tbuckley/cabot-search huggingface dataset:
Three Distinct Stroma Types in Human Pancreatic Cancer Identified by Image Analysis of Fibroblast Subpopulations and Collagen
Authors: Yurina Ogawa, Yohei Masugi, Tokiya Abe, Ken Yamazaki, Akihisa Ueno, Yoko Fujii-Nishimura, Shutaro Hori, Hiroshi Yagi, Yuta Abe, Minoru Kitago, Michiie Sakamoto
Journal: Clinical Cancer Research (2020)

Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaceted roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression, and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics.A novel multiplex IHC-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-naïve PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein α (FAP)-dominant fibroblast-rich stroma, and α smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses and with clinicopathologic factors, including CD8+ cell density.FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status, and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival [HR, 0.57; 95% confidence interval (CI), 0.33-0.99], while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06-2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8+ cell infiltrates and intense neutrophil infiltration.This study identified three distinct stroma types differentially associated with survival, immunity, and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of antistromal therapies.
Anxiety due to COVID-19 and impact on patients receiving chemotherapy in an inner-city minority population.
Authors: Muhammad Junaid Tariq, Muhammad Usman Almani, Syed Ali Amir Sherazi, Muhammad Usman, Abdul Wahab Arif, Barbara Yim, Shweta Gupta
Journal: Journal of Clinical Oncology (2020)

108 Background: Cook County Health (CCH) is one of the largest public safety net hospitals in the United States. COVID-19 pandemic significantly affected patient care. Although hospitals took measures to keep patients safe, there is a general level of anxiety in patients about coming to the hospital. This study was undertaken to see the impact of COVID-19 and anxiety in patients actively receiving infusional therapy at our institution. Methods: All patients coming to our Infusion Center were offered an anonymous written questionnaire. The survey was given for 10 calendar days in June 2020 after Chicago moved into Phase-3 of re-opening that indicated significant control of COVID-19. The survey was offered in English, Spanish and Polish. It also included the GAD scale for anxiety assessment. Statistics were done using the t-test and z-test. Results: A total of 107 patients completed the survey. About 55% were women with 67% patients over 50 years old. Of the 90 people that specified their race, 44% were black and 42% were Hispanic, 9% whites, and 5% others. Overall 68% had high school or less level of education with Hispanics having significantly lower education than blacks. About 30% had testing for COVID-19 with 81% being negative. Treatment interruption occurred in 39% patients. Despite 75% finding our infusion center extremely or very safe for treatments 28% still felt moderately or severely anxious on the GAD scale. Blacks had similar levels of anxiety compared to Hispanics in March 2020 but no significant change over the months compared to Hispanics who had a significant reduction in anxiety over time. Blacks also had significantly higher rates of moderate to severe anxiety on the GAD scale (33%), while no Hispanic had severe anxiety and 18% had moderate anxiety. Despite a higher level of anxiety, blacks were less likely to have treatment interruptions compared to Hispanics (Table). Conclusions: Despite low levels of anxiety, Hispanics were more likely to have treatment interruptions during the COVID pandemic compared to blacks who had a higher level of anxiety but lower levels of treatment interruptions. The cause of this may be the level of education and awareness between the groups. However, overall there is still a significant amount of anxiety in the inner-city minority population regarding COVID-19. [Table: see text]
Ultrasound with microbubbles improves memory, ameliorates pathology and modulates hippocampal proteomic changes in a triple transgenic mouse model of Alzheimer's disease
Authors: Yuanyuan Shen, Lingchen Hua, Chih-Kuang Yeh, Liming Shen, Ming Ying, Zaijun Zhang, Gongping Liu, Shupeng Li, Siping Chen, Xin Chen, Xifei Yang
Journal: Theranostics (2020)

