tbuckley/cabot-search huggingface dataset:
Selected Articles from This Issue
Journal: Clinical Cancer Research (2024)

Highlights| April 01 2024 Selected Articles from This Issue Author & Article Information Online ISSN: 1557-3265 Print ISSN: 1078-0432 ©2024 American Association for Cancer Research2024American Association for Cancer Research Clin Cancer Res (2024) 30 (7): 1215. https://doi.org/10.1158/1078-0432.CCR-30-7-HI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record April 1 2024 Citation Selected Articles from This Issue. Clin Cancer Res 1 April 2024; 30 (7): 1215. https://doi.org/10.1158/1078-0432.CCR-30-7-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Platinum-based chemotherapy maintenance regimens are often limited by toxicities, highlighting a need for chemotherapy-free strategies that retain efficacy. Previous studies have demonstrated the success of PARP inhibitors (PARPi) in maintenance therapy, even in patients negative for germline BRCA mutations. Additional work illustrating a PARPi-mediated upregulation of immune checkpoint molecules and enhanced immune response suggests a potential for synergism between PARPi and immune checkpoint inhibitors (ICI). In the phase II DORA study, Tan and colleagues investigate the use of the PARPi olaparib with or without the PD-L1-targeted ICI durvalumab in patients with advanced triple negative breast cancer previously treated with platinum-based chemotherapy. Treatments were tolerable, and the authors report a median progression-free survival of 4.0 months with olaparib and 6.1 months with olaparib plus durvalumab, both significantly longer than previously observed outcomes. Germline BRCA mutation or PD-L1 status had no observable effect on clinical benefit, yet patients who had achieved partial... You do not currently have access to this content.
Laser Capture Microscopy <scp>RNA</scp> Sequencing for Topological Mapping of Synovial Pathology During Rheumatoid Arthritis
Authors: Benjamin Van Espen, E. Barton Prideaux, Andrew R. Wilson, Camilla R. L. Machado, Sho Sendo, James Parker, Grégory Seumois, Cristiano Sacchetti, Anna C. Belongia, Narayanan B. Perumal, Pandurangan Vijayanand, Matthew D. Linnik, Robert J. Benschop, Wei Wang, Nunzio Bottini, Gary S. Firestein, Stephanie M. Stanford
Journal: Arthritis & Rheumatology (2024)

Objective Rheumatoid arthritis (RA) is an autoimmune disease in which the joint lining or synovium becomes highly inflamed and majorly contributes to disease progression. Understanding pathogenic processes in RA synovium is critical for identifying therapeutic targets. We performed laser capture microscopy (LCM) followed by RNA sequencing (LCM‐RNAseq) to study regional transcriptomes throughout RA synovium. Methods Synovial lining, sublining, and vessel samples were captured by LCM from seven patients with RA and seven patients with osteoarthritis (OA). RNAseq was performed on RNA extracted from captured tissue. Principal component analysis was performed on the sample set by disease state. Differential expression analysis was performed between disease states based on log 2 fold change and q value parameters. Pathway analysis was performed using the Reactome Pathway Database on differentially expressed genes among disease states. Significantly enriched pathways in each synovial region were selected based on the false discovery rate. Results RA and OA transcriptomes were distinguishable by principal component analysis. Pairwise comparisons of synovial lining, sublining, and vessel samples between RA and OA revealed substantial differences in transcriptional patterns throughout the synovium. Hierarchical clustering of pathways based on significance revealed a pattern of association between biologic function and synovial topology. Analysis of pathways uniquely enriched in each region revealed distinct phenotypic abnormalities. As examples, RA lining samples were marked by anomalous immune cell signaling, RA sublining samples were marked by aberrant cell cycle, and RA vessel samples were marked by alterations in heme scavenging. Conclusion LCM‐RNAseq confirms reported transcriptional differences between the RA synovium and the OA synovium and provides evidence supporting a relationship between synovial topology and molecular anomalies in RA.
B-cell-directed CAR-T cell therapy activates CD8+ cytotoxic CARneg bystander T-cells in non-human primates and patients
Authors: James Kaminski, Ryan A. Fleming, Francesca Alvarez-Calderon, Marlana B. Winschel, Connor McGuckin, Emily E. Ho, Fay Eng, Xianliang Rui, Paula Keskula, Lorenzo Cagnin, Joanne Charles, Jillian Zavistaski, Steven P. Margossian, Malika A. Kapadia, James B. Rottman, Jennifer Lane, Susanne H. C. Baumeister, Victor Tkachev, Alex K. Shalek, Leslie S. Kean, Ulrike Gerdemann
Journal: Blood (2024)
Altered serum metabolome as an indicator of paraneoplasia or concomitant cancer in patients with rheumatic disease
Authors: Karolina Gente, Manuel Feisst, Dorothea Marx, Karel D Klika, Petros Christopoulos, Jürgen Graf, Julia Will, Thomas Luft, Jessica C Hassel, Carsten Müller-Tidow, Rui A Carvalho, Hanns-Martin Lorenz, M Margarida Souto-Carneiro
Journal: Annals of the Rheumatic Diseases (2024)

