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Angiocentric gliomas (AGs) are epileptogenic low-grade gliomas in young patients. We aimed to investigate the MRI findings of AGs and systematically review previous publications and three new cases.We searched PubMed, Elsevier's abstract and citation database, and Embase databases and included 50 patients with pathologically proven AGs with analyzable preoperative MRI including 3 patients from our institution and 47 patients from 38 publications (median age, 13 years [range, 2-83 years]; 35 men). Two board-certified radiologists reviewed all images. The relationships between seizure/epilepsy history and MRI findings were statistically analyzed. Moreover, clinical and imaging differences were evaluated between supratentorial and brainstem AGs.Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain parenchymal atrophy were observed in 23 out of 50 (46.0%), 10 out of 50 (20.0%), and 14 out of 50 (28.0%) patients, respectively. Intratumoral T1-weighted high-intensity areas were observed significantly more frequently in patients with stalk-like signs (positive, 9/10 vs. negative, 14/40, p = .0031) and regional atrophy (13/14 vs. 10/36, p = .0001). There were significant relationships between the length of seizure/epilepsy history and presence of intratumoral T1-weighted high-intensity area (median 3 years vs. 0.5 years, p = .0021), stalk-like sign (13.5 vs. 1 year, p .0001), and regional atrophy (14 vs. 0.5 years, p .0001). Patients with brainstem AGs (n = 7) did not have a seizure/epilepsy history and were significantly younger than those with supratentorial AGs (median, 5 vs. 13 years, p .0001, respectively).Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain atrophy were frequent imaging features in AG. We also found that affected age was different between supratentorial and brainstem AGs.

Anal adenocarcinoma is a rare clinical entity for which the optimal management is not defined.This study aimed to describe the multidisciplinary management and outcomes of patients with anal adenocarcinoma.This is a retrospective cohort study.This study was conducted at a quaternary cancer center.Men and women with anal adenocarcinoma treated between 1995 and 2016 were selected.Fifty-two patients were treated with either chemoradiotherapy or trimodality therapy including radiation therapy, chemotherapy, and surgical resection.Local failure, regional failure, and distant metastasis rates were estimated using the cumulative incidence method. The Kaplan-Meier method was used to estimate progression-free survival and overall survival. The multivariable Cox proportional hazards model was used to evaluate the clinical predictors of outcome.There was a higher 5-year rate of local failure in patients treated with chemoradiotherapy compared with trimodality therapy (53% vs 10%; p0.01). The 5-year incidence of distant metastases was 29% (trimodality therapy) versus 30% (chemoradiotherapy; p = 0.9); adjuvant chemotherapy did not reduce the incidence of distant metastases (p = 0.8). Five-year overall survival was 73% (trimodality therapy) versus 49.4% (chemoradiotherapy; p = 0.1). On multivariable analysis, factors associated with worse overall survival were treatment with chemoradiotherapy, cT3-4 category disease, and node-positive disease.This study is limited by its small sample size and retrospective nature.Although treatment may continue to be tailored to individual patients, better outcomes with a trimodality therapy approach were observed. See Video Abstract at http://links.lww.com/DCR/B708.ADENOCARCINOMA ANAL: UNA ENTIDAD POCO FRECUENTE EN NECESIDAD DE UN MANEJO MULTIDISCIPLINARIO.El adenocarcinoma anal es una entidad clínica poco frecuente por lo que aún no se define el manejo óptimo.Describir el manejo multidisciplinario y los resultados de los pacientes con adenocarcinoma anal.Estudio de cohorte retrospectivo.Centro de cáncer cuaternario.Hombres y mujeres con adenocarcinoma anal tratados entre 1995 y 2016.Cincuenta y dos pacientes fueron tratados con quimiorradioterapia o terapia trimodal que incluyó: radioterapia, quimioterapia y resección quirúrgica.Se estimaron las tasas de falla local, falla regional y metástasis a distancia mediante el método de incidencia acumulada. Se utilizó el método de Kaplan-Meier para estimar la supervivencia libre de progresión y la supervivencia global. Los riesgos proporcionales de multivariable Cox se utilizaron para evaluar los predictores clínicos de los resultados.Hubo una mayor tasa de falla local a cinco años en pacientes tratados con quimiorradioterapia en comparación con terapia trimodal (53% vs 10%; p0,01). La incidencia a cinco años de metástasis a distancia fue del 29% (terapia trimodal) versus 30% (quimiorradioterapia) (p = 0,9); la quimioterapia adyuvante no redujo la incidencia de metástasis a distancia (p = 0,8). La supervivencia global a cinco años fue del 73% (terapia trimodal) versus 49,4% (quimiorradioterapia); p = 0,1. En el análisis multivariable, los factores asociados con una peor supervivencia general fueron el tratamiento con quimiorradioterapia, enfermedad de categoría cT3-4 y enfermedad con ganglios positivos.Este estudio está limitado por su pequeño tamaño de muestra y su naturaleza retrospectiva.Aunque el tratamiento puede seguir adaptándose a pacientes individuales, se observaron mejores resultados con un enfoque TTM. Conslute Video Resumen en http://links.lww.com/DCR/B708. (Traducción- Dr. Francisco M. Abarca-Rendon).