Alzheimer's disease (AD) is a progressive neurodegenerative disease manifested by cognitive impairment. As a unique approach to open the blood-brain barrier (BBB) noninvasively and temporarily, a growing number of studies showed that low-intensity focused ultrasound in combination with microbubbles (FUS/MB), in the absence of therapeutic agents, is capable of ameliorating amyloid or tau pathology, concurrent with improving memory deficits of AD animal models. However, the effects of FUS/MB on both the two pathologies simultaneously, as well as the memory behaviors, have not been reported so far. Methods: In this study, female triple transgenic AD (3×Tg-AD) mice at eight months of age with both amyloid-β (Aβ) deposits and tau phosphorylation were treated by repeated FUS/MB in the unilateral hippocampus twice per week for six weeks. The memory behaviors were investigated by the Y maze, the Morris water maze and the step-down passive avoidance test following repeated FUS/MB treatments. Afterwards, the involvement of Aβ and tau pathology were assessed by immunohistochemical analysis. Neuronal health and phagocytosis of Aβ deposits by microglia in the hippocampus were examined by confocal microscopy. Further, hippocampal proteomic alterations were analyzed by employing two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with mass spectrometry. Results: The three independent memory tasks were indicative of evident learning and memory impairments in eight-month-old 3×Tg-AD mice, which developed intraneuronal Aβ, extracellular diffuse Aβ deposits and phosphorylated tau in the hippocampus and amygdala. Following repeated FUS/MB treatments, significant improvement in learning and memory ability of the 3×Tg-AD mice was achieved. Amelioration in both Aβ deposits and phosphorylated tau in the sonicated hemisphere was induced in FUS/MB-treated 3×Tg-AD mice. Albeit without increase in neuron density, enhancement in axonal neurofilaments emerged from the FUS/MB treatment. Confocal microscopy revealed activated microglia engulfing Aβ deposits in the FUS/MB-treated hippocampus. Further, proteomic analysis revealed 20 differentially expressed proteins, associated with glycolysis, neuron projection, mitochondrial pathways, metabolic process and ubiquitin binding etc., in the hippocampus between FUS/MB-treated and sham-treated 3×Tg-AD mice. Conclusions: Our findings reinforce the positive therapeutic effects on AD models with both Aβ and tau pathology induced by FUS/MB-mediated BBB opening, further supporting the potential of this treatment regime for clinical applications.
A deoxyribonuclease 1–like 3 genetic variant associates with asthma exacerbations
Authors: Esther Herrera-Luis, Fabian Lorenzo-Diaz, Lesly-Anne Samedy-Bates, Celeste Eng, Jesús Villar, Jose R. Rodriguez-Santana, Esteban G. Burchard, Maria Pino-Yanes
Journal: Journal of Allergy and Clinical Immunology (2020)
Efficacy of Ertugliflozin on Heart Failure–Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease
Authors: Francesco Cosentino, Christopher P. Cannon, David Z.I. Cherney, Urszula Masiukiewicz, Richard Pratley, Sam Dagogo-Jack, Robert Frederich, Bernard Charbonnel, James Mancuso, Weichung J. Shih, Steven G. Terra, Nilo B. Cater, Ira Gantz, Darren K. McGuire
Journal: Circulation (2020)

In patients with type 2 diabetes mellitus, sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure (HHF). We assessed the effect of ertugliflozin on HHF and related outcomes.VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial), a double-blind, placebo-controlled trial, randomly assigned patients with type 2 diabetes mellitus and atherosclerotic cardiovascular (CV) disease to once-daily ertugliflozin 5 mg, 15 mg, or placebo. Prespecified secondary analyses compared ertugliflozin (pooled doses) versus placebo on time to first event of HHF and composite of HHF/CV death, overall and stratified by prespecified characteristics. Cox proportional hazards modeling was used with the Fine and Gray method to account for competing mortality risk, and Andersen-Gill modeling to analyze total (first+recurrent) HHF and total HHF/CV death events.A total of 8246 patients were randomly assigned to ertugliflozin (n=5499) or placebo (n=2747); n=1958 (23.7%) had a history of heart failure (HF) and n=5006 (60.7%) had pretrial ejection fraction (EF) available, including n=959 with EF ≤45%. Ertugliflozin did not significantly reduce first HHF/CV death (hazard ratio [HR], 0.88 [95% CI, 0.75-1.03]). Overall, ertugliflozin reduced risk for first HHF (HR, 0.70 [95% CI, 0.54-0.90]; P=0.006). Previous HF did not modify this effect (HF: HR, 0.63 [95% CI, 0.44-0.90]; no HF: HR, 0.79 [95% CI, 0.54-1.15]; P interaction=0.40). In patients with HF, the risk reduction for first HHF was similar for those with reduced EF ≤45% versus preserved EF >45% or unknown. However, in the overall population, the risk reduction tended to be greater for those with EF ≤45% (HR, 0.48 [95% CI, 0.30-0.76]) versus EF >45% (HR, 0.86 [95% CI, 0.58-1.29]). Effect on risk for first HHF was consistent across most subgroups, but greater benefit of ertugliflozin was observed in 3 populations: baseline estimated glomerular filtration rate <60 mL·min-1·1.73 m-2, albuminuria, and diuretic use (each P interaction <0.05). Ertugliflozin reduced total events of HHF (rate ratio, 0.70 [95% CI, 0.56-0.87]) and total HHF/CV death (rate ratio, 0.83 [95% CI, 0.72-0.96]).In patients with type 2 diabetes mellitus, ertugliflozin reduced the risk for first and total HHF and total HHF/CV death, adding further support for the use of sodium-glucose cotransporter 2 inhibitors in primary and secondary prevention of HHF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01986881.
Gamma Probe–Guided Surgery in Postoperative Recurrent Osteoid Osteoma of Left Index Finger
Authors: Padma Subramanyam, Shanmuga Sundaram Palaniswamy
Journal: Clinical Nuclear Medicine (2020)

