tbuckley/cabot-search huggingface dataset:
A SIMPLE TOOL FOR RISK STRATIFICATION OF DRUG PROVOCATION TEST WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUG
Authors: Nathalia Vital, Caroline Ferreira, Raissa Roque, Alex Lacerda, Chayanne Araujo, Dirceu Sole, Ines Nunes, Luis Felipe Ensina
Journal: Journal of Allergy and Clinical Immunology (2020)
The effect of deep AR suppression with enzalutamide or apalutamide on endogenous glucocorticoids: Implications for adverse effects and development of combination therapies.
Authors: Nima Sharifi, Mohammad Alyamani, Jianbo Li, Mona Patel, Michael Berk, Susan Taylor, Christopher Przybycin, Edwin M. Posadas, Ravi Amrit Madan, James L. Gulley, Brian I. Rini, Jorge A. Garcia, Eric A. Klein
Journal: Journal of Clinical Oncology (2020)

17 Background: Metabolic consequences of potent AR suppression with enzalutamide and apalutamide are unresolved. Endocrine perturbations induced by potent AR antagonists may promote adverse effects and impinge on the potential efficacy of combination therapies, including for example, immunotherapies. We hypothesized that enzalutamide and apalutamide will block 11β-HSD2, the major enzyme that inactivates cortisol in peripheral tissues and results in increased systemic exposure to endogenous active glucocorticoids. We further hypothesized that AR is co-expressed with 11β-HSD2, suggesting a mechanism of suppression. Methods: Cortisol and cortisol/cortisone ratio (substrate/product of 11β-HSD2) were measured in serum using mass spectrometry before and on-treatment in 3 clinical trials: 1) neoadjuvant apalutamide + leuprolide 2) enzalutamide +/- PROSTVAC for metastatic castration-resistant prostate cancer 3) enzalutamide +/- PROSTVAC for non-metastatic castration-sensitive prostate cancer. AR and 11β-HSD2 expression were assessed in kidneys of 13 men and 9 women. Results: A rise in cortisol concentration and cortisol/cortisone ratio occurs uniformly across all 3 trials of potent AR antagonists. For example, a rise in cortisol/cortisone ratio occurred in 23/25 (92%) patients (p&lt;0.001), 30/38 (79%) patients (p=0.051), and 36/64 (67%) patients (p&lt;0.001), in the 3 respective trials. AR is only expressed alongside 11β-HSD2 in the kidneys of men but not women. Conclusions: Treatment with enzalutamide or apalutamide increases systemic exposure to active glucocorticoids. This effect is likely mediated by AR suppression of 11β-HSD2 in the kidney. These findings have potential consequences for immune suppression, the efficacy of treatment combinations using next-generation AR antagonists, and adverse effects of these drugs.
Examining the Doing of Ethics Support Staff. A Dialogical Approach Toward Assessing the Quality of Facilitators of Moral Case Deliberation
Authors: Margreet Stolper, Reidar Pedersen, Bert Molewijk
Journal: The American Journal of Bioethics (2020)

This article refers to:What the HEC-C? An Analysis of the Healthcare Ethics Consultant-Certified Program: One Year in
Clare Gerada: We need to stop being frightened of the bogeyman
Authors: Clare Gerada
Journal: BMJ (2020)

For years I’ve been caring for doctors with mental illness. This has involved numerous interactions with the General Medical Council (GMC). Years ago, together with others, I raised concerns about the impact of GMC investigations on doctors’ mental health, including links to suicide. On a personal level even I was frightened entering the GMC’s London headquarters on Euston Road (which I had to do fairly often)—but this didn’t compare to the fear my patients felt when the white envelope marked “confidential” landed on their doorstep or when they had to attend meetings or hearings at the …
Nephrectomy after complete response to immune checkpoint inhibitors for metastatic renal cell carcinoma (mRCC): A new surgical challenge?
Authors: Geraldine Pignot, Antoine Thiery-Vuillemin, Jochen Walz, Herve Lang, Pierre Werle, Loic Balssa, Lionnel Geoffrois, Louis Leblanc, Laurence Albiges, Vincenzo Di Nunno, Karim Bensalah, Sylvain Ladoire, Gwenaelle Gravis, Philippe Barthelemy
Journal: Journal of Clinical Oncology (2020)