Objectives A timely diagnosis is imperative for curing cancer. However, in patients with rheumatic musculoskeletal diseases (RMDs) or paraneoplastic syndromes, misleading symptoms frequently delay cancer diagnosis. As metabolic remodelling characterises both cancer and RMD, we analysed if a metabolic signature can indicate paraneoplasia (PN) or reveal concomitant cancer in patients with RMD. Methods Metabolic alterations in the sera of rheumatoid arthritis (RA) patients with (n=56) or without (n=52) a history of invasive cancer were quantified by nuclear magnetic resonance analysis. Metabolites indicative of cancer were determined by multivariable regression analyses. Two independent RA and spondyloarthritis (SpA) cohorts with or without a history of invasive cancer were used for blinded validation. Samples from patients with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, non-invasive (NI) precancerous lesions and non-melanoma skin cancer and systemic lupus erythematosus and samples prior to the development of malignancy were used to test the model performance. Results Based on the concentrations of acetate, creatine, glycine, formate and the lipid ratio L1/L6, a diagnostic model yielded a high sensitivity and specificity for cancer diagnosis with AUC=0.995 in the model cohort, AUC=0.940 in the blinded RA validation cohort and AUC=0.928 in the mixed RA/SpA cohort. It was equally capable of identifying cancer in patients with PN. The model was insensitive to common demographic or clinical confounders or the presence of NI malignancy like non-melanoma skin cancer. Conclusions This new set of metabolic markers reliably predicts the presence of cancer in arthritis or PN patients with high sensitivity and specificity and has the potential to facilitate a rapid and correct diagnosis of malignancy.
Vaso-Lock for sutureless anastomosis in a pig arteriovenous loop model
Authors: Xiaowei Li, Emma R. Young, Cameron Martin, Joseph G. Ribaudo, Mohamed Zaghloul, Sophia Roberts, Rodrigo Meade, Batool Arif, William R. Moritz, Sarah Madira, Jonathon B. Schofield, Helen Xun, Caitlin W. Hicks, Sung H. Kang, Mohamed A. Zayed, Justin M. Sacks
Journal: Biomaterials (2024)
Axicabtagene ciloleucel versus standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume
Authors: Frederick L. Locke, Olalekan O. Oluwole, John Kuruvilla, Catherine Thieblemont, Franck Morschhauser, Gilles Salles, Steven P. Rowe, Saran Vardhanabhuti, Joshua Winters, Simone Filosto, Christina To, Paul Cheng, Marco Schupp, Ronald Korn, Marie José Kersten
Journal: Blood (2024)

Metabolic tumor volume (MTV) assessed using 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [median or less] vs high [greater than median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466). Patients with LBCL relapsed within 12 months of or refractory to first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel (axi-cel; autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem cell transplantation in patients who had a response). All P values are descriptive. Within high- and low-MTV subgroups, event-free survival (EFS) and progression-free survival (PFS) were superior with axi-cel vs standard care. EFS in patients with high MTV (vs low MTV) was numerically shorter with axi-cel and was significantly shorter with standard care. PFS was shorter in patients with high MTV vs low MTV in both the axi-cel and standard-care arms, and median MTV was lower in patients in ongoing response at data cutoff vs others. Median MTV was higher in patients treated with axi-cel who experienced grade ≥3 neurologic events or cytokine release syndrome (CRS) than in patients with grade 1/2 or no neurologic events or CRS, respectively. Baseline MTV less than or equal to median was associated with better clinical outcomes in patients receiving axi-cel or standard care for second-line LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.
Watering Collecting Duct Cysts: Are Aquaporin2+ Progenitors the Answer?
Authors: Mauricio Ostrosky-Frid, Vishal Patel
Journal: Journal of the American Society of Nephrology (2024)

