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PURPOSE: Report relevance of molecular groups to clinicopathologic features, germline SMARCB1/SMARCA4 alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials. MATERIALS AND METHODS: Seventy-four participants with newly diagnosed ATRT were treated in two trials: infants (SJYC07: age < 3 years; n = 52) and children (SJMB03: age 3-21 years; n = 22), using surgery, conventional chemotherapy (infants), or dose-dense chemotherapy with autologous stem cell rescue (children), and age- and risk-adapted radiotherapy [focal (infants) and craniospinal (CSI; children)]. Molecular groups ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR) were determined from tumor DNA methylation profiles. RESULTS: Twenty-four participants (32%) were alive at time of analysis at a median follow-up of 8.4 years (range, 3.1-14.1 years). Methylation profiling classified 64 ATRTs as TYR (n = 21), SHH (n = 30), and MYC (n = 13), SHH group being associated with metastatic disease. Among infants, TYR group had the best overall survival (OS; P = 0.02). However, outcomes did not differ by molecular groups among infants with nonmetastatic (M0) disease. Children with M0 disease and

Chest-X ray (CXR) radiography can be used as a first-line triage process for non-COVID-19 patients with pneumonia. However, the similarity between features of CXR images of COVID-19 and pneumonia caused by other infections makes the differential diagnosis by radiologists challenging. We hypothesized that machine learning-based classifiers can reliably distinguish the CXR images of COVID-19 patients from other forms of pneumonia. We used a dimensionality reduction method to generate a set of optimal features of CXR images to build an efficient machine learning classifier that can distinguish COVID-19 cases from non-COVID-19 cases with high accuracy and sensitivity. By using global features of the whole CXR images, we successfully implemented our classifier using a relatively small dataset of CXR images. We propose that our COVID-Classifier can be used in conjunction with other tests for optimal allocation of hospital resources by rapid triage of non-COVID-19 cases.

ObjectiveTo report onset and progression of clinical signs of a neuroendocrine neoplasm (NEN) presumed metastatic to the choroid in a dog.Animals studiedA 7.5-year-old female spayed German shepherd dog mix referred for advanced imaging and evaluation of a subretinal mass in the right eye.ProceduresProcedures performed included general physical and ophthalmic examinations; ocular, orbital, and abdominal ultrasonography; thoracic radiographs; cranial magnetic resonance imaging; serologic testing for infectious agents; analysis of hematologic as well as serum and urine biochemical parameters; echocardiography; electrocardiography; cytologic assessment of lymph nodes; and histopathology and immunohistochemistry of the enucleated globe.ResultsExamination and imaging identified a pigmented mass within and expanding the superior choroid. Following enucleation, a choroidal NEN with tumor emboli in scleral blood vessels was diagnosed by histopathologic assessment and confirmed by immunohistochemical labelling. Despite extensive and repeated diagnostic testing over many months, a putative primary site was not identified until 19 months after the initial ocular signs were noted. At that time, a heart-base mass and congestive heart failure were highly suggestive of a chemodectoma.ConclusionThis comprehensive report of a NEN presumed metastatic to the choroid in a dog suggests that ocular disease can be a very early and solitary sign of NEN in the dog.

ObjectiveTo provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recommendations are also provided for children with hyperinflammation during coronavirus disease 2019 (COVID-19), the acute, infectious phase of SARS-CoV-2 infection.MethodsThe Task Force was composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting.ResultsThe first version of the guidance was approved in June 2020, and consisted of 40 final guidance statements accompanied by a flow diagram depicting the diagnostic pathway for MIS-C. The document was revised in November 2020, and a new flow diagram with recommendations for initial immunomodulatory treatment of MIS-C was added.ConclusionOur understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.

Multisystem inflammatory syndrome in children following severe acute respiratory syndrome coronavirus 2 infection is characterized by fever, elevated inflammatory markers, and multisystem organ involvement. Presentations are variable but often include gastrointestinal symptoms. We describe 5 children with fever and gastrointestinal symptoms initially concerning for multisystem inflammatory syndrome in children who were ultimately diagnosed with bacterial enteritis, highlighting the diagnostic challenges presented by the severe acute respiratory syndrome coronavirus 2 pandemic.

The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inborn errors of immunity. As the next formal report from the IUIS Expert Committee will not be published until 2022, we felt it important to provide the community with a brief update of recent contributions to the field of inborn errors of immunity. Herein, we highlight studies that have identified 26 additional monogenic gene defects that reach the threshold to represent novel causes of immune defects.

Key Clinical Message Patients with an infected charcot spine (ICS) may experience little or no back pain despite severe vertebral destruction. Understanding the pathophysiology underlying ICS and its differential diagnoses is crucial for its accurate diagnosis. Worsening symptoms of chronic charcot spine should raise suspicions of an infection.

ABSTRACT Schwannomas commonly develop in the cervical region, 25% – 45% of cases are diagnosed in this anatomical region. Tracheal neurogenic tumors are exceedingly rare and can be misdiagnosed as invasive thyroid carcinomas or other infiltrating malignancies when present at the level of the thyroid gland. Here, we present a case of synchronous benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma in a patient who was initially hospitalized for COVID-19. The patient presented with dyspnea that was later found to be caused by tracheal extension of a cervical tumor. Surgical excision was performed, and the surgical team proceeded with segmental tracheal resection, removal of the cervical mass, and total thyroidectomy. The specimen was sent for pathological analysis, which revealed synchronous findings of a benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma. The literature on this subject, together with the present case report, suggests that neurogenic tumors should be included in the differential diagnosis of obstructing tracheal cervical masses. Surgical excision is the first-line of treatment for benign cervical schwannomas.

Angiosarcomas are rare, accounting for only 1–2% of sarcomas in the head and neck region. We present an extremely rare case of primary non-radiation-induced angiosarcoma of the parotid with epithelioid morphology which required a tertiary center second opinion for its histological characteristics. We discuss the presentation, imaging, diagnosis, characteristics, and pathway of this case. As parotid lumps are common, a surgical sieve is required to rule out other possible conditions. Early correct diagnosis is crucial in conditions such as angiosarcomas due to their quick metastatic potential. [ABSTRACT FROM AUTHOR]

Protothecosis and chlorellosis are sporadic algal diseases that can affect small ruminants. In goats, protothecosis is primarily associated with lesions in the nose and should be included in the differential diagnosis of causes of rhinitis. In sheep, chlorellosis causes typical green granulomatous lesions in various organs. Outbreaks of chlorellosis have been reported in sheep consuming stagnant water, grass from sewage-contaminated areas, and pastures watered by irrigation canals or by effluents from poultry-processing plants. Prototheca and Chlorella are widespread in the environment, and environmental and climatic changes promoted by anthropogenic activities may have increased the frequency of diseases produced by them. The diagnosis of these diseases must be based on gross, microscopic, and ultrastructural lesions, coupled with detection of the agent by immunohistochemical-, molecular-, and/or culture-based methods.

A 7-y-old backyard Leghorn chicken (Gallus domesticus) was submitted to the California Animal Health and Food Safety Laboratory System (CAHFS)-Turlock branch for postmortem examination, with a history of unexpected death. At postmortem examination, a hemorrhagic soft tissue mass was observed in the cervical region. Microscopically, a densely cellular neoplasm of polygonal epithelial cells and small lymphocytes was observed. The microscopic features of the neoplasm in combination with positive immunohistochemistry for pancytokeratin and CD3 were used to classify the lesion as a thymoma. Thymoma was diagnosed in only 5 birds submitted to CAHFS from 1990 to 2019. Thymoma has been described only rarely in birds, and is an unusual diagnosis in backyard chickens.

PurposeDiffusion-weighted MRI (DW-MRI) is a contrast-free modality that has demonstrated ability to discriminate between predefined benign and malignant breast lesions. However, how well DW-MRI discriminates cancer from all other breast tissue voxels in a clinical setting is unknown. Here we explore the voxelwise ability to distinguish cancer from healthy breast tissue using signal contributions from the newly developed three-component multi-b-value DW-MRI model.Experimental designPatients with pathology-proven breast cancer from two datasets (n = 81 and n = 25) underwent multi-b-value DW-MRI. The three-component signal contributions C 1 and C 2 and their product, C 1 C 2, and signal fractions F 1, F 2, and F 1 F 2 were compared with the image defined on maximum b-value (DWI max), conventional apparent diffusion coefficient (ADC), and apparent diffusion kurtosis (K app). The ability to discriminate between cancer and healthy breast tissue was assessed by the false-positive rate given a sensitivity of 80% (FPR80) and ROC AUC.ResultsMean FPR80 for both datasets was 0.016 [95% confidence interval (CI), 0.008-0.024] for C 1 C 2, 0.136 (95% CI, 0.092-0.180) for C 1, 0.068 (95% CI, 0.049-0.087) for C 2, 0.462 (95% CI, 0.425-0.499) for F 1 F 2, 0.832 (95% CI, 0.797-0.868) for F 1, 0.176 (95% CI, 0.150-0.203) for F 2, 0.159 (95% CI, 0.114-0.204) for DWI max, 0.731 (95% CI, 0.692-0.770) for ADC, and 0.684 (95% CI, 0.660-0.709) for K app. Mean ROC AUC for C 1 C 2 was 0.984 (95% CI, 0.977-0.991).ConclusionsThe C 1 C 2 parameter of the three-component model yields a clinically useful discrimination between cancer and healthy breast tissue, superior to other DW-MRI methods and obliviating predefining lesions. This novel DW-MRI method may serve as noncontrast alternative to standard-of-care dynamic contrast-enhanced MRI.

PURPOSE: Microbial infection stimulates neutrophil/macrophage/monocyte extracellular trap formation, which leads to the release of citrullinated histone H3 (CitH3) catalyzed by peptidylarginine deiminase (PAD) 2 and 4. Understanding these molecular mechanisms in the pathogenesis of septic shock will be an important next step for developing novel diagnostic and treatment modalities. We sought to determine the expression of CitH3 in patients with septic shock, and to correlate CitH3 levels with PAD2/PAD4 and clinically relevant outcomes. METHODS: Levels of CitH3 were measured in serum samples of 160 critically ill patients with septic and non-septic shock, and healthy volunteers. Analyses of clinical and laboratory characteristics of patients were conducted. RESULTS: Levels of circulating CitH3 at enrollment were significantly increased in septic shock patients (n = 102) compared to patients hospitalized with non-infectious shock (NIC) (n = 32, p

Calcifying fibrous tumors are rare lesions that occur throughout the body. A 35-year-old man presented with exertional dyspnea. Computed tomography showed a polypoid mass abutting pericardium, diaphragm, and left chest wall, and a pleural-based lesion adjacent to T12. Thoracoscopy revealed a large mass with diaphragmatic stalk, two pleural-based nodules, and four diaphragmatic nodules. Pathologic analysis of resected lesions showed calcifying fibrous tumors. Three lesions contained heterogenous mutations associated with this tumor type. The patient is disease free 1 year later. Calcifying fibrous tumors should be recognized as rare multifocal pleural and diaphragmatic-based tumors. Complete resection leads to excellent survival for patients with this uncommon disease.

SignificanceCurrent imaging paradigms for differential diagnosis of suspicious breast lesions suffer from high false positive rates that force patients to undergo unnecessary biopsies. Diffuse optical spectroscopic imaging (DOSI) noninvasively probes functional hemodynamic and compositional parameters in deep tissue and has been shown to be sensitive to contrast between normal and malignant tissues.AimDOSI methods are under investigation as an adjunct to mammography and ultrasound that could reduce false positive rates and unnecessary biopsies, particularly in radiographically dense breasts.MethodsWe performed a retrospective analysis of 212 subjects with suspicious breast lesions who underwent DOSI imaging. Physiological tissue parameters were z-score normalized to the patient's contralateral breast tissue and input to univariate logistic regression models to discriminate between malignant tumors and the surrounding normal tissue. The models were then used to differentiate malignant lesions from benign lesions.ResultsModels incorporating several individual hemodynamic parameters were able to accurately distinguish malignant tumors from both the surrounding background tissue and benign lesions with area under the curve (AUC) ≥0.85. Z-score normalization improved the discriminatory ability and calibration of these predictive models relative to unnormalized or ratio-normalized data.ConclusionsFindings from a large subject population study show how DOSI data normalization that accounts for normal tissue heterogeneity and quantitative statistical regression approaches can be combined to improve the ability of DOSI to diagnose malignant lesions. This improved diagnostic accuracy, combined with the modality's inherent logistical advantages of portability, low cost, and nonionizing radiation, could position DOSI as an effective adjunct modality that could be used to reduce the number of unnecessary invasive biopsies.

INTRODUCTION: Catatonia is classically associated with psychiatric conditions but may occur in medical and neurologic disorders. Status epilepticus (SE) is a seizure lasting more than five minutes or two or more seizures within a five-minute period without interictal recovery of consciousness. Non-convulsive status epilepticus (NCSE) is SE without prominent motor activity that may present with catatonic symptoms. The relevance of NCSE as a potential etiology for catatonia is not clear in the literature. METHODS: A systematic review was completed to evaluate the literature on NCSE presenting with catatonia. PubMed and PsycInfo databases were searched and articles were reviewed for the presence of catatonia and NCSE. RESULTS: 15 articles describing 27 cases meeting inclusion criteria were identified. The authors add 1 case to the literature. The most common catatonic symptoms identified in NCSE were mutism and stupor. Clinical features frequent in NCSE presenting with catatonia included new catatonic symptoms, age over 50 years, comorbid neurological conditions, or a change in medications that affect seizure threshold. A documented psychiatric history was also common and may contribute to delayed diagnosis. DISCUSSION/CONCLUSION: It is important to consider NCSE in the differential diagnosis of new catatonic symptoms. A suggested approach to diagnostic evaluation is provided.

RATIONALE & OBJECTIVE: Kidney biopsy data inform us about pathologic processes associated with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a multicenter evaluation of kidney biopsy findings in living patients to identify various kidney disease pathology findings in patients with coronavirus disease 2019 (COVID-19) and their association with SARS-CoV-2 infection. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We identified 14 native and 3 transplant kidney biopsies performed for cause in patients with documented recent or concurrent SARS-CoV-2 infection treated at 7 large hospital systems in the United States. OBSERVATIONS: Men and women were equally represented in this case series, with a higher proportion of Black (n=8) and Hispanic (n=5) patients. All 17 patients had SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction, but only 3 presented with severe COVID-19 symptoms. Acute kidney injury (n=15) and proteinuria (n=11) were the most common indications for biopsy and these symptoms developed concurrently or within 1 week of COVID-19 symptoms in all patients. Acute tubular injury (n=14), collapsing glomerulopathy (n=7), and endothelial injury/thrombotic microangiopathy (n=6) were the most common histologic findings. 2 of the 3 transplant recipients developed active antibody-mediated rejection weeks after COVID-19. 8 patients required dialysis, but others improved with conservative management. LIMITATIONS: Small study size and short clinical follow-up. CONCLUSIONS: Cases of even symptomatically mild COVID-19 were accompanied by acute kidney injury and/or heavy proteinuria that prompted a diagnostic kidney biopsy. Although acute tubular injury was seen among most of them, uncommon pathology such as collapsing glomerulopathy and acute endothelial injury were detected, and most of these patients progressed to irreversible kidney injury and dialysis.

BackgroundD. Frank Benson and colleagues first described the clinical and neuropathological features of posterior cortical atrophy (PCA) from patients in the UCLA Neurobehavior Program.ObjectiveWe reviewed the Program's subsequent clinical experience with PCA, and its potential for clarifying this relatively rare syndrome in comparison to the accumulated literature on PCA.MethodsUsing the original criteria derived from this clinic, 65 patients with neuroimaging-supported PCA were diagnosed between 1995 and 2020.ResultsOn presentation, most had visual localization complaints and related visuospatial symptoms, but nearly half had memory complaints followed by symptoms of depression. Neurobehavioral testing showed predominant difficulty with visuospatial constructions, Gerstmann's syndrome, and Balint's syndrome, but also impaired memory and naming. On retrospective application of the current Consensus Criteria for PCA, 59 (91%) met PCA criteria with a modification allowing for "significantly greater visuospatial over memory and naming deficits." There were 37 deaths (56.9%) with the median overall survival of 10.3 years (95% CI: 9.6-13.6 years), consistent with a slow neurodegenerative disorder in most patients.ConclusionTogether, these findings recommend modifying the PCA criteria for "relatively spared" memory, language, and behavior to include secondary memory and naming difficulty and depression, with increased emphasis on the presence of Gerstmann's and Balint's syndromes.

BackgroundAge-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer's disease (AD), although their interactive effects have yet to be fully examined.ObjectiveThe current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI).MethodsThis study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1-42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified.ResultsMultiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ42 (B = -1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s

Mitochondrial diseases are rare, often go undiagnosed and can lead to devastating cascades of multisystem organ dysfunction. This report of a young woman with hearing loss and gestational diabetes illustrates a novel presentation of a cardiomyopathy caused by a previously described mutation in a mitochondrial gene, MT-TL1. She initially had biventricular heart dysfunction and ventricular arrhythmia that ultimately recovered with beta blockade and time. She continues to participate in sport without decline. It is important to keep mitochondrial diseases in the differential diagnosis and understand the testing and management strategies in order to provide the best patient care.

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Renal oncocytoma (RO) accounts for 5% of renal cancers and generally behaves as a benign tumor with favorable long-term prognosis. It is difficult to confidently distinguish between benign RO and other renal malignancies, particularly chromophobe renal cell carcinoma (chRCC). Therefore, RO is often managed aggressively with surgery. We sought to identify molecular biomarkers to distinguish RO from chRCC and other malignant renal cancer mimics. In a 44-patient discovery cohort, we identified a significant differential abundance of nine genes in RO relative to chRCC. These genes were used to train a classifier to distinguish RO from chRCC in an independent 57-patient cohort. The trained classifier was then validated in five independent cohorts comprising 89 total patients. This nine-gene classifier trained on the basis of differential gene expression showed 93% sensitivity and 98% specificity for distinguishing RO from chRCC across the pooled validation cohorts, with a c-statistic of 0.978. This tool may be a useful adjunct to other diagnostic modalities to decrease the diagnostic and management uncertainty associated with small renal masses and to enable clinicians to recommend more confidently less aggressive management for some tumors. PATIENT SUMMARY: Renal oncocytoma is generally a benign form of kidney cancer that does not necessarily require surgical removal. However, it is difficult to distinguish renal oncocytoma from other more aggressive forms of kidney cancer, so it is treated most commonly with surgery. We built a classification tool based on the RNA levels of nine genes that may help avoid these surgeries by reliably distinguishing renal oncocytoma from other forms of kidney cancer.

Laugier-Hunziker syndrome (LHS) is a sporadic, acquired, and infrequent condition characterized by the onset of brown macules on the lips, the oral mucosa, and the acral glabrous skin (mainly fingers and toes) in middle-aged patients. In several cases melanonychia of fingernails and toenails coexists. No other systemic involvement is observed. A case of LHS in a 50-year-old woman is described, with particular attention to dermoscopic features. No dermoscopic specific findings of mucosal/cutaneous maculae have been to date described in the literature. Accumulation of dermoscopic observations of pigmented lesions in LHS is needed and if found to be distinct, it may contribute to a more accurate diagnosis in the future

BackgroundMolecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein aggregation. A lead MT, called CLR01, has been demonstrated to inhibit the aggregation and toxicity of multiple amyloidogenic proteins in vitro and in vivo. Previously, we evaluated the effect of CLR01 in the 3 × Tg mouse model of Alzheimer's disease, which overexpresses mutant human presenilin 1, amyloid β-protein precursor, and tau and found that subcutaneous administration of the compound for 1 month led to a robust reduction of amyloid plaques, neurofibrillary tangles, and microgliosis. CLR01 also has been demonstrated to inhibit tau aggregation in vitro and tau seeding in cell culture, yet because in Alzheimer's disease (AD) and in the 3 × Tg model, tau hyperphosphorylation and aggregation are thought to be downstream of Aβ insults, the study in this model left open the question whether CLR01 affected tau in vivo directly or indirectly.MethodsTo determine if CLR01 could ameliorate tau pathology directly in vivo, we tested the compound similarly using the P301S-tau (line PS19) mouse model. Mice were administered 0.3 or 1.0 mg/kg per day CLR01 and tested for muscle strength and behavioral deficits, including anxiety- and disinhibition-like behavior. Their brains then were analyzed by immunohistochemical and biochemical assays for pathological forms of tau, neurodegeneration, and glial pathology.ResultsCLR01 treatment ameliorated muscle-strength deterioration, anxiety-, and disinhibition-like behavior. Improved phenotype was associated with decreased levels of pathologic tau forms, suggesting that CLR01 exerts a direct effect on tau in vivo. Limitations of the study included a relatively short treatment period of the mice at an age in which full pathology is not yet developed. In addition, high variability in this model lowered the statistical significance of the findings of some outcome measures.ConclusionsThe findings suggest that CLR01 is a particularly attractive candidate for the treatment of AD because it targets simultaneously the two major pathogenic proteins instigating and propagating the disease, amyloid β-protein (Aβ), and tau, respectively. In addition, our study suggests that CLR01 can be used for the treatment of other tauopathies in the absence of amyloid pathology.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Differentiation between IBD and SCL can be diagnostically challenging. We characterized the fecal metabolome of 14 healthy cats and 22 cats with naturally occurring CE (11 cats with IBD and 11 cats with SCL). Principal component analysis and heat map analysis showed distinct clustering between cats with CE and healthy controls. Random forest classification revealed good group prediction for healthy cats and cats with CE, with an overall out-of-bag error rate of 16.7%. Univariate analysis indicated that levels of 84 compounds in cats with CE differed from those in healthy cats. Polyunsaturated fatty acids held discriminatory power in differentiating IBD from SCL. Metabolomic profiles of cats with CE resembled those in people with CE with significant alterations of metabolites related to tryptophan, arachidonic acid, and glutathione pathways.

Background and scope of reviewVarying severities and frequencies of head trauma may result in dynamic acute and chronic pathophysiologic responses in the brain. Heightened attention to long-term effects of head trauma, particularly repetitive head trauma, has sparked recent efforts to identify neuroimaging biomarkers of underlying disease processes. Imaging modalities like structural magnetic resonance imaging (MRI) and positron emission tomography (PET) are the most clinically applicable given their use in neurodegenerative disease diagnosis and differentiation. In recent years, researchers have targeted repetitive head trauma cohorts in hopes of identifying in vivo biomarkers for underlying biologic changes that might ultimately improve diagnosis of chronic traumatic encephalopathy (CTE) in living persons. These populations most often include collision sport athletes (e.g., American football, boxing) and military veterans with repetitive low-level blast exposure. We provide a clinically-oriented review of neuroimaging data from repetitive head trauma cohorts based on structural MRI, FDG-PET, Aβ-PET, and tau-PET. We supplement the review with two patient reports of neuropathology-confirmed, clinically impaired adults with prior repetitive head trauma who underwent structural MRI, FDG-PET, Aβ-PET, and tau-PET in addition to comprehensive clinical examinations before death.Review conclusionsGroup-level comparisons to controls without known head trauma have revealed inconsistent regional volume differences, with possible propensity for medial temporal, limbic, and subcortical (thalamus, corpus callosum) structures. Greater frequency and severity (i.e., length) of cavum septum pellucidum (CSP) is observed in repetitive head trauma cohorts compared to unexposed controls. It remains unclear whether CSP predicts a particular neurodegenerative process, but CSP presence should increase suspicion that clinical impairment is at least partly attributable to the individual's head trauma exposure (regardless of underlying disease). PET imaging similarly has not revealed a prototypical metabolic or molecular pattern associated with repetitive head trauma or predictive of CTE based on the most widely studied radiotracers. Given the range of clinical syndromes and neurodegenerative pathologies observed in a subset of adults with prior repetitive head trauma, structural MRI and PET imaging may still be useful for differential diagnosis (e.g., assessing suspected Alzheimer's disease).

Background/Aim. The field of lung ultrasonography (US) is a fast-developing one, and it provides the medical community with numerous new diagnostic opportunities. The aim of this study was to examine the etiology of dyspnea on admission and assess the stage of heart failure (HF) according to the US examination of the heart and lungs. Methods. The cross-sectional study included a total of 110 patients treated for the symptoms of dyspnea. The study included all patients treated for any heart or pulmonary condition, as well as patients who reported the first episode of dyspnea without any previous illness. The most important diagnostic sign in the US of the lungs in patients with HF was the appearance of B-lines or "comets" (ultrasound artifacts reminiscent of comet tails), which indicate the accumulation of fluid in the interstitium of the lungs. Results. The mean number of registered "comets" in the total number of patients was 14.2 ± 7.4 (minimum 2, maximum 30). The mean number of "comets" among patients with HF was 18.8 ± 5.9. The mean number of "comets" among patients without HF was 8.0 ± 3.7 (p < 0.001). Multivariate linear regression analyses showed the association between the number of "comets" and HF (p < 0.001). Conclusion. As the assessment of present "comets" in pulmonary US examination is safe and non-invasive, it can easily be integrated into the daily clinical practice because it has been shown that the number of pulmonary "comets" is significantly higher in patients with HF compared to those with dyspnea of other etiologies. [ABSTRACT FROM AUTHOR]

• Identifies the importance of the subjective experience of seizures to recognition, assessment, and management of seizure disorders. • Explores challenges in taking accurate seizure histories, including indescribable experiences, difficulties with recall, and top-down influences on perception. • Highlights emerging areas of research interest that could harness seizure subjectivity for clinical application. The typical adult patient presenting with a first seizure has a normal clinical examination, uninformative investigations, and often has no witness to their episode. The assessing clinician, therefore, has one primary source of information to guide their assessment; the patient's experience. However, seizure phenomenology – the subjective seizure experience – has received relatively less attention by researchers than objective semiology or investigations. This essay reviews the clinical importance of seizure phenomenology, and the challenges clinicians face in eliciting accurate and clinically relevant descriptions of ictal experience. I conclude by discussing tools that clinicians may use to support the clinical application of seizure phenomenology, and exploring the subjectivity of epilepsy more broadly. [ABSTRACT FROM AUTHOR]

Although the comparison of fully differential ionization data for particle and antiparticle impact provides the ultimate tests of theoretical models, only very low antiparticle beam intensities are available. Hence, few experiments of this type have been performed. Therefore, available experimentally obtained single and double differential cross-sections, which are much easier to obtain, are compared in order to demonstrate differences when only the projectile mass or charge (+1 or −1) is changed. Included in the comparison are cross-sections calculated for positron and electron impact using a three-particle classical trajectory Monte Carlo method. The calculated cross-sections provide independent information about the ejected electron and the scattered projectile contributions, plus information about the impact parameters, all as functions of the collision kinematics. From these comparisons, suggestions as to where future investigations are both feasible and useful are provided. [ABSTRACT FROM AUTHOR]

This article presents the design and optimization of a tunable quadrature differential LC CMOS voltage-controlled oscillator (VCO) with a D flip-flop (DFF) frequency divider. The VCO is designed for the low-power and low-phase-noise applications of 2.4 GHz IoT/BLE receivers and wireless sensor devices. The proposed design comprises the proper stacking of an LC VCO and a DFF frequency divider and is simulated using a TSMC 65 nm CMOS technology, and it has a tuning range of 4.4 to 5.7 GHz. The voltage headroom is preserved using a high-impedance on-chip passive inductor at the tail for filtering and enabling true differential operation. The VCO and frequency divider consume as low as 2.02 mW altogether, with the VCO section consuming only 0.47 mW. The active area of the chip including the pads is only 0.47 mm2. The designed VCO achieved a much better phase noise of −118.36 dBc/Hz at a 1 MHz offset frequency with 1.2 V supply voltages. The design produced a much better FoM of −196.44 dBc/Hz compared to other related research. [ABSTRACT FROM AUTHOR]