707 Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy in the case of complete response on metastatic sites is still unknown. We aimed to evaluate the feasibility of nephrectomy for residual disease in patients with metastatic renal cell carcinoma (mRCC) and complete response (CR) on metastatic sites following ICI. Methods: Patients who underwent partial or radical nephrectomy after prior ICI between 2015 and 2018 were retrospectively included and clinicopathological data were reviewed. Perioperative data and postoperative outcomes were recorded. Results: Eleven patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of complete response on metastatic sites. Median age was 59.8 years [38-67]. All patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (81.8%) or poor (18.2%). ICI was administered as first-line therapy in 36.4% of cases (4/11) and as second-line option after TKI in 63.6% of cases (7/11). Treatments regimens were: nivolumab + ipilimumab (n = 3), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 6). The median duration of ICI treatment was 10 months (range: 3-38 months) and the mean number of cycles was 27 (range: 6-75). Median operative time was 243 minutes [135-345] and mean blood loss was 909 cc [40-4000]. In 81.8% (n = 9) of the cases, surgeons experienced challenges for finding dissection planes due to inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 54.6%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 54.6% and complete pathological response in 2 cases. Median follow-up was 15 months, with 73% of patients free from progression and 54% free from systemic treatment at 1 year. Conclusions: Nephrectomy following ICI for mRCC could allow achieving CR in selected patients. Due to technically complexity and complications rates, this surgery should be performed in centers with extensive experience.
Association between potassium level and outcomes in heart failure with reduced ejection fraction: a cohort study from the Swedish Heart Failure Registry
Authors: Lauren B. Cooper, Lina Benson, Robert J. Mentz, Gianluigi Savarese, Adam D. DeVore, Juan‐Jesus Carrero, Ulf Dahlström, Stefan D. Anker, Mitja Lainscak, Adrian F. Hernandez, Bertram Pitt, Lars H. Lund
Journal: European Journal of Heart Failure (2020)
Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis
Authors: Martino F. Pengo, Davide Soranna, Alice Giontella, Elisa Perger, Paola Mattaliano, Esther Irene Schwarz, Carolina Lombardi, Grzegorz Bilo, Antonella Zambon, Joerg Steier, Gianfranco Parati, Pietro Minuz, Cristiano Fava
Journal: European Respiratory Journal (2020)

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment. The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of −2.09 (95% CI −2.78– −1.40) mmHg for systolic BP and −1.92 (95% CI −2.40– −1.43) mmHg for diastolic BP and −1.27 (95% CI −2.34– −0.20) mmHg for systolic BP and −1.11 (95% CI −1.82– −0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged &lt;60 years (systolic BP −2.93 mmHg), with uncontrolled BP at baseline (systolic BP −4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry &lt;77%) at baseline (24-h systolic BP −7.57 mmHg). Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.
The Effects of a Remote-based Weight Loss Program on Adipocytokines, Metabolic Markers, and Telomere Length in Breast Cancer Survivors: the POWER-Remote Trial
Authors: Cesar A. Santa-Maria, Janelle W. Coughlin, Dipali Sharma, Mary Armanios, Amanda L. Blackford, Colleen Schreyer, Arlene Dalcin, Ashley Carpenter, Gerald J. Jerome, Deborah K. Armstrong, Madhu Chaudhry, Gary I. Cohen, Roisin M. Connolly, John Fetting, Robert S. Miller, Karen L. Smith, Claire Snyder, Andrew Wolfe, Antonio C. Wolff, Chiung-Yu Huang, Lawrence J. Appel, Vered Stearns
Journal: Clinical Cancer Research (2020)

Abstract Purpose: We initiated a clinical trial to determine the proportion of breast cancer survivors achieving ≥5% weight loss using a remotely delivered weight loss intervention (POWER-remote) or a self-directed approach, and to determine the effects of the intervention on biomarkers of cancer risk including metabolism, inflammation, and telomere length. Experimental Design: Women with stage 0–III breast cancer, who completed local therapy and chemotherapy, with a body mass index ≥25 kg/m2 were randomized to a 12-month intervention (POWER-remote) versus a self-directed approach. The primary objective was to determine the number of women who achieved at least 5% weight loss at 6 months. We assessed baseline and 6-month change in a panel of adipocytokines (adiponectin, leptin, resistin, HGF, NGF, PAI1, TNFα, MCP1, IL1β, IL6, and IL8), metabolic factors (insulin, glucose, lipids, hs-CRP), and telomere length in peripheral blood mononuclear cells. Results: From 2013 to 2015, 96 women were enrolled, and 87 were evaluable for the primary analysis; 45 to POWER-remote and 42 to self-directed. At 6 months, 51% of women randomized to POWER-remote lost ≥5% of their baseline body weight, compared with 12% in the self-directed arm [OR, 7.9; 95% confidence interval (CI), 2.6–23.9; P = 0.0003]; proportion were similar at 12 months (51% vs 17%, respectively, P = 0.003). Weight loss correlated with significant decreases in leptin, and favorable modulation of inflammatory cytokines and lipid profiles. There was no significant change in telomere length at 6 months. Conclusions: A remotely delivered weight loss intervention resulted in significant weight loss in breast cancer survivors, and favorable effects on several biomarkers.
Hypersensitivity drug reactions To Betalactams In Children in a reference Hospital.
Authors: Natalia Blanca-López, Ana María Prieto-Moreno Pfeifer, Isabel Torres-Rojas, Maria Somoza Alvarez, Diana Perez Alzate, Francisco Javier Ruano Pérez, Elisa Haroun-Diaz, Maria Vázquez de La Torre Gaspar, Paula López-González, Gabriela Canto Diez
Journal: Journal of Allergy and Clinical Immunology (2020)
Discrepancy between clinical stage and pathological stage based on the tumor location of urothelial carcinoma: A hospital-based cancer registry in Japan.
Authors: Yoshiyuki Nagumo, Takahiro Kojima, Kosuke Kojo, Tomokazu Kimura, Shuya Kandori, Koji Kawai, Ayako Okuyama, Takahiro Higashi, Hiroyuki Nishiyama
Journal: Journal of Clinical Oncology (2020)