Division of Nephrology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas Correspondence: Dr. Vishal Patel, email: [email protected] See related article, "Pkd2 Deficiency in Embryonic Aqp2+ Progenitor Cells Is Sufficient to Cause Severe Polycystic Kidney Disease," on pages 398–409.
The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the Classification of Residual Tumor After Resection for the Forthcoming (Ninth) Edition of the TNM Classification of Lung Cancer
Authors: Frank C. Detterbeck, Marcin Ostrowski, Hans Hoffmann, Ramón Rami-Porta, Ray U. Osarogiagbon, Jessica Donnington, Maurizio Infante, Mirella Marino, Edith M. Marom, Jun Nakajima, Andrew G. Nicholson, Paul van Schil, William D. Travis, Ming S. Tsao, John G. Edwards, Hisao Asamura
Journal: Journal of Thoracic Oncology (2024)
Petitions for Extreme Risk Protection Orders and Second Amendment Sanctuary Status in Colorado
Authors: Christopher E. Knoepke, Leslie M. Barnard, Nisha Batta, Megan McCarthy, Kimberly Thies, Christian Olivencia, Caitlin Robinson, Shalyn Kettering, Sheila Huss, Marian E. Betz
Journal: JAMA Network Open (2024)

Importance Extreme risk protection orders (ERPOs) temporarily bar individuals adjudicated as being at risk of violence (including suicide) from buying or possessing firearms. In protest, many US jurisdictions have declared themselves “Second Amendment sanctuaries” (2A sanctuaries). Many 2A sanctuaries continue to use ERPOs in low numbers, suggesting a poorly defined risk threshold at which they are acceptable. Objective To characterize circumstances under which ERPOs are used in 2A sanctuaries, highlighting their most broadly acceptable applications. Design, Setting, and Participants This cross-sectional study of civil court documents analyzed petitions for ERPOs filed in Colorado from January 2020 to December 2022. All petitions during the study period were included following de-duplication. These include petitions filed by law enforcement and family members against adults allegedly at risk of firearm violence across the state. Data were analyzed on a rolling basis between January 2020 and June 2023. Exposure ERPO petition filed in Colorado. Main Outcomes and Measures Seventy-seven data elements defined a priori were abstracted from all petitions and case files, including respondent demographics, petitioner types (family or law enforcement), types of threats (self, other, mass violence, combination), violence risk factors, and case outcomes (granted, denied). Results Of a total 338 ERPOs filed in Colorado, 126 (37.3%) occurred in 2A sanctuaries. Sixty-one of these 2A petitions were granted emergency orders, and 40 were full 1-year ERPOs after a hearing. Forty ERPOs (31.7%) were petitioned for by law enforcement. Petitions in non-2A counties were more likely to have been filed by law enforcement (138 of 227 [64.9%] vs 40 of 126 [31.7%]; P &amp;amp;lt; .001) and to have had an emergency order granted (177 of 227 [78.0%] vs 61 of 126 [48.4%]; P &amp;amp;lt; .001) than in 2A sanctuaries. Qualitative analysis of cases in 2A sanctuaries revealed common aggravating risk characteristics, including respondents experiencing hallucinations, histories of police interaction, and substance misuse. ERPOs have been granted in 2A sanctuaries against individuals threatening all forms of violence we abstracted for (themselves, others, and mass violence). Conclusions and Relevance In this examination of ERPO petitions across Colorado, more than a third of filings occurred in 2A sanctuaries. Nonetheless, law enforcement represent proportionately fewer petitions in these areas, and petitions are less likely to be granted. Serious mental illness, substance misuse, and prior interactions with law enforcement featured prominently in 2A sanctuary petitions. These case circumstances highlight dangerous situations in which ERPOs are an acceptable risk-prevention tool, even in areas politically predisposed to opposing them.
Cutaneous, Subcutaneous, and Bilateral Adrenal Gland Metastases in Progressive Prostate Carcinoma: Theranostic Potential of 68Ga-PSMA-11 PET/CT Imaging and 177Lu-PSMA-617 Therapy
Authors: Rahul V. Parghane, Sandip Basu
Journal: Clinical Nuclear Medicine (2024)

