General vaccination willingness and current vaccination status in relation to clinical and psychological variables in patients with multiple sclerosis

BackgroundInfections can have a significant impact on morbidity and mortality in multiple sclerosis (MS) patients. Therefore, vaccinations are of immense importance. If vaccination willingness is to be increased, possible influencing factors should be identified. The aim of the present study was to investigate the status of active immunisation in MS patients in association with sociodemographic, clinical-neurological, psychopathological and personality variables using the NEO-Five Factor Inventory, the Temperament and Character Inventory-Revised and the Hospital Anxiety and Depression Scale.MethodFour hundred and four MS patients from two German neurological hospitals were examined for their vaccination attitudes, in detail, the general willingness to vaccinate and the current vaccination status of mumps, measles and rubella (MMR) as well as tetanus and influenza. We also looked at the current level of disability in relation to the current vaccination status, as well as possible associated personality and psychopathological variables.ResultsPatients with a complete MMR vaccination status were significantly younger and those with a complete influenza vaccination status were significantly older than those with related incomplete vaccination status. Tetanus vaccination status completeness did not differ depending on age and did not show substantial association with personality scores. However, influenza vaccination completeness was associated with differences in personality and psychopathological variables; extraversion, openness, novelty seeking, harm avoidance and anxiety. A reported general vaccination willingness was significantly correlated with the current completeness of tetanus and influenza vaccinations. Novelty seeking, persistence, extraversion, agreeableness, conscientiousness and neuroticism were found associated with an increased vaccination willingness. Anxiety and depression were not related to general vaccination willingness.ConclusionsNo specific personality trait could be defined on its own in relation to general vaccination willingness or complete vaccination status. Younger patients should be made more aware of influenza vaccination. Reasons for rather low vaccination rates need to be further investigated.     

Evaluation of unsupervised 30-second chair stand test performance assessed by wearable sensors to predict fall status in multiple sclerosis

BackgroundOne in two people with multiple sclerosis (PwMS) will fall in a three-month period. Predicting which patients will fall remains a challenge for clinicians. Standardized functional assessments provide insight into balance deficits and fall risk but their use has been limited to supervised visits.Research questionThe study aim was to characterize unsupervised 30-second chair stand test (30CST) performance using accelerometer-derived metrics and assess its ability to classify fall status in PwMS compared to supervised 30CST.MethodsThirty-seven PwMS (21 fallers) performed instrumented supervised and unsupervised 30CSTs with a single wearable sensor on the thigh. In unsupervised conditions, participants performed bi-hourly 30CSTs and rated their balance confidence and fatigue over 48-hours. ROC analysis was used to classify fall status for 30CST performance.ResultsNon-fallers (p = 0.02) but not fallers (p = 0.23) differed in their average unsupervised 30CST performance (repetitions) compared to their supervised performance. The unsupervised maximum number of 30CST repetitions performed optimized ROC classification AUC (0.79), accuracy (78.4%) and specificity (90.0%) for fall status with an optimal cutoff of 17 repetitions.SignificanceBrief durations of instrumented unsupervised monitoring as an adjunct to routine clinical assessments could improve the ability for predicting fall risk and fluctuations in functional mobility in PwMS.     

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

Noise characterization of “effective quiet” areas on a U.S. Navy aircraft carrier

