Faculty Bibliography

Rationale: During roll-out of Pfizer-BioNTech, Moderna, and Johnson & Johnson (J&J) COVID-19 vaccines, adverse reactions led patients to seek Allergy evaluation following vaccination.
Method(s): We conducted retrospective chart review of patients >= 18 years seeking vaccine counseling between December 1, 2020 - May 1, 2021 after experiencing COVID-19 vaccine reactions. Demographics, atopic history, anaphylaxis history and vaccine administration/reactions were recorded. Follow up phone calls were used to complete data collection.
Result(s): We identified 24 patients (N= 21 Female, 3 Male) reporting reactions to COVID-19 vaccination; 19 after 1^st dose, 2 after 2^nd dose, and 3 after both. The 27 total reactions were classified as immediate (12), or delayed (15) and subdivided further based on features. Two patients had symptoms consistent with anaphylaxis and were evaluated in the ER, one received epinephrine and subsequently tolerated J+J. The other did not pursue additional vaccination. Among the additional 10 immediate reactions, 6 were cutaneous/mucocutaneous-only and 4 involved subjective systemic symptoms. Six patients were evaluated in the emergency room (3 delayed, 3 immediate). Overall, 22 of 24 patients completed vaccination series (defined as one dose of J&J or 2 doses of an mRNA vaccine).
Conclusion(s): Many patients reported reactions to COVID-19 vaccine, most following first vaccine dose with isolated cutaneous or mucocutaneous symptoms. No patients with delayed cutaneous reactions went on to have more severe reactions and only 1 patient had return cutaneous symptoms with 2nd dose. Patients with adverse reactions may be reluctant to pursue additional vaccination; 2 of our patient cohort remain incompletely vaccinated to COVID-19.
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Rationale: Adverse reactions following COVID-19 vaccination are common. We sought to characterize the most common cutaneous manifestations following COVID-19 vaccine administration and identify potential predictive factors.
Method(s): A retrospective chart review was conducted for patients seen in the allergy clinic between December 2020 and May 2021 for COVID-19 vaccine counseling. Details of reactions to either mRNA COVID-19 vaccine were noted. Cutaneous findings were defined as any local reaction including pain, redness or swelling, or generalized rash.
Result(s): Twenty-four patients out of 115 patients (20.9%) had any type of cutaneous reaction after vaccination. Most were female (n=21, 87.5%). Seven of these 24 patients had a local reaction alone. Two patients had immediate onset of generalized pruritus and rash (1 of these patients had symptom resolution by the next morning, the other resolved 8 days post-vaccination). Four patients (16.7%) had a delayed (>6 hours after vaccination) generalized pruritic rash, three of which resolved within 2 weeks and one resolved after 6 weeks. Four patients with a history of chronic urticaria (CU) had a flare of urticaria following vaccination beginning 1-2 days later. One additional patient with CU had delayed pruritus only. One patient developed urticaria 1 day after receiving vaccination with persistence of urticaria beyond 6 weeks.
Conclusion(s): Cutaneous ARs were common (20%) following COVID-19 vaccination. Most rashes were delayed and resolved within 2 weeks with no additional sequelae. In this cohort, patients with a history of CU were seen to have flares of symptoms following vaccination. Cutaneous reactions were more commonly seen in women.
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An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.

PURPOSE/OBJECTIVE:People with pre-existing conditions may be more susceptible to severe COVID-19 when infected by SARS-CoV-2. The relative risk and severity of SARS-CoV-2 infection in people with rare diseases such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) is unknown. METHODS:We investigated the proportions of people with NF1, NF2, or SWN in the National COVID Cohort Collaborative (N3C) electronic health record data set who had a positive test result for SARS-CoV-2 or COVID-19. RESULTS:The cohort sizes in N3C were 2501 (NF1), 665 (NF2), and 762 (SWN). We compared these with N3C cohorts of patients with other rare diseases (98-9844 individuals) and the general non-NF population of 5.6 million. The site- and age-adjusted proportion of people with NF1, NF2, or SWN who had a positive test result for SARS-CoV-2 or COVID-19 (collectively termed positive cases) was not significantly higher than in individuals without NF or other selected rare diseases. There were no severe outcomes reported in the NF2 or SWN cohorts. The proportion of patients experiencing severe outcomes was no greater for people with NF1 than in cohorts with other rare diseases or the general population. CONCLUSION/CONCLUSIONS:Having NF1, NF2, or SWN does not appear to increase the risk of being SARS-CoV-2 positive or of being a patient with COVID-19 or of developing severe complications from SARS-CoV-2.