Type A acute aortic syndrome (urgent AAS, UAAS) has a low incidence and high mortality rate; however, it is often missed or diagnosed late. Our aim was to create a new tool for distinguishing UAAS by using multiple modalities to select patients for CT aortography. This study included 75 patients with UAAS, 77 with acute coronary syndrome (ACS), and 81 with heart failure (HF) who received urgent treatment after propensity matching. Specific symptoms, past medical history, mediastinal width, region of interest (ROI) ratio in the lung base/apex, D-dimers, and troponin I were investigated to differentiate UAAS from ACS and HF. The most significant variables were selected to create a new scoring system. The UAAS score exhibited a performance AUC of 0.982. A simple UAAS score >1, excluding ROI ratios in lung base/apex, showed an AUC of 0.977, a sensitivity of 96%, and specificity of 92.41%. The results were validated using an external data set of 292 patients (simple UAAS score > 1: AUC of 0.966, sensitivity 93.33%, and specificity 95.36%). The simple UAAS score may be a valuable tool for suspecting UAAS and may reduce the likelihood of misdiagnosis or performing unnecessary CT aortography. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinicopathological and immunohistochemical characteristics of ovarian Brenner tumor. Methods: The clinical data, pathological features, immunophenotypes, and molecular characteristics of six patients with ovarian Brenner tumor between January 2019 and February 2023 at Suzhou Ninth Hospital Affiliated to Soochow University (our hospital) were retrospectively analyzed. Results: The age of the six patients varied from 54 to 73 years, with a median age of 66 years. Among these patients, four were diagnosed with benign ovarian Brenner tumor, while two were malignant. Biochemical indicators of 4 patients with benign ovarian Brenner tumor and one with malignant ovarian Brenner tumor were within normal ranges, while the level of carbohydrate antigen 125 (CA125) in another one patient with malignant ovarian Brenner tumor was significant increased. Microscopic examination revealed that the tissue of benign ovarian Brenner tumor was consisted of transitional cell epithelial nests, accompanied by fibrous stroma. These cells did not display any atypia and had oval nuclei with small nucleoli. In contrast, the tissue of malignant ovarian Brenner tumor exhibited clear stromal infiltration, evident atypia, a high nuclear plasma ratio, and increased mitotic activity, which was accompanied by benign ovarian Brenner tumor and borderline ovarian Brenner tumor components. Immunohistochemical staining showed that the tumor cells were positive for cytokeratin 7 (CK7), P63 and GATA binding protein 3 (GATA3), but negative for paired box 8 (PAX8), Wilm′s tumor gene 1 (WT1) and CK20. Ki-67 proliferation index was lowered 1% in benign ovarian Brenner tumor and about 20%-60% in malignant ovarian Brenner tumor. Four patients with benign ovarian Brenner′s tumor underwent adnexectomy on the affected side, with a good prognosis. One case of malignant ovarian Brenner′s tumor underwent laparoscopic ovarian staging surgery, and no recurrence or metastasis was found after 11 months of follow -up. Another case of ovarian malignant ovarian Brenner tumor was lost due to not undergoing surgery in our hospital. Conclusions: The diagnosis of ovarian Brenner tumor depends on the histopathological characteristics and immunohistochemistry. The differential diagnosis of benign and malignant ovarian Brenner tumor is based on the degree of cell atypia and stromal invasion. In addition, Ki-67 proliferation index can be used as a reference index. [ABSTRACT FROM AUTHOR]

This paper introduces a discrete-time stochastic game class on Z d , which plays the role of a toy model for the well-known problem of stochastic homogenization of Hamilton–Jacobi equations. Conditions are provided under which the n-stage game value converges as n tends to infinity, and connections with homogenization theory are discussed. Funding: The second author acknowledges the support of the French Agence Nationale de la Recherche (ANR) [Grant ANR-21-CE40-0020] (CONVERGENCE project). [ABSTRACT FROM AUTHOR]

Introduction. Complex visual hallucinations with retention of insight due to visual impairment are key symptoms of Charles Bonnet syndrome. The syndrome is a standalone diagnosis in the International Classification of Diseases, 11th Revision. Nevertheless, in clinical praxis, it is often misdiagnosed as psychosis or early stages of dementia, and it goes underreported by patients because of the fear of being diagnosed with a mental illness. Case report. We presented four elderly patients, who were referred for psychiatric consultation due to visual hallucinations, with preserved insight, but with impaired vision. All four patients had complex, vivid, and colorful hallucinations consisting of realistic objects, people, animals, or scenery that tend to recur. Their emotional response and impact on quality of life differed, and psychopharmacotherapy was determined according to their psychological symptoms. Empathic explanation of the symptoms' origin and reassurance of the absence of mental illness for patients and caregivers were of vital importance in all cases. Conclusion. With the aging of the population, the number of patients with impaired vision also increases, and the importance of a multidisciplinary approach in the diagnostic procedures and treatment of Charles Bonnet syndrome is emphasized. Increased awareness of clinical characteristics and therapeutic approaches is required among all physicians who are in contact with elderly and/or impaired vision patients. [ABSTRACT FROM AUTHOR]

Catatonia can be defined as an etiologically heterogeneous syndrome, with predominant psychomotor disturbances. Historically, the concept of catatonia has been associated with mental disorders, especially schizophrenia. However, nowadays our understanding of catatonia has evolved to recognize it as neuropsychiatric syndrome that can arise from diverse etiological factors ranging from neurological to systemic diseases. Furthermore, there is now a recognized association between catatonia and a broader spectrum of mental disorders. Catatonia as a secondary neuropsychiatric syndrome may be a clinical manifestation of COVID-19 also due to the known neuroinvasive potential of the SARS-CoV-2 virus or in connection with the overall somatic alteration of the patient. In clinical practice, co-infection with SARS-CoV-2 could impede the process of diagnosing and treating catatonia as the primary psychopathological syndrome. The administration of benzodiazepines and electroconvulsive therapy could endanger the patient's physical health with active COVID-19 infection. Management of catatonic syndrome associated with COVID-19 is a challenge and requires a comprehensive therapeutic approach. The article demonstrates the abovementioned difficulties of treatment through two case presentations (Tab. 2, Ref. 29). [ABSTRACT FROM AUTHOR]

Introduction/Aim. Lentigo maligna (LM) represents an in situ melanoma that develops on chronically photo-damaged skin. Clinical diagnosis of LM is often difficult, even for experienced dermatologists. The aim of the study was to analyze the clinical and dermoscopic features of patients with pathohistologically verified lentigo maligna (LM) and to determine a possible influence of anatomical topography, age and gender in the dermoscopic features of LM. Patients and methods. This retrospective study included 32 patients with 32 LM changes in total, diagnosed between 2017 and 2020. Clinical data recorded from each patient included the following: demographic features (age, gender), anatomic localization (facial or extrafacial) and clinical size (< 10 mm or > 10 mm). Facial area was subdivided into eight topographical sites, while extrafacial localization involved any location outside the face region. All dermoscopic images were analyzed for the presence of dermoscopic features previously described as LM. Results. In the total of 32 patients, there were 19 males and 13 females. The patients' age ranged from 34 to 80 years (median age 60.1 ± 10.4 years). Significant female predominance was observed for localization on the cheeks (p = 0.018). Localization on the nose was significantly associated with patients older than 65 (p = 0.039). The most frequent dermoscopic features were asymmetric pigmented follicular openings in 23 (71.9%) cases, gray color in 22 (68.8%) and pigmented rhomboidal structures in 15 (46.9%) cases. In relation to age and specific dermoscopic features, gray color (p = 0.035) and white scar-like areas (p = 0.012) were significantly higher in patients older than 65, while pigmented rhomboidal structures (p = 0.041) were significantly associated with younger patients. Conclusion. The observed differences in the frequency of clinical and dermoscopic features of LM have significant importance in everyday clinical practice and can assist clinicians in the early diagnosis of this malignant tumor. [ABSTRACT FROM AUTHOR]

Background: Early detection is necessary for the treatment of dementia. Computerized testing has become more widely used in clinical trials; however, it is unclear how sensitive these measures are to early signs of neurodegeneration. We investigated the use of the NIH Toolbox-Cognition (NIHTB-CB) and Cogstate-Brief computerized neuropsychological batteries in the identification of mild cognitive impairment (MCI) versus healthy older adults [healthy control (HC)] and amnestic (aMCI) versus nonamnestic MCI (naMCI). Exploratory analyses include investigating potential racial differences. Methods: Two hundred six older adults were diagnosed as aMCI (n = 58), naMCI (n = 15), or cognitively healthy (HC; n = 133). Results: The NIH Toolbox-CB subtests of Flanker, Picture Sequence Memory, and Picture Vocabulary significantly differentiated MCI from HC. Further, subtests from both computerized batteries differentiated patients with aMCI from those with naMCI. Although the main effect of race differences was noted on tests and in diagnostic groups was significant, there were no significant race-by-test interactions. Conclusions: Computer-based subtests vary in their ability to help distinguish MCI subtypes, though these tests provide less expensive and easier-to-administer clinical screeners to help identify patients early who may qualify for more comprehensive evaluations. Further work is needed, however, to refine computerized tests to achieve better precision in distinguishing impairment subtypes. [ABSTRACT FROM AUTHOR]

The oscillation of frequency can cause the generator to run out of sync in a power system. Therefore, load frequency control (LFC) is needed to reduce frequency oscillation and prevent out of sync operation. The LFC regulates the governor to balance the turbine speed with changes in the load of existing. In this paper, a proportional integral differential (PID) controller and a battery energy storage system (BESS) are added to an LFC to improve the frequency stability of a power system. The parameters of the PID controller and BESS are optimized using the Bat algorithm (BA) to attain a good coordination. The frequency performance analysis is done by introducing disturbance in the form of changes in load power. The simulation results show that the frequency deviation of the system with the PID controller and BESS, has a faster settling time and smaller overshoot value. The system performs better than those with only the PID controller or the BESS. In conclusion, the BA algorithm can be used to find optimal parameter values of the PID controller and BESS for a synchronized coordination of an LFC. [ABSTRACT FROM AUTHOR]

In this present study, the tumor growth model using the Gompertz equation with the Allee effect is developed under a fuzzy environment using the Generalized Hukuhara Derivative (GHD) approach. To capture the tumor growth patterns with the Allee threshold, the parameters present in the model vary from time to time, and in real life, it is very difficult to estimate the exact cell count. In this vague situation, the initial condition, coefficient, and both together are taken as the fuzzy number. In this paper, the GHD approach is used to solve the fuzzy tumor growth model in which four different cases are considered with respect to (i)-gH differentiability and (ii)-gH differentiability concept. The main objective of this study is to present a significant reduction in uncertainty while modeling the tumor growth in a fuzzy environment with the Allee effect. Finally, the proposed model and technique are illustrated by numerical simulation and analysis of tumor growth is conducted. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We previously developed a convolutional neural networks (CNN)-based algorithm to distinguish atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS) using a mammographic dataset. The purpose of this study is to further validate our CNN algorithm by prospectively analyzing an unseen new dataset to evaluate the diagnostic performance of our algorithm. MATERIALS AND METHODS: In this institutional review board-approved study, a new dataset composed of 280 unique mammographic images from 140 patients was used to test our CNN algorithm. All patients underwent stereotactic-guided biopsy of calcifications and underwent surgical excision with available final pathology. The ADH group consisted of 122 images from 61 patients with the highest pathology diagnosis of ADH. The DCIS group consisted of 158 images from 79 patients with the highest pathology diagnosis of DCIS. Two standard mammographic magnification views (craniocaudal and mediolateral/lateromedial) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D slicer and resized to fit a 128 × 128 pixel bounding box. Our previously developed CNN algorithm was used. Briefly, a 15 hidden layer topology was used. The network architecture contained 5 residual layers and dropout of 0.25 after each convolution. Diagnostic performance metrics were analyzed including sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. The positive class was defined as the pure ADH group in this study and thus specificity represents minimizing the amount of falsely labeled pure ADH cases. RESULTS: Area under the receiver operating characteristic curve was 0.90 (95% confidence interval, ± 0.04). Diagnostic accuracy, sensitivity, and specificity was 80.7%, 63.9%, and 93.7%, respectively. CONCLUSION: Prospectively tested on new unseen data, our CNN algorithm distinguished pure ADH from DCIS using mammographic images with high specificity.

On 31 December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, China, and caused the outbreak of the Coronavirus Disease 2019 (COVID-19). To date, computed tomography (CT) findings have been recommended as major evidence for the clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the imaging characteristics and changes throughout the disease course in patients with COVID-19 in order to provide some help for clinicians. Typical CT findings included bilateral ground-glass opacity, pulmonary consolidation, and prominent distribution in the posterior and peripheral parts of the lungs. This review also provides a comparison between COVID-19 and other diseases that have similar CT findings. Since most patients with COVID-19 infection share typical imaging features, radiological examinations have an irreplaceable role in screening, diagnosis and monitoring treatment effects in clinical practice.

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.

