SARS-CoV-2 Seroprevalence among Healthcare Workers after the First and Second Pandemic Waves

Background: The Grand Hôpital de Charleroi is a large non-academic Belgian hospital that treated a large number of COVID-19 inpatients. In the context of this pandemic, all professions-combined healthcare workers (HCWs), and not only direct caregivers, are a frontline workforce in contact with suspected and confirmed COVID-19 cases and seem to be a high-risk group for exposure. The aim of our study was to estimate the prevalence of anti-SARS-CoV-2 antibodies in HCWs in our hospital after the first and second pandemic waves and to characterize the distribution of this seroprevalence in relation to various criteria. Methods: At the end of the two recruitment periods, a total of 4008 serological tests were performed in this single-center cross-sectional study. After completing a questionnaire including demographic and personal data, possible previous COVID-19 diagnostic test results and/or the presence of symptoms potentially related to COVID-19, the study participants underwent blood sampling and serological testing using DiaSorin’s LIAISON® SARS-CoV-2 S1/S2 IgG test for the first phase and LIAISON® SARS-CoV-2 TrimericS IgG test for the second phase of this study. Results: In total, 302 study participants (10.72%) in the first round of the study and 404 (33.92%) in the second round were positive for SARS-CoV-2-IgG antibodies. The prevalence of seropositivity observed after the second wave was 3.16 times higher than after the first wave. We confirmed that direct, prolonged, and repeated contact with patients or their environment was a predominant seroconversion factor, but more unexpectedly, that this was the case for all HCWs and not only caregivers. Finally, the notion of high-risk contact seemed more readily identifiable in one’s workplace than in one’s private life. Conclusions: Our study confirmed that HCWs are at a significantly higher risk of contracting COVID-19 than the general population, and suggests that repeated contacts with at-risk patients, regardless of the HCWs’ professions, represents the most important risk factor for seroconversion (Clinicaltrials.gov number, NCT04723290).SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mutations in the glucokinase regulatory protein gene in 2p23 in obese French caucasians.

AIMS/HYPOTHESIS: Glucokinase regulatory protein (GKRP) controls the activity of glucokinase in liver but possibly also in some areas of the central nervous system, suggesting that it could play a role in body mass control. Its gene is located in a region (2p21-23) linked to serum leptin levels. Our goal was to investigate whether mutations in the GKRP gene were associated with obesity. METHODS: Mutations were sought in the GKRP gene of 57 patients from the families of the French genome-wide scan for obesity that contributed most to the positive LOD score with 2p21-23. The identified mutations were further sought in 720 unrelated obese individuals and 384 individuals of normal weight and their effect on the properties of recombinant GKRP were investigated. RESULTS: The most frequent mutation (Pro446Leu) had a similar allele frequency in the obese (0.63) and normal weight (0.64) subjects and did not affect the properties of GKRP. Similarly, no effect on the properties of GKRP was observed with Arg590Tyr, found in 10 out of 720 obese subjects and in 2 out of 384 control subjects (p=0.18). Mutation Arg227Stop was found in one obese family and in 1 out of 384 control subjects and led to an insoluble protein. Mutation Arg518Gln, replacing a conserved residue, led to a marked decrease in the affinity of GKRP for both fructose 6-phosphate and fructose 1-phosphate and to a destabilization of GKRP. However, this mutation did not co-segregate with obesity in the single family in which it was found. CONCLUSIONS/INTERPRETATION: Mutations that affect the properties of GKRP are found in the French population, but they do not seem to account for the linkage between the 2p23 locus and quantitative markers of obesity

The place of S-ketamine in fibromyalgia treatment (ESKEFIB): study protocol for a prospective, single-center, double-blind, randomized, parallel-group, dose-escalation controlled trial

