tbuckley/cabot-search huggingface dataset:
Bernard Lown: a principled life
Authors: Jeanne Lenzer
Journal: BMJ (2021)

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Photo credit: Boris Spremo, Toronto Star, Getty images

The remarkable achievements of Bernard Lown, a renowned cardiologist and activist, have been catalogued in numerous obituaries since he died. For a list of his awards and accomplishments, the New York Times obituary is instructive.

But what is missing from virtually all obituaries are the principles that drove him and how his stands would cost him dearly.

Lown, most often noted for co-inventing the modern cardiac defibrillator, kept a letter of gratitude from a Cleveland Clinic surgeon who thanked him for his invention. Without the defibrillator, surgeons didn’t have a reliable way to restart a patient’s heart after surgery—with it, the floodgates for heart surgeries were opened.

Lown would come to rue this widespread use of his own invention. Convinced that love of technology and profits were driving unnecessary heart surgeries, he studied 171 patients who were told they needed surgery and came to him for a second opinion. He reported his results in 1992 in the Journal of the …
TROPiCS-04: Study of sacituzumab govitecan in metastatic or locally advanced unresectable urothelial cancer that has progressed after platinum and checkpoint inhibitor therapy.
Authors: Petros Grivas, Scott T. Tagawa, Joaquim Bellmunt, Maria De Santis, Ignacio Duran, Peter-Juergen Goebell, Andrea Necchi, Srikala S. Sridhar, Cora N. Sternberg, M Usman Aziz, Cabilia C. Pichardo, Yohann Loriot
Journal: Journal of Clinical Oncology (2021)

TPS498 Background: Treatment options are limited for patients with locally advanced unresectable or metastatic urothelial carcinoma (mUC) who progress following prior platinum-based and checkpoint inhibitor (CPI) therapy. Sacituzumab govitecan (SG) is an antibody-drug conjugate consisting of an anti–Trop-2 monoclonal antibody coupled to SN-38 (an active metabolite of irinotecan, a topoisomerase-I inhibitor) via a unique hydrolyzable linker. A phase II registrational study, TROPHY-U-01 study, confirmed the initial positive efficacy signal in mUC. SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months in patients with mUC (median 3 prior lines of therapy and 87% with ≥1 Bellmunt risk factors) who progressed after prior platinum-based and CPI therapies (n=113; Loriot ESMO 2020). The results compared favorably with historic single-agent chemotherapy (ORR ~10%; OS ≤7 months). A phase III trial has been initiated to confirm these findings. Methods: TROPiCS-04 (NCT04527991) is a global, multicenter, open-label, randomized, controlled trial in patients with locally advanced unresectable or mUC who progressed after prior platinum-based and CPI therapies (with Eastern Cooperative Oncology Group performance status 0–1 and adequate hematologic, hepatic, and renal function). Patients will be randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on day 1 and 8 of 21-day cycles or single-agent treatment of physician’s choice (paclitaxel 175 mg/m 2 , docetaxel 75 mg/m 2 , or vinflunine 320 mg/m 2 IV on day 1 of 21-day cycles) until progressive disease, unacceptable toxicity, or withdrawal of consent. Treatment beyond progressive disease may be permitted in patients deemed to be receiving clinical benefit per investigator assessment. Approximately 482 patients will be enrolled to provide 90% power on the primary endpoint of OS. Secondary endpoints include progression-free survival, ORR, clinical benefit rate, duration of response (all per Response Evaluation Criteria in Solid Tumors v1.1), safety, and quality of life. Study initiation is ongoing and enrollment begins in Q4 2020 across ~90 sites. Clinical trial information: NCT04527991.
Diagnostic Yield of Advanced Colorectal Neoplasia at Colonoscopy, According to Indications: An Investigation from the Korean Association for the Study of Intestinal Diseases (KASID)
Authors: D. Park, Y. Kim, H. Kim, W. Kim, T. Kim, H. Kim, S. Yang, J. Byeon, M. Lee, I. Jung, M. Chung, S. Jung, Y. Jeen, J. Choi, H. Choi, D. Han, J. Song
Journal: Endoscopy (2006)

Correction to: Diagnostic Yield of Advanced Colorectal Neoplasia at Colonoscopy, According to Indications: An Investigation from the Korean Association for the Study of Intestinal Diseases (KASID)Endoscopy 2006; 38(05): 449-455DOI: 10.1055/s-2006-925227
Single-cell analysis of cellular state heterogeneity in human localized prostate cancer.
Authors: Hanbing Song, Hannah N.W. Weinstein, Paul Allegakoen, Marc Wadsworth, Jamie Xie, Heiko Yang, Felix Y Feng, Peter R. Carroll, Bruce Wang, Matthew R. Cooperberg, Alex Shalek, Franklin W. Huang
Journal: Journal of Clinical Oncology (2021)

254 Background: Prostate cancer is the second most common malignancy in men worldwide. The development of cancer from prostate tissue involves complex interactions of tumor cells with surrounding epithelial and stromal cells and can occur multifocally, suggesting that prostate epithelial cells may undergo cellular state transitions towards carcinogenesis. Previous studies on localized prostate cancer molecular changes have focused on unsorted bulk tissue samples, leaving a gap in our understanding of the cellular heterogeneity in the tumor microenvironment. Single-cell analyses of tumor specimens have the potential to reveal, at unprecedented resolution, cellular composition, as well as instructive intercellular interactions. Methods: To characterize the localized prostate cancer tumor microenvironment, we performed single-cell RNA-sequencing (scRNA-seq) on prostate biopsies, radical prostatectomy specimens, and matched patient-derived organoids from localized prostate cancer patients. Results: Within prostate epithelial cells, we identified a population of club cells that may act as progenitor cells. Furthermore, we uncovered luminal-like epithelial cellular states augmented in androgen signaling across basal and club cell populations. By classifying tumor cells based on ERG expression status, we found that ERG- tumor cells, in contrast to ERG+ cells, share transcriptomic heterogeneity with surrounding luminal epithelial cells and are associated with common stromal and immune microenvironment responses. These results suggest that specific immune niches may arise based on TMPRSS2-ERG fusion status. Finally, we generated prostate epithelial organoids derived from matched localized prostate cancer patients and characterized their transcriptomic profiles by scRNA-seq. These patient-derived organoids recapitulated tumor-associated epithelial cell states but also harbored distinct cell types and states from their parent tissues. Conclusions: Our data from localized prostate cancer specimens and organoids provide diagnostically relevant insights and will help advance our understanding of the cancer cellular states associated with prostate carcinogenesis.
Benefits of early ambulation within 24 h after total knee arthroplasty: a multicenter retrospective cohort study in China
Authors: Yi-Ting Lei, Jin-Wei Xie, Qiang Huang, Wei Huang, Fu-Xing Pei
Journal: Military Medical Research (2021)

Abstract Background Postoperative care has been evolving since the concept of enhanced recovery after surgery (ERAS) was introduced in China. This study aimed to evaluate the effects of early ambulation within 24 h after unilateral total knee arthroplasty (TKA) on postoperative rehabilitation and costs in a Chinese population. Methods This cohort study of patients with knee osteoarthritis who had undergone TKA at 24 large teaching hospitals between January 2014 and November 2016 involved 2687 patients who began ambulating within 24 h (Group A) and 3761 who began ambulating later than 24 h (Group B). The outcome measurements, such as length of stay (LOS), total hospitalization costs, dynamic pain level, knee flexion range of motion (ROM), results of the 12-Item Short Form Survey (SF-12), incidence of thromboembolic events and other complications, were recorded and compared. Results The early ambulation group (Group A) had a shorter LOS and lower hospitalization costs and pain levels than the late ambulation group (Group B). There was a favorable effect in enhancing ROM for patients in Group A compared with patients in Group B. In Group A, patients had significantly higher postoperative SF-12 scores than those in Group B. The incidence of deep venous thrombosis (DVT) and pulmonary infection was significantly lower in Group A than in Group B. The incidence of pulmonary embolism (PE) and other complications did not differ between the two groups. Conclusion Early ambulation within 24 h after TKA was associated with reduced LOS, improved knee function, lower hospitalization costs and lower incidence of DVT and pulmonary infection in the Chinese population.
Treatment and Renal Outcomes Up to 96 Weeks After Tenofovir Alafenamide Switch From Tenofovir Disoproxil Fumarate in Routine Practice
Authors: Hidenori Toyoda, Jennifer Leong, Charles Landis, Masanori Atsukawa, Tsunamasa Watanabe, Daniel Q. Huang, Joanne Liu, Sabrina Xin Zi Quek, Toru Ishikawa, Taeang Arai, Keisuke Yokohama, Makoto Chuma, Koichi Takaguchi, Haruki Uojima, Tomonori Senoo, Hansen Dang, Mayumi Maeda, Joseph Hoang, Richard H. Le, Satoshi Yasuda, Khin N. Thin, Sally Tran, Nicholas Chien, Linda Henry, Akira Asai, Shinya Fukunishi, Ramsey Cheung, Seng Gee Lim, Huy N. Trinh, Mindie H. Nguyen
Journal: Hepatology (2021)

