tbuckley/cabot-search huggingface dataset:
Molecular and clinical characterization of metastatic castration-resistant prostate cancer (mCRPC) patients achieving deep PSA responses to bipolar androgen therapy (BAT).
Authors: Mark Christopher Markowski, Sushant Kachhap, Angelo M De Marzo, Samuel R. Denmeade, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2021)

127 Background: BAT is an emerging treatment strategy for men with mCRPC, whereby testosterone concentrations are cycled from supraphysiologic to castrate levels each month. BAT has been shown to be safe, and induces clinical responses in a proportion of patients, some of which are extreme. We explored the clinical and molecular characteristics of mCRPC pts that achieved deep PSA responses on BAT. Methods: We identified N= 22/114 (19%) mCRPC pts who achieved &gt;70% PSA reductions on treatment with BAT. All pts were treated on-protocol at Johns Hopkins using 400mg testosterone cypionate intramuscularly every 28 days, together with continuous LHRH agonist therapy. Pts remained on study until clinical or radiographic progression, as per protocol. Clinical-grade molecular sequencing was obtained using commercially available assays. Results: Next-generation somatic DNA sequencing was obtained on 15/22 (68%) pts. Of these 15 pts with sequencing data who achieved a &gt;70% PSA response on BAT, 14/15 (93%) harbored a pathogenic mutation in TP53 and/or a homologous recombination DNA repair (HRD) gene. Among patients with measureable disease (N=15), 10 pts (67%) achieved an objective response including one pt with a complete response. The median radiographic progression-free survival (rPFS) of these deep PSA responders on BAT was 11.3 (95% CI, 7.9-25) months. Conclusions: We observed an enrichment of TP53 and/or HRD mutations in mCRPC pts with extreme PSA responses to BAT, with durability lasting about a year These data support the hypothesis that BAT may work best in DNA repair-deficient mCRPC pts. Further study of BAT in biomarker selected mCRPC populations (i.e. TP53/HRD mutated) is warranted. [Table: see text]
Abstract 3634: Increase in Carotid Intima-Media Thickness in Grade I Hypertensives in a 5-year Prospective Study
Authors: Paolo Pauletto, Massimo Puato, Marco Zanardo, Marcello Rattazzi, Mikolaj Winnicki, Daniele Longo, Paolo Palatini
Journal: Circulation (2006)

Although blood pressure plays a key role in the increase in carotid intima-media thickness (IMT), prospective data are lacking in hypertensives. Aim of this study was to define the rate of increase...
Is there a role for urine cytology following BCG therapy for non-muscle-invasive bladder cancer (NMIBC)?
Authors: Sarah Prattley, Ruth Jarvis, Jon Featherstone, Krishna Narahari, Murali Varma, Owen Hughes, Howard Kynaston
Journal: Journal of Clinical Oncology (2021)

