tbuckley/cabot-search huggingface dataset:
Why should I test my athletes in the heat several months before Tokyo 2020?
Authors: Sebastien Racinais, Mohammed Ihsan
Journal: British Journal of Sports Medicine (2020)

The 2020 Tokyo Olympics will be held from 24 July to 9 August, in hot and humid environments, in the world’s largest metropolitan area. Two years to the day before the 2020 Olympics, temperatures surpassed 41°C with over 65 heat-related deaths recorded in a single week. Protecting the health and performance of the athlete under these conditions is a shared responsibility among the International Olympic Committee (IOC), the local organiser (LOC), the International Federations (IFs), the National Olympic Committees (NOCs), the national federation medical staff, the coaching staff and the athletes themselves. Unfortunately, these various stake holders do not always have the appropriate information to adopt the necessary preventive countermeasures. Following the motto ‘By failing to prepare you are preparing to fail’ (Benjamin Franklin, 1706–1790), a series of editorials will be published between now and the Olympics with clear information for practitioners on how to prepare.

First of all, endurance and team sports athletes should be aware that heat stress dramatically decreases performance. Fortunately, the acute effects of heat stress can be progressively attenuated by repeated training in …
Abstract 245: Clinical Use of Miniaturized Chest Compressor for Cardiopulmonary Resuscitation
Authors: Xiuhua Wang, Chao Zhang, Wei Chen
Journal: Circulation (2012)

Introduction: During cardiopulmonary resuscitation (CPR), high quality chest compression is the most important factor for successful resuscitation. In the present study, we investigated the effectiveness of a mechanical miniaturized chest compressor (MCC) on successful resuscitation in human patients. Hypothesis: We hypothesized that MCC is safe and equally as effective for CPR when compared with conventional manual chest compression. Methods: This is a retrospective study comparing the effectiveness of MCC between 2 separate cohorts of patients. From May 2011 - April 2012, MCC was used in all out of hospital cardiac arrest (CA) patients brought to our emergency room, except those who were 18 years old or under and patients of trauma and terminal stage diseases. A total of 25 patients were included in MCC group. Another 22 patients with similar conditions received conventional manual chest compression from May 2010 - April 2011 that were included as the control group. MCC device was used with a fixed compression rate of 100/min and compression depth between 3.8 and 5 cm. Manual chest compression was performed based on the current CPR guidelines. ACLS guideline procedures were followed in all patients. The protocol was continued until successful resuscitation or for a total of 30 mins. Successful resuscitation was defined as return of spontaneous circulation with blood pressure &gt; 90/60 mmHg for more than 30 mins. Results: Mean age, gender and duration from CA to CPR did not differ significantly between MCC and manual groups. The success of resuscitation was numerically greater in MCC group when compared with the manual group (Table). There was no single incidence of rib fracture in patients treated with MCC. Conclusion: MCC is safe and as effective as manual chest compression. It may, therefore, provide a new option for CPR.
The impact of physician specialty on general and bladder cancer-specific quality of life among patients with muscle invasive bladder cancer.
Authors: Hannah McCloskey, Sean McCabe, Kathryn Gessner, Pauline Filippou, Judy Hamad, Allison Mary Deal, John L. Gore, Angela Smith
Journal: Journal of Clinical Oncology (2020)

