SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic.

We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge.

Cholesterol levels in plasma and cerebrospinal fluid in patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis.

Cholesterol is essential for myelin formation, but may also modulate mechanisms involved in adaptive immune responses. It is unclear whether lack of remyelination in multiple sclerosis (MS) results from an insufficient capacity of oligodendrocyte precursor cells to differentiate or from cholesterol insufficiency. Several studies have assessed the potential association of lipid profile and its metabolism with demyelination, disability, and disease progression. The aim of the present study was to measure cholesterol levels in plasma and cerebrospinal fluid (CSF) of patients with relapsing remitting MS (RRMS) or with clinically isolated syndrome (CIS), and to investigate whether there is an association between cholesterol levels and disease characteristics. Sixty-two patients with CIS and 46 patients with RRMS were included in the study. All patients had low EDSS and were medication-free at assessment. Forty-eight subjects within the same age range served as controls. Cholesterol concentrations were measured in plasma and in CSF by the same enzymatic - colorimetric method, and were related to clinical status, disease activity in magnetic resonance imaging (MRI) and presence of oligoclonal bands in CSF (OBs). Significantly lower levels of plasma and CSF cholesterol were found in patients compared to controls. Patients with OBs showed significantly lower levels of CSF cholesterol but not plasma cholesterol compared to OBs-negative patients. A positive correlation of plasma cholesterol with age and of CSF cholesterol with EDSS was found. Our results suggest that low CSF cholesterol in MS patients with positive OBs might reflect extensive demyelination and a more aggressive disease course associated with an increased humoral immune response against membrane components.

CADASIL in Greece: Mutational spectrum and clinical characteristics based on a systematic review and pooled analysis of published cases.

BACKGROUND: Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece. METHODS: After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece. RESULTS: We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations). CONCLUSIONS: The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered.

Dopamine transporter SPECT imaging in corticobasal syndrome: A peak into the underlying pathology?

BACKGROUND: Multiple pathologies may underlie corticobasal syndrome (CBS), including Alzheimer's disease (AD). Dopamine transporter density imaging with Ioflupane 123 I SPECT (DaTscan) may be normal in CBS. No studies to date have examined the relationship between DaTscan status and underlying pathology in CBS. OBJECTIVES: The main objective of the study was to test whether a normal DaTscan in CBS patients is indicative of an underlying AD pathology, as determined by cerebrospinal fluid (CSF) biomarkers. METHODS: Eighteen CBS patients were included. They were divided into patients with an AD and a non-AD disease pathology, based on their cerebrospinal fluid biochemical profile. A typical AD CSF profile was defined as an increase in total and phosphorylated at threonine 181 tau protein in addition to a decrease in amyloid-beta with 42 amino acids. DaTscan data were compared in these two groups. RESULTS: Eight of the 18 CBS patients (44%) had a normal DaTscan. Seven of the 18 CBS patients (39%) had an AD cerebrospinal fluid biochemical profile. Two of seven CBS patients with AD biomarker profile had abnormal DaTscans. Three of 11 CBS patients with a non-AD biomarker profile had normal DaTscans. A normal DaTscan was indicative of AD pathology with suboptimal (~70%) sensitivity and specificity. Semi-quantitative DaTscan analysis did not differentiate between AD from non-AD CSF biomarker profile in CBS. CONCLUSION: A normal DaTscan is indicative of AD in CBS, but the sensitivity and specificity of DaTscan as an in vivo marker of AD pathology is suboptimal.

Myasthenia gravis, atypical polyneuropathy and multiple autoimmune phenomena in the same patient, with HLA-immunogenetic profile expectable for Greek chronic inflammatory demyelinating polyneuropathy: a case report.