Abstract Osteoid osteomas are painful benign osteoblastic tumors that usually affect the metaphysis or diaphysis of long bones. Hands are rarely involved. Identification of recurrent lesion by anatomical imaging modalities is a challenge especially in postoperative setting. Diagnosis of osteoid osteoma is based on typical clinical signs, radiographs, bone scintigraphy, thin-slice computed tomography, or magnetic resonance imaging. Atypical locations, multicentricity of nidus, or incomplete excision of the nidus result in a high rate of recurrence. Here we present a case of recurrent osteoid osteoma at an unusual site in left index finger and was operated under gamma probe guidance.
A Mobile Intracardiac Mass in a Middle-aged Woman
Authors: Wei Zhang, Mingchao Mu, Fei Pei
Journal: JAMA Cardiology (2020)

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The COVID-19 pandemic impact on breast cancer care delivery at an academic center in New York City.
Authors: Tejus Satish, Rohit Raghunathan, Jake Prigoff, Jason Dennis Wright, Grace Hillyer, Meghna S. Trivedi, Kevin Kalinsky, Katherine D. Crew, Dawn L. Hershman, Melissa Kate Accordino
Journal: Journal of Clinical Oncology (2020)

88 Background: The coronavirus disease 2019 (COVID-19) pandemic has altered healthcare delivery. To save resources and reduce patient exposure, non-urgent care has been postponed. Previous work has focused on cancer patients with COVID-19, but little has been reported on the impact on patients without COVID-19. We aimed to characterize breast cancer (BC) patients without COVID-19 whose care was impacted by the COVID-19 pandemic at an academic center in New York City. Methods: We performed a retrospective cohort study of BC patients treated at a medical oncology practice between 2/1/2020-4/30/2020. Patients were included if they were scheduled to receive intravenous or injectable therapy or were scheduled as a new patient. Patients were excluded if they tested positive for COVID-19 or transferred care during the study period. Demographic and treatment information were obtained by chart review. Delays/changes in systemic therapy, imaging, interventional radiology procedures, radiation, and surgery were tracked. Delays were defined as postponements of scheduled care. Changes were defined as care alterations without postponements. Care impact was defined as any change/delay in any of the above oncologic care a patient was scheduled for. We conducted a univariate analysis to compare demographics and care impact using χ 2 analyses. Results: Of 351 eligible patients, the majority had stage 0-III BC (71.9%) and hormone receptor-positive HER2-negative BC (69.5%). Less than half were Caucasian (43.9%). Care was impacted due to the pandemic in 149 (42.5%) of patients. Surgery changes/delays were most frequent (37 of 84 patients, 44.0%), followed by changes/delays in systemic therapy (90 of 351 patients, 25.6%) and imaging (58 of 282 patients, 20.6%). Patients of Asian, Black, and other non-reported races were more likely to experience a care impact vs. Caucasian patients (47.1% vs. 44.4% vs. 55.6% vs. 31.2%, p = 0.001). Hispanic patients were more frequently impacted vs. non-Hispanic patients (47.6% vs. 35.9%, p = 0.06). Medicaid and Medicare patients were also more frequently impacted vs. commercially insured patients (54.7% vs. 41.4% vs. 36.2%, p = 0.02). BC stage and hormone receptor status were not significantly associated with care impacts. Conclusions: We found that nearly half of our BC patients experienced a change/delay in workup or treatment during the COVID-19 pandemic. We also found significant racial and socioeconomic disparities in the likelihood of care impact. Ongoing studies will determine the impact of alterations in care on cancer outcomes.
Mitigating provider burnout due to infusion center delays: Analysis of sustainability.
Authors: Sarah Sewaralthahab, Shaunika Thorne, Linda King, Debolina Goswami, Carrie Miller, Christopher Gallagher, Laura Kaufman, Irina Veytsman
Journal: Journal of Clinical Oncology (2020)