579 Background: Accurate staging in patients with urothelial carcinoma (UC) of the bladder (UCB) or the upper urinary tract (UTUC) is essential for planning the appropriate treatment strategy. Although an underestimation of the pathological stage may result in missing the opportunity to perform preoperative treatment, the actual rate of the discrepancy between the clinical and pathological stages in UC is not known. Methods: We used Hospital-Based Cancer Registry (HBCR) data in Japan to extract 3,747 cases of UCB and 6,831 cases of UTUC with cT1-4N0M0 that were diagnosed in 2012–2015, histologically confirmed, and treated with radical surgery. We excluded patients who received chemotherapy or radiotherapy and those with an unknown clinical or pathological stage. Results: The proportion of UCB patients whose pathological stage was up-staged was 25%, and that of the UTUC patients was 30%. Among the patients with cT1 at each tumor location, up-staging to muscle-invasive cancer occurred in 30.9% (UCB, n=1132: pT2, 21.6%; pT3, 7.9%; pT4, 1.5%) and 37.5% (UTUC, n=2526: pT2, 16.9%; pT3, 20.2%; pT4, 0.4%), respectively. In particular, in the group of UTUC patients with cT1, the proportion of up-staging for pT3 was higher than that in the group of UCB patients with cT1. In the cases with cTis, up-staging to muscle-invasive cancer occurred in 10.5% (UCB, n=391: pT2, 6.9%; pT3, 1.8%; pT4, 1.8%) and 18.5% (UTUC, n=872: pT2, 9.7%; pT3, 8.7%). In contrast, the proportion of down-staging to non-muscle-invasive cancer in cases with cT2 or higher was 12% in the UCB group (n=2291) and 15% in the UTUC group (n=504). Conclusions: Among UC patients, up-staging from non-muscle-invasive cancer to muscle-invasive cancer is relatively common, and the frequency of this discrepancy in clinical and pathological stages tends to be especially higher in UTUC patients. More accurate diagnostic imaging techniques and biomarkers are urgently needed for the identification of the appropriate UC candidates for preoperative treatment.
Outcome with immune checkpoint inhibitors in metastatic renal cell carcinoma across different treatment lines.
Authors: Andreas Bruchbacher, Johannes Franke, Zumreta Alic, Sebastian Nachbargauer, Harun Fajkovic, Mesut Remzi, Manuela Schmidinger
Journal: Journal of Clinical Oncology (2020)