PURPOSE: The comorbidity of myasthenia gravis (MG), with other autoimmune disorders like systemic lupus erythematosus (SLE), is relatively frequent but the co-occurrence with chronic inflammatory demyelinating polyneuropathy (CIDP) along with various autoimmune manifestations in the absence of thymoma is of extreme rarity. Our aim is to report a case of a woman who presented the concomitant appearance of MG, axonal sensory-motor polyneuropathy and hepatitis that may indicate an underlying pathogenetic link among the different autoimmune disorders. MATERIALS AND METHODS/RESULTS: We present a case of a 54-year-old woman, with a generalized MG and a chronic sensory-motor polyneuropathy, hypothyroidism, anaemia, hepatitis, livedo reticularis and facial flush, of assumed autoimmune background, like SLE, although with persistent negative ANA antibodies, from the beginning and through the whole following years. The Human Leukocyte Antigen (HLA)-DRB1 genotyping showed a profile of alleles (DRB1*11:01/11:04) compatible with CIDP of mainly female gender in Greece and frequencies close to those of Sjogren's syndrome and scleroderma's in the Greek population. The diagnostic problems, the atypical clinical, electrophysiological and immunological features are discussed, along with the rarity of the case, with this exceptional combination of autoimmune manifestations, which could be truly associated under the clinical umbrella of a systemic disease, like SLE. However, our patient did not ever fulfil the SLE criteria. CONCLUSIONS: To raise awareness among clinicians about the exceptional combination of autoimmune manifestations driven by a specific HLA background.

The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin.

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

Salivary inflammatory markers in tension type headache and migraine: the SalHead cohort study.

OBJECTIVE: To investigate the possible association between salivary CRP, IL-1ß, and IL-6 levels, depression/anxiety and migraine, and tension type headache (TTH) in saliva of these patients. METHOD: A longitudinal prospective study was conducted on 30 migraineurs, 30 TTH patients, and 30 age-matched healthy controls. Anxiety and depression were measured by using the Hamilton Anxiety Rating Scale (HAM-A), and the Beck Depression Inventory (BDI). Salivary IL-6, IL-1ß, and CRP were collected in distinct time points as A: headache-free period, B: during headache, C: 1 day after headache attack, and measured by using ELISA kits. RESULTS: No significant differences were found in time variation of CRP, IL-1ß, and IL-6 levels between migraine and TTH (p > 0.05). IL1-ß had the highest discriminative value (area under the curve = 0.924, p value < 0.001), and then CRP (area under the curve = 0.763, p value < 0.001) and IL-6 (area under the curve = 0.537, p value = 0.58). CRP and IL-6 were negatively correlated with HAM-A and BDI scores. CONCLUSION: IL1-ß had the highest discriminative value between headache patients and controls compared with CRP and IL-6. CRP and IL-6 were correlated with lower symptom scores of anxiety and depression prior or immediately after the headache period in patients groups.

The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID.

Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.

Investigating ABO Blood Groups and Secretor Status in Relation to SARS-CoV-2 Infection and COVID-19 Severity.

The ABO blood groups, Lewis antigens, and secretor systems are important components of transfusion medicine. These interconnected systems have been also shown to be associated with differing susceptibility to bacterial and viral infections, likely as the result of selection over the course of evolution and the constant tug of war between humans and infectious microbes. This comprehensive narrative review aimed to explore the literature and to present the current state of knowledge on reported associations of the ABO, Lewis, and secretor blood groups with SARS-CoV-2 infection and COVID-19 severity. Our main finding was that the A blood group may be associated with increased susceptibility to SARS-CoV-2 infection, and possibly also with increased disease severity and overall mortality. The proposed pathophysiological pathways explaining this potential association include antibody-mediated mechanisms and increased thrombotic risk amongst blood group A individuals, in addition to altered inflammatory cytokine expression profiles. Preliminary evidence does not support the association between ABO blood groups and COVID-19 vaccine response, or the risk of developing long COVID. Even though the emergency state of the pandemic is over, further research is needed especially in this area since tens of millions of people worldwide suffer from lingering COVID-19 symptoms.

Vaccines for the Elderly and Vaccination Programs in Europe and the United States.

The share of the elderly population is growing worldwide as life expectancy increases. Immunosenescence and comorbidities increase infectious diseases' morbidity and mortality in older adults. Here, we aimed to summarize the latest findings on vaccines for the elderly against herpes zoster, influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease and to examine vaccine recommendation differences for this age group in Europe and the United States. PubMed was searched using the keywords "elders" and "vaccine" alongside the disease/pathogen in question and paraphrased or synonymous terms. Vaccine recommendations were also sought in the European and US Centers for Disease Control and Prevention databases. Improved vaccines, tailored for the elderly, mainly by using novel adjuvants or by increasing antigen concentration, are now available. Significant differences exist between immunization policies, especially between European countries, in terms of the recipient's age, number of doses, vaccination schedule, and implementation (mandatory or recommended). Understanding the factors that influence the immune response to vaccination in the elderly may help to design vaccines that offer long-term protection for this vulnerable age group. A consensus-based strategy in Europe could help to fill the gaps in immunization policy in the elderly, particularly regarding vaccination against RSV and pneumococcus.