462 Background: Treatment delivery for muscle invasive bladder cancer (MIBC) may involve general urologists, urologic oncologists or a multidisciplinary team that includes medical oncology and radiation oncology. Our objective was to evaluate differences in general and bladder cancer-specific quality of life (QOL) based on treating physician among MIBC patients. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine general and bladder cancer-specific QOL using the EORTC QLQ-C30 and Bladder Cancer Index, respectively. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. Patients were asked whether they sought care from a general urologist, urologic oncologist, medical oncologist and/or radiation oncologist. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 270 respondents identified as MIBC patients. Among MIBC respondents, 38% were female and 97% were white. The mean age was 67.4 years (range 30 to 93 years). Respondents were highly educated (67% completed college). Among MIBC patients, 17% sought care from a general urologist only, 33% from a urologic oncologist only, and 50% from a multidisciplinary team that included either a medical or radiation oncologist. Physician specialty was not associated with generic, sexual, or bowel QOL. Patients seeing a general urologist had—on average—better urinary function compared with those seeing a urologic oncologist or multidisciplinary team. On multivariable analysis, physician specialty remained a significant predictor of urinary function (p = 0.02), controlling for age, sex, race, recurrence, and comorbidity. Conclusions: Among MIBC patients, physician specialty does not substantially impact general QOL but may be associated with urinary function. This may relate to cancer severity or other unmeasured patient characteristics.
Abstract 11941: Visit-to-visit Variability of Postural Changes in Systolic Blood Pressure is Associated With Greater Risk of Dementia in Older Black and White Adults
Authors: Laure Rouch, Jean-Sébastien Vidal, Tina Hoang, Philippe Cestac, Olivier Hanon, Kristine Yaffe
Journal: Circulation (2019)

Introduction: Older adults are at increased risk of orthostatic hypotension (OHYPO) and orthostatic hypertension (OHYPER) due to impaired compensatory vascular mechanisms, yet less is known about t...
Pathologic outcomes of MRI invisible tumors in prostate cancer.
Authors: Sandeep Gurram, Amir H. Lebastchi, Michael Ahdoot, Alex Z. Wang, Bradford J. Wood, Baris Turkbey, Peter A. Pinto
Journal: Journal of Clinical Oncology (2020)

282 Background: Magnetic resonance imaging (MRI) invisible tumors are a diagnostic challenge in prostate cancer due to the lack of ability to reliably monitor these lesions radiographically or pathologically. The progression and natural history of these lesions are unknown and outcomes over time are unclear. Methods: Men with multiparametric MRI of the prostate and MRI/Transrectal ultrasound (TRUS) fusion guided biopsy were assessed for the presence of MRI invisible tumors (MIT). An MIT is defined as cancer detected only on extended sextant biopsy and not visible on MRI. All men first underwent an MRI/TRUS fusion biopsy with tracked extended sextant biopsy which originally detected the MIT. The original biopsy needle course sampling these MITs was tracked and set as a future target using the MRI/TRUS fusion platform. Men subsequently underwent a combined MRI/TRUS fusion biopsy, systematic extended sextant biopsy, and a Targeted Tracked biopsy of the MIT (TT-MIT) that was recorded and tracked from the original biopsy. We describe the outcomes of tracking these MITs and compare the ability to monitor them with TT-MIT biopsy as opposed to systematic extended sextant biopsy. Results: 105 MITs were identified, 84 (80%) of which were originally Gleason 6 tumors. The median time between biopsies was 16.6 months. The overall cancer detection rate with TT-MIT was 77.4% compared to 59.7% using systematic extended sextant biopsy. Using TT-MIT, these invisible tumors showed higher Gleason scores in 16 (15.2%) tumors. When TT-MIT was compared to the systematic extended sextant biopsy sampling the corresponding location, it showed increased Gleason scores in 30 (28.6%) MITs while 58 (55.2%) showed concordant pathology and 17 (16.2%) showed less aggressive pathology. Conclusions: The ability to follow MRI invisible tumors suggests that these tumors are more effectively tracked using TT-MIT biopsy technique. These MITs change over time and 15% of them will upgrade to higher Gleason scores. Tracking these tumors with TT-MIT biopsy increases cancer detection rate compared to standard sextant biopsy and more accurately samples these MITs, unveiling a more aggressive pathology.
MetAP2 inhibitors induce p53 in HT-1080 fibrosarcoma cells
Authors: Pingping Lou, Qian Zhang, Lora Tucker-Garcia, Xiaoan Ruan, Paul Kroeger, George S. Sheppard, Randy Bell, Jieyi Wang
Journal: Cancer Research (2004)