235 Background: Physician burnout affects over 50% of physicians in the US and is related to the high workload and loss of anonymity. The result is physical exhaustion, moral distress, and increased rates of suicide. At our institution, burnout was identified in 42.1% of providers &amp; 55.6% of staff surveyed using AMA/ASCO burnout questionnaires with treatment delays in the infusion center (IC) implicated as the biggest culprit. Methods: We tracked causes of delay in starting chemotherapy in the IC and utilizing Pareto Chart identified that over 80% of delays were due to missing chemotherapy orders on the day of IC appointment. Process flow charts for providers noted significant variations in practices. Retrospective chart review, 6/21/2019 to 8/30/ 2019, revealed that an average of 13.18% of patients scheduled to receive chemotherapy at the IC had missing orders on the day of the infusion, resulting in up to a 111-minute delay in starting chemotherapy. We set out to sustainably decrease the number of missing chemotherapy orders in the IC by 50%, decreasing the resultant stress on providers and IC nurses. Results: Four interventions were implemented over 2 plan-study-do-act (PDSA) cycles and resulted in decreasing the average number of missing orders on the day of IC appointment to 7% achieving our aim (Table). To ensure sustainability of results, we continued the interventions and maintained faculty engagement via periodic updates. Sustainability analysis revealed that the median number of patients with missing orders between 12/2/2019 and 2/28/2020 remained at 5% effectively achieving our goal. The effects of this intervention on physician/staff burnout will be reassessed after 1 year of intervention implementation using the same AMA/ASCO burnout questionnaires. Conclusions: Systematically standardizing a process achieves a sustainable impact, promotes a more effective workplace environment and decreases burnout on physicians and staff. [Table: see text]
Stromal cells and B cells orchestrate ectopic lymphoid tissue formation in nasal polyps
Authors: Zhe‐Zheng Wang, Jia Song, Hai Wang, Jing‐Xian Li, Qiao Xiao, Ze Yu, Zhi‐Chao Wang, Jin‐Xin Liu, Li Pan, Yin Yao, Cai‐Ling Chen, Xiang Lu, Chaohong Liu, Peisong Gao, Zheng Liu
Journal: Allergy (2020)

Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear.To study the role of interleukin (IL)-17A, C-X-C motif chemokine ligand 13 (CXCL13) and lymphotoxin (LT) in eLT formation in NPs.The expression levels of CXCL13 and LT and their receptors, in addition to the phenotypes of stromal cells in NPs, were studied by flow cytometry, immunostaining, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Purified nasal stromal cells and B cells were cultured, and a murine model of nasal type 17 inflammation was established by intranasal curdlan challenge for the mechanistic study.The excessive CXCL13 production in NPs correlated with enhanced IL-17A expression. Stromal cells, with CD31- Pdpn+ fibroblastic reticular cell (FRC) expansion, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1 β2 in NPs with eLTs. CXCL13 upregulated LTα1 β2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα1 β2 induced expansion of FRCs and CD31+ Pdpn+ lymphoid endothelial cells, which were the predominant stromal cell types in NPs with eLTs. IL-17A knockout and CXCL13 and LTβR blockage diminished nasal eLT formation in the murine model.We identified an important role of IL-17A-induced stromal cell remodeling in the initiation and crosstalk between B and stromal cells via CXCL13 and LTα1 β2 in the enlargement of eLTs in NPs.
The effect of COVID-19 on revenue cycle staff.
Authors: Stacey L Poole, Johnetta Blakely, Cheryl Crouse, Pam Colangelo, Natalie R. Dickson
Journal: Journal of Clinical Oncology (2020)

42 Background: The COVID-19 pandemic caused a public health emergency declaration in March 2020. A safer at home order was issued by the Tennessee governor on March 12 urging non-essential employees to stay at home. The decision was made to offer telecommuting to employees at Tennessee Oncology (TO) who could effectively work from home. 90% of the revenue cycle staff (RCS) began working remotely within a week of the decision. Methods: TO had been conducting a telecommuting pilot involving 20 RCS. This pilot was expanded within a week to accommodate 130 RCS including billing, credentialing, collections, financial counseling, analysts, authorization and benefit specialists. Employees signed telecommuting agreements and provided equipment based on IT recommendations. IT installed software which allowed secure connection through a Citrix gateway. Surveys were later conducted to measure work-from-home satisfaction. Less than 10 RCS remained onsite to perform essential duties. Results: Compared to the prior year there was an 80% reduction in turnover and an 82% reduction in unscheduled absences for telecommuting employees vs in-office employees. 92% reported an improved work/life balance. Productivity metrics by team are displayed below: Key financial metrics including payer turnaround, days in AR and patient payments improved over prior months. Payer turnaround dropped by 3 days and days in AR decreased by 3.9 compared to February. Patient payments were up 14% compared to the prior year. Conclusions: COVID-19 has been a challenging time in healthcare but it has taught us some valuable lessons. Telecommuting could be the wave of the future showing positive financial return in the form of employee retention, reduction of non-productive time (including unplanned absences) and increased employee satisfaction. Data shows these factors lead to higher producing team members who yield superior results. [Table: see text]
A wave of bipotent T/ILC-restricted progenitors shapes the embryonic thymus microenvironment in a time-dependent manner
Authors: Ramy Elsaid, Sylvain Meunier, Odile Burlen-Defranoux, Francisca Soares-da-Silva, Thibaut Perchet, Lorea Iturri, Laina Freyer, Paulo Vieira, Pablo Pereira, Rachel Golub, Antonio Bandeira, Elisa Gomez Perdiguero, Ana Cumano
Journal: Blood (2020)