Background and Aims Real‐world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer prodrug tenofovir alafenamide (TAF) from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population. Approach and Results We analyzed 834 patients with CHB previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 US and Asian centers for changes in viral (HBV DNA &lt; 20 IU/mL), biochemical (alanine aminotransferase [ALT] &lt; 35/25 U/L for male/female), and complete (viral+biochemical) responses, as well as estimated glomerular filtration rate (eGFR; milliliters per minute per 1.73 square meters) up to 96 weeks after switch. Viral suppression ( P &lt; 0.001) and ALT normalization ( P = 0.003) rates increased significantly after switch, with a trend for increasing complete response ( P trend = 0.004), while the eGFR trend ( P trend &gt; 0.44) or mean eGFR ( P &gt; 0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension, or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR &lt; 90 (chronic kidney disease [CKD] stage ≥2), mean eGFR decreased significantly while on TDF ( P = 0.029) but not after TAF switch ( P = 0.90). By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1 and 35% (30/85) of CKD stage 3‐5 patients improved to stage 2 and 1.2% (1/85) to stage 1. Conclusions Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.
Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline
Authors: James D. Chalmers, Megan L. Crichton, Pieter C. Goeminne, Bin Cao, Marc Humbert, Michal Shteinberg, Katerina M. Antoniou, Charlotte Suppli Ulrik, Helen Parks, Chen Wang, Thomas Vandendriessche, Jieming Qu, Daiana Stolz, Christopher Brightling, Tobias Welte, Stefano Aliberti, Anita K. Simonds, Thomy Tonia, Nicolas Roche
Journal: European Respiratory Journal (2021)

Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes.A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations.Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made.The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.
Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma
Authors: Kevin Bi, Meng Xiao He, Ziad Bakouny, Abhay Kanodia, Sara Napolitano, Jingyi Wu, Grace Grimaldi, David A. Braun, Michael S. Cuoco, Angie Mayorga, Laura DelloStritto, Gabrielle Bouchard, John Steinharter, Alok K. Tewari, Natalie I. Vokes, Erin Shannon, Maxine Sun, Jihye Park, Steven L. Chang, Bradley A. McGregor, Rizwan Haq, Thomas Denize, Sabina Signoretti, Jennifer L. Guerriero, Sébastien Vigneau, Orit Rozenblatt-Rosen, Asaf Rotem, Aviv Regev, Toni K. Choueiri, Eliezer M. Van Allen
Journal: Cancer Cell (2021)

Immune checkpoint blockade (ICB) results in durable disease control in a subset of patients with advanced renal cell carcinoma (RCC), but mechanisms driving resistance are poorly understood. We characterize the single-cell transcriptomes of cancer and immune cells from metastatic RCC patients before or after ICB exposure. In responders, subsets of cytotoxic T cells express higher levels of co-inhibitory receptors and effector molecules. Macrophages from treated biopsies shift toward pro-inflammatory states in response to an interferon-rich microenvironment but also upregulate immunosuppressive markers. In cancer cells, we identify bifurcation into two subpopulations differing in angiogenic signaling and upregulation of immunosuppressive programs after ICB. Expression signatures for cancer cell subpopulations and immune evasion are associated with PBRM1 mutation and survival in primary and ICB-treated advanced RCC. Our findings demonstrate that ICB remodels the RCC microenvironment and modifies the interplay between cancer and immune cell populations critical for understanding response and resistance to ICB.
Cancer Stage, Treatment, and Survival Among Transgender Patients in the United States
Authors: Sarah S Jackson, Xuesong Han, Ziling Mao, Leticia Nogueira, Gita Suneja, Ahmedin Jemal, Meredith S Shiels
Journal: JNCI Journal of the National Cancer Institute (2021)