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiple immunologic abnormalities and has the potential to involve the central nervous system (CNS). The prevalence of SLE seems to be growing, possibly because of earlier diagnosis and improved survival; however, the associated mortality is still high. The mortality is associated with disease-related risk factors such as lupus disease activity, young age, and organ damage or with antiphospholipid syndrome (APS). Neuropsychiatric SLE (NPSLE), which is caused by SLE-related CNS involvement, comprises a broad range of neurologic and psychiatric manifestations with varying severity, which can make this disease indistinguishable from other conditions that are unrelated to SLE. No unifying pathophysiology has been found in the etiology of NPSLE, suggesting that this condition has multiple contributors such as various immune effectors and the brain-intrinsic neuroimmune interfaces that are breached by the immune effectors. The postulated neuroimmune interfaces include the blood-brain barrier, blood-cerebrospinal fluid barrier, meningeal barrier, and glymphatic system. On the basis of the immunologic, pathologic, and imaging features of NPSLE, the underlying pathophysiology can be classified as vasculitis and vasculopathy, APS, demyelinating syndrome, or autoimmune antibody-mediated encephalitis. Each pathophysiology has different imaging characteristics, although the imaging and pathophysiologic features may overlap. Moreover, there are complications due to the immunocompromised status caused by SLE per se or by SLE treatment. Radiologists and clinicians should become familiar with the underlying mechanisms, radiologic findings, and complications of NPSLE, as this information may aid in the diagnosis and treatment of NPSLE.

Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Each panel plots the rank of expression value in the cohort on the y-axis and the positive quantile transformation (PQT) value on the x-axis. Solid blue circles indicate adrenocortical carcinomas, open red circles indicate adrenocortical adenomas, and black X-marks indicate undetermined histology. In each plot, the gray rectangle highlights the large gap in the distribution that discriminates adenomas from carcinomas which was identified by the DGS criterion.

The Primary Antibodies Used for Immunohistochemistry Studies

Supplementary Fig 1. Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Supplementary Fig 2. Immunohistochemical analysis of CD3, CD4, and CD8 expression.

Immunohistochemical analysis of CD3, CD4, and CD8 expression. Row: a) adenoma; b) stage I carcinoma; and c) stage III carcinoma. Note that cells with short processes are dimly positive for CD4, consistent with macrophages; cells with long process are also dimly positive for CD4, consistent with dendritic cells (Magnification, 100x; inset, 400x).

Probe-sets that Best Discriminated between Adenoma and Carcinoma in the IPACTR Cohort and Association with PFS in the COG Cohort

Clinical Data for Pediatric Adrenocortical Tumor patients

Association of HLA-DPA1 Expression with Clinical and Biological Characteristics of Uniformly Managed Pediatric Adrenocortical Carcinoma

Purpose: Histologic markers that differentiate benign and malignant pediatric adrenocortical tumors are lacking. Previous studies have implicated an association of MHC class II expression with adrenocortical tumor prognosis. Here, we determined the expression of MHC class II as well as the cell of origin of these immunologic markers in pediatric adrenocortical tumor. The impact of MHC class II gene expression on outcome was determined in a cohort of uniformly treated children with adrenocortical carcinomas.Experimental Design: We analyzed the expression of MHC class II and a selected cluster of differentiation genes in 63 pediatric adrenocortical tumors by Affymetrix Human U133 Plus 2.0 or HT HG-U133+PM gene chip analyses. Cells expressing MHC class II were identified by morphologic and immunohistochemical assays.Results: MHC class II expression was significantly greater in adrenocortical adenomas than in carcinomas (P = 4.8 ×10−6) and was associated with a higher progression-free survival (PFS) estimate (P = 0.003). Specifically, HLA-DPA1 expression was most significantly associated with PFS after adjustment for tumor weight and stage. HLA-DPA1 was predominantly expressed by hematopoietic infiltrating cells and undetectable in tumor cells in 23 of 26 cases (88%).Conclusions: MHC class II expression, which is produced by tumor-infiltrating immune cells, is an indicator of disease aggressiveness in pediatric adrenocortical tumor. Our results suggest that immune responses modulate adrenocortical tumorigenesis and may allow the refinement of risk stratification and treatment for this disease. Clin Cancer Res; 22(24); 6247–55. ©2016 AACR.

