Poststroke Executive Function in Relation to White Matter Damage on Clinically Acquired CT Brain Imaging.

BACKGROUND: Executive function (EF) impairments are prevalent post stroke and are associated with white matter (WM) damage on MRI. However, less is known about the relationship between poststroke EF and WM damage on CT imaging. OBJECTIVE: To investigate the relationship between poststroke EF and WM damage associated with stroke lesions and WM hypointensities (WMHs) on clinically acquired CT imaging. METHOD: This study analyzed data from the Oxford Cognitive Screening Program, which recruited individuals aged ≥18 years with a confirmed stroke from an acute stroke unit. The individuals completed a follow-up assessment 6 months post stroke. We included individuals with a CT scan showing a visible stroke who completed follow-up EF assessment using the Oxford Cognitive Screen-Plus rule-finding task. We manually delineated stroke lesions and quantified then dichotomized WM damage caused by the stroke using the HCP-842 atlas. We visually rated then dichotomized WMHs using the Age-Related White Matter Changes Scale. RESULTS: Among 87 stroke survivors (M age = 73.60 ± 11.75; 41 female; 61 ischemic stroke), multivariable linear regression showed that stroke damage to the medial lemniscus ( B = -8.86, P < 0.001) and the presence of WMHs ( B = -5.42, P = 0.005) were associated with poorer EF 6 months post stroke after adjusting for covariates including age and education. CONCLUSION: Poorer EF was associated with WM damage caused by stroke lesions and WMHs on CT. These results confirm the importance of WM integrity for EF post stroke and demonstrate the prognostic utility of CT-derived imaging markers for poststroke cognitive outcomes.

Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

BACKGROUND: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. OBJECTIVE: We aim to explore patients' and clinicians' perspectives of the utility and real-world application of PRMs to improve the management of CRS. METHODS: Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. CONCLUSIONS: Findings from this study provide information on clinicians' and patients' perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081.

Rapid screening for neglect following stroke: A systematic search and European Academy of Neurology recommendations.

BACKGROUND AND PURPOSE: Unilateral neglect is a common cognitive disorder following stroke. Neglect has a significant impact on functional outcomes, so it is important to detect. However, there is no consensus on which are the best screening tests to administer to detect neglect in time-limited clinical environments. METHODS: Members of the European Academy of Neurology Scientific Panel on Higher Cortical Functions, neuropsychologists, occupational therapists, and researchers produced recommendations for primary and secondary tests for bedside neglect testing based on a rigorous literature review, data extraction, online consensus meeting, and subsequent iterations. RESULTS: A total of 512 articles were screened, and 42 were included. These reported data from 3367 stroke survivors assessed using 62 neglect screens. Tests were grouped into cancellation, line bisection, copying, reading/writing, and behavioral. Cancellation tasks were most frequently used (97.6% of studies), followed by bisection, copying, behavioral, and reading/writing assessments. The panel recommended a cancellation test as the primary screening test if there is time to administer only one test. One of several cancellation tests might be used, depending on availability. If time permits, one or more of line bisection, figure copying, and baking tray task were recommended as secondary tests. Finally, if a functional and ecological test is feasible, the Catherine Bergego Scale was recommended. Overall, the literature suggests that no single test on its own is sufficient to exclude a diagnosis of neglect. Therefore, the panel recommended that multiple neglect tests should be used whenever possible. CONCLUSIONS: This study provides consensus recommendations for rapid bedside detection of neglect in real-world, clinical environments.

Forest restoration treatments increased growth and did not change survival of ponderosa pines in severe drought, Arizona.

We report on survival and growth of ponderosa pines (Pinus ponderosa Douglas ex P. Lawson & C. Lawson) 2 decades after forest restoration treatments in the G. A. Pearson Natural Area, northern Arizona. Despite protection from harvest that conserved old trees, a dense forest susceptible to uncharacteristically severe disturbance had developed during more than a century of exclusion of the previous frequent surface-fire regime that ceased upon Euro-American settlement in approximately 1876. Trees were thinned in 1993 to emulate prefire-exclusion forest conditions, accumulated forest floor was removed, and surface fire was re-introduced at 4-years intervals (full restoration). There was also a partial restoration treatment consisting of thinning alone. Compared with untreated controls, mortality of old trees (mean age 243 years, maximum 462 years) differed by <1 tree ha-1 and old-tree survival was statistically indistinguishable between treatments (90.5% control, 92.3% full, 82.6% partial). Post-treatment growth as measured by basal area increment of both old (pre-1876) and young (post-1876) pines was significantly higher in both treatments than counterpart control trees for more than 2 decades following thinning. Drought meeting the definition of megadrought affected the region almost all the time since the onset of the experiment, including 3 years that were severely dry. Growth of all trees declined in the driest 3 years, but old and young treated trees had significantly less decline. Association of tree growth with temperature (negative correlation) and precipitation (positive correlation) was much weaker in treated trees, indicating that they may experience less growth decline from warmer, drier conditions predicted in future decades. Overall, tree responses after the first 2 decades following treatment suggest that forest restoration treatments have led to substantial, sustained improvement in the growth of old and young ponderosa pines without affecting old-tree survival, thereby improving resilience to a warming climate.