Transgender persons face many barriers to health care that may delay cancer diagnosis and treatment, possibly resulting in decreased survival. Yet, data on cancer in this population are limited. We examined cancer stage at diagnosis, treatment, and survival among transgender patients compared with cisgender patients in the National Cancer Database (NCDB).Gender (male, female, or transgender) was extracted from medical records from patients diagnosed with cancer between 2003 and 2016. Logistic regression estimated odds ratios (ORs) for the associations between gender and stage at diagnosis and treatment receipt. Cox proportional hazards regression estimated hazard ratios (HRs) for associations between gender and all-cause survival.Among 11 776 699 persons with cancer in NCDB, 589 were transgender. Compared with cisgender patients, transgender patients may be more likely to be diagnosed with advanced stage lung cancer (OR = 1.76, 95% confidence interval [CI] = 0.95 to 3.28); be less likely to receive treatment for kidney (OR = 0.19, 95% CI = 0.08 to 0.47) and pancreas (OR = 0.33, 95% CI = 0.11 to 0.95) cancers; and have poorer survival after diagnosis with non-Hodgkin lymphoma (HR = 2.34, 95% CI = 1.51 to 3.63), prostate (HR = 1.91, 95% CI = 1.06 to 3.45), and bladder cancers (HR = 2.86, 95% CI = 1.36 to 6.00). Similar associations were found for other cancer sites, although not statistically significant.Transgender patients may be diagnosed at later stages, be less likely to receive treatment, and have worse survival for many cancer types. Small sample size hampered our ability to detect statistically significant differences for some cancer sites. There is a need for transgender-focused cancer research as the population ages and grows.
Abstract 17365: Deep-Learning-Based Intravascular Ultrasound Segmentation for the Assessment of Coronary Artery Disease
Authors: Takeshi Nishi, Rikiya Yamashita, Shinji Imura, Kazuki Kozuka, Paul G Yock, Yasuhiro Honda, Peter Fitzgerald
Journal: Circulation (2020)

Background: Accurate segmentation of the coronary arteries with intravascular ultrasound (IVUS) is important to optimize coronary stent implantation. Recently, deep learning (DL) methods have been proposed to develop automatic IVUS segmentation. However, most of those have been limited to the lumen and vessel segmentation, not applied to segmenting stent dimension. Hence, this study aimed to develop a DL method for automatic IVUS segmentation of stent area in addition to lumen and vessel area. Methods: This study included a total of 45449 images from 1576 (40- or 45-MHz) IVUS pullback runs. The datasets were randomly split into training, validation, and test datasets (0.7:0.15:0.15). After constructing the convolutional neural network to segment IVUS images using the training and validation datasets, we evaluated the performance through the independent test dataset. Results: The DL-based segmentation correlated well with the expert-analysed segmentation with a mean intersection over union of 0.84, the correlation coefficient of 0.99, 0.98, and 0.99 and the mean difference of -0.04±0.05, -0.20±0.11 and -0.12±0.06 mm^2 for lumen, vessel and stent area derived from respectively. Conclusion: This automated DL-based IVUS segmentation of stent area in conjunction with lumen and vessel area showed good agreement with manual segmentation by experts, supporting the feasibility of artificial-intelligence-assisted IVUS assessment and strategy-making in patients undergoing coronary stent implantation.
Immunoprofiling of <i>Drosophila</i> Hemocytes by Single-Cell Mass Cytometry
Authors: József Á. Balog, Viktor Honti, Éva Kurucz, Beáta Kari, László G. Puskás, István Andó, Gábor J. Szebeni
Journal: Genomics Proteomics & Bioinformatics (2021)