IMPORTANCE: Patient-derived xenografts (PDXs) offer the opportunity to identify patients with oral cavity squamous cell carcinoma (OSCC) who are at risk for recurrence and optimize clinical decision-making. OBJECTIVE: To develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, PDX models were generated from patients with OSCC treated with curative intent at Princess Margaret Cancer Centre (Toronto, Canada) between 2006 and 2018. The cohort included 288 patients (aged ≥18 years) with a new diagnosis of nonmetastatic (M0) OSCC whose tumor samples were available for engraftment under the skin of xenograft mice. Patients were scored as a nonengrafter if PDX formation did not occur within 6 months. Data analysis was performed between August 2006 and May 2018. INTERVENTIONS: All patients received up-front curative-intent surgery followed by either observation or postoperative radiation with or without concurrent chemotherapy based on institutional guidelines. MAIN OUTCOMES AND MEASURES: Main outcomes were LRF, DM, and overall survival (OS). Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups. RESULTS: Overall, 288 patients (mean [SD] age at diagnosis, 63.3 [12.3] years; 112 [39%] women and 176 [61%] men) with OSCC were analyzed. The MVA identified pT3-4, pathologic extranodal extension, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (hazard ratio [HR], 1.98; 95% CI, 1.24-3.18) and DM (HR, 2.64; 95% CI, 1.21-5.75) compared with nonengrafters. A prediction score based on the aforementioned variables identified patients at high risk and low risk for LRF (43.5% vs 26.5%), DM (38.2% vs 8.4%), and inferior OS (34% vs 66%) at 5 years. Additionally, rapid engraftment was shown to be similarly prognostic, with rapid engrafters demonstrating higher rates of relapse and poor OS. CONCLUSIONS: In this cohort study, a prediction score using OSCC PDX engraftment, in conjunction with pT3-4 and pathologic extranodal extension, was associated with improved prognostic utility of existing clinical models and predicted patients at risk for LRF, DM, and poor survival.

IMPORTANCELarge language model (LLM) artificial intelligence (AI) chatbots direct the power of large training datasets towards successive, related tasks, as opposed to single-ask tasks, for which AI already achieves impressive performance. The capacity of LLMs to assist in the full scope of iterative clinical reasoning via successive prompting, in effect acting as virtual physicians, has not yet been evaluated.OBJECTIVETo evaluate ChatGPT’s capacity for ongoing clinical decision support via its performance on standardized clinical vignettes.DESIGNWe inputted all 36 published clinical vignettes from the Merck Sharpe & Dohme (MSD) Clinical Manual into ChatGPT and compared accuracy on differential diagnoses, diagnostic testing, final diagnosis, and management based on patient age, gender, and case acuity.SETTINGChatGPT, a publicly available LLMPARTICIPANTSClinical vignettes featured hypothetical patients with a variety of age and gender identities, and a range of Emergency Severity Indices (ESIs) based on initial clinical presentation.EXPOSURESMSD Clinical Manual vignettesMAIN OUTCOMES AND MEASURESWe measured the proportion of correct responses to the questions posed within the clinical vignettes tested.RESULTSChatGPT achieved 71.7% (95% CI, 69.3% to 74.1%) accuracy overall across all 36 clinical vignettes. The LLM demonstrated the highest performance in making a final diagnosis with an accuracy of 76.9% (95% CI, 67.8% to 86.1%), and the lowest performance in generating an initial differential diagnosis with an accuracy of 60.3% (95% CI, 54.2% to 66.6%). Compared to answering questions about general medical knowledge, ChatGPT demonstrated inferior performance on differential diagnosis (β=-15.8%, pCONCLUSIONS AND RELEVANCEChatGPT achieves impressive accuracy in clinical decision making, with particular strengths emerging as it has more clinical information at its disposal.