Abstract Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.
Suicidal Thoughts and Behaviors Among Children and Adolescents With Autism Spectrum Disorder
Authors: Benjamin Joffe Schindel, Briella Baer Chen, Holly C. Wilcox, Alison R. Marvin, J. Kiely Law, Paul H. Lipkin
Journal: JAMA Pediatrics (2024)

This survey study uses data from the Mental Health and Suicidal Behaviors Questionnaire to examine the age at onset of suicidal thoughts and behaviors among children and adolescents aged 8 to 17 years who have been diagnosed with autism spectrum disorder (ASD).
Novel Peripheral Intravenous Catheter Securement for Children and Catheter Failure Reduction
Authors: Brooke Charters, Kelly Foster, Benjamin Lawton, Leonard Lee, Joshua Byrnes, Gabor Mihala, Corey Cassidy, Jessica Schults, Tricia M. Kleidon, Ruth McCaffery, Kristy Van, Vanessa Funk, Amanda Ullman
Journal: JAMA Pediatrics (2024)

Peripheral intravenous catheters (PIVCs) facilitate essential treatment. Failure of these essential devices is frequent and new securement strategies may reduce failure and improve patient outcomes.
Interrupted Time Series Analysis of Bar/Tavern Closing Hours and Violent Crime
Authors: Erika M. Rosen, Pamela J. Trangenstein, Patrick L. Fullem, Jih-Cheng Yeh, David H. Jernigan, Ziming Xuan
Journal: JAMA Internal Medicine (2024)

Importance It is well established that alcohol outlets (ie, places that sell alcohol) attract crime, particularly during late-night hours. Objective To evaluate the association of Maryland Senate Bill 571 (SB571), which reduced the hours of sale for bars/taverns in 1 Baltimore neighborhood from 6 am to 2 am to 9 am to 10 pm, with violent crime within that neighborhood. Design, Setting, and Participants This controlled interrupted time series analysis compared the change in violent crime density within an 800-ft buffer around bars/taverns in the treatment neighborhood (ie, subject to SB571) and 3 control areas with a similar mean baseline crime rate, alcohol outlet density, and neighborhood disadvantage score in the City of Baltimore between May 1, 2018, and December 31, 2022. The interrupted time series using Poisson regression with overdispersion adjustment tested whether the violent crime density differed before vs after the policy change in the treatment neighborhood and whether this difference was localized to the treatment neighborhood. Exposure Statutory reduction of bar/tavern selling hours from 20 to 13 hours per day in the treatment neighborhood. Main Outcomes and Measures The primary outcome was all violent crime, including homicide, robbery, aggravated and common assault, and forcible rape. Secondary outcomes were homicides and assaults. All violent crime measures summed the monthly incidents within 800 ft of bars/taverns from 8 pm to 4 am . For each outcome, a level change estimated the immediate change (first month after implementation), and a slope change estimated the sustained change after implementation (percent reduction after the first month). These level and slope changes were then compared between the treatment and control neighborhoods. Results The treatment neighborhood included 13 bars/taverns (mean [SD] population, 528.3 [291.6] residents), and the control neighborhoods included 52 bars/taverns (mean [SD] population per census block, 809.0 [416.0] residents). There was a 14% immediate level decrease in density of all violent crimes the month after implementation of SB571; further, compared with the control neighborhoods, the slope of all violent crime density decreased by 29% per year in the treatment neighborhood after SB571 implementation (annualized incidence rate ratio, 0.71; 95% CI, 0.52-0.97; P = .03). Similar results were seen for homicides and assaults. Several sensitivity analyses supported the robustness of these results. Conclusions and Relevance This study’s findings suggest that alcohol policies that reduce hours of sale could be associated with a reduction in violent crimes. Given these findings, SB571 may serve as a model for other cities looking to create safer neighborhoods.
FDG PET/CT and MRI Findings of Extraskeletal Myxoid Chondrosarcoma Showing a Nonmyxoid Cellular Variant
Authors: Minami Hirasawa, Yoshinao Kikuchi, Kenji Sato, Akihiko Yoshida, Asako Yamamoto
Journal: Clinical Nuclear Medicine (2024)