Background: TAS-102 (trifluridine/tipiracil) is a novel oral antimetabolite for late line metastatic colorectal cancer (CRC) approved in 2018. Many patients are treated early in their course with oxaliplatin (OX), particularly adjuvant, and may benefit from re-treatment. In this trial we combine the typical late line use of TAS with OX (BEV [bevacizumab] added at investigator discretion) with goal of improved response.
Method(s): Eligibility included measurable CRC previously treated with all approved drugs per TAS package insert (irinotecan, oxaliplatin, 5FU, anti-VEGF, anti-EGF) as appropriate, PS = 0-1, labs within usual range, neuropathy < grade 2, ability to take oral meds, appropriate contraception. If no contraindication to BEV, this could be added at patient. TAS was dosed at 35 mg/m2 days 1-5 with OX 85/m2 d1 every 14 days (and BEV 5 mg/kg, if given). All supportive care was allowed including growth factors.
Result(s): 47 patients (pts, median age 55) were enrolled in a Simon mini-max design, including 45% female, 21% black, 11% Asian, 11% Hispanic and 5% mixed. 26 pts received BEV. For the first 40 pts, 385 cycles were given (mean = 7 cycles, median 8) with 18 pts (45%) requiring dose reductions (1 dose reduction = 9 pts, 2 = 6, 3 = 3), and 9 receiving (peg)/filgrastim. Toxicities leading to SAEs included gr 3 heme (2), heart failure, abd pain/n/v (6), sepsis (2), urinary (4); and related gr 3 included one gr 3 vomiting and one gr 3 neutropenia. Independently reviewed RECIST Response (N = 32) included PR 2(6%), SD 23 (72%), PD 7 (22%). Mean TTP was 4.5 m (median 4, range 1 - 18) with 9 (28%) pts more than 6 months.
Conclusion(s): In patients with late-line CRC and candidates for TAS (trifluridine/tipiracil), treatment with TAS plus OX is both well tolerated and active. RR is higher than single agent and 78% (95% CI, 60-91%) of patients had stable disease or response, with 60% receiving 8 or more cycles. Randomized trials comparing to single agent TAS are warranted in this setting

In complex visuomotor tasks, such as cooking, people make many saccades to continuously search for items before and during reaching movements. These tasks require cognitive resources, such as short-term memory and task-switching. Cognitive load may impact limb motor performance by increasing demands on mental processes, but mechanisms remain unclear. The Trail-Making Tests, in which participants sequentially search for and make reaching movements to 25 targets, consist of a simple numeric variant (Trails-A) and a cognitively challenging variant that requires alphanumeric switching (Trails-B). We have previously shown that stroke survivors and age-matched controls make many more saccades in Trails-B, and those increases in saccades are associated with decreases in speed and smoothness of reaching movements. However, it remains unclear how patients with neurological injuries, e.g., stroke, manage progressive increases in cognitive load during visuomotor tasks, such as the Trail-Making Tests. As Trails-B trial progresses, switching between numbers and letters leads to progressive increases in cognitive load. Here, we show that stroke survivors with damage to frontoparietal areas and age-matched controls made more saccades and had longer fixations as they progressed through the 25 alphanumeric targets in Trails-B. Furthermore, when stroke survivors made saccades during reaching movements in Trails-B, their movement speed slowed down significantly. Thus, damage to frontoparietal areas serving cognitive motor functions may cause interference between oculomotor, visual, and limb motor functions, which could lead to significant disruptions in activities of daily living. These findings augment our understanding of the mechanisms that underpin cognitive-motor interference during complex visuomotor tasks.

OBJECTIVE:This study examined the extent to which demographic variables (i.e., age, education, premorbid IQ, sex, ethnoracial identity, and presence/absence of external incentive) affect performance validity test (PVT) performance. METHOD/METHODS:= 111). All patients completed a battery including five PVTs. Premorbid IQ was assessed using the Test of Premorbid Functioning (TOPF) in the AMC sample. RESULTS:Multiple correlations between demographic variables and individual PVT performance were statistically significant, but accompanying effect sizes were small, except for the relationship of premorbid IQ and reliable digit span (RDS). Regressions showed demographic variables accounted for 7%-11% of the variance in individual PVT scores in the AMC sample, and 6%-26% in the VA sample, premorbid IQ driving results in the AMC sample and compensation-seeking status in the VA sample. Other demographic variables did not correlate with compensation-seeking status. Additionally, premorbid IQ was found to be significantly higher in validly performing individuals compared to those performing invalidly in the AMC sample. CONCLUSION/CONCLUSIONS:Most demographic factors evaluated accounted for relatively little variance in individual PVT performance and did not significantly predict overall validity categorization. Compensation-seeking status correlated with validity classification across both groups, but offers limited diagnostic utility itself compared to objective PVT scores. Premorbid IQ within the AMC group demonstrated influence on particular PVTs (i.e., RDS) reflecting the difficulty of assessing validity within low IQ populations, particularly with PVTs more strongly correlated with IQ. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

INTRODUCTION:Executive functioning (EF) is a salient factor in both ADHD as well as depressive disorders. However, sparse literature has examined whether depression severity impacts EF concurrently among adults with ADHD. The goal of this study was to examine differences in EF between adult patients diagnosed with ADHD and those diagnosed with a non-ADHD primary psychopathological condition, as a function of both ADHD presentation and depression severity in a diverse clinical sample. METHOD:This crosssectional study included 404 adult patients clinically referred for neuropsychological evaluation to assist with differential diagnosis and/or treatment planning related to known or suspected ADHD. Various EF tasks and a measure of depression severity were administered. One-way MANOVA analyses were conducted to compare EF performance between individuals diagnosed with ADHD or a non-ADHD primary psychopathological condition, with additional analyses examining group differences based on ADHD presentation and depression severity. Regression analyses also examined the potential contribution of depression severity to each EF measure within each group. RESULTS:No significant EF performance differences were found when comparing individuals diagnosed with ADHD and those with a non-ADHD primary psychopathological condition, nor based on ADHD presentation. When comparing across groups using cut-offs for high or low depression, only one EF measure showed significant differences between groups. Further, depression severity generally did not predict reduced EF performances with the exception of verbal fluency and working memory performances in select groups. CONCLUSIONS:This study demonstrated that individuals with ADHD generally perform comparably on EF measures regardless of the presence or absence of comorbid depression. These results suggest further examination of EF deficits when they emerge for adults with ADHD, especially beyond comorbid depression severity.