients and 38 (64.4.0%) patients, respectively. No substantial associations between gender, body mass index - BMI, PASI at baseline and prior exposition to biological therapies and the efficacy endpoints were retrieved. No serious safety issues or discontinuations related to adverse events were reported. In our real-life study, tildrakizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors