OBJECTIVE: Diagnosing Hashimoto\'s encephalopathy (HE) is challenging. In contrast to other types of autoimmune encephalitis, HE shows an excellent response to steroid treatment. We aimed to investigate the rates of antithyroid antibodies (ATAs) and probable HE in patients with unexplained mental dysfunction and compare the clinical characteristics between the good- and poor-outcome groups.
METHODS: We retrospectively reviewed the medical records and electroencephalography (EEG) and neuroimaging findings of patients admitted to the Department of Neurology of our hospital from March 1, 2006, to February 28, 2023. Using our proposed diagnostic criteria for probable HE, we compared the clinical characteristics between the good- and poor-outcome groups. We also investigated the rates of ATA positivity and probable HE.
RESULTS: In total, 198 patients exhibited altered mentation, rapidly progressive cognitive decline, or myoclonus. ATA tests were performed on 86 patients, and the detection rates of ATAs and probable HE were 29.1% and 25.6%, respectively. Of the 22 patients enrolled, the good- and poor-outcome groups comprised 19 and 3 patients, respectively. Clinical seizures occurred in seven patients. Nonconvulsive status epilepticus on EEG was observed in six patients, all of whom were intractable to antiepileptic drugs. Nineteen of 21 patients (90.5%) treated with immunosuppressants showed good outcomes.
CONCLUSIONS: HE is a rare clinical disorder, but not as rare as previously thought. When HE is suspected, steroids should be considered the first-line treatment. Early diagnosis and adequate treatment are critical to achieve good outcomes in HE.

UNASSIGNED: Studies have reported that repeated annual vaccination may influence the effectiveness of the influenza vaccination in the current season. The mechanisms underlying these differences are unclear but might include \"focusing\" of the adaptive immune response to older strains.
UNASSIGNED: We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok, Sanofi Pasteur) in adults 18-45 years of age. Participants were randomized equally between five groups, with planned annual receipt of vaccination (V) or saline placebo (P) as follows: P-P-P-P-V, P-P-P-V-V, P-P-V-V-V, P-V-V-V-V, or V-V-V-VV. Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of sera were tested by hemagglutination inhibition assays, focus reduction neutralization tests and enzyme-linked immunosorbent assays against vaccine strains.
UNASSIGNED: From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. We selected sera from 95 participants at five timepoints from the first two study years for testing. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with substantial increases for first-time vaccinees and smaller increases for repeat vaccinees, who had higher pre-vaccination titers in year 2. There were statistically significant reductions in the proportion of participants achieving a four-fold greater rise in antibody titer for the repeat vaccinees for A(H1N1), B/Victoria and B/Yamagata, but not for influenza A(H3N2). There were no statistically significant differences between groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains.
UNASSIGNED: In the first two years, repeat vaccinees and first-time vaccinees had similar post-vaccination geometric mean titers to all four vaccine strains, indicative of similar levels of clinical protection. The vaccine strains of A(H1N1) and A(H3N2) were updated in year 2, providing an opportunity to explore antigenic distances between those strains in humans in subsequent years.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

BACKGROUND: Tuberculosis (TB) poses a major public health challenge, particularly in children. A substantial proportion of children with TB disease remain undetected and unconfirmed. Therefore, there is an urgent need for a highly sensitive point-of-care test. This study aims to assess the performance of serological assays based on various antigen targets and antibody properties in distinguishing children (0-18 years) with TB disease (1) from healthy TB-exposed children, (2) children with non-TB lower respiratory tract infections, and (3) from children with TB infection.
METHODS: The study will use biobanked plasma samples collected from three prospective multicentric diagnostic observational studies: the Childhood TB in Switzerland (CITRUS) study, the Pediatric TB Research Network in Spain (pTBred), and the Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infections in children and adolescents (ProPAED) study. Included are children diagnosed with TB disease or infection, healthy TB-exposed children, and sick children with non-TB lower respiratory tract infection. Serological multiplex assays will be performed to identify M. tuberculosis antigen-specific antibody features, including isotypes, subclasses, Fc receptor (FcR) binding, and IgG glycosylation.
CONCLUSIONS: The findings from this study will help to design serological assays for diagnosing TB disease in children. Importantly, those assays could easily be developed as low-cost point-of-care tests, thereby offering a potential solution for resource-constrained settings.
RESULTS:
UNASSIGNED: NCT03044509.

