tbuckley/cabot-search huggingface dataset:
Abstract 18266: Correlation and Agreement of Acute Measurements of Echocardiography and Right Heart Catheterizations in Submassive Pulmonary Embolism
Authors: Averie Dowell, Julie Clary, Jeffrey A Kline, Daren M Beam
Journal: Circulation (2017)

Introduction: Multidisciplinary pulmonary embolism response teams (PERT) have gained popularity in the treatment of submassive and massive pulmonary embolism (PE). One purpose of the PERT is to determine which patient(s) could benefit from advance treatment, including catheter directed lysis (CDL). A proven effect of CDL is more rapid lowering of right ventricular (RV) pressures. Findings of RV strain on echocardiography (echo) can predict in hospital mortality in patients with PE, but less is known about its accuracy for catheter-derived RV pressure in patients with acute PE. Hypothesis: Echo measurements of the RVSP (from Bernoulli’s equation), RV fractional area change (FAC), right ventricle: left ventricle (RV:LV) ratio and tricuspid annular plane systolic excursion (TAPSE) can predict catheter-measured RV systolic pressures. Methods: All patients had image proven PE and signs of right heart strain by evidence-based guidelines. Echo was obtained via a RDCS certified sonographer. Catheter-measured RV p...
Salvage chemotherapy for relapsed germ cell tumors: A phase II trial of gemcitabine, paclitaxel, ifosfamide, and cisplatin (Gem-TIP).
Authors: Matthew James Wheater, Robert Anthony Huddart, Jeff D. White, Gordon J. S. Rustin, Ivo M. Hennig, Kelly Cozens, Megan Bowers, Nadia Cross, Graham Mead
Journal: Journal of Clinical Oncology (2014)

4560 Background: Cure is possible for patients with relapsed germ cell tumours using further intensive cisplatin based combination chemotherapy. The Medical Research Council TIP trial reported a complete response (CR) rate of 19%, 1 year progression free survival (PFS) of 38% and overall survival (OS) 65% (Br J Cancer 2005;93:178). The previously reported phase I Gem-TIP trial demonstrated the feasibility of delivering full dose gemcitabine (Gem) in combination with TIP (J Clin Oncol 27, 2009 [suppl; abstr e16031]). We now report efficacy and safety data on an expanded cohort of patients treated within a phase II trial. Methods: Patients with germ cell cancers at first relapse following cisplatin based chemotherapy received a maximum of 4 cycles of Gem-TIP (Gem 1200mg/m2 d1, paclitaxel 175mg/m2 d1, ifosfamide 1g/m2 d2-6, cisplatin 20mg/m2d2-6) with pegfilgrastim 6mg d7 of a planned 21 day cycle. Subsequent cycles were started on adequate haematological recovery with no planned dose reductions. Results: 20 patients were treated, 19 male, 1 female, median age 32 years (range 20-61). Histology 6 seminoma, 14 non-seminoma. 6 patients had poor prognostic features using the Memorial criteria. The mean relative dose intensity (RDI) for TIP for patients treated with Gem-TIP was paclitaxel 95%, ifosfamide 91% and cisplatin 94% compared with 92%, 92% and 94% respectively in the MRC TIP trial. Response was CR 9 patients (45%), CR surgery 1 (5%), PR marker negative 6 (30%), incomplete response 3 (15%), 1 unevaluable. 1 year PFS was 57.9% (95% CI 33.2-76.3%), 1 year overall survival 84.2% (95% CI 58.7%-94.6%). Of the 16 patients with a favourable response this was sustained for 11 (69%) with a median overall follow up of 29 months. Toxicity was manageable and predominantly haematological. Grade 3/4 neutropaenia 60%, thrombocytopaenia 75% febrile neutropaenia 15%. There were no toxic deaths. Conclusions: The addition of gemcitabine to TIP chemotherapy is a feasible chemotherapy combination with no detrimental impact on RDI of TIP drugs and acceptable toxicity. Response rate and duration are improved on those reported in the MRC TIP trial and warrant further evaluation in a larger study. Clinical trial information: 37453564.
Pooled Analyses of Total Symptom Score (TSS) Responses in Patients with Myelofibrosis (MF) Treated with Pacritinib (PAC) Vs Best Available Therapy (BAT) in Phase 3 Studies (PERSIST-1, PERSIST-2)
Authors: Ruben A. Mesa, Francisco Cervantes, Claire N. Harrison, Adam J. Mead, Alessandro M. Vannucchi, Srdan Verstovsek, Lixia Wang, Tanya Granston, John Mascarenhas
Journal: Blood (2018)
OWE-004 Iscan OE improves detection of early barretts oesophagus associated neoplasia in trainee and expert endoscopists
Authors: Martin Everson, Raf Bisschops, Sachin Wani, David Graham, Matthew Banks, Cormac Magee, Durayd Alzoubaid, O Omer Ahmad, Jacobo Ortiz-Fernandez-Sordo, Laurence Lovat, Rami Sweis, Jose Esteban, Krish Ragunath, Rehan Haidry
Journal: Endoscopy (2018)