Background: Fibromyalgia is a chronic multidimensional pain disease with no curative treatment currently available. Its management relies on a multimodal approach involving pharmacologic and non-pharmacologic elements. Because a suggested factor in its etiology is a central sensitization phenomenon involving the N-methyl-D-aspartate receptor (NMDAR), NMDAR antagonists have been proposed as a treatment target. Ketamine and its levogyre form, S-ketamine, have been used to treat chronic pain for many years without consensus about their therapeutic efficiency. We aim to assess the efficacy of S-ketamine as a co-treatment for fibromyalgia. Methods: This prospective, randomized, single-center, double-blind, parallel-group, dose-escalation trial will compare a co-treatment with S-ketamine (intervention) to a control treatment without S-ketamine (control). It will consist of two successive cohorts with 2:1 randomization ratio (S-ketamine at two different doses: control) with 105 participants in each cohort. The protocol follow-up time will be 12 weeks, including 3 visits for the treatment (week 0, week 2, and week 4) and 3 visits for follow-up (week 6, week 9, and week 12). Our primary outcome, pain relief and/or better patient function, will be assessed with the Brief Pain Inventory questionnaire. The statistical analysis will be performed on an intention-to-treat basis. If the primary outcome is reached at the end of follow-up in the first cohort with low-dose S-ketamine (0.2 mg/kg), the trial will end. If not, the trial will continue with the second cohort and high-dose S-ketamine (0.4 mg/kg). Discussion: The challenge of our trial is the inclusion of a large number of participants in comparison to other trials involving ketamine or S-ketamine infusions for chronic pain management. The originality of our protocol is to include functionality in addition to pain relief as a primary outcome because these two endpoints are not linked in a linear way. For some patients, functional status is more important than pain relief. Trial registration: EudraCT reference: 2020-000473-25, ClinicalTrials.gov: NCT04436250, first posted June 18, 2020; last updated July 21, 2020. Protocol version 2.2 issued on September 30, 2020, after a revision by the ethics committee. https://clinicaltrials.gov/ct2/show/NCT04436250SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Facial, vocal and musical emotion recognition is altered in paranoid schizophrenic patients

Disturbed processing of emotional faces and voices is typically observed in schizophrenia. This deficit leads to impaired social cognition and interactions. In this study, we investigated whether impaired processing of emotions also affects musical stimuli, which are widely present in daily life and known for their emotional impact. Thirty schizophrenic patients and 30 matched healthy controls evaluated the emotional content of musical, vocal and facial stimuli. Schizophrenic patients are less accurate than healthy controls in recognizing emotion in music, voices and faces. Our results confirm impaired recognition of emotion in voice and face stimuli in schizophrenic patients and extend this observation to the recognition of emotion in musical stimuli. © 2015 Elsevier Ireland Ltd

Tumour response and safety of cetuximab in a window pre-operative study in patients with squamous cell carcinoma of the head and neck.

Short-course pre-operative administration of cetuximab is safe and shows a high rate of (18)FDG-PET response. (18)FDG-PET response was correlated with residual tumour cellularity suggesting that (18)FDG-PET deserves further investigation as a potential early marker of cetuximab activity in SCCHN

Association of primary melanoma ulceration and clinical benefit of adjuvant vaccination with tumor-specific antigenic peptides

Background: Therapeutic vaccination of metastatic melanoma patients with detectable disease is followed by tumor regression in ±10% of the patients, mostly with locoregional disease. Considering the absence of an effective treatment to prevent relapses of cutaneous melanoma, we have applied a multipeptide vaccine in the adjuvant setting

Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-Based Therapy.

LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%). BACKGROUND: Cabazitaxel is a second-generation taxane that improves the survival of patients with metastatic castrate-resistant prostate cancer following docetaxel therapy. Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. In this randomized phase II trial, we investigated cabazitaxel in patients with recurrent SCCHN. METHODS: Patients with incurable SCCHN with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2 for subsequent cycles in the absence of nonhematological adverse events [AEs] greater than grade 2 and hematological AEs greater than grade 3) or methotrexate (40 mg/m2/week). The patients were stratified according to their performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary endpoint was the progression-free survival rate (PFSR) at 18 weeks. RESULTS: Of the 101 patients, 53 and 48, with a median age of 58.0 years (range, 41-80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFSR at 18 weeks was 13.2% (95% confidence interval [CI], 5%-25%) for cabazitaxel and 8.3% (95% CI, 2%-20%) for methotrexate. The median progression-free survival was 1.9 months in both arms. The median overall survival was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced serious adverse events with cabazitaxel than with methotrexate (54% vs. 36%). The most common drug-related grade 3-4 AE in the cabazitaxel arm was febrile neutropenia (17.3%). CONCLUSION: This study did not meet its primary endpoint. Cabazitaxel has low activity in recurrent SCCHN