1519  Methionine aminopeptidase-2 (MetAP2) is a molecular target of TNP-470, an anti-angiogenic agent that has been evaluated in clinical trials as a cancer treatment. MetAP2 uniquely catalyzes the removal of the N-terminal methionine from a small number of nascent proteins whereas MetAP1 and other aminopeptidases carry out this methionine processing for the majority of cellular proteins. There are several lines of evidence that support MetAP2 as a promising cancer drug target. First, MetAP2 is over-expressed in tumors. Second, MetAP2 anti-sense oligonucleotides inhibit cell growth and induce apoptosis in tumor lines. Lastly, we have shown that a rationally designed reversible MetAP2 inhibitor, A-357300, recapitulates the anti-tumor activity of TNP-470 in murine cancer models. A-357300 selectively induced cytostasis by cell cycle arrest at the G1 phase in endothelial cells and in a subset of tumor cells such as HT-1080 human fibrosarcoma, but not in most primary cells of non-endothelial type. TNP-470 was reported to upregulate p53 and also to engage in the p53 pathway to exert p21 dependent G1 checkpoint control in endothelial cells. Here we report that the effect of A-357300 and TNP-470 on cell cycle and p53 in HT-1080 cells and normal human primary cells. MetAP2 inhibitors block the proliferation of HT-1080 cells. Thus, they provide an in vitro system for studying the molecular mechanism of cell cycle arrest by MetAP2 inhibitors. We treated HT-1080 cells with TNP-470 and A-357300 and determined the alteration of cell cycle proteins by Western Blot analysis. As a comparison, we also studied normal human primary cells. Our data showed that TNP-470 and A-357300 induced p53 and p21 in HT-1080 cells. Up-regulation of p53 protein by MetAP2 inhibitors was seen within 3 hours of drug exposure and occurred without serine phosphorylation of p53. In contrast, the DNA damaging agent etoposide induced p53 protein and its phosphorylation. To further understand the upregulation of p53, we performed QPCR to determine the mRNA expression. We observed that p53 mRNA was not affected, however, the level of p21 mRNA was increased. A-357300 and TNP-470 did not significantly alter the cell cycle of normal human mammary epithelial cells, bronchial epithelial cells, and smooth muscle cells. These MetAP2 inhibitors did not show significant induction of p53 and p21 in normal human primary cells. The data demonstrate that MetAP2 inhibitors activate the p53 pathway in HT-1080 tumors cells but not in normal cells.
The association between PSA pattern changes and progression in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with abiraterone and prednisone (AA/P).
Authors: Iris Yeong- Fung Sheng, Jaleh Fallah, Ruby Gupta, Hong Li, Kimberly D. Allman, Allison Martin, Pedro C. Barata, Moshe Chaim Ornstein, Timothy D. Gilligan, Brian I. Rini, Jorge A. Garcia
Journal: Journal of Clinical Oncology (2020)