Autoinflammatory diseases are monogenic and polygenic disorders due to dysregulation of the innate immune system. The inherited conditions have been clustered with primary immunodeficiencies in the latest practice parameters; however, these diseases have unique clinical presentations, genetics, and available therapies. Given the presentation of fevers, rashes, and mucosal symptoms observed in many of these syndromes, patients are likely to present to an allergist/immunologist. Although there has been attention in the literature to diagnosis and treatment of rare, genetically defined autoinflammatory disorders, physicians are challenged by increasing numbers of patients with intermittent or periodic fevers who face unnecessary morbidities due to a lack of a diagnosis. The broad differential of diseases presenting with fever includes autoinflammatory syndromes, infections associated with immunodeficiency and/or allergies complicated by infection, and less commonly, autoimmune disorders or malignancy. To address this challenge, we review the history of the medical approach to fever, current diagnostic paradigms, and controversies in management. We describe the spectrum of disorders referred to a recurrent fever disorders clinic established in an Allergy/Immunology division at a tertiary pediatric care center. Finally, we provide practical recommendations including historical features and initial laboratory investigations that can help clinicians appropriately manage these patients.

Cerebrospinal fluid (CSF) biomarkers amyloid-β and tau have been validated for the antemortem diagnosis of Alzheimer disease (AD) and are included in the AT(N) research framework for AD. Recently, an AT(N) CSF profile has been described for dementia with Lewy bodies (DLB), a disorder which is difficult to distinguish clinically from AD, particularly early in the disease course. Herein we describe a 71-year old male who presented with an atypical dementia syndrome including years of stability after an initial abrupt decline, marked visuospatial dysfunction, and relative sparing of memory. CSF biomarkers combined with the pattern of cognitive symptoms made AD unlikely and were consistent with DLB. This classification was confirmed clinically, with the emergence of classic DLB symptoms, and at postmortem pathologic examination. This case highlights the role for AD CSF biomarkers in facilitating earlier diagnosis of non-Alzheimer neurodegenerative dementias.

The distinction between well-differentiated intrahepatic cholangiocarcinoma (iCCA) from its morphological mimics such as bile duct adenoma (BDA) and hamartoma (BDH) can be challenging, particularly in small biopsies. Although a few cases of BDA and BDH have been reported to undergo malignant transformation into iCCA, their neoplastic versus benign nature remains debated. DNA flow cytometry was performed on 47 formalin-fixed paraffin-embedded samples of iCCA, 14 BDA, and 18 BDH. Aneuploidy was detected in 22 iCCA (47%) but in none of the 32 BDA and BDH samples. Among the 34 iCCA patients who underwent complete resection and were followed up to tumor recurrence, tumor-related death, or at least for 1 year, the overall recurrence or death rates (regardless of flow cytometric results) were 18, 56, and 71% within 1, 3, and 5 years, respectively. The 1-, 3-, and 5-year recurrence or death rates in 18 iCCA patients with aneuploidy were 28, 66, and 66%, respectively, whereas 16 iCCA patients in the setting of normal DNA content had 1-, 3-, and 5-year rates of 6, 44, and 72%, respectively. Although aneuploid tumors were associated with worse outcomes during the first 3 years, this difference was not statistically significant (hazard ratio = 1.4, p = 0.473) in the present sample size. In conclusion, the frequency of aneuploidy was significantly higher in iCCA (47%) than in its benign morphological mimics (0%), suggesting that it may potentially serve as a diagnostic marker of malignancy in challenging situations. Our findings also suggest that most BDAs and BDHs, if not all, are benign entities and may not represent precursor lesions to iCCAs that often harbor aneuploidy. Although a larger cohort will be necessary to further determine the prognostic significance of aneuploidy in iCCA patients after resection, the patients with aneuploid tumors may have a higher risk for tumor progression, especially during the first 3 years.

Degree of memory impairment is often used to infer early versus late amnestic mild cognitive impairment (aMCI). Previously, 318 Alzheimer's Disease Neuroimaging Initiative participants with aMCI-determined by a single memory test-were divided based on Rey Auditory Verbal Learning Task (AVLT) delayed recall: AVLT-impaired (n = 225) and AVLT-normal (n = 93). Equally consistent with differential progression or differential diagnosis, the AVLT-impaired group had more abnormal Alzheimer's disease (AD) biomarkers, more neurodegeneration over time, and was more likely to develop AD. In the present study, higher AD polygenic risk scores were associated with increased odds of being AVLT-impaired (odds ratio 1.8, p < 0.001). Thus, impairment severity does not necessarily reflect early versus late aMCI because disease progression cannot alter polygenic risk. Presumed early MCI is likely a heterogeneous category that includes excess false-positives. The additional cognitive test improved diagnostic precision by reducing false positives. Impairment severity may reflect differences in underlying disease risk but cannot be used to infer early versus late MCI based on cross-sectional data alone.

RATIONALE: Primary central nervous system lymphoma (PCNSL) involving the choroid plexus is exceedingly rare. The differential diagnosis for choroid plexus enhancing lesions in addition to lymphoma includes infections, sarcoidosis, tuberculosis, papilloma, meningioma, subependymoma, and metastatic lesions. PATIENT CONCERNS: A 71-year-old man presented with 3 days of episodic memory loss and gait disturbance. Brain magnetic resonance imaging showed homogenously enhancing lesions with mildly restricted diffusion and T2 hypointensity in the lateral ventricles, as well as T2 hyperintensity and enhancement in the right hippocampus. His episodic memory loss was thought to be secondary to subclinical focal seizures, supported by EEG revealing right temporal lobe epileptiform discharges. DIAGNOSES: Large B-cell lymphoma, nongerminal center type was revealed on pathological examination. INTERVENTIONS: Stereotactic biopsy of his right thalamic lesion was performed. OUTCOMES: The patient underwent induction therapy with high-dose methotrexate, temozolomide, and rituximab, which resulted in complete resolution of the enhancing lesions. He then underwent conditioning chemotherapy with carmustine and thiotepa, followed by autologous stem cell transplantation. His PCNSL remains in remission 42 weeks after the onset of symptoms. LESSONS: We report a patient with multifocal PCNSL involving the choroid plexus, who presented with abnormal gait and episodic confusion and memory loss. PCNSL should be considered in the differential diagnosis of acute encephalopathy among immunocompetent older individuals who have choroid plexus enhancing lesions.