Prevalence of ocular toxoplasmosis among people living with HIV: a systematic review and meta-analysis.

Aim: To determine the prevalence of ocular toxoplasmosis among people living with HIV through a systematic review and meta-analysis. Materials & methods: A literature search was conducted, estimating pooled prevalence and performing quality assessment, outlier, influential and meta-regression analyses. Results: Twenty-nine studies were included in the analysis, revealing that the rate of ocular toxoplasmosis among people living with HIV was 0.37% (95% CI: 0.2-0.6). Substantial heterogeneity was observed among the studies. Despite analyzing continuous variables, including year of publication, proportion of males, mean age and proportion of patients receiving antiretroviral therapy, no statistically significant associations were found. Conclusion: This study provides an overview of the prevalence of ocular toxoplasmosis in people living with HIV, emphasizing the need for further research to uncover factors contributing to its development.

This study looked at how common ocular toxoplasmosis, a type of parasitic infection, is among people living with HIV. We did this by reviewing other studies, combining their results and evaluating the quality of each study. We also looked for any unusual findings and other factors that might affect the prevalence of ocular toxoplasmosis. After analyzing 29 studies, we found that approximately 0.37% of people living with HIV had ocular toxoplasmosis, ranging from 0.2% to 0.6%. There was a significant variation in the results among the studies. Our study provides an overview of the prevalence of ocular toxoplasmosis in people living with HIV, highlighting the need for further research to identify the factors contributing to its development.

Adverse events of acute nephrotoxicity reported to EudraVigilance and VAERS after COVID-19 vaccination.

OBJECTIVES: The present study aimed to estimate the reporting rates (RRs) of acute kidney injury (AKI) and renal failure (RF) after COVID-19 vaccination in the European Economic Area (EEA) and the United States. METHODS: We retrieved and analyzed pharmacovigilance data on suspected AKI and RF cases and fatalities post COVID-19 vaccination with licensed vaccines reported to EudraVigilance and VAERS between week 52/2020 and week 52/2022 or week 1/2023, respectively. Reporting rates with 95% confidence intervals were estimated per million administered vaccine doses. RESULTS: In total, 4,244 AKI and 1,557 RF suspected cases were notified to EudraVigilance (1,692 AKI/971 RF) and VAERS (2,552 AKI/586 RF) during the study period following the administration of >1.6 billion COVID-19 vaccine doses (EEA: 970,934,453/US: 666,511,603). The overall RRs were 3.03 (95 % CI: 2.94-3.12) for AKI and 1.11 (95 % CI: 1.06-1.17) for RF per million administered vaccine doses. Indices for statistically significant increased risks were found in subjects, especially males, ≥65 years compared to 18-64 years old (AKI: OR = 7.23, 95 % CI: 6.63-7.88, p = 0.000, and RF: OR = 4.74, 95 % CI: 3.99-5.63, p < 0.001). AKI reporting rates were higher in the US, while RF reporting rates were higher in Europe. Both potential side effects were elevated following vectored rather than mRNA vaccines, with the highest reporting rates post AD26.COV2.S vaccination in the US (AKI: RR = 12.24, 95 % CI: 10.66-13.81; RF: RR = 3.17, 95 % CI: 2.36-3.97). There were 1,312 deaths possibly associated with AKI (RR = 0.94, 95 % CI: 0.89-0.99) and 460 deaths possibly associated with RF (RR = 0.33, 95 % CI: 0.30-0.36) per million vaccine doses. Fatalities were lower in Europe than in the US (AKI: OR = 0.25, 95 % CI: 0.22-0.28, p < 0.001; RF: OR = 0.82, 95 % CI: 0.69-0.99, p = 0.036). CONCLUSIONS: AKI and RF may be observed rarely following vaccination against COVID-19. Further studies are warranted to confirm these findings and uncover the underlying pathophysiological mechanism.