18 Background: Despite treatment with AA/P, many patients with mHSPC will develop castrate resistant disease (CRPC). Early recognition of progression is difficult. Changes in PSA patterns in patients with mHSPC treated with AA/P may help identify evolution to mCRPC. Methods: All patients with mHSPC who initiated ADT and AA/P from June 2017 to February 2019 at the Cleveland Clinic were eligible. Patterns of PSA change were evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months (mo) from AA/P initiation. Time to PSA&lt;0.03 and CRPC were estimated using Kaplan-Meier method. Progression was defined as a PSA rise at two consecutive time points. Results: Of the 143 patients who initiated AA/P, 134 men (median Gleason score 8, baseline PSA 15.0 ng/mL) with follow up were included. 52% had de novo mHSPC, 47.8% had prior therapy (21% surgery, 20% radiation, 7% both), and 16% had visceral disease. PSA levels dropped 98.2% in the first 3 mo (p&lt;0.001), slowed from 3-9 mo (p&lt;0.05) and plateaued after 9 mo. The % PSA reduction from time 0 to the other time points was small. The median time to PSA&lt;0.03 was 11 mo. Of those who progressed to CRPC, the reduction within the first 3 mo was more significant than in those who did not (Table). Measurable PSA was higher in patients who progressed to CRPC at all-time points and plateaued by 6 mo. 12-mo CRPC-free after AA/P was 86.7% (95% CI: 79.2, 94.1). Patients with ≥ 98% 3-mo PSA reduction had better CRPC-free survival than patients with &lt;98% reduction (12-mo CRPC-free: 94.4% vs 78.4%), p&lt;0.001. Conclusions: The degree of PSA decline within 3 mo of AA/P may be used as treatment efficacy measurement. Tracking PSA pattern changes may alert clinicians for potential progression, consider frequent PSA and imaging, as well as initiate sequential therapy.[Table: see text]
Periprostatic venous androgen levels in a subset of patients with prostate cancer: An investigation into a novel role of testosterone in localized prostate cancer.
Authors: Lewis Thomas, Mohammad Alyamani, Jianbo Li, Andrei Purysko, Eric A. Klein, Nima Sharifi
Journal: Journal of Clinical Oncology (2020)

341 Background: While androgens drive prostate cancer (PCa), studies of systemic levels in eugonadal patients have not shown a relationship with development or progression of PCa. This study characterizes the relationship between systemic, local venous, and tissue androgen levels to understand the regulation and influence of androgens on localized PCa. Methods: Peripheral &amp; periprostatic venous blood &amp; prostate tissue were collected from patients undergoing radical prostatectomy (RP). Androgen levels (testosterone (T) and dihydrotestosterone (DHT)) were assessed by mass spectrometry. PCa grade and stage, PSA, prostate volume, and periprostatic vein diameter (PPVD) on MRI were recorded. A second cohort of patients undergoing just prostate MRI (non-surgical) was assessed to investigate the relationship between PPVD and disease severity. Results: Samples were collected from 176 patients. Analysis identified a subset of patients with elevated periprostatic T (ppT) relative to systemic T (sT) including 25% with ppT/sT &gt; 2, 14% with ppT/sT &gt; 4, and 7% with ppT/sT &gt; 10. Patients with ppT/sT &gt; 4 had supraphysiologic T levels in the periprostatic venous blood (mean 4223ng/mL). These patients also had higher than predicted levels of tissue T and DHT (tT/sT of 0.48 vs 0.24 (p = 0.004) and tDHT/sT of 7.31 vs 4.72 (p = 0.011)). In the surgical cohort, PPVD was increased in patients with elevated ppT/sT levels (5.8mm vs 3.7mm, p = 0.013). In the biopsy cohort (n = 200), increased PPVD was associated with an increased risk of diagnosis of PCa (4.39mm vs 3.43mm p = 0.006) and clinically significant PCa (4.35mm vs 3.43mm p = 0.01). Conclusions: In a subset of patients with PCa, periprostatic venous T levels were highly elevated compared to peripheral levels. Tissue T and DHT were also increased, and MRI demonstrated increased PPVD. We hypothesize that collateralization of venous drainage from the gonadal vein leads to both high local T and dilated veins. In a biopsy cohort, increased PPVD was associated with an increased risk of diagnosis of any and clinically significant PCa, suggesting that high periprostatic androgen levels may play a role in development of PCa.
Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma (S/R RCC) to reveal potential determinants of poor prognosis and response to immune checkpoint inhibitors (ICI).
Authors: Ziad Bakouny, David A. Braun, Sachet A. Shukla, Wenting Pan, Xin Gao, Yue Hou, Abdallah Flaifel, Amin Nassar, Sarah Abou Alaiwi, Ronan Flippot, John A. Steinharter, Pier Vitale Nuzzo, Yuko Ishii, Petra Ross-Macdonald, Gwo-Shu Mary Lee, David F. McDermott, Daniel Yick Chin Heng, Sabina Signoretti, Eliezer Mendel Van Allen, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2020)