BACKGROUNDChatGPT, a popular new large language model (LLM) built by OpenAI, has shown impressive performance in a number of specialized applications. Despite the rising popularity and performance of AI, studies evaluating the use of LLMs for clinical decision support are lacking.PURPOSETo evaluate ChatGPT’s capacity for clinical decision support in radiology via the identification of appropriate imaging services for two important clinical presentations: breast cancer screening and breast pain.MATERIALS AND METHODSWe compared ChatGPT’s responses to the American College of Radiology (ACR) Appropriateness Criteria for breast pain and breast cancer screening. Our prompt formats included an open-ended (OE) format, where ChatGPT was asked to provide the single most appropriate imaging procedure, and a select all that apply (SATA) format, where ChatGPT was given a list of imaging modalities to assess. Scoring criteria evaluated whether proposed imaging modalities were in accordance with ACR guidelines.RESULTSChatGPT achieved an average OE score of 1.83 (out of 2) and a SATA average percentage correct of 88.9% for breast cancer screening prompts, and an average OE score of 1.125 (out of 2) and a SATA average percentage correct of 58.3% for breast pain prompts.CONCLUSIONOur results demonstrate the feasibility of using ChatGPT for radiologic decision making, with the potential to improve clinical workflow and responsible use of radiology services.

PURPOSE To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution. METHODS AND MATERIALS NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) and rENE-negative (rENE-) patients. Multivariable analysis (MVA) confirmed the prognostic importance of rENE and its grade. Staging schemas including rENE in N-classification were proposed and their performance evaluated. RESULTS A total of 274 patients were eligible (43 cN0; 231 cN-positive). rENE was identified in 83/231 (36%) cN-positive, including grade 1/2/3 rENE in 14/58/11 cases. Compared to rENE-, rENE+ patients had a lower OS (68% vs 89%, p

The author traveled for 2.5 months by canoe and other modes of transport down the entire length of the Mississippi River with the Mississippi. An Anthropocene River project. Reflecting on this journey, this essay revisits Catherine Brown and William Morrish’s 1991 essay, The Fourth Coast: An Expedition on the Mississippi River, in which Brown and Morrish document their research efforts to identify coherent anthropogenic structures and systems that could warrant the characterization of the Mississippi River as a Fourth Coast. To encourage a flourishing of overlapping multispecies life, the essay moves beyond their spatial reimagining by defining the “distributed nature of home” as a model for conceptualizing distributed spatialities and plural temporalities along the Mississippi River.

PurposeTo demonstrate Dynamic Contrast-Enhanced (DCE) perfusion changes in brain metastasis patients after chemoradiation therapy within the treatment responders (true-response group and pseudoprogression group) and between the true-response and pseudoprogression groups.Materials and Methods38 true-response patients with 38 brain metastases (13 melanoma, 11 lung, 7 breast, 7 others) with 3 consecutive DCE-MRI examinations (pretreatment, first follow-up and second follow-up) and 7 pseudoprogression patients with 10 melanoma metastases with 2 consecutive DCE-MRI examinations (pretreatment, first follow-up) were evaluated. DCE-MRI parameters and permeability graphs increase (rapid, slow, medium) and course pattern (washout, plateau, persistent) were analyzed and compared between the timing of the examinations and between the true-response and pseudoprogression groups, using paired t-tests and Mann-Whitney U-tests as appropriate. Automatic assessment of washout curves by Olea Brain Software was reviewed.ResultsPretreatment mean wash-in (15.3±24.7 vs 6.50±14.2, P4±18×104vs 5×104±10×104, PConclusionWash-in, Vp, Ktrans, peak enhancement, AUC values in DCE perfusion were significantly decreased after chemoradiation therapy in the responders. No statistically significant difference was shown between the true-response and pseudoprogression groups on either pre-or post-treatment, indicating the homogeneous permeability profiles in the responders.

Background: KCNH2 -mediated arrhythmia syndromes are caused by loss-of-function (type 2 long QT syndrome [LQT2]) or gain-of-function (type 1 short QT syndrome [SQT1]) pathogenic variants in the KCNH2 -encoded K v 11.1 potassium channel, which is essential for the cardiac action potential. Methods: A dual-component “suppression-and-replacement” (SupRep) KCNH2 gene therapy was created by cloning into a single construct a custom-designed KCNH2 short hairpin RNA with ~80% knockdown (suppression) and a “short hairpin RNA-immune” KCNH2 cDNA (replacement). Induced pluripotent stem cell-derived cardiomyocytes and their CRISPR-Cas9 variant-corrected isogenic control (IC) induced pluripotent stem cell-derived cardiomyocytes were made for 2 LQT2- (G604S, N633S) and 1 SQT1- (N588K) causative variants. All variant lines were treated with KCNH2-SupRep or non-targeting control short hairpin RNA (shCT). The action potential duration (APD) at 90% repolarization (APD 90 ) was measured using FluoVolt voltage dye. Results: KCNH2-SupRep achieved variant-independent rescue of both pathologic phenotypes. For LQT2-causative variants, treatment with KCNH2-SupRep resulted in shortening of the pathologically prolonged APD 90 to near curative (IC-like) APD 90 levels (G604S IC, 471±25 ms; N633S IC, 405±55 ms) compared with treatment with shCT (G604S: SupRep-treated, 452±76 ms versus shCT-treated, 550±41 ms; P P 90 (IC: 429±16 ms; SupRep-treated: 396±61 ms; shCT-treated: 274±12 ms). Conclusions: We provide the first proof-of-principle gene therapy for correction of both LQT2 and SQT1. KCNH2-SupRep gene therapy successfully normalized the pathologic APD 90 , thereby eliminating the pathognomonic feature of both LQT2 and SQT1.