Epidemiological Transition and Strategies for the Control of Hepatitis A in Serbia.

BACKGROUND: Improvements in socioeconomic and hygienic conditions during the past decades led to declining hepatitis A (HA) seroprevalence in many countries. Aiming at informing HA vaccination policy, we assessed current epidemiological trends in Serbia by analyzing surveillance data for 2002-2021. METHODS: Data on cases and outbreaks were obtained from the Serbian national surveillance database and descriptively analyzed. HA incidence was calculated in relation to time, patients' residence, and demographics. RESULTS: Overall, 13,679 HA cases and 419 outbreaks were recorded with the highest incidence in the southeast. Downward HA trends were observed, while infant mortality was halved, and gross domestic product based on purchasing power parity (GDP PP) per capita, tripled. The average incidence dropped from 14.8 (95% CI 14.4-15.2)/100,000) in 2002-2006 to 1 (95% CI 0.9-1.1)/100,000)/100,000 in 2017-2021, while the number of outbreaks decreased (from 174 to 14). Sporadic cases and family clusters living in poor sanitary conditions occurred in recent years. The contact route of transmission was dominant (410/419, 97.9%). The highest average age-specific HA incidence shifted from 5-9 years in 2002-2006 to 10-19 years in 2017-2021.Serbia is transitioning towards very low HA endemicity. Enhanced surveillance and vaccination of high-risk groups are recommended as future public health priorities.

CSF Aß42 and Aß42/Aß40 Ratio in Alzheimer's Disease and Frontotemporal Dementias.

BACKGROUND: Alzheimer's disease dementia (ADD) may manifest with atypical phenotypes, resembling behavioral variant frontotemporal dementia (bvFTD) and corticobasal syndrome (CBS), phenotypes which typically have an underlying frontotemporal lobar degeneration with tau proteinopathy (FTLD-tau), such as Pick's disease, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or FTLD with TDP-43 proteinopathy (FTLD-TDP). CSF biomarkers total and phosphorylated tau (τT and τP-181), and amyloid beta with 42 and 40 amino acids (Aß42 and Aß40) are biomarkers of AD pathology. The primary aim of this study was to compare the diagnostic accuracy of Aß42 to Aß42/Aß40 ratio in: (a) differentiating ADD vs. frontotemporal dementias; (b) patients with AD pathology vs. non-AD pathologies; (c) compare biomarker ratios and composite markers to single CSF biomarkers in the differentiation of AD from FTD; Methods: In total, 263 subjects were included (ADD: n = 98; bvFTD: n = 49; PSP: n = 50; CBD: n = 45; controls: n = 21). CSF biomarkers were measured by commercially available ELISAs (EUROIMMUN). Multiple biomarker ratios (Aß42/Aß40; τT/τP-181; τT/Aß42; τP-181/Aß42) and composite markers (t-tau: τT/(Aß42/Aß40); p-tau: τP-181/(Aß42/Aß40) were calculated. ROC curve analysis was performed to compare AUCs of Aß42 and Aß42/Aß40 ratio and relevant composite markers between ADD and FTD, as defined clinically. BIOMARKAPD/ABSI criteria (abnormal τT, τP-181 Aß42, and Aß42/Aß40 ratio) were used to re-classify all patients into AD pathology vs. non-AD pathologies, and ROC curve analysis was repeated to compare Aß42 and Aß42/Aß40; Results: Aß42 did not differ from Aß42/Aß40 ratio in the differentiation of ADD from FTD (AUCs 0.752 and 0.788 respectively; p = 0.212). The τT/Aß42 ratio provided maximal discrimination between ADD and FTD (AUC:0.893; sensitivity 88.8%, specificity 80%). BIOMARKAPD/ABSI criteria classified 60 patients as having AD pathology and 211 as non-AD. A total of 22 had discrepant results and were excluded. Aß42/Aß40 ratio was superior to Aß42 in the differentiation of AD pathology from non-AD pathology (AUCs: 0.939 and 0.831, respectively; p < 0.001). In general, biomarker ratios and composite markers were superior to single CSF biomarkers in both analyses. CONCLUSIONS: Aß42/Aß40 ratio is superior to Aß42 in identifying AD pathology, irrespective of the clinical phenotype. CSF biomarker ratios and composite markers provide higher diagnostic accuracy compared to single CSF biomarkers.