715 Background: S/R RCC are highly aggressive tumors but recent pilot clinical data have suggested that these tumors respond well to ICI. Our aim was to perform integrative molecular characterization of S/R RCC tumors in order to characterize potential features that underlie their poor prognosis and responses to ICI. Methods: We compared genomic (1), transcriptomic (2) and immune microenvironment (3) data between S/R and non-S/R tumors. (1) S/R patients from 3 cohorts [N = 209]: The Cancer Genome Atlas [TCGA], CheckMate 010/025 &amp; panel sequencing from Dana-Farber/Harvard Cancer Center [DF/HCC]. (2) RNA-seq on S/R from 2 cohorts [N = 98]: TCGA &amp; CheckMate 010/025. (3) Immunofluorescence for CD8+ T cells [N = 17] &amp; Immunohistochemistry for PD-L1 expression on tumor cells [N = 118] from CheckMate 010/025. Overall Response Rate (ORR), Progression Free Survival (PFS), and Overall Survival (OS) in S/R RCC was compared between ICI and non-ICI in clinical cohorts (Table). Results: S/R tumors were significantly enriched in mutations in BAP1, NF2, RELN, and MUTYH, deletions of CDKN2A/B &amp; amplifications of EZH2 (q &lt; 0.05) compared to non-S/R tumors. Gene Set Enrichment Analysis showed upregulation of epithelial-mesenchymal transition, immune pathways, and proliferation programs compared to non-S/R tumors in both RNA-seq cohorts independently (q &lt; 0.25). S/R tumors exhibited greater infiltration by CD8+ T cells at the tumor margin (p = 0.048) and PD-L1 expression on tumor cells (43.2% vs 21.0%, p &lt; 0.01) compared to non-S/R. S/R had improved ORR, PFS, and OS on ICI vs. non-ICI (Table). Conclusions: S/R RCC tumors have distinctive molecular features that may account for their association with poor prognosis and outcomes on ICI.[Table: see text]
A Bartonella Effector Acts as Signaling Hub for Intrinsic STAT3 Activation to Trigger Anti-inflammatory Responses
Authors: Isabel Sorg, Christoph Schmutz, Yun-Yueh Lu, Katja Fromm, Lena K. Siewert, Alexandra Bögli, Kathrin Strack, Alexander Harms, Christoph Dehio
Journal: Cell Host & Microbe (2020)
Atezolizumab in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy: Results of real-life experience.
Authors: Deniz Tural, Omer Fatih Olmez, Ahmet Taner Sumbul, Mehmet Artac, Nail Ozhan, Emre Akar, Burcu Cakar, Osman Kostek, Nail Paksoy, Mustafa Erman, Hasan Senol Coskun, Fatih Selcukbiricik, Özge Keskin, Fatma Paksoy Turkoz, Kerem Oruc, Selami Bayram, Ugur Yilmaz, Irem Bilgetekin, Birol Yildiz, Saadettin Kilickap
Journal: Journal of Clinical Oncology (2020)