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children.
OBJECTIVE: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT.
METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed.
RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ.
CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cancer with often poor outcomes. Limited biomarkers exist for predicting clinical outcomes. The Merkel cell polyomavirus (MCPyV) serum antibody test (AMERK) has shown potential for indicating better recurrence-free survival in a single-institution study. The study aimed to evaluate the link between initial AMERK serostatus and survival. Secondary objectives included examining the relationship between initial AMERK titer levels and tumor burden.
METHODS: A retrospective cohort study across two institutions analyzed patients tested with AMERK within 90 days of MCC diagnosis. Regression models assessed the association of survival outcomes with serostatus, considering various factors. The relationship between AMERK titer and tumor burden indicators was evaluated using ANOVA. Significance testing was exploratory, without a fixed significance level.
RESULTS: Of 261 MCC patients tested, 49.4% were initially seropositive (titer ≥75). Multivariable analysis showed that seropositivity improved recurrence, event-free, overall, and MCC-specific survival rates. Strong associations were found between initial AMERK titer and clinical, tumor, and nodal stages, tumor size, and disease extent. Notably, improved survival with seropositivity was observed only in patients with localized disease at initial presentation.
CONCLUSIONS: Circulating antibodies to MCPyV oncoproteins, as indicated by the AMERK test, are linked with better survival in MCC patients with localized disease at presentation. This could enhance patient risk profiling and treatment personalization. The study\'s retrospective nature and exploratory analysis are key limitations.
CONCLUSIONS: Merkel cell carcinoma (MCC) is a potentially aggressive skin cancer, and tools to predict patient outcomes are limited. A blood test called anti-Merkel cell panel (AMERK), which checks for specific antibodies related to this cancer, might give us some clues. In this study, we looked at 261 MCC patients who took the AMERK test within 90 days of diagnosis. We found that patients with an initial positive AMERK result tended to have better outcomes, especially if their cancer was in the early stages. However, it is important to note that this study has limitations, including using retrospective data and exploratory analyses.

Zika virus (ZIKV) remains a public health concern, with epidemics in endemic regions and sporadic outbreaks in new areas posing significant threats. Several mosquito-borne flaviviruses that can cause human illness, including West Nile, Usutu, and St. Louis encephalitis, have associations with birds. However, the susceptibility of chickens to ZIKV and their role in viral epidemiology is not currently known. We investigated the susceptibility of chickens to experimental ZIKV infection using chickens ranging from 1-day-old chicks to 6-week-old birds. ZIKV caused no clinical signs in chickens of all age groups tested. Viral RNA was detected in the blood and tissues during the first 5 days post-inoculation in 1-day and 4-day-old chicks inoculated with a high viral dose, but ZIKV was undetectable in 6-week-old birds at all timepoints. Minimal antibody responses were observed in 6-week-old birds, and while present in younger chicks, they waned by 28 days post-infection. Innate immune responses varied significantly between age groups. Robust type I interferon and inflammasome responses were measured in older chickens, while limited innate immune activation was observed in younger chicks. Signal transducer and activator of transcription 2 (STAT2) is a major driver of host restriction to ZIKV, and chicken STAT2 is distinct from human STAT2, potentially contributing to the observed resistance to ZIKV infection. The rapid clearance of the virus in older chickens coincided with an effective innate immune response, highlighting age-dependent susceptibility. Our study indicates that chickens are not susceptible to productive ZIKV infection and are unlikely to play a role in the ZIKV epidemiology.