404 Background: Voided urine cytology has been used as an adjunct in the diagnosis of non-muscle invasive bladder cancer (NMIBC), with a sensitivity and specificity ranging between 13-75% and 76-100% respectively. There is limited data on the accuracy and utility of cytology following BCG therapy. We reviewed the results of cytology in patients undergoing induction and maintenance BCG immunotherapy in our institution. Methods: Newly diagnosed patients who had received induction and maintenance intravesical BCG therapy from 2004 - 2019 were identified from a prospective database and their outcomes reviewed retrospectively. Histopathology results of biopsies / resected specimens and voided urine cytology results were examined for 273 patients. Results: A total of 2567 cytology results and 638 biopsy results were recorded. The average age was 73.2 years and median number of BCG treatments was four (induction followed by three maintenance courses). Median follow up was 38 months. 94 patients (34.4%) had recurrence following BCG therapy. Of those 33 patients (12.1%) had progression to muscle invasive disease. The number of cytology samples per patient after BCG therapy ranged from 1-23 (median 7), with several patients having repeated, potentially unnecessary negative urine cytology. Overall accuracy of cytology (n = 526) was sensitivity 44.2%, specificity 84.7%, PPV 38.9%, NPV 87.3%. Patients that had an erythematous bladder or red patch at flexible cystoscopy underwent subgroup analysis; this gave a very high NPV of 95.9%, with additional sensitivity being 65.5%, specificity 85.9% and PPV 33.3%. Number of positive cytology results (Chi 2 = 44.30, P = 0.002), any positive cytology (Chi 2 = 27.94, P &lt; 0.001) and positive cytology after induction BCG therapy (Chi 2 = 30.381, P &lt; 0.001) were all strongly associated with recurrence. Conclusions: Positive urine cytology in patients undergoing intravesical BCG therapy predicts increased risk of recurrence and has good specificity. We would recommend using voided urine cytology in patients who have an erythematous bladder or red patch at flexible cystoscopy. If the cytology is positive then proceed to biopsy, however, if it is negative continue with surveillance. [Table: see text]
Diagnostic utility of (18)f-fluciclovine positron emission tomography (FACBC) in biochemically recurrent (BCR) prostate cancer (PCa) based on prior primary treatment modality for localized disease and the impact of FACBC findings on treatment selection.
Authors: Marina Nasrin Sharifi, Petra Lovrec, Jens C. Eickhoff, Aria Kenarsary, David Frazier Jarrard, John Floberg, Steve Y. Cho, Christos Kyriakopoulos, Hamid Emamekhoo
Journal: Journal of Clinical Oncology (2021)

34 Background: Management of BCR PCa requires accurate assessment of location and extent of recurrent disease. FACBC has been shown to be a sensitive modality for detection and localization of recurrent disease but treatment guidelines are based on the findings of conventional (conv) imaging, including computed tomography, magnetic resonance imaging, or bone scintigraphy, and little is known about how prior treatment impacts FACBC findings and concordance with conv scans. Methods: This single-center retrospective study included 137 patients (pts) who had FACBC for BCR at the University of Wisconsin-Madison from 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts were classified by type of primary treatment for localized PCa, either radical prostatectomy (RP) or radiation therapy (RT). Findings of conv scans performed within 4 weeks prior or any time after FACBC were collected. Results: 105 pts had RP and 32 pts had RT as their primary PCa treatment. Gleason score and PSA at diagnosis were similar between groups. Median PSA at time of FACBC was higher in the RT compared to RP group (3.3 vs 0.7 ng/dL) and median time from initial diagnosis to FACBC was longer (70 vs 55 months). Frequency of (+) FACBC findings was higher in the RT group (66% vs 47%); only 3% of pts in the RT group had a (-) FACBC compared to 29% in the RP group. The rate of (+) lesions in the prostate/prostate bed was higher in the RT group (41% vs 22%), while the rate of (+) lesions in pelvic nodes and distant sites was similar between groups. Of 69 pts who also had conv imaging, 61% had concordant conv imaging findings. In the RT group, conv and FACBC findings were similar in 47% of pts and not similar in 28%. In the RP group, conv and FACBC findings were similar in 26% of pts and not similar in 17%. Management after FACBC is listed in table. Median time from FACBC to first (+) conv scans was 6 (range: 0-18) and 5 (range: 0-17) months for RT and RP groups, respectively. Conclusions: In this large retrospective cohort, pts treated with initial RT had a longer median time from diagnosis to FACBC and higher median PSA at the time of FACBC compared to the RP group. RT patients had a higher rate of (+) FACBC findings but were more likely to continue on observation. The median time from FACBC to first (+) conv scan was 5-6 months, supporting the role of FACBC in earlier detection of recurrent disease in both groups of patients. Further analysis of concordance between FACBC and conv imaging is in process. [Table: see text]
Neurokinin 1 Receptor Antagonists for Pruritus
Authors: Majid Alam, Joerg Buddenkotte, Fareed Ahmad, Martin Steinhoff
Journal: Drugs (2021)