<h3>Introduction</h3> The Seattle protocol for BE surveillance samples a small proportion of the mucosal surface area – risking a high miss rate of early neoplastic lesions. We assessed if the new iScan Optical Enhancement system (OE, Pentax) improves the detection of early BE associated neoplasia compared to high definition white light endoscopy (HD-WLE) in both expert and trainee endoscopists. Such a system may both improve early neoplasia detection and reduce the need for random biopsies. <h3>Methods</h3> Patients undergoing endoscopic BE surveillance from Jan 2016-Nov 2017 were recruited from 3 international referral centres. Matched still images in both HD-WLE and iScan OE were obtained from HD videos of endoscopic examinations. Two experts, unblinded to the videos and histology, delineated known neoplasia – forming a consensus 'gold standard'. 7 expert and 7 trainee endoscopists marked one position per image where they would expect a target biopsy to identify dysplastic tissue. Sensitivity, specificity and accuracy were calculated. Improvements in dysplasia detection in HD-WLE vs OE and interobserver agreement (IA) were assessed using McNemars test and Krippendorf's alpha respectively. <h3>Results</h3> Accuracy of neoplasia detection improved in all trainees using OE vs WLE (pooled 76% vs 63%) and in 6 experts (pooled 86% vs 78%). OE improved detection sensitivity compared to WLE in 6 trainees (pooled: 81% [62–94%] vs 71% [50–86%]) and 5 experts (pooled: 79.4% [62–92.5%] vs 65% [52–82%]). Specificity improved in 6 trainees using OE vs WLE (pooled: 71% [50–84%] vs 55% [40–91%]) and in 5 experts (pooled: 92% [78.5–100%] vs 90.3% [55.9–99%]) Trainees and experts made significantly more correct diagnoses using OE (pooled: 689 vs 570, p≤0.001, pooled: 789 vs 699 p≤0.001 respectively). IA in both groups improved using OE and was fair and moderate for each group respectively (trainees OE vs WLE: 0.39 vs 0.23, experts OE vs WLE: 0.46 vs 0.39). <h3>Conclusion</h3> iScan OE improves the diagnostic accuracy of expert and trainee endoscopists performing BE surveillance. OE significantly improves sensitivity and specificity of neoplasia detection. It does not meet the Preservation and Incorporation of Valuable Endoscopic Innovations guidelines (PIVI) but shows promise for use in the training environment or in a secondary care setting where caseloads of early BE neoplasia may be lower.
AUGMENT: A phase 3, randomized trial to compare efficacy and safety of lenalidomide plus rituximab versus placebo plus rituximab in patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL).
Authors: John Leonard, John G. Gribben, Marek Trneny, Phillip Scheinberg, Nurgul Kilavuz, Meera Patturajan, Pierre Fustier
Journal: Journal of Clinical Oncology (2014)