451 Background: Anti-tumor activity and manageable safety profile of atezolizumab (ATZ) has been demonstrated in the previous clinical trials in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. In this study, we reported the results of real-life data of urothelial carcinoma patients in Turkey who were treated with ATZ. Methods: Data of the patients with metastatic urothelial carcinoma registered to ATZ Expanded-Access Program and treated with at least one course of ATZ from 36 oncology centers in Turkey were collected. The primary endpoint was the overall response rate (ORR); secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of the ATZ treatment and safety. Results: Data of 115 eligible patients were analyzed. Of the patients, 100 (87%) were male and 13% were female. The median age was 65.3 years (37-86). Most of the patients (92.3%) had received only one chemotherapy regimen prior to ATZ. The median follow-up time was 23.5 months. The complete response rate to ATZ, partial response rate, and ORR were 8.7% (n=10), 20.0% (n=23), and 28.7% (n=33), respectively. The median duration of response was 20.4 months (95% CI 6.47–28.8). Of the thirty-three patients who responded to treatment, 20 (60%) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 months (95% 2.25–5.49) and 9.8 months (95% 6.7–12.9), respectively. The 12-month PFS rate was 22.3% and the 24-month PFS rate was 16.9%. The 12-month OS rate was 42.2% and the 24-month OS rate was 23.5%, respectively. Sixty-four percent of patients experienced a treatment-related adverse event of any grade, and 24 (20%) of patients had a grade 3–4 treatment-related adverse event. Because of treatment-related side effects, dose reduction was performed in 9 (7.8%) patients and ATZ was discontinued in 8 patients (7.0%). Adverse event that required systemic steroid use was reported in only 7 (6.1%) patients. Four patients (3.5%) died due to treatment-related causes. Conclusions: ATZ is an effective and tolerable treatment for patients with metastatic platinum-resistant urothelial carcinoma.
Abstract 13087: Comparison of Performance for Rqi Cpr Training With and Without Dynamic Feedback: Implications for Skill Measurement, System Design, and Certification Policy
Authors: Kevin Gluck, Michael Krusmark, Suzie Kardong-Edgren, Marilyn Oermann, Russell Griffin, Jack Harris, Tiffany Jastrzembski
Journal: Circulation (2018)

Introduction: The value of simulation in medicine is not to merely train, but to assess medical competency to maximize trainee benefit and reduce patient risk. The American Heart Association has im...
Immune checkpoint inhibitors (ICI) in clear cell renal cell carcinoma (ccRCC) following high-dose interleukin-2 (IL-2).
Authors: Roy Elias, Isaac Alexander Bowman, Hans J. Hammers, James Brugarolas
Journal: Journal of Clinical Oncology (2020)

635 Background: IL-2 can be curative in a small subset of ccRCC patients (pts). Recent data suggest that ICIs may lead to long lasting responses, and ICI therapy following progression on IL-2 seems reasonable. However, data regarding the safety and efficacy of ICI following IL-2 is limited. Methods: ccRCC pts treated with ICI after first line were identified at UT Southwestern Medical Center from 2014 – 2018 and assessed by comparison to IL-2 naïve pts at the time of ICI initiation. Outcomes included objective response rates (ORR) determined by RECIST v1.1, time to next treatment (TNT) and overall survival (OS). Immune-related adverse events (irAEs) were graded per CTCAE v4.0. Comparisons were performed using Pearson Chi-square, independent t-tests, and Fischer’s exact tests as appropriate. The log-rank test was utilized for Kaplan-Meier survival analyses. Results: We identified 127 ccRCC pts treated with ICI after first line, 17.3% (22) who had received prior IL-2 and 83.7% (105) who were IL-2 naïve. Pts in the IL-2 group were younger (mean age, 56 vs. 63 years; p=0.003), and more heavily pretreated (median 2 prior lines vs. 1; p &lt;0.0001). The distribution by IMDC criteria was similar with 86.4% (19) and 76.4% (81) in intermediate/ poor group in IL-2 vs. IL-2 naïve groups, respectively (p = 0.431). The ORR was 9.1% (2/22) vs. 21.2% (22/104) in the IL-2 vs. IL-2 naïve groups, respectively (p=0.244). The median TNT was 7.5 (95% CI: 1.8 to 13.2) vs. 9.2 (95% CI: 6.0 – 12.4; p= 0.667) months in the IL-2 vs. IL-2 naïve groups, respectively. The median OS was 26.4 (95% CI: 17.3 – 35.5) vs. 29.8 (23.1 to 36.4) months in the IL-2 vs. IL-2 naïve group, respectively. 18.2% (4) vs. 21.9% (23) pts developed a grade 3/4 irAE in the IL-2 vs. IL-2 naïve group, respectively (p=0.698). Conclusions: Our study suggests that ICI therapy following treatment with high-dose IL-2 remains efficacious and is not associated with an increased risk of irAEs.