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Since their discovery, antibodies capable of broad neutralisation have been at the forefront of HIV-1 research and are of particular interest due to  in vivo  passive transfer studies demonstrating their potential to provide protection. Currently an exact definition of what is required for a monoclonal antibody to be classed as a broadly neutralising antibody (bnAb) has not yet been established. This has led to hundreds of antibodies with varying neutralisation breadth being studied and has given insight into antibody maturation pathways and epitopes targeted. However, even with this knowledge, immunisation studies and vaccination trials to date have had limited success in eliciting antibodies with neutralisation breadth. For this reason there is a growing need to identify factors specifically associated with bnAb development, yet to do this a set of criteria is necessary to distinguish bnAbs from non-bnAbs. This review aims to define what it means to be a HIV-1 bnAb by comparing neutralisation breadth, genetic features and epitopes of bnAbs, and in the process highlights the challenges of comparing the array of antibodies that have been isolated over the years.

Objective This study uses the Wechsler intelligence and memory scales to characterize the cognitive function of patients with autoimmune encephalitis (AE) in the chronic stage of the disease. AE is a group of neuroinflammatory disorders, and cognitive impairment is a significant source of chronic morbidity in these patients. Methods Fifty patients with an average disease duration of 3.2 years after diagnosis were prospectively recruited from four hospitals. They underwent a comprehensive cognitive examination using the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Summary statistics were computed, and single-sample and independent-samples t tests were used to compare the cohort to normative data. Results The results revealed significantly reduced performances in perceptual reasoning, processing speed, and working memory among AE patients. Seropositive AE patients exhibited below-norm processing speed, while the seronegative group showed reduced working memory and processing speed. Delayed memory performance was significantly below expectations only in seronegative patients. Pattern analysis indicated that intact cognition was the most observed outcome after AE, but significant heterogeneity was observed among the impaired patients. Conclusions The study identified deficits in perceptual reasoning, processing speed, and working memory among chronic AE patients. Pattern analysis highlighted positive long-term cognitive outcomes for many but varied outcomes for those with ongoing difficulties. Although severely cognitively impaired patients were not included, the findings apply to  AE cohorts who attend outpatient clinical neuropsychology consultations emphasizing the need for thorough cognitive assessment. The results suggest a need for further research targeting other cognitive domains, including executive functions.

Chronic HIV infection drives B cell dysfunction associated with the accumulation of tissue-like memory (TLMs) and activated memory B cells (MBCs) but decline in resting memory B cells. TLMs express multiple inhibitory receptors and lack response to soluble antigens. However, their origin and the mechanisms driving their expansion in HIV infection remain unclear. From bulk heavy chain BCR sequencing of MBC subsets from 5 PLWH with no detectable viremia, we hypothesized that TLMs (CD21- CD27- B cells) were significantly less mutated but also less diverse than other MBCs, suggesting an enrichment for innate-like B cells or that they belong to a less mature subset. Subsequent detailed multi-omics study of an immune response to a transient HIV viremia in an elite controller demonstrated a functional increase in Env-reactive IgG and MBCs with non-TLM phenotype. Single-cell RNA/BCR sequencing of PBMCs enriched for B cells revealed an orchestrated TNF-α response followed by interferon-α and -γresponses across all B cell subsets. This study provides new insights into multifaceted functional B cell response to transient HIV viremia and highlights TLM heterogeneity.

Background and objective Autoimmune encephalitis (AE) is often associated with clinically significant memory impairment. This study aimed to evaluate memory in a cross-sectional prospective AE cohort using multiple memory paradigms. Methods 52 patients (50% seropositive) meeting Graus criteria for possible AE were prospectively recruited between October 2019 and August 202. A comprehensive examination of memory was performed, including tests of supraspan verbal memory (list learning), logicosemantic memory (story learning), figural memory (learning of geometric designs), and verbal associative learning (verbal paired associates). Memory scores were compared to demographically adjusted normative data. Pattern analysis was conducted to assist in the identification of patterns in memory performances. Results Mean memory scores were not significantly below the normative mean. At an individual patient level, over 20% of the cohort exhibited impaired delayed figural memory, supraspan verbal memory learning and recall. Observed performances were significantly below expected performance for story learning ( p  = 0.017) and recall ( p  = 0.003), figural recall ( p  < 0.0001), initial acquisition ( p  < 0.001) and final acquisition of a list ( p  < 0.001) and all delayed recall measures of the list ( p  < 0.00001). 54.76% of patients exhibited intact psychometrics, and 16 distinct patterns of impairment emerged, indicating variability in memory outcomes. Discussion While statistical evidence for memory impairment did not emerge at an aggregate level, a proportion of patients present with evidence of abnormal memory performance on psychometrics. Variability in impaired memory measures argues for an individualised patient-focused approach to clinical assessment in AE. Future research should validate these findings with a larger sample size and explore the relationships between memory profiles and other cognitive functions.

Background and objectiveAutoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups.MethodsFifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence–Second Edition. The results were standardised with normative data.ResultsThe mean age of our cohort was 52.5 years old, with the average time from hospital admission to recruitment being 38.41 months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004).DiscussionWhile, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial.