An Updated Evaluation of Intrathecal IgG Synthesis Markers in Relation to Oligoclonal Bands.

The aim was to evaluate the performance of the latest quantitative marker for intrathecal IgG synthesis and to compare it with other established markers used for the same purpose. We retrospectively applied Auer's and Reiber's intrathecal IgG synthesis formulae in a cohort of 372 patients under investigation for central nervous system demyelination who had undergone lumbar puncture and oligoclonal bands (OCBs) detection for demonstrating intrathecal IgG synthesis. A ROC analysis revealed Auer's formula had lower sensitivity (68%) compared to Reiber's formula (83%) and IgG index (89%), in our cohort of patients that exhibited normal to mildly elevated albumin quotients (4.48 ± 3.93). By excluding possible sources of errors, we assume that Auer's formula is less sensitive than other established tools for the "prediction" of the detection of OCBs in routine cerebrospinal fluid (CSF) analyses due to the mathematical model used. Given the ability of Reiber's hyperbolic formula to describe the blood-CSF IgG distribution across a wide range of blood-brain barrier functionality, its use and the use of similar formulae are recommended for the discrimination between CNS-derived and blood-derived molecules in clinical laboratories.

Hippocampal subfield volumetry in corticobasal syndrome of diverse underlying pathologies.

INTRODUCTION: Multiple pathologies may underlie corticobasal syndrome (CBS), including Alzheimer's disease (AD). Typical amnestic AD is characterized by early selective hippocampal atrophy. The profile of hippocampal atrophy in AD patients presenting as CBS (CBS-AD), compared to CBS patients of non-AD pathologies (CBS-nAD) and amnestic AD patients, has not been studied. OBJECTIVES: To compare hippocampal subfield atrophy patterns between CBS-AD, CBS-nAD, typical amnestic AD patients, and control subjects. METHODS: Automated hippocampal subfield volumetry was performed via the hippocampal subfield segmentation pipeline of Freesurfer 6.0 on 3D T1-weighted images. CBS patients were classified as CBS-AD or CBS-nAD based on CSF AD biomarkers by applying the AT(N) classification system. Mean volumes of nine hippocampal subfields, head-body-tail segments, total hippocampus, and entorhinal and parahippocampal gyrus cortical thickness were measured. RESULTS: Eighty-three subjects were included (CBS-AD: n = 14; CBS-nAD: n = 17; amnestic AD: n = 29; controls: n = 23). CBS-AD patients had greater whole hippocampal and hippocampal subfield atrophy compared to CBS-nAD. CBS-AD and amnestic AD patients did not differ in subfield volumes. CBS-nAD did not exhibit hippocampal atrophy compared to controls, with the exception of fimbria. (Cohen's d = 1.27; p = 0.038). Presubiculum (Cohen's d = 1.00; p = 0.002) and hippocampal body (Cohen's d = 0.95; p = 0.001) volumes exhibited the greatest differences between CBS-AD and CBS-nAD. Hippocampal subfield volume provided combined sensitivity and specificity < 80% for the discrimination of CBS-AD from CBS-nAD. CONCLUSION: CBS-AD and amnestic AD patients exhibit comparable, and significantly greater hippocampal atrophy compared to CBS-nAD patients. Hippocampal subfield volumetry in CBS is indicative of an AD underlying pathology.

Anaphylactic Reactions to COVID-19 Vaccines: An Updated Assessment Based on Pharmacovigilance Data.