Pruritus, commonly known as itch, is a very common symptom in numerous dermatological disorders and systemic diseases. It can manifest as acute, or when lasting longer than 6 weeks, it is considered chronic and can lead to significant distress and reduced quality-of-life of those suffering. Current therapeutics are limited and are lacking in efficacy, and the development of more effective treatments is needed. The neurokinin 1 receptor (NK1R) antagonists are a novel class of drugs that possess several properties such as antidepressant, anxiolytic and antiemetic activities. Recently, several studies have described the antipruritic activity of NK1R antagonists for treating chronic pruritus. In this review we outline the pathogenesis of chronic pruritus, the mechanism by which the neuropeptide substance P (SP) and its receptor NK1R may be targeted to inhibit pruritic activity, and the efficacy and tolerability of NK1R antagonists, which have been, or are currently being investigated for treating conditions where chronic pruritus is a major symptom. Increasing evidence from ongoing and completed studies demonstrates the importance of SP and NK1R signalling in mediating pruritic activity. Several NK1R antagonists have shown significant antipruritic activity and thus targeting the SP-NK1R pathway may provide a therapeutic option for treating chronic pruritus of certain origin/s in the foreseeable future.
Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material
Authors: Rui Guo, Feng Wan, Masatoshi Morimatsu, Qing Xu, Tian Feng, Hang Yang, Yichen Gong, Shuhong Ma, Yun Chang, Siyao Zhang, Youxu Jiang, Heqing Wang, Dehua Chang, Hongjia Zhang, Yunpeng Ling, Feng Lan
Journal: Bioactive Materials (2021)

Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades. However, optimal cell types and transplantation methods remain unclear. This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell (hUCMSC) sheet on myocardial infarction (MI).hUCMSCs expressing luciferase were generated by lentiviral transduction for in vivo bio-luminescent imaging tracking of cells. We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet. Cell retention was evaluated using an in vivo bio-luminescent imaging tracking system. Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, angiogenesis and left ventricular remodelling.When transplanted to the infarcted mouse hearts, hUCMSC sheet significantly improved the retention and survival compared with cell suspension. At the early stage of MI, hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages, preserving the cardiomyocytes from acute injury. Moreover, the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue, providing mechanical support and routes for revascularsation. These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI.hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs, mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart.Due to its excellent availability as well as superior local cellular retention and survival, allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs, such as modulating inflammation and enhancing angiogenesis. Moreover, the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial, further improving its clinical applicability.
A phase I, dose-expansion cohort study on the safety of a cannabidiol for biochemical recurrence in prostate cancer patients.
Authors: Zin Myint, William H. St Clair, Stephen Strup, Peng Wang, Andrew Callaway James, Donglin Yan, Derek B. Allison, Carleton Scott Ellis, Danielle E. Otto, Jill Kolesar, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2021)

TPS263 Background: Cannabinoids, widely used in pain control, as an appetite stimulant, and anti-emetic in cancer patients, may play role as an anti-carcinogenic agent. A preclinical study demonstrated that cannabinoid receptors (CB1 and CB2) were highly expressed in human androgen-responsive prostate cancer (PCa) cells (LNCaP) as compared to normal prostate epithelial cells (PrEC). When these two cell lines were treated with a potent cannabinoid receptor agonist, PCa cells showed a decrease in prostate-specific antigen (PSA) protein expression and increased apoptosis in a dose and time-dependent manner with no effect seen in PrEC cells. An FDA-approved cannabidiol (CBD) agent, is derived from Cannabis sativa L. plants. Extracts from these plants are processed to yield pure CBD and contain less than 0.5% THC. We will expand these preclinical studies with a phase I trial. Methods: This trial is an open-label, single-center, phase I dose escalation study followed by dose expansion to evaluate acute toxicity, long-term safety and tolerability, and preliminary antitumor activity of cannabidiols in patients with biochemically recurrent (BCR) PC after primary definitive local therapy and prostate-specific antigen doubling time ≤ 12 months. The dose escalation will be determined by a Bayesian Optimal Interval design and the target dose-limiting toxicity rate is set at 30%. An additional 6-9 patients will be enrolled as an expansion cohort once the maximum tolerated dose is determined. Patients will be treated for a total 90 days with a 10 day taper. The primary objective is to evaluate the acute toxicity and long-term safety and tolerability of cannabidiols in patients with BCR. The secondary objective includes measuring changes in serial PSA levels, PSA velocity, and testosterone levels and to assess health-related quality of life (EORTC QLQ-C30 and QLQ-PR 25) from baseline throughout the treatment period. CB receptor 1 and 2 expression levels by immunohistochemistry staining will be evaluated from archival prostatectomy specimens if available as an exploratory objective. This trial opened on 7.28.2020 and has started enrollment. Clinical trial information: NCT04428203.
Medical algorithm: Diagnosis and treatment of hypersensitivity reactions to cancer chemotherapy
Authors: Ricardo Madrigal‐Burgaleta, Paula Vazquez‐Revuelta, Jaume Marti‐Garrido, Ramon Lleonart‐Bellfill, Fawzia Runa Ali, Emilio Alvarez‐Cuesta
Journal: Allergy (2021)