In the present study, 2-propanol pyrolysis experiments were conducted in a rapid compression facility for a range of temperatures from 965 to 1193 K, pressures from 4.4 to 10.0 atm conditions, and times ranging from 2 to 47 ms after end-of-compression. Mixtures were composed of 2-propanol, nitrogen, and argon with the 2-propanol concentration held constant at 1.5% by mole fraction. The production of seven stable intermediate species (methane, acetylene, ethene, ethane, acetaldehyde, propene, and acetone) were measured using fast-gas sampling and gas chromatography. The high concentrations of propene observed experimentally indicated thermal decomposition of 2-propanol via dehydration was significant at all conditions studied. The observation of the simultaneous presence of methane and acetone indicated H atom abstraction from 2-propanol by H and CH

This study aimed to evaluate the diagnostic performance of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging and apparent diffusion coefficient (ADC) for differentiating common posterior fossa tumors, pilocytic astrocytoma (PA), medulloblastoma (MB), and hemangioblastoma (HB). Between January 2016 and April 2022, we enrolled 23 (median age, 7 years [range, 2-26]; 12 female), 13 (10 years [1-24]; 3 female), and 12 (43 years [23-73]; 7 female) patients with PA, MB, and HB, respectively. Normalized relative cerebral blood volume and flow (nrCBV and nrCBF) and normalized mean ADC (nADCmean) were calculated from volume-of-interest and statistically compared. nADCmean was significantly higher in PA than in MB (PA: median, 2.2 [range, 1.59-2.65] vs MB: 0.93 [0.70-1.37], P .001). nrCBF was significantly higher in HB than in PA and MB (PA: 1.10 [0.54-2.26] vs MB: 1.62 [0.93-3.16] vs HB: 7.83 [2.75-20.1], all P .001). nrCBV was significantly different between all 3 tumor types (PA: 0.89 [0.34-2.28] vs MB: 1.69 [0.93-4.23] vs HB: 8.48 [4.59-16.3], P = .008 for PA vs MB; P .001 for PA vs HB and MB vs HB). All tumors were successfully differentiated using an algorithmic approach with a threshold value of 4.58 for nrCBV and subsequent threshold value of 1.38 for nADCmean. DSC parameters and nADCmean were significantly different between PA, MB, and HB. An algorithmic approach combining nrCBV and nADCmean may be useful for differentiating these tumor types.

Background: The transient outward current (Ito) that mediates early (phase 1) repolarization is conducted by the KCND3 -encoded Kv4.3 pore-forming α-subunit. KCND3 gain-of-function mutations have been reported previously as a pathogenic substrate for J wave syndromes (JWS), including the Brugada syndrome and early repolarization syndrome, as well as autopsy-negative sudden unexplained death (SUD). Acacetin, a natural flavone, is a potent Ito current blocker. Acacetin may be a novel therapeutic for KCND3 -mediated J wave syndrome. Methods: KCND3-V392I was identified in an 18-year-old male with J wave syndrome/early repolarization syndrome, and a history of cardiac arrest including ventricular tachycardia/ventricular fibrillation and atrial fibrillation/atrial flutter. Pathogenic KCND3 mutation was engineered by site-directed mutagenesis and co-expressed with wild-type KChIP2 in TSA201 cells. Gene-edited/variant-corrected isogenic control and patient-specific pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) from the p. Val392Ile-KCND3-positive patient were generated. I to currents and action potentials were recorded before and after treatment with Acacetin using the whole cell patch-clamp and multielectrode array technique. Western blot and immunocytochemistry were performed to investigate KCND3 expression. Results: KCND3-V392I demonstrated a marked gain-of-function phenotype, increasing peak I to current density by 92.2% ( P P P P Conclusions: This preclinical study provides pharmacological and functional evidence to suggest that Acacetin may be a novel therapeutic for patients with KCND3 gain-of-function-associated J wave syndrome by inhibiting I to and abolishing the accentuated action potential notch in patient-derived iPSC-CMs.