Compensation for radiotherapy treatment interruptions due to a cyberattack: An isoeffective DVH-based dose compensation decision tool.

Unscheduled interruptions to radiotherapy treatments lead to decreased tumor control probability (TCP). Rapid cell repopulation in the tumor increases due to the absence of radiation dose, resulting in the loss of TCP. Compensation for this loss is required to prevent or reduce an extension of the patient's overall treatment time and regain the original TCP. The cyberattack on the Irish public health service in May 2021 prevented radiotherapy treatment delivery resulting in treatment interruptions of up to 12 days. Current standards for treatment gap calculations are performed using the Royal College of Radiologists (RCR) methodology, using a point-dose for planning target volume (PTV) and the organs at risk (OAR). An in-house tool, named EQD2 VH, was created in Python to perform treatment gap calculations using the dose-volume histogram (DVH) information in DICOM data extracted from commercial treatment planning system plans. The physical dose in each dose bin was converted into equivalent dose in 2-Gy fractions (EQD2 ), accounting for tumor cell repopulation. This EQD2 -based DVH provides a 2D representation of the impact of treatment gap compensation strategies on both PTV and OAR dose distributions compared to the intended prescribed treatment plan. This additional information can aid clinicians' choice of compensation options. EQD2 VH was evaluated using five high-priority patients experiencing a treatment interruption when the cyberattack occurred. Compensation plans were created using the RCR methodology to evaluate EQD2 VH as a decision-making tool. The EQD2 VH method demonstrated that the comparison of compensated treatment plans alongside the original intended treatment plans using isoeffective DVH analysis can be achieved. It enabled a visual and quantitative comparison between treatment plan options and provided an individual analysis of each structure in a patient's plan. It demonstrated potential to be a useful decision-making tool for finding a balance between optimizing dose to PTV while protecting OARs.

Aligning formal and functional assessments of Visuospatial Neglect: A mixed-methods study.

ABSTRACTThe occurrence of visuospatial neglect acts as a key predictor of recovery outcome following stroke. However, the specific behavioural profiles associated with various neglect subtypes are not well understood. This study aims to identify real-world functional impairments associated with neglect, to determine whether functional impairment profiles differ across patients with egocentric and allocentric neglect, and to investigate how neglect severity predicts functional impairments.Notes from 290 stroke patients' occupational therapy functional assessments were qualitatively and quantitatively analysed in the context of neglect type and severity as reported by the OCS Cancellation Task. Overall, neglect patients had more references to having difficulty initiating tasks, finding items, exhibiting spatial inattention, and having difficulty using both arms than patients without neglect. The proportion of theme references did not differ significantly across patients with egocentric and allocentric neglect. The quantitative severity of egocentric neglect was acted as a significant predictor of reference occurrence over and above stroke severity within difficulty finding items, spatial inattention, body inattention, and upper limb use.This study expands on previous findings by identifying real-world functional impairments differentiating patients with and without neglect. This data provides novel insight into the impact of neglect on functional abilities.

Beyond advising and mentoring: Competencies for coaching in medical education.

BACKGROUND: Coaching supports academic goals, professional development and wellbeing in medical education. Scant literature exists on training and assessing coaches and evaluating coaching programs. To begin filling this gap, we created a set of coach competencies for medical education using a modified Delphi approach. METHODS: An expert team assembled, comprised of seven experts in the field of coaching. A modified Delphi approach was utilized to develop competencies. RESULTS: Fifteen competencies in five domains resulted: coaching process and structure, relational skills, coaching skills, coaching theories and models, and coach development. CONCLUSION: These competencies delineate essential features of a coach in medical education. Next steps include creating faculty development and assessment tools for coaching.

Non-Spatial Impairments Affect False-Positive Neglect Diagnosis Based on Cancellation Tasks.