IntroductionIntegrating palliative care (PC) early in the illness course for patients with serious cancers improves their outcomes and is recommended by national organisations such as the American Society of Clinical Oncology. However, monthly visits with PC clinicians from the time of diagnosis can be challenging to implement due to the lack of specialty-trained PC clinicians and resources. Therefore, we developed a stepped care model to triage PC service based on patients’ needs.Methods and analysisWe are conducting a non-blinded, randomised trial to evaluate the non-inferiority of a stepped PC model compared with an early integrated PC model for improving patients’ quality of life (QOL) at 24 weeks (primary outcome). Patients assigned to early integrated PC meet with PC every 4 weeks throughout their illness. Patients assigned to stepped PC have PC visits only at clinically significant points in their illness (eg, cancer progression) unless their QOL decreases, at which time they are ‘stepped up’ and meet with PC every 4 weeks throughout the remainder of their illness. Secondary aims include assessing whether stepped PC is non-inferior to early integrated PC regarding patient-clinician communication about end of life care and length of stay on hospice as well as comparing resource utilisation. Patients are recruited from the Massachusetts General Hospital Cancer Center, Boston, Massachusetts; Duke Cancer Center, Durham, North Carolina and University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania. The target sample size is 510 patients.Ethics and disseminationThe study is funded by the National Cancer Institute, approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board and will be reported in accordance with the Consolidated Standards of Reporting Trials statement. We will disseminate results through professional society meetings, peer-reviewed publications and presentations to patient organisations.Trial registration numberNCT03337399.

Purpose As pediatric cancer survival rates have exponentially increased in the past decade, with the vast majority surviving five years or more, the long-term impacts of treatment on the quality of survivorship must be explored. This study examines the effects of pediatric cancer treatment regimens on education outcomes among a demographically diverse regional population. The primary objective is to identify potential factors that may impact the educational and cognitive quality of life in this population.  Methods Four hundred sixty-eight pediatric oncology patients diagnosed at age <20 between January 1990 - August 2019 and treated for cancer with radiation therapy at a large public or a multi-center private hospital in South Florida were identified. A novel survey available in English and Spanish was electronically distributed at least three times to each patient from August 2020 - July 2021 via email, phone call, and text message. Variables relating to demographics, treatment, cognitive impairment, and school re-entry were collected through the survey and electronic medical record review. Descriptive statistical analysis was performed.  Results Of the patients, 10.5% responded to the survey (26 male, 21 female, two unidentified sex). The mean age was 8.9 years old (range 0-20) at diagnosis, 24.0 years old (range 8-39) at the time of survey completion, and 55.1% self-identified as Hispanic. Nearly one-quarter of respondents (22.4%) were unable to correctly identify the treatment modalities they received; Hispanic self-identifying patients were 1.75 times more likely than non-Hispanic patients to incorrectly report the treatment modalities received. One-quarter (26.5%) of respondents reported long-term cognitive deficits post-treatment, of which, over three-quarters (76.9%) identified as Hispanic.  Conclusion This study illuminates patients' perspectives on their long-term cognitive impacts after pediatric cancer treatment. Given the diverse study population, ethnic disparities in post-treatment survivorship were explored. A substantial subset of Hispanic participants was unable to correctly identify their treatment regimen, and a disproportionately large group of Hispanic patients experienced cognitive long-term cognitive deficits, suggesting that ethnic disparities play a critical role in post-treatment survivorship. Further research on prioritizing educational intervention during and after treatment is essential to improving both the quality and equity of survivorship among pediatric oncology patients.

IntroductionAutoimmune encephalitis (AE) is an acute neuroinflammatory disease that has high prevalence of chronic (>3 months post-acute illness) morbidity characterized by cognitive and functional impairment. It remains unclear if this morbidity is residual injury from the acute event or driven by ongoing neurodegeneration.ObjectiveEvaluate NfL and GFAP in serum and CSF in AE across subtypes, timepoints and outcomes.MethodsPatients with AE were recruited through the Australian Autoimmune Encephalitis Consortium and serum and CSF was analysed for GFAP and neurofilament light chain (NfL) using the Quanterix Simoa system. Subtypes included LGI-1, NMDAR and seronegative (SN) and timepoints included acute and chronic (>3 months). Timepoints and serum/CSF samples were paired where possible. Relationship to cognition and functional status (mRS) were also evaluated.ResultsWe recruited 26 patients with acute AE, 33 patients SN AE, 19 LGI-1 AE, 15 NMDAR AE, 10 patients with non-inflammatory neurological diseases (NIND) and 28 healthy controls. Compared with controls the acute AE cohort had higher serum NfL (30.59 pg/ml vs 8.89 pg/ml, p < 0.01) and GFAP (614.2 pg/mL vs 104.3 pg/Ml, p < 0.05). CSF GFAP was not significantly altered in AE compared with NIND. AE patients with severe cognitive dysfunction demonstrated higher serum NfL and GFAP (p<0.05).ConclusionWhilst markers of neurodegeneration in AE are highest during the acute disease, higher levels persist in patients with ongoing severely impaired cognition despite treatment. Further evaluation of NfL and GFAP may provide biomarkers of prognosis and impetus for ongoing therapy after the acute illness.