SARS-CoV-2 serology may be helpful to retrospectively understand infection dynamics in specific settings including kindergartens. We assessed SARS-CoV-2 seroprevalence in individuals connected to kindergartens in Berlin, Germany in September 2021. Children, staff, and household members from 12 randomly selected kindergartens were interviewed on COVID-19 history and sociodemographic parameters. Blood samples were collected on filter paper. SARS-CoV-2 anti-S and anti-N antibodies were assessed using Roche Elecsys. We assessed seroprevalence and the proportion of so far unrecognized SARS-CoV-2 infections. We included 277 participants, comprising 48 (17.3%) kindergarten children, 37 (13.4%) staff, and 192 (69.3%) household members. SARS-CoV-2 antibodies were present in 65.0%, and 52.7% of all participants were vaccinated. Evidence of previous infection was observed in 16.7% of kindergarten children, 16.2% of staff, and 10.4% of household members. Undiagnosed infections were observed in 12.5%, 5.4%, and 3.6%, respectively. Preceding infections were associated with facemask neglect. In conclusion, two-thirds of our cohort were SARS-CoV-2 seroreactive in September 2021, largely as a result of vaccination in adults. Kindergarten children showed the highest proportion of non-vaccine-induced seropositivity and an increased proportion of previously unrecognized SARS-CoV-2 infection. Silent infections in pre-school children need to be considered when interpreting SARS-CoV-2 infections in the kindergarten context.

BACKGROUND: Autoimmune encephalitis (AE) comprises a heterogeneous group of autoantibody-mediated disorders targeting the brain parenchyma. Therapeutic plasma exchange (TPE), one of several first-line therapies for AE, is often initiated when AE is suspected, albeit prior to an established diagnosis. We sought to characterize the role of TPE in the treatment of suspected AE.
METHODS: A single-center, retrospective analysis was performed of adults (≥18 years) who underwent at least one TPE procedure for \"suspected AE.\" The following parameters were extracted and evaluated descriptively: clinicopathologic characteristics, treatment course, TPE-related adverse events, outcomes (e.g., modified Rankin scale [mRS]), and diagnosis once investigation was complete.
RESULTS: A total of 37 patients (median age 56 years, range 28-77 years, 62.2% male) were evaluated. Autoimmune antibody testing was positive in serum for 43.2% (n = 16) and cerebrospinal fluid for 29.7% (n = 11). Patients underwent a median of five TPE procedures (range 3-16), with 97.3% (n = 36) via a central line and 21.6% (n = 8) requiring at least one unit of plasma as replacement fluid. Fifteen patients (40.5%) experienced at least one TPE-related adverse event. Compared with mRS at admission, the mRS at discharge was improved in 21.6% (n = 8), unchanged in 59.5% (n = 22), or worse in 18.9% (n = 7). Final diagnosis of AE was determined to be definite in 48.6% (n = 18), probable in 8.1% (n = 3) and possible in 27.0% (n = 10). Six (16.2%) patients were ultimately determined to have an alternate etiology.
CONCLUSIONS: Empiric TPE for suspected AE is generally well-tolerated. However, its efficacy remains uncertain in the absence of controlled trials, particularly in the setting of seronegative disease.

There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted chemotherapeutic drugs has always been one of the main techniques. This work aims to develop a polycaprolactone/chitosan electrospun mat incorporated with paclitaxel/Fe3O4-loaded niosomes (SPNs) decorated with trastuzumab (TbNs) for cancer therapy. SPNs and TbNs were analyzed by DLS, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. Fabricated mats with distinct concentrations of TbNs were classified into four groups (G0 (0), G1 (1), G2 (2.5), and G3 (5%)) and were studied physicochemically, mechanically, and biologically. Paclitaxel release was also studied for 7 days under an alternative magnetic field (AMF). The optimized mat was nominated for an in vivo study to evaluate its tumor growth inhibition. Based on the results, the TbNs had a spherical core and shell morphology with a smooth surface. The zeta potential and the mean size of TbNs were equal to -14.7 mV and 221 nm. TbNs did not affect the morphology and quality of nanofibers, but in general, the presence of TbNs increased the elastic modulus, water uptake, and degradation. Regarding the release study, AMF showed a significant increase in accelerating paclitaxel release from mats, and most releases belonged to the mat with 5% of TbNs. Results from the in vivo study showed the effective and synergistic effects of AMF on drug release and significant tumor growth inhibition. To summarize, the proposed nanocarrier under AMF can be a good candidate for cancer therapy.