Citations

AbstractBackgroundThe safety of a third dose of SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease is unknown.MethodsWe compared symptoms following a third SARS-CoV-2 mRNA vaccine dose with symptoms after the second dose in IBD.ResultsThe study group included 594 patients (70% female, 58% BNT162b2). Overall, 41% reported symptoms after a third dose. Symptom frequency and severity were lower after the third dose relative to the second dose for every organ system, except for gastrointestinal symptoms which were marginally worse.ConclusionThe frequency and severity of symptoms after a third mRNA vaccine dose are generally similar or milder than after a second dose for most organ systems.

AbstractBackground:Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Patients with TNBC are primarily treated with neoadjuvant chemotherapy (NAC). Response to NAC is prognostic, with reductions in low overall survival and disease-free survival rates in those patients who do not achieve pathological complete response (pCR). Based on this premise, we focused on patients with residual disease and hypothesized that paired analysis of primary and residual TNBC tumors following NAC could identify unique biomarkers associated with post-NAC recurrence.Methods and Results: We investigated 24 TNBC tumors from 12 patients with pre- and post-NAC data, including four patients who recurred shortly after surgery(<24 months) and eight who remained recurrence-free (> 48 months). These tumors were collected from a prospective NAC breast cancer study (BEAUTY) conducted at the Mayo Clinic. Differential expression analysis of pre-NAC biopsies showed minimal gene expression differences between early recurrent and non-recurrent TNBC tumors; however, post-NAC samples demonstrated a significant alteration in expression patterns in response to intervention. Topological-level differences associated with early recurrence were implicated in 251 gene sets, and an independent assessment of microarray gene expression data from the paired NAC I-SPY1 trial confirmed 56 genesets. Underlying these 56 gene sets, 113 genes were observed to be differentially expressed in the I-SPY1 and BEAUTY post-NAC studies. An independent (n=392) breast cancer data set with relapse-free survival (RFS) data was used to refine our gene list to a 17 gene signature. A three-fold cross-validation analysis of the gene signature with the combined BEAUTY and I-SPY1 data yielded an average AUC of 0.88 for six machine learning models. Due to the limited studies with pre-and post-NAC TNBC tumor data, further validation of the signature is needed.Conclusion:Analysis of multi-omics data from post-NAC TNBC chemoresistant tumors showed downregulation of mismatch repair, purin, and tubulin pathways. Additionally, weidentified a 17 gene signature in TNBC associated with post-NAC recurrence enriched with down-regulation of immune genes.

The spleen is a commonly encountered specimen in surgical pathology. However, little is known about the incidence, morphologic pattern, and clinical features of spleens involved by amyloidosis. We retrospectively identified 69 spleen amyloid cases typed using a proteomics-based method between 2008 and 2020. The frequency of amyloid types, clinicopathologic features, and distribution of amyloid deposits were assessed. Four amyloid types were detected: immunoglobulin light chain (AL) (N=30; 43.5%); leukocyte chemotactic factor 2 amyloidosis (ALECT2) (N=30; 43.5%); amyloid A (AA) (N=8; 11.6%); and fibrinogen alpha (AFib) (N=1; 1.4%). The splenic amyloid showed 5 distinct distribution patterns: (1) diffuse pattern, exhibited by most AL cases; (2) red pulp pattern, exhibited by most ALECT2 cases; (3) multinodular pattern, seen in subsets of AA and AL-kappa cases; (4) mass-forming pattern, seen in the AFib case; and (5) vascular only, seen in a subset of AA cases. Atraumatic splenic rupture was the most common reason for splenectomy in AL cases, while most ALECT2 spleens were removed incidentally during an unrelated abdominal surgery. Splenomegaly was significantly more common in AA spleens than in AL or ALECT2 spleens and was often the reason for splenectomy in this group. In conclusion, splenic amyloid may be underrecognized as it is often an incidental finding. Although, as expected, many of the spleens were involved by AL amyloidosis, ALECT2 emerged as another common spleen amyloid type. Although the spleen amyloid types exhibited characteristic distribution patterns, proteomics-based typing is warranted as some morphologic overlap still exists. Awareness of ALECT2 as a major spleen amyloid type is important for appropriate diagnostic workup and patient management.