OBJECTIVE: To diagnose egocentric neglect after stroke, the spatial bias of performance on cancellation tasks is typically compared to a single cutoff. This standard procedure relies on the assumption that the measurement error of cancellation performance does not depend on non-spatial impairments affecting the total number of cancelled targets. Here we assessed the impact of this assumption on false-positive diagnoses. METHOD: We estimated false positives by simulating cancellation data using a binomial model. Performance was summarised by the difference in left and right cancelled targets (R-L) and the Centre of Cancellation (CoC). Diagnosis was based on a fixed cutoff versus cutoffs adjusted for the total number of cancelled targets and on single test performance versus unanimous or proportional agreement across multiple tests. Finally, we compared the simulation findings to empirical cancellation data acquired from 651 stroke patients. RESULTS: Using a fixed cutoff, the rate of false positives depended on the total number of cancelled targets and ranged from 10% to 30% for R-L scores and from 10% to 90% for CoC scores. The rate of false positives increased even further when diagnosis was based on proportional agreement across multiple tests. Adjusted cutoffs and unanimous agreement across multiple tests were effective at controlling false positives. For empirical data, fixed versus adjusted cutoffs differ in estimation of neglect prevalence by 13%, and this difference was largest for patients with non-spatial impairments. CONCLUSIONS: Our findings demonstrate the importance of considering non-spatial impairments when diagnosing neglect based on cancellation performance.

TIM-3 in endometrial carcinomas: an immunotherapeutic target expressed by mismatch repair-deficient and intact cancers.

The checkpoint molecule TIM-3 is a target for emerging immunotherapies and has been identified on a variety of malignancies. Mismatch repair-deficient endometrial carcinomas have demonstrated durable responses to other checkpoint inhibitors due to high neoantigen loads and robust tumor-associated immune responses. However, little is known about TIM-3 expression in this tumor type. Tumor-associated immune and tumoral expression of TIM-3 were evaluated by immunohistochemistry on 75 endometrial carcinomas [25 MLH1 promoter hypermethylated (MLH1-hypermethylated), 25 non-hypermethylated mismatch repair-deficient, and 25 mismatch repair-intact]. All cases showed at least focal immune staining, but moderate and robust immune cell expression were more often observed in mismatch repair-deficient vs intact cases [66 vs 12%, P = 0.00002]. While the majority (77%) of endometrial cancers showed ≥1% tumoral TIM-3 expression, the MLH1-hypermethylated subset was more likely to demonstrate >5% tumoral staining when compared to both mismatch repair-intact and non-methylated mismatch repair-deficient cancers [64 vs. 28% and 32%, respectively; P = 0.02 and P = 0.05]. Within the non-methylated mismatch repair-deficient subset, high-level expression was most often associated with MSH6 loss. Across mismatch repair subgroups, tumoral TIM-3 expression was more common among intermediate and high-grade vs. low-grade tumors using both the 1% (P = 0.02) and 5% expression cut-offs (P = 0.02). In conclusion, tumoral TIM-3 expression is common in both mismatch repair-intact and deficient endometrial cancers, with particularly high levels of expression identified in the setting of MLH1-hypermethylation, MSH6 loss, and intermediate to high histologic grade. Although focal immune cell expression was seen in all tumors, robust expression was significantly more common in the context of mismatch repair deficiency. These data support a potential role for checkpoint inhibitors targeting TIM-3 in a subset of endometrial cancers, including some mismatch repair-intact tumors which are not currently considered immunotherapy candidates.

Off-axis dose distribution with stand-in and stand-off configurations for superficial radiotherapy treatments.

Current practice when delivering dose for superficial skin radiotherapy is to adjust the monitor units so that the prescribed dose is delivered to the central axis of the superficial unit applicator. Variations of source-to-surface distance due to patient's anatomy protruding into the applicator or extending away from the applicator require adjustments to the monitor units using the inverse square law. Off-axis dose distribution varies significantly from the central axis dose and is not currently being quantified. The dose falloff at the periphery of the field is not symmetrical in the anode-cathode axis due to the heel effect. This study was conducted to quantify the variation of dose across the surface being treated and model a simple geometric shape to estimate a patient's surface with stand-in and stand-off. Isodose plots and color-coded dose distribution maps were produced from scans of GAFChromic EBT-3 film irradiated by a Gulmay D3300 orthovoltage x-ray therapy system. It was clear that larger applicators show a greater dose falloff toward the periphery than smaller applicators. Larger applicators were found to have a lower percentage of points above 90% of central axis dose (SA90). Current clinical practice does not take this field variation into account. Stand-in can result in significant dose falloff off-axis depending on the depth and width of the protrusion, while stand-off can result in a flatter field due to the high-dose region near the central axis being further from the source than the peripheral regions. The central axis also received a 7% increased or decreased dose for stand-in or stand-off, respectively.