Single-cell mass cytometry (SCMC) combines features of traditional flow cytometry (i.e., fluorescence-activated cell sorting) with mass spectrometry, making it possible to measure several parameters at the single-cell level for a complex analysis of biological regulatory mechanisms. In this study, weoptimizedSCMC to analyze hemocytes of the Drosophila innate immune system. We used metal-conjugated antibodies (against cell surface antigens H2, H3, H18, L1, L4, and P1, and intracellular antigens 3A5 and L2) and anti-IgM (against cell surface antigen L6) to detect the levels of antigens, while anti-GFP was used to detect crystal cells in the immune-induced samples. We investigated the antigen expression profile of single cells and hemocyte populations in naive states, in immune-induced states, in tumorous mutants bearing a driver mutation in the Drosophila homologue of Janus kinase (hopTum) and carrying a deficiency of the tumor suppressor gene lethal(3)malignant blood neoplasm-1 [l(3)mbn1], as well as in stem cell maintenance-defective hdcΔ84 mutant larvae. Multidimensional analysis enabled the discrimination of the functionally different major hemocyte subsets for lamellocytes, plasmatocytes, and crystal cells, anddelineated the unique immunophenotype of Drosophila mutants. We have identified subpopulations of L2+/P1+ and L2+/L4+/P1+ transitional phenotype cells in the tumorous strains l(3)mbn1 and hopTum, respectively, and a subpopulation of L4+/P1+ cells upon immune induction. Our results demonstrated for the first time that SCMC, combined with multidimensional bioinformatic analysis, represents a versatile and powerful tool to deeply analyze the regulation of cell-mediated immunity of Drosophila.
Abstract P193: Increased High Density Lipoprotein Cholesterol:ApolipoproteinA1 Ratio is Associated with Less Progression of Coronary Atherosclerosis in Statin-Treated Patients
Authors: Preethi Mani, Kiyoko Uno, Julie Thornton, Stephen Nicholls
Journal: Circulation (2012)

Background HDL cholesterol (HDL-C) and apolipoprotein AI (apoAI) levels are inversely related to adverse cardiovascular outcome. Associations between these HDL related measures and their ratio with coronary plaque progression have not been studied. It has been proposed that increasing HDL particle cholesterol content impairs HDL function, but impact on disease progression is unknown. We hypothesize that all HDL related measures are inversely associated with coronary plaque progression. Methods Retrospective analysis was performed of 1528 statin treated patients with angiographic CAD who had serial evaluation of atheroma burden with intravascular ultrasound. Relationships between achieved levels of HDL related measures with clinical characteristics and changes in plaque burden were determined. Results Strong correlation between HDL-C and apoAI (r=0.73, p&lt;0.0001) was noted. Patients with highest levels of HDL-C:apoAI were more likely to be female, black, and have lower BMI and less likely to be smokers or have previous revascularization (all p&lt;0.001) or acute coronary syndrome (p=0.013). HDL-C, apoAI, and HDL-C:apoAI demonstrated negative correlation with change in total atheroma volume (p&lt;0.01). For HDL-C:apoAI and HDL-C, increasing tertiles of achieved levels were associated with a linear benefit in slowing progression. For apoAI, a nonlinear association was seen, with similar benefit on progression in the middle and upper tertiles ( Table ). There was no statistical interaction for heterogeneity between HDL-C:apoAI and atheroma burden based on achieved levels of HDL-C (p=0.581). Change in IVUS Measures By Tertiles of Achieved HDL-related Parameters Percent Atheroma Volume Parameter T1 T2 T3 P Value HDL-C 0.58±0.27 0.26±0.27 0.11±0.27 0.012 ApoAI 0.28±0.26 −0.04±0.26 −0.08±0.26 0.10 HDL-C:ApoAI 0.22±0.27 0.13±0.27 −0.27±0.27 0.021 Total Atheroma Volume Parameter T1 T2 T3 P Value HDL-C −2.46±2.21 −4.18±2.20 −5.31±2.20 0.035 ApoAI −4.94±2.13 −6.30±2.13 −7.40±2.13 0.135 HDL-C:ApoAI −4.59±2.25 −6.38±2.24 −8.07±2.26 0.022 Conclusions Increase in all HDL related measures was associated with less progression of coronary atherosclerosis. Association of higher HDL-C:ApoAI with favorable effect on plaque progression at all levels of HDL-C suggests intact HDL functionality of larger cholesterol rich particles. Interventions that increase HDL particle cholesterol content, such as CETP inhibitors, may thus have beneficial effect at the artery wall.