Background: Thirty-six states, including Florida, have legalized marijuana for medical and/or recreational use, yet how it is used and perceived by persons with cancer is not well understood. Objectives: The purpose of this study was to identify patterns of use, perceived benefits, and side effects of medical marijuana (MMJ) among cancer patients in Florida. Methods: For this descriptive, cross-sectional study, anyone residing within the state of Florida who was diagnosed or treated for a malignancy within the last five years and had used MMJ was eligible. An online survey containing questions about dosing, side effects, perceived benefits, and barriers to use was used. Descriptive statistics including frequencies, percentages, means, and standard deviations were used to analyze quantitative data. Responses to open-ended questions were coded and categorized. Results: Sleep ( n = 112), pain ( n = 96), and anxiety ( n = 82) were the most common symptoms participants used MMJ to relieve and overall felt it was highly effective. MMJ was well tolerated with a minority (10.3%) reporting any adverse effects. Cost was the most frequent barrier reported by participants (42.8%). A variety of legal, bureaucratic, and system-related barriers were described. Conclusion: Participants perceived MMJ to be helpful in alleviating cancer symptoms. They held negative perceptions of the way MMJ is implemented and integrated into their oncology treatment plan. Enhanced communication and patient/provider education on MMJ are needed to inform patient decision making.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

AbstractThe temporal evolutions and relative orderings of Alzheimer disease biomarkers, including CSF amyloid-β42 (Aβ42), Aβ40, total tau (Tau) and phosphorylated tau181 (pTau181), standardized uptake value ratio (SUVR) from the molecular imaging of cerebral fibrillar amyloid-β with PET using the 11C-Pittsburgh Compound-B (PiB), MRI-based hippocampal volume and cortical thickness and cognition have been hypothesized but not yet fully tested with longitudinal data for all major biomarker modalities among cognitively normal individuals across the adult lifespan starting from 18 years. By leveraging a large harmonized database from 8 biomarker studies with longitudinal data from 2609 participants in cognition, 873 in MRI biomarkers, 519 in PET PiB imaging and 475 in CSF biomarkers for a median follow-up of 5–6 years, we estimated the longitudinal trajectories of all major Alzheimer disease biomarkers as functions of baseline age that spanned from 18 to 103 years, located the baseline age window at which the longitudinal rates of change accelerated and further examined possible modifying effects of apolipoprotein E (APOE) genotype. We observed that participants 18–45 years at baseline exhibited learning effects on cognition and unexpected directions of change on CSF and PiB biomarkers. The earliest acceleration of longitudinal change occurred for CSF Aβ42 and Aβ42/Aβ40 ratio (with an increase) and for Tau, and pTau181 (with a decrease) at the next baseline age interval of 45–50 years, followed by an accelerated increase for PiB SUVR at the baseline age of 50–55 years and an accelerated decrease for hippocampal volume at the baseline age of 55–60 years and finally by an accelerated decline for cortical thickness and cognition at the baseline age of 65–70 years. Another acceleration in the rate of change occurred at the baseline age of 65–70 years for Aβ42/Aβ40 ratio, Tau, pTau181, PiB SUVR and hippocampal volume. Accelerated declines in hippocampal volume and cognition continued after 70 years. For participants 18–45 years at baseline, significant increases in Aβ42 and Aβ42/Aβ40 ratio and decreases in PiB SUVR occurred in APOE ɛ4 non-carriers but not carriers. After age 45 years, APOE ɛ4 carriers had greater magnitudes than non-carriers in the rates of change for all CSF biomarkers, PiB SUVR and cognition. Our results characterize the temporal evolutions and relative orderings of Alzheimer disease biomarkers across the adult lifespan and the modification effect of APOE ɛ4. These findings may better inform the design of prevention trials on Alzheimer disease.

Abstract Background Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions. Methods After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing. Results CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. Conclusions Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

Objective This study aimed to examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care, and subsequent Parkinson disease. Methods Patients were ≥50 years and received neuroimaging for non‐stroke indications in the Kaiser Permanente Southern California system from 2009 to 2019. Natural language processing identified incidentally discovered covert brain infarction and white matter disease and classified white matter disease severity. The Parkinson disease outcome was defined as 2 ICD diagnosis codes. Results 230,062 patients were included (median follow‐up 3.72 years). A total of 1,941 Parkinson disease cases were identified (median time‐to‐event 2.35 years). Natural language processing identified covert cerebrovascular disease in 70,592 (30.7%) patients, 10,622 (4.6%) with covert brain infarction and 65,814 (28.6%) with white matter disease. After adjustment for known risk factors, white matter disease was associated with Parkinson disease (hazard ratio 1.67 [95%CI, 1.44, 1.93] for patients <70 years and 1.33 [1.18, 1.50] for those ≥70 years). Greater severity of white matter disease was associated with increased incidence of Parkinson disease(/1,000 person‐years), from 1.52 (1.43, 1.61) in patients without white matter disease to 4.90 (3.86, 6.13) in those with severe disease. Findings were robust when more specific definitions of Parkinson disease were used. Covert brain infarction was not associated with Parkinson disease (adjusted hazard ratio = 1.05 [0.88, 1.24]). Interpretation Incidentally discovered white matter disease was associated with subsequent Parkinson disease, an association strengthened with younger age and increased white matter disease severity. Incidentally discovered covert brain infarction did not appear to be associated with subsequent Parkinson disease. ANN NEUROL 2022;92:620–630