Citations

AbstractINTRODUCTIONThe Rey Auditory Verbal Learning Test (RAVLT) is a useful neuropsychological test for describing episodic memory impairment in dementia. However, there is limited research on its utility in early‐onset Alzheimer's disease (EOAD). We assess the influence of amyloid and diagnostic syndrome on several memory scores in EOAD.METHODSWe transcribed RAVLT recordings from 303 subjects in the Longitudinal Early‐Onset Alzheimer's Disease Study. Subjects were grouped by amyloid status and syndrome. Primacy, recency, J‐curve, duration, stopping time, and speed score were calculated and entered into linear mixed effects models as dependent variables.RESULTSCompared with amyloid negative subjects, positive subjects exhibited effects on raw score, primacy, recency, and stopping time. Inter‐syndromic differences were noted with raw score, primacy, recency, J‐curve, and stopping time.DISCUSSIONRAVLT measures are sensitive to the effects of amyloid and syndrome in EOAD. Future work is needed to quantify the predictive value of these scores.Highlights RAVLT patterns characterize various presentations of EOAD and EOnonAD Amyloid impacts raw score, primacy, recency, and stopping time Timing‐based scores add value over traditional count‐based scores

Background Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far. Methods As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals. Results The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families. Conclusion The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term ‘GDACCF syndrome’ with ‘ZNF148-related neurodevelopmental disorder’.

(1) Background: Acute kidney injury (AKI) kidneys have high non-utilization rates due to concerns regarding unfavorable outcomes. In this paper, we aimed to review the past, present, and future opinions on AKI kidneys. (2) Methods: A PubMed search was conducted for topics relevant to AKI kidney transplantation. (3) Results: Current short- and long-term data on AKI kidneys have demonstrated good outcomes including favorable graft function and survival. The role of procurement biopsies is controversial, but they have been shown to be beneficial in AKI kidneys by allowing clinicians to differentiate between reversible tubular injury and irreversible cortical necrosis. Machine perfusion has also been applied to AKI kidneys and has been shown to reduce delayed graft function (DGF). The incidence of DGF increases with AKI severity and its management can be challenging. Strategies employed to counteract this have included early initiation of dialysis after kidney transplantation, early targeting of adequate immunosuppression levels to minimize rejection risk, and establishment of outpatient dialysis. (4) Conclusions: Despite good outcomes, there continue to be barriers that impact AKI kidney utilization. Successful strategies have included use of procurement biopsies or machine perfusion and expectant management of DGF. With increasing experience, better use of AKI kidneys can result in additional opportunities to expand the donor pool.

AbstractIntroductionExpedited out‐of‐sequence deceased donor kidney allocation is a strategy to avoid discards after early placement attempts have been unsuccessful. Our study aimed to assess outcomes and characteristics of these transplanted kidneys.MethodsKDPI matching was performed between expedited allocation (EA) and standard allocation (SA) deceased donor kidney transplants performed at our center.ResultsBetween 2018 and 2021, there were 225 EA offers, and 189 (84%) were transplanted. EA recipients were older (p = .007) and had shorter dialysis vintage (p < .0001). EA kidneys were likely to be nationally allocated (p < .001), have AKI (p < .0001) and longer CIT (p < .0001). There were no differences in EA and SA time‐zero kidney biopsies (ci, p = .07; ct, p = .89; cv, p = .95; ah, p = .79). EA kidneys had more DGF (p = .0006), but there were no differences in DGF duration (p = .83), hospital length of stay (p = .43), 1‐ and 2‐year eGFR (p = .16, p = .99), patient (p = .34), or death‐censored graft (p = .66) survival.ConclusionDuring this study period, our center transplanted 189 kidneys through EA following local‐regional declines. These kidneys often came from AKI donors and had more DGF but had similar outcomes to KDPI‐matched SA kidneys. Although it has been suggested that EA has the potential to worsen transplant disparities, transplant center level decisions on organ acceptance contribute to these variations.

Abstract The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve the reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. Informed by data from a cohort of glioblastoma patients and other evaluations of RANO criteria that allowed evaluation of features of the different criteria, we propose updates to the RANO criteria (RANO 2.0). Based on the 2021 WHO classification of gliomas, we recommend a standard set of criteria for both high and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the post-radiotherapy MRI, rather than the post-surgical MRI, will be used as the baseline for future comparison. Since the incidence of pseudoprogression is high in the 12 weeks following radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, is required to define tumor progression. However, confirmation scans are not mandatory after this period nor for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is an option. The primary measurement remains the maximum cross-sectional area of tumor (2-dimensional) but volumetric measurements are an option. For IDH-wildtype glioblastoma, the non-enhancing disease will no longer be evaluated. In IDH-mutated tumors with a significant non-enhancing component, clinical trials may require evaluating both the enhancing and non-enhancing tumor components for response assessment.

AbstractINTRODUCTIONWe used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early‐onset Alzheimer's disease (EOAD).METHODSWe included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non‐Alzheimer's disease (EOnonAD) participants from the Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel‐wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden.RESULTSEOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non‐carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non‐carriers also had greater gray matter atrophy than female ε4 carriers.DISCUSSIONThe effects of sex and APOE ε4 must be considered when studying these populations.HIGHLIGHTS Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early‐onset Alzheimer's disease (EOAD), early‐onset non‐AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.