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Shift work is associated with positive COVID-19 status in hospitalised patients
Authors: Robert Maidstone, Simon G Anderson, David W Ray, Martin K Rutter, Hannah J Durrington, John F Blaikley
Journal: Thorax (2021)

Introduction Shift work is associated with lung disease and infections. We therefore investigated the impact of shift work on significant COVID-19 illness. Methods 501 000 UK Biobank participants were linked to secondary care SARS-CoV-2 PCR results from Public Health England. Healthcare worker occupational testing and those without an occupational history were excluded from analysis. Results Multivariate logistic regression (age, sex, ethnicity and deprivation index) revealed that irregular shift work (OR 2.42, 95% CI 1.92 to 3.05), permanent shift work (OR 2.5, 95% CI 1.95 to 3.19), day shift work (OR 2.01, 95% CI 1.55 to 2.6), irregular night shift work (OR 3.04, 95% CI 2.37 to 3.9) and permanent night shift work (OR 2.49, 95% CI 1.67 to 3.7) were all associated with positive COVID-19 tests compared with participants that did not perform shift work. This relationship persisted after adding sleep duration, chronotype, premorbid disease, body mass index, alcohol and smoking to the model. The effects of workplace were controlled for in three ways: (1) by adding in work factors (proximity to a colleague combined with estimated disease exposure) to the multivariate model or (2) comparing participants within each job sector (non-essential, essential and healthcare) and (3) comparing shift work and non-shift working colleagues. In all cases, shift work was significantly associated with COVID-19. In 2017, 120 307 UK Biobank participants had their occupational history reprofiled. Using this updated occupational data shift work remained associated with COVID-19 (OR 4.48 (95% CI 1.8 to 11.18). Conclusions Shift work is associated with a higher likelihood of in-hospital COVID-19 positivity. This risk could potentially be mitigated via additional workplace precautions or vaccination.
Abstract 15692: Voltage Mapping in Atrial Fibrillation vs Sinus Rhythm: Results From the Mavs Study
Authors: Carola Gianni, Jerri A Cunningham, Sanghamitra Mohanty, CHINTAN TRIVEDI, Domenico G Della Rocca, Amin Al-ahmad, Mohamed A Bassiouny, J D Burkhardt, G J Gallinghouse, Rodney P Horton, Patrick M Hranitzky, Javier E Sanchez, Luigi Di Biase, Andrea Natale
Journal: Circulation (2020)