This study aimed at producing an updated assessment of the incidence of anaphylaxis associated with COVID-19 vaccines based on pharmacovigilance data. Anaphylactic reaction and anaphylactic shock data post-COVID-19-vaccination reported from week 52, 2020 to week 1 or week 2, 2023 were collected from the VAERS and EudraVigilance databases, respectively, and analyzed comparatively. Incidence rates were calculated using the corresponding administered vaccine doses as denominators for all licensed vaccines and both platform types (mRNA or vectored). The latest data from the present analysis showed lower anaphylaxis incidence associated with COVID-19 vaccination compared to previous estimates from week 52, 2020 to week 39, 2021 (anaphylactic reaction: 8.96 (95% CI 8.80-9.11)/million doses overall (EEA: 14.19 (95% CI 13.92-14.47)/million/US: 3.17 (95% CI 3.03-3.31)/million); anaphylactic shock: 1.46 (95% CI 1.39-1.52)/million doses overall (EEA: 2.47 (95% CI 2.36-2.58)/million/US: 0.33 (95% CI 0.29-0.38)/million)). Incidence rates varied by vaccine and were higher as captured in EudraVigilance compared to the VAERS and for vectored compared to mRNA vaccines. Most reported cases had a favorable outcome. The extremely rare fatalities (overall rates across continents 0.04 (95% CI 0.03-0.06)/million doses for anaphylactic reaction and 0.02 (95% CI 0.01-0.03)/million vaccine doses for anaphylactic shock) were also associated with vector-rather than mRNA-based vaccines. The diminished incidence of anaphylaxis post-vaccination with COVID-19 vaccines offers assurance about their safety, as does the continuous potential adverse events monitoring through specialized pharmacovigilance databases.

Alzheimer's Disease CSF Biomarkers as Possible Indicators of Tap-Test Response in Idiopathic Normal Pressure Hydrocephalus.

The aim of the present study is the evaluation of established Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in patients with idiopathic normal-pressure hydrocephalus (iNPH), both individually and as a total profile, and the investigation of their use as potential predictors of Tap-test responsiveness. Fifty-three patients with iNPH participated in the study. Aß42, Aß40, total Tau and phospho-Tau proteins were measured in duplicate with double-sandwich ELISA assays. Clinical evaluation involved a 10 m timed walk test before an evacuative lumbar puncture (LP) and every 24 h for three consecutive days afterwards. Neuropsychological assessment involved a mini-mental state examination, frontal assessment battery, 5-word test and CLOX drawing test 1 and 2, which were also performed before and 48 h after LP. Response in the Tap-test was defined as a 20% improvement in gait and/or a 10% improvement in neuropsychological tests. The Aß42/Aß40 ratio was found to be significantly higher in Tap-test responders than non-responders. Total Tau and phospho-Tau CSF levels also differed significantly between these two groups, with Tap-test responders presenting with lower levels compared to non-responders. Regarding the AD CSF biomarker profile (decreased amyloid and increased Tau proteins levels), patients with a non-AD profile were more likely to have a positive response in the Tap-test than patients with an AD profile.

Application of the AT(N) and Other CSF Classification Systems in Behavioral Variant Frontotemporal Dementia.

BACKGROUND: Patients with a frontotemporal lobar degeneration (FTLD) usually manifest with behavioral variant frontotemporal dementia (bvFTD). Alzheimer's disease (AD) may also manifest with a predominant behavioral-dysexecutive syndrome, similar to bvFTD. Cerebrospinal fluid (CSF) biomarkers, such as total tau (τT), phosphorylated tau (τP-181) and amyloid beta with 42 amino-acids (Aß42), can predict AD pathology in vivo. The aim of this study was to compare the τT/Aß42 and τP-181/Aß42 ratios, the BIOMARKAPD/ABSI criteria and the AT(N) classification system in a cohort of bvFTD patients. METHODS: A total of 105 bvFTD patients (21 possible bvFTD; 20%) with CSF data, examined from 2008 to 2022, were included. Seventy-eight AD patients and 62 control subjects were included. The CSF biomarkers were measured with Innotest (2008-2017 subcohort) and EUROIMMUN (2017-2022 subcohort) ELISAs. RESULTS: Depending on the classification system, 7.6 to 28.6% of bvFTD had an AD biochemical profile. The τT/Aß42 and τP-181/Aß42 ratios classified more patients as AD compared to the BIOMARKAPD/ABSI and AT(N) systems. The patients with possible bvFTD had higher frequencies of AD compared to the probable bvFTD patients. CONCLUSIONS: The four classification criteria of CSF AD biomarkers resulted in differences in AD allocation in this bvFTD cohort. A consensus on the optimal classification criteria of CSF AD biomarkers is pivotal.