Survival rates indicate that correlations between community-weighted mean traits and environments can be unreliable estimates of the adaptive value of traits.

Correlations between community-weighted mean (CWM) traits and environmental gradients are often assumed to quantify the adaptive value of traits. We tested this assumption by comparing these correlations with models of survival probability using 46 perennial species from long-term permanent plots in pine forests of Arizona. Survival was modelled as a function of trait × environment interactions, plant size, climatic variation and neighbourhood competition. The effect of traits on survival depended on the environmental conditions, but the two statistical approaches were inconsistent. For example, CWM-specific leaf area (SLA) and soil fertility were uncorrelated. However, survival was highest for species with low SLA in infertile soil, a result which agreed with expectations derived from the physiological trade-off underpinning leaf economic theory. CWM trait-environment relationships were unreliable estimates of how traits affected survival, and should only be used in predictive models when there is empirical support for an evolutionary trade-off that affects vital rates.

Advancing a new evidence-based professional in health care: job task analysis for health and wellness coaches.

BACKGROUND: The pressing need to manage burgeoning chronic disease has led to the emergence of job roles such as health and wellness coaches (HWCs). As use of this title has increased dramatically, so has the need to ensure consistency, quality and safety for health and wellness coaching (HWC) provided in both practice and research. Clear and uniform role definitions and competencies are required to ensure appropriate scope of practice, to allow best practices to emerge, and to support the implementation of well-designed, large scale studies to accumulate a rigorous evidence base. Since the nascent field is replete with heterogeneity in terms of role delineations and competencies, a collaborative volunteer non-profit organization, the National Consortium for Credentialing Health and Wellness Coaches (NCCHWC), has been built over the past six years to support professionalization of the field. METHODS: In 2014, a professionally led Job Task Analysis (JTA) was conducted with 15 carefully selected subject matter experts (SMEs) with diverse education and professional backgrounds who were practicing HWC in a wide variety of settings. After establishing a thorough list of specific tasks employed during HWC, the expert panel discussed the knowledge and skills necessary to competently perform the tasks. Subsequently, a large validation survey assessed the relative importance and frequency of each identified job task in conducting HWC. RESULTS: The JTA identified 21 job tasks as essential to HWC. In the subsequent validation survey, 4026 practicing health and wellness coaches were invited to rate each of the 21 job tasks in terms of their importance and frequency. A response rate of 25.6 % provided a diverse sample (n = 1031) in terms of background, and represented a wide variety of training programs from academia, industry, the private sector and associations. Per best practices, the subset of practicing HWCs (n = 885) provided importance and frequency ratings to be used to calculate task and domain weights that can serve as a foundation for a NCCHWC national certification examination. CONCLUSIONS: This JTA provides a significant step forward in the building of a clear and consistent definition of HWC that will allow for uniform practice standards and enable more stringent methodology to evaluate this promising approach within evidence-based medicine.

A pilot study of health and wellness coaching for fibromyalgia.

BACKGROUND: The purpose of this study was to test the hypothesis that a health and wellness coaching (HWC)-based intervention for fibromyalgia (FM) would result in sustained improvements in health and quality of life, and reductions in health care utilization. METHODS: Nine female subjects meeting American College of Rheumatology criteria for a diagnosis of primary FM were studied. The HWC protocol had two components, which were delivered telephonically over a twelve-month period. First, each patient met individually with a coach during the 12 month study at the patient's preference of schedule and frequency (Range:22-32 × 45-min sessions). Coaches were health professionals trained in health and wellness coaching tasks, knowledge, and skills. Second, each patient participated in bimonthly (first six months) and monthly (second six months) group classes on self-coaching strategies during the 12 month study. Prior to the intervention, and after 6 months and 12 months of coaching, the Revised Fibromyalgia Impact Questionnaire (FIQR) was used to measure health and quality of life, and the Brief Pain Inventory-Short Form (BPI) was used to measure pain intensity and interference with function. Total and rheumatology-related health encounters were documented using electronic medical records. Data were analyzed using repeated measures ANOVA. RESULTS: All nine patients finished the HWC protocol. FIQR scores improved by 35 % (P = 0.001). BPI scores decreased by 32 % overall (P = 0.006), 31 % for severity (P = 0.02), and 44 % for interference (P = 0.006). Health care utilization declined by 86 % (P = 0.006) for total and 78 % (P < 0.0001) for rheumatology-related encounters. CONCLUSION: The HWC program added to standard FM therapy produced clinically significant improvements in quality of life measures (FIQR), pain (BPI), and marked reductions in health care utilization. Such improvements do not typically occur spontaneously in FM patients, suggesting that HWC deserves further consideration as an intervention for FM.