Background: Left atrial (LA) scar can be identified with bipolar voltage mapping during sinus rhythm (SR). It is not clear whether the same voltage criteria can be applied during atrial fibrillation (AF). Objective: Aim of this study was to compare voltage maps performed in the same patient both in AF and SR. Methods: Voltage mapping was performed using a 10-pole circular mapping catheter in patients with non-paroxysmal AF undergoing first time RF ablation. For descriptive purposes, the LA was divided in 6 regions: septum, posterior wall (PW), inferior wall (IW), lateral wall, anterior wall, and roof. The threshold for low voltage was &lt;0.5 mV (with a color range setting 0.2-0.5 mV). Mild “scar” was defined as an area low voltage 5-20%, moderate 20-35% and severe as &gt;35%. Results: 16 patients (62% persistent AF, 38% longstanding persistent AF) were included in the study. The map density was comparable during AF and SR (mean points per map 551 vs 547, paired t test P = NS). 2 patients displayed normal voltage during both AF and SR. 14 patients showed areas of low voltage during AF, which were still present during SR in 8. All patients with mild “scarring” during AF (n = 4), showed normal voltage during SR. Of the 7 patients with moderate “scarring”, 2 patients showed normal voltage during SR, while in the remaining 5 “scarring” was only mild during SR. 3 patients showed extensive “scarring” during AF, which was only moderate during SR. During AF, areas of low voltage were more commonly observed in the PW (12/14) followed by the IW (6/14) and antero-septum (4/14); while in SR, in the antero-septum (4/8), PW (3/8) and IW (3/8). Interestingly, in all patients both the PW/IW and (less dramatically) the antero-septum showed more “scarring” during AF as compared to SR. Conclusion: Areas of low voltage are more severe and diffuse during AF when compared to SR. When areas of low voltage are detected during AF, they are more commonly seen in the PW, IW and antero-septal areas.
Abstract PO-054: Development of machine learning based early warning for rapid response system in a single cancer center
Authors: Bo-Gun Kho, Min-Seok Kim, Tae-Ok Kim, Cheol-Kyu Park, Young-Chul Kim, Soo-Hyung Kim, In-Jae Oh
Journal: Clinical Cancer Research (2021)

Abstract Background: Rapid response systems identify deteriorating hospitalized patients and prevent unexpected mortality by providing immediate interventions. But there are also difficulties in costs and human resources for clinical implementation. Machine learning is an application of artificial intelligence that provides systems the ability to automatically learn and improve from experience without being explicitly programmed. We try to develop a machine learning based early warning system to predict intubation and cardiopulmonary resuscitation (CPR) using vital signs and laboratory values. Methods: The training set was composed of all patients admitted to a cancer hospital named Chonnam National University Hwasun Hospital for two years (event group 277 vs. non-event group 3576 cases), and the test set was made from all patients admitted to non-cancer hospital named Chonnam National University Hospital for four months (event group 61 vs. non-event group 2334 cases). The time point at which the patient's clinical deterioration was recognized in the ward was defined as ‘detection time’, and the time point at which the patient suffered airway intubation or CPR was defined as ‘event time’. The algorithm is developed using five vital signs (blood pressure, heart rate, body temperature, respiratory rate and oxygen saturation) and laboratory values. We compared the efficacy of developed models which were ensemble model, recurrent neural network (RNN), low gradient boosting (LGB), extreme gradient boosting (XGB) and random forest with established modified early warning score (MEWS) using receiver operating characteristic area under curve (ROC AUC) and precision recall AUC (PR AUC) analyses. Results: The ROC AUC value of the ensemble model using five vital signs was 0.9219 and the PR AUC was 0.0732. After adding laboratory values, the ROC AUC values of the ensemble, RNN, LGB, XGB, random forest improved to 0.9964, 0.9814, 0.9950, 0.9862 and 0.9962. The PR AUC values were also increased to 0.2326, 0.2140, 0.3252, 0.2095 and 0.1985, respectively. The developed models showed higher performance than MEWS (ROC AUC: 0.7253, PR AUC: 0.0468) Conclusion: Machine learning based early warning system using vital signs and laboratory results was feasible. And the performance was better than traditional MEWS model because the ensemble model showed highest value in ROC AUC and LGB showed highest value in PR AUC. Citation Format: Bo-Gun Kho, Min-Seok Kim, Tae-Ok Kim, Cheol-Kyu Park, Young-Chul Kim, Soo-Hyung Kim, In-Jae Oh. Development of machine learning based early warning for rapid response system in a single cancer center [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-054.