Abstract We present a new, extremely rare nonmyxoid cellular variant of extraskeletal myxoid chondrosarcoma. Although diagnosis is radiologically and pathologically challenging, FDG PET/CT and MRI accurately showed the malignancy and high tumor density. A 52-year-old woman complained of a left dorsal mass, which presented inhomogeneous intermediate signals on T2-weighted images, with diffusion restriction, strong enhancement, and increased accumulation of FDG (SUV max , 5.2). Although biopsy was inconclusive, a highly malignant tumor was suspected radiologically. The resected specimen was histologically diagnosed as extraskeletal myxoid chondrosarcoma by detection of EWSR1::NR4A3 fusion using fluorescence in situ hybridization.
Omental Hernia as a Potential Cause of False-Positive GI Bleeding on 99mTc-RBC Scintigraphy
Authors: Farivash Karamian, Pegah Sahafi, Amin Saber Tanha, Ramin Sadeghi
Journal: Clinical Nuclear Medicine (2024)

Abstract Gastrointestinal bleeding scintigraphy is a noninvasive study used to determine the presence of active bleeding, localize the bleeding site, and estimate the bleeding volume for prognostic purposes in patients with suspected gastrointestinal bleeding. However, it is important to note that false-positive results can occur due to various reasons. In this case, we present the scenario of a middle-aged woman who exhibited symptoms of gastrointestinal bleeding and underwent 99m Tc-RBC scintigraphy. The imaging revealed an accumulation of radiotracer in the hypogastric region, which was later determined to be caused by an omental hernia on SPECT/CT images. The herniated structure caused congestion in the mesenteric vessels, leading to the accumulation of 99m Tc-RBC. This case highlights the significance of considering anatomical anomalies and nonbleeding pathologies when interpreting the 99m Tc-RBC scintigraphy results for gastrointestinal bleeding.
18F-FDG PET/CT Findings of Surgically Transposed Ovaries After Radical Hysterectomy in a Young Adult Patient
Authors: Hiroki Sakurada, Ryusuke Nakamoto, Yumi Takao, Yusaku Moribata, Chio Okuyama
Journal: Clinical Nuclear Medicine (2024)

A 35-year-old woman underwent 18 F-FDG PET/CT 2 months after a radical hysterectomy for uterine cervical cancer. An apparent FDG uptake was observed in an oval-shaped mass with an attached surgical clip in the right paracolic gutter. A similar non-FDG-avid mass with a clip was observed in the left. In this case, ovarian transposition had also been performed with metallic clips placed on both sides of the paracolic gutters. The increased FDG uptake in the right paracolic gutter was interpreted as physiological uptake in the right transposed ovary, not metastasis. Recognizing the possibility of FDG uptake in transposed ovaries is important.
Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative Disorders
Authors: Jeffrey Cummings, Krista Lanctot, George Grossberg, Clive Ballard
Journal: JAMA Neurology (2024)

Importance Neuropsychiatric syndromes (NPSs) are common in neurodegenerative disorders (NDDs); compromise the quality of life of patients and their care partners; and are associated with faster disease progression, earlier need for nursing home care, and poorer quality of life. Advances in translational pharmacology, clinical trial design and conduct, and understanding of the pathobiology of NDDs are bringing new therapies to clinical care. Observations Consensus definitions have evolved for psychosis, agitation, apathy, depression, and disinhibition in NDDs. Psychosocial interventions may reduce mild behavioral symptoms in patients with NDD, and pharmacotherapy is available for NPSs in NDDs. Brexpiprazole is approved for treatment of agitation associated with Alzheimer disease dementia, and pimavanserin is approved for treatment of delusions and hallucinations associated with psychosis of Parkinson disease. Trials are being conducted across several of the NDDs, and a variety of mechanisms of action are being assessed for their effect on NPSs. Conclusions and Relevance Detection and characterization of NPSs in patients with NDDs is the foundation for excellent care. New definitions for NPSs in NDDs may inform choices regarding clinical trial populations and translate into clinical practice. Psychosocial and pharmacologic therapies may reduce behavioral symptoms and improve quality of life for patients and caregivers. Approved agents may establish regulatory precedents, demonstrate successful trial strategies, and provide the foundation for further advances in treatment development.