The purpose of this investigation was to characterize noise levels in spaces designated as “effective quiet” areas on a U.S. Navy aircraft carrier. Noise dosimetry samples were collected in 15 designated spaces, representing 15 noise measurements, while at-sea during airwing carrier qualifications. Equivalent sound level (L_eq) measurements were collected during flight operations (L_{eq (flt ops)}), non-flight operations (L_{eq (non-flt ops)}), and over 24-hr periods (L_{eq (24-hr)}). These data were compared to the 70 dBA American Conference of Governmental Industrial Hygienists (ACGIH^®) Threshold Limit Value (TLV^®) for “effective quiet” areas intended for temporary threshold shift recovery when personnel live and work in a potentially noise hazardous environment for periods greater than 24?hr. The monitored areas were selected based on personnel occupancy/use during off-duty time periods. Areas were classified by either (1) leisure areas that included mess (eating areas), gyms, lounges, an internet cafe, and the fantail social area or (2) berthing (sleeping) areas. The L_eq measurements in decibels “A” weighted (dBA) were compared to determine significant differences between L_{eq (flt ops)}, L_{eq (non-flt ops)}, and L_{eq (24-hr)} and were compared between leisure area and berthing area. Measured noise levels according to time period ranged as follows: (1) L_{eq (24-hr)}: 70.8–105.4 dBA; (2) L_{eq (flt ops)}: 70–101.2 dBA; and (3) L_{eq (non-flt ops)}: 39.4–104.6 dBA. All area measurements over the 24-hr period and during flight operations and 46.7% of the areas during the non-flight operation time period exceeded the “effective quiet” 70 dBA ACGIH TLV. Mean L_eqs were 15 dBA higher during flight operations compared to non-flight operations in “effective quiet” areas (p?=?0.001). The L_eqs in leisure areas were significantly higher than berthing areas by approximately 21 dBA during non-flight operation periods (p?=?0.001). Results suggest noise levels in “effective quiet” areas frequented by aircraft carrier personnel during off-duty hours when at-sea may inhibit auditory recovery from occupational noise exposures that occur on-duty.     

肿瘤坏死因子-α-308基因对导管相关性脓毒症患者病情的影响

目的探究肿瘤坏死因子-α(Tumornecrosis factor-α,TNF-α)-308基因对导管相关性脓毒症(Catheter related sepsis,CRS)患者病情的影响,旨在为临床治疗CRS提供科学依据。方法选取2017年7月-2018年10月于浙江大学医学院附属杭州市第一人民医院接受治疗的86例CRS患者为研究对象,按照是否并发多器官功能障碍综合征将患者分为试验组和对照组,对照组共48例,未并发多器官功能障碍综合征,试验组共38例,并发多器官功能障碍综合征,分析两组患者TNF-α-308基因多态性差异,使用多因素Logistic回归分析CRS患者并发多器官功能障碍综合征的危险因素。结果试验组GA基因型频率34.21%、AA基因型频率50.00%、高G等位基因频率18.42%均高于对照组,GG基因型频率52.63%、A等位基因频率28.95%均低于对照组,差异均具有统计学意义(P<0.05);多因素Logistic回归分析结果显示,低GG基因型频率、低G等位基因频率、高GA基因型频率、高AA基因型频率、高A等位基因频率是CRS患者并发多器官功能障碍综合征的危险因素(P<0.05)。结论TNF-α-308基因与CRS患者病情密切相关,GG基因型频率和G等位基因频率降低,GA基因型频率、AA基因型频率、A等位基因频率升高会加重患者的病情,增加多器官功能障碍综合征的发生风险,临床上应该加以重视。     

Lack of ceramide synthase 2 suppresses the development of experimental autoimmune encephalomyelitis by impairing the migratory capacity of neutrophils

Ceramide synthases (CerS) synthesise ceramides of defined acyl chain lengths, which are thought to mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed a significant elevation of CerS2 and its products, C24-ceramides, in CD11b⁺ cells (monocytes and neutrophils) isolated from blood. This result correlates with the clinical finding that CerS2 mRNA expression and C24-ceramide levels were significantly increased by 2.2- and 1.5-fold, respectively, in white blood cells of MS patients. The increased CerS2 mRNA/C24-ceramide expression in neutrophils/monocytes seems to mediate pro-inflammatory effects, since a specific genetic deletion of CerS2 in blood cells or a total genetic deletion of CerS2 significantly delayed the onset of clinical symptoms, due to a reduced infiltration of immune cells, in particular neutrophils, into the central nervous system. CXCR2 chemokine receptors, expressed on neutrophils, promote the migration of neutrophils into the central nervous system, which is a prerequisite for the recruitment of further immune cells and the inflammatory process that leads to the development of MS. Interestingly, neutrophils isolated from CerS2 null EAE mice, as opposed to WT EAE mice, were characterised by significantly lower CXCR2 receptor mRNA expression resulting in their reduced migratory capacity towards CXCL2. Most importantly, G-CSF-induced CXCR2 expression was significantly reduced in CerS2 null neutrophils and their migratory capacity was significantly impaired. In conclusion, our data strongly indicate that G-CSF-induced CXCR2 expression is regulated in a CerS2-dependent manner and that CerS2 thereby promotes the migration of neutrophils, thus, contributing to inflammation and the development of EAE and MS.