Slow lifelong growth predisposes Populus tremuloides trees to mortality.

Widespread dieback of aspen forests, sometimes called sudden aspen decline, has been observed throughout much of western North America, with the highest mortality rates in the southwestern United States. Recent aspen mortality has been linked to drought stress and elevated temperatures characteristic of conditions expected under climate change, but the role of individual aspen tree growth patterns in contributing to recent tree mortality is less well known. We used tree-ring data to investigate the relationship between an individual aspen tree's lifetime growth patterns and mortality. Surviving aspen trees had consistently higher average growth rates for at least 100 years than dead trees. Contrary to observations from late successional species, slow initial growth rates were not associated with a longer lifespan in aspen. Aspen trees that died had slower lifetime growth and slower growth at various stages of their lives than those that survived. Differences in average diameter growth between live and dead trees were significant (α = 0.05) across all time periods tested. Our best logistical model of aspen mortality indicates that younger aspen trees with lower recent growth rates and higher frequencies of abrupt growth declines had an increased risk of mortality. Our findings highlight the need for species-specific mortality functions in forest succession models. Size-dependent mortality functions suitable for late successional species may not be appropriate for species with different life history strategies. For some early successional species, like aspen, slow growth at various stages of the tree's life is associated with increased mortality risk.

Innovations and challenges in predicting cognitive trajectories after stroke.

This scientific commentary refers to 'Deep learning disconnectomes to accelerate and improve long-term predictions for post-stroke symptoms', by Matsulevits et al. (https://doi.org/10.1093/braincomms/fcae338).

Attentional and lexical factors underlying word-centred neglect dyslexia errors in healthy readers.

Word-centred neglect dyslexia is most commonly conceptualised as a deficit caused by attentional biases within spatially coded internal representations of words. However, recent research has suggested that at least some cases of word-centred neglect dyslexia are unrelated to visuospatial neglect and may instead be modulated by self-inhibition and lexical factors. Here, we set out to provide novel insight into potential underlying mechanisms modulating the occurrence of word-centred lateralised reading errors in healthy participants. A sample of 47 healthy readers completed a novel attentional cueing paradigm in which they sequentially identified lateral cues and read presented words under limited exposure conditions. Reading responses were analysed to determine whether word-centred neglect dyslexia could be simulated in healthy readers, to compare the strengths of induced biases, and to identify systematic differences in lexical characteristics between target words and neglect dyslexia reading errors. Healthy participants produced frequent lateralised reading errors in both horizontal and vertical reading stimuli with > 50% of errors classed as neglect dyslexic. Cues appended to word beginnings elicited significantly more reading errors than cues at word ends, illustrating the interaction between existing reading spatial attentional biases and cue-induced biases. Neglect dyslexia reading errors were found to contain significantly more letters per word and had higher concreteness ratings than target words. These findings demonstrate that word-centred neglect dyslexia can be simulated using attentional cues in healthy readers. These results provide important insight into the mechanisms underlying word-centred neglect dyslexia and further fundamental understanding of this syndrome.

Multivariate and network lesion mapping reveals distinct architectures of domain-specific post-stroke cognitive impairments.

BACKGROUND: The purpose of this study was to identify patterns of structural disconnection and multivariate lesion-behaviour relationships associated with post-stroke deficits across six commonly impacted cognitive domains: executive function, language, memory, numerical processing, praxis, and visuospatial attention. METHODS: Stroke survivors (n = 593) completed a brief domain-specific cognitive assessment (the Oxford Cognitive Screen (OCS)) during acute hospitalisation. Network-level and multivariate (sparce canonical correlation) lesion mapping analyses were conducted to identify focal neural correlates and distributed patterns of structural disconnection associated with impairment on each of the 16 OCS measures. RESULTS: Network-level and multivariate lesion mapping analyses identified significant correlates for 12/16 and 10/16 OCS measures, respectively which were largely consistent with correlates reported in past work. Language impairments were reliably localised to network- and voxel-level correlates centred in left fronto-temporal regions. Memory impairments were associated with disconnection in a large network of left hemisphere regions. Number processing deficits were associated with damage to voxels centred in the left insular/opercular cortex, as well as disconnection within the surrounding white matter tracts. Within the domain of attention, different subtypes of visuospatial neglect were linked to distinct but partially overlapping patterns of disconnection and voxel-level damage. Praxis impairment was not linked to any voxel-level regions but was significantly associated with disconnection within the left hemisphere dorsal attention network. CONCLUSION: These results highlight the utility of routine, domain-specific cognitive assessment and imaging data for theoretically-driven lesion mapping analyses, while providing novel insight into the complex anatomical correlates of common and debilitating post-stroke cognitive impairments.