651 Background: The introduction of immune checkpoint inhibitors (ICPI) has led to a paradigm change in the management of metastatic Renal Cell Carcinoma (mRCC). Prospective trials focused on ICPI treatment in first- or second-line. The aim of this analysis was to evaluate the benefit of ICPI across different treatment lines. Methods: This is a single center retrospective study from the Medical University of Vienna which included all mRCC patients who received ICPIs in various treatment lines. Overall response rates (ORR), progression free survival (PFS) and overall survival (OS) were evaluated for the entire cohort and by treatment line. Results: Between January 2014 and October 2019, a total of 113 patients received ICPIs. Ninety-four patients were eligible for full evaluation (83% clear cell and 17% non-clear cell). 26.8%, 61.6% and 14.8% were classified good, intermediate and poor IMDC-risk, respectively. 59%, 20% and 21% were treated with ICPI monotherapy, dual ICPI therapy and ICPI + tyrosine kinase inhibitor, respectively. ORR, median PFS and median OS for the entire cohort was 39.4%, 9.67 months (95%CI: 6.9-12.4 months) and 23.6 months (95%CI: 13.3-33.9 months), respectively. The ORR by treatment line was: 33% in first-line (9 patients), 40.4%, in second- (42 patients), 35% in third- (20 patients) and 43.5% in fourth and beyond-fourth-line (23 patients). The median PFS by treatment line was: 8.6 months, 10.3 months, 7.9 months and 7.23 months, respectively. The median OS was not reached (NR) in first-line and 26.2 months, 18.1 months and 20.7 months in second-, third-, and fourth and beyond- ICPI treatment line, respectively. The global OS for the whole patient cohort calculated from diagnosis of metastasis was 80 months (CL 95%: 50.5 – 109.5 months). Conclusions: ICPIs are active in all treatment lines and should also be offered in heavily pre-treated patients, who have not had access in earlier treatment lines.
Early transmission patterns of coronavirus disease 2019 (COVID-19) in travellers from Wuhan to Thailand, January 2020
Authors: Pilailuk Okada, Rome Buathong, Siripaporn Phuygun, Thanutsapa Thanadachakul, Sittiporn Parnmen, Warawan Wongboot, Sunthareeya Waicharoen, Supaporn Wacharapluesadee, Sumonmal Uttayamakul, Apichart Vachiraphan, Malinee Chittaganpitch, Nanthawan Mekha, Noppavan Janejai, Sopon Iamsirithaworn, Raphael TC Lee, Sebastian Maurer-Stroh
Journal: Eurosurveillance (2020)

We report two cases of coronavirus disease 2019 (COVID-19) in travellers from Wuhan, China to Thailand. Both were independent introductions on separate flights, discovered with thermoscanners and confirmed with RT-PCR and genome sequencing. Both cases do not seem directly linked to the Huanan Seafood Market in Hubei but the viral genomes are identical to four other sequences from Wuhan, suggesting early spread within the city already in the first week of January.
Feasibility of neobladder reconstruction after pelvic irradiation.
Authors: April Vassantachart, Gus Miranda, Siamak Daneshmand, Anne K. Schuckman, Hooman Djaladat, Leslie Ballas
Journal: Journal of Clinical Oncology (2020)

479 Background: To assess the effects of pelvic radiotherapy (RT) on orthotopic neobladder reconstruction (ONR), this review presents retrospective data of surgical outcomes following prior RT. Methods: Our institutional IRB approved bladder cancer database was queried for all patients who underwent radical cystectomy and ONR between 1980 and 2018. Radiation data was abstracted from the electronic medical record (EMR) with inclusion of patients receiving &gt;40 Gy to the pelvis prior to surgery. Surgical outcomes including estimated blood loss (EBL), operative time, margin status, overall survival (OS), and need for subsequent surgeries were evaluated. Results: Of 2117 ONRs performed, 96 patients received prior RT. Of those, RT details could be obtained on 24 patients. Fifteen patients underwent definitive bladder RT with a median dose of 6480 cGy (range, 4500 - 8640 cGy); 7 of these patients received concurrent chemoradiotherapy, 2 received chemotherapy and RT with timing uncertain, and 6 received RT alone. Eight patients had prior prostate RT (median 7200 cGy) and one patient underwent prior cervical RT (7910 cGy). The median time interval between bladder RT and ONR was 7 months (range, 2 – 116 months) verses a median of 29 months between other pelvic RT and ONR (range, 6 – 163 months). Median EBL was 875 cc (range, 200-3000 cc) in patients with prior pelvic RT. Median operative time was 355 minutes (range, 231-600) in those who had prior RT compared with 354 minutes (range, 111-778) in those who underwent ONR without prior RT. Twenty-three patients had negative margins on surgical resection and one had a positive ureteral or urethral margin. The median OS following surgery was 50 months. Two patients died within 1 year due to disease progression. Seven patients (29%) required a surgical intervention after ONR: two patients developed fistulas (both with pouch to cutaneous fistulas), four patients had artificial urinary sphincters placed, and one developed small bowel obstruction due to adhesions. One patient required urethrectomy for recurrent disease. Conclusions: Orthotopic ileal neobladder reconstruction after pelvic irradiation is feasible with acceptable functional results.
Practical Speedup of Bayesian Inference of Species Phylogenies by Restricting the Space of Gene Trees
Authors: Yaxuan Wang, Huw A Ogilvie, Luay Nakhleh
Journal: Molecular Biology and Evolution (2020)