Domain-specific cognitive impairment 6 months after stroke: The value of early cognitive screening.

BACKGROUND: Cognitive screening following stroke is widely recommended, yet few studies have considered the prognostic value of acute domain-specific function for longer-term cognitive outcome. Identifying which post-stroke cognitive impairments more commonly occur, recover, and persist, and which impairments hold prognostic value, could inform care planning, and resource allocation. AIMS: This study aimed to determine the prevalence of domain-specific impairment acutely and at 6 months, assess the proportion of change in cognitive performance, and examine the prognostic value of acute domain-specific cognitive screening. METHODS: A prospective stroke cohort completed the Oxford Cognitive Screen acutely (⩽2 weeks) and 6 months post-stroke. We determined the prevalence of acute and 6-month domain-specific impairment and proportion of change in performance from acute to 6 months. Hierarchical multivariable regression was used to predict global and domain-specific cognitive impairment at 6 months adjusted for demographic/vascular factors, stroke severity, and lesion volume. RESULTS: A total of 430 stroke survivors (mean/SD age 73.9/12.5 years, 46.5% female, median/interquartile range (IQR) National Institute of Health Stroke Scale (NIHSS) 5/2-10) completed 6-month follow-up. Acutely, domain-specific impairments were highly prevalent ranging from 26.7% (n = 112) in praxis to 46.8% (n = 183) in attention. At 6 months, the proportion of domain-specific recovery was highest in praxis (n = 73, 71%) and lowest in language (n = 89, 46%) and memory (n = 82, 48%). Severity of 6-month cognitive impairment was best predicted by the addition of acute cognitive impairment (adj R2 = 0.298, p < 0.0001) over demographic and clinical factors alone (adj R2 = 0.105, p < 0.0001). Acute cognitive function was the strongest predictor of 6-month cognitive performance (p < 0.0001). Acute domain-specific impairments in memory (p < 0.0001), language (p < 0.0001), and praxis (p < 0.0001) significantly predicted overall severity of cognitive impairment at 6 months. CONCLUSION: Post-stroke cognitive impairment is highly prevalent across all domains acutely, while impairments in language, memory, and attention predominate at 6 months. Early domain-specific screening can provide valuable prognostic information for longer-term cognitive outcomes.

Assessment for acceleration and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma using histologic and immunohistochemical features: a case series.

Morphologic features of aggressive/ "accelerated" chronic lymphocytic leukemia/small lymphocytic lymphoma (aCLL/SLL) have been described. Richter transformation (RT) also occurs in a subset of CLL/SLL cases. This case series examined inter-observer variability when assessing for aCLL/SLL and RT, with attention to how immunohistochemical (IHC) markers may assist in this evaluation. Twelve cases of CLL/SLL with available FFPE tissue were identified. H&E staining and IHC (CD3, CD20, CD5, CD23, LEF1, LAG3, C-MYC, PD-1, MUM1, Cyclin D1, BCL-6, p53, and Ki-67) were performed. Three hematopathologists reviewed each case. The pathologists provided a final interpretation of (1) CLL/SLL, (2) CLL/SLL with expanded and/or confluent proliferation centers or increased Ki-67 (aCLL/SLL), or (3) large cell transformation/DLBCL. The pathologists lacked consensus in the diagnosis in 6/12 cases (50%). The reviewers disagreed on the presence of expanded/confluent proliferation centers in 8/12 cases (67%). With the exception of Ki-67, no IHC marker showed a difference in the staining profile in aCLL/SLL or RT compared to low-grade cases. This series showed inter-observer variability in the evaluation for aCLL/SLL and RT. A study that serially examines genetic alterations in FFPE tissue and correlates the features with histology and IHC, at diagnosis and throughout the disease course, may help refine indicators of aggressive disease.