Species tree inference from multilocus data has emerged as a powerful paradigm in the postgenomic era, both in terms of the accuracy of the species tree it produces as well as in terms of elucidating the processes that shaped the evolutionary history. Bayesian methods for species tree inference are desirable in this area as they have been shown not only to yield accurate estimates, but also to naturally provide measures of confidence in those estimates. However, the heavy computational requirements of Bayesian inference have limited the applicability of such methods to very small data sets. In this article, we show that the computational efficiency of Bayesian inference under the multispecies coalescent can be improved in practice by restricting the space of the gene trees explored during the random walk, without sacrificing accuracy as measured by various metrics. The idea is to first infer constraints on the trees of the individual loci in the form of unresolved gene trees, and then to restrict the sampler to consider only resolutions of the constrained trees. We demonstrate the improvements gained by such an approach on both simulated and biological data.
Early Experience With Cerebral Embolic Protection During Transcatheter Aortic Valve Replacement in the United States
Authors: Mohamad Alkhouli, Fahad Alqahtani, Alyssa Hartsell Harris, Samuel F. Hohmann, Charanjit S. Rihal
Journal: JAMA Internal Medicine (2020)

Cerebral Embolic Protection Devices in Transcatheter Aortic Valve Replacement—Effective in Stroke Prevention?
Impact of metastasectomy on progression free and overall survival in metastatic renal cell carcinoma: Analysis of the REMARCC registry.
Authors: Margaret Frances Meagher, Ricardo Autorino, Maximilian Kriegmair, Maria Carmen Mir, Jose Rubio, Riccardo Campi, Andrea Mari, Matthias Heck, Francesco Porpiglia, Siska Van Bruwaene, Estefania Linares Espinos, Mireia Musquera, Fadi Ghali, Alessandro Veccia, Georgi Guruli, Eduard Rousel, Nicola Pavan, Alessandro Antonelli, Michele Marchioni, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2020)

753 Background: The role of metastasectomy has been in flux as treatment paradigms for management of metastatic renal cell carcinoma (mRCC) have shifted. We examined outcomes of surgical metastasectomy stratified in the setting of different mRCC risk groups. Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was subdivided by Motzer RCC criteria (low, intermediate, and high risk), and impact of metastasectomy was analyzed via multivariable analysis (MVA) and Kaplan Meier analyses (KMA). Primary outcome was progression free survival (PFS) and secondary outcome was overall survival (OS). Results: 438 patients (46 low risk, 262 intermediate risk, 140 high risk) with median follow-up 16 months were analyzed. Metastasectomy was performed in 18 (39%), 63 (24%), and 32 (23%) of low, intermediate and high risk groups (p=0.04). Risk groups differed significantly with respect to ECOG performance status (p&lt;0.001), metastases at diagnosis (low 1.72, intermediate 3.49, high 6.45, p&lt;0.001), hemoglobin (p&lt;0.001) and LDH (p&lt;0.001). MVA for PFS revealed age (OR=1.03, p=0.05), BMI (OR=1.05, p=0.01), and higher risk category [vs. low (referent) intermediate OR=7.4, p&lt;0.001, high OR=3.4, p=0.01] to be independent risk factors. MVA for OS revealed age (OR=1.03, p=0.02), BMI (OR=1.06, p=0.01), and higher risk category [low (referent) vs. intermediate OR=2.8, p=0.03, high OR=2.3, p=0.01] to be independent risk factors. KMA for PFS demonstrated that metastasectomy was associated with longer PFS in intermediate (24.0 vs. 6.7 months, p=0.01) but not high risk (4.2 vs. 4.0 months, p=0.58) and low risk (p=0.51) groups. KMA for OS demonstrated that metastasectomy was associated with longer median OS in the intermediate (56.9 vs. 29.3 months, p=0.01) and high risk (18.2 vs. 10.5, p=0.01), but not low risk (p=0.21) groups. Conclusions: Receipt of metastasectomy was associated with improved PFS in intermediate risk and improved OS in intermediate and high risk mRCC patients. These findings challenge prevailing assumptions about utility of metastasectomy. Further investigation is requisite to refine criteria for employment.
Quality of Life Analysis in the Galaxy Trialtm (NCT01348126): A Randomized Phase IIB/III Study of Ganetespib (STA-9090) in Combination with Docetaxel Versus Docetaxel Alone in Patients with Stage IIIB or IV NSCLC
Authors: Z.G. Andric, L. Havel, I. Di Hariry, V. Vukovic, F. Teofilovici, W. Guo, S. Mulcahey, R. Bradley, T. Ceric
Journal: Annals of Oncology (2012)