TPS8614 Background: Lenalidomide (L) is an immunomodulatory drug with both anti-inflammatory and antiangiogenic properties. Preclinical studies demonstrate that the immunological function of tumor-infiltrating lymphocytes is impaired in patients with follicular lymphoma (FL) and that treatment with L can repair this dysfunction (Ramsay, Blood, 2009). In phase 2 investigations of frontline L + rituximab (R), in patients with indolent NHL, overall response rate (ORR) reached 90% and complete response/complete response unconfirmed (CR/CRu) was 64% (Fowler, ASH, 2012); a second study in patients with FL achieved 93% ORR and 72% CR (Martin, ICML, 2013). In patients with recurrent FL, treatment with L+R yielded higher response rates (73% ORR, 36% CR) compared with L alone (51% ORR, 13% CR; Leonard, ASCO 2012 oral presentation). Together, these preclinical and phase 2 data provide a rationale for further investigation of L+R in indolent NHL. Methods: This phase 3, multicenter, double-blind, randomized study (AUGMENT) is designed to evaluate the efficacy and safety of L+R versus placebo (P)+R in patients with relapsed/refractory indolent lymphoma. Eligible patients must have grade 1, 2, or 3a FL or marginal zone lymphoma; have received previous systemic therapy; be refractory to or have relapsed after their last treatment; be R-sensitive if prior R therapy was administered; have ≥1 measurable lesion; and have adequate bone marrow, liver, and renal function (moderate renal impairment acceptable). Approximately 350 patients will be randomized 1:1 to one of two study arms (experimental or control). During each 28-day cycle, patients enrolled in the experimental group will receive L (20 mg/day; days 1 to 21 up to 12 cycles) + R (375 mg/m2; days 1, 8, 15, 22 of cycle 1 and day 1 of cycles 2 to 5). Patients in the control group will receive P+R (375 mg/m2) in the same schedule. The primary endpoint is progression-free survival. Key secondary endpoints include rate of durable CR, overall survival, ORR, safety, and time to next anti-lymphoma treatment. This trial is currently enrolling patients. Clinical trial information: NCT01938001.
Enhancement of docetaxel efficacy by zoledronic acid pretreatment in docetaxel-resistant prostate cancer cells (PC-3/R and DU-145/R).
Authors: Zeki Surmeli, Emir Bozkurt, Ozge Ozer, Harika Atmaca, Asli Kisim, Selim Uzunoglu, Ruchan Uslu, Burcak Karaca
Journal: Journal of Clinical Oncology (2014)

e16105 Background: Docetaxel-based chemotherapy is the only globally approved first-line therapy for hormone refractory prostate cancer. Although docetaxel treatment improves survival, all patients will eventually become refractory to docetaxel treatment. Zoledronic acid (ZA) is the most potent member of nitrogen-containing bisphosphonate family and has anti-tumor activity in some types of cancer, including prostate cancer. In this study, we investigated whether ZA pretreatment enhances the cytotoxic and apoptotic effect of docetaxel in docetaxel resistant (Doc-R) prostate cancer cells. Methods: Doc-R prostate cancer cells were pretreated with the increasing concentrations of ZA for 36 h and with the increasing concentrations of docetaxel for additional 36 h. Cell proliferation was assessed by XTT cell proliferation Kit (Roche). Cell Death Detection Elisa Plus Kit (Roche) and Caspase-Glo 3/7 (Invitrogen) assays were used for investigating apoptosis. Results: The sequential treatment of 20 µM ZA followed by 10 nM docetaxel resulted in significantly enhanced cytotoxicity as compared to single agents alone in both at Doc-R prostate cancer cells. Moreover, docetaxel mediated DNA fragmentation and caspase 3/7 activity was increased by ZA pretreatment. Conclusions: These findings strongly suggest that pretreatment with ZA enhances docetaxel-induced cytotoxicity and apoptosis in Doc-R prostate cancer cells. These preliminary results make ZA a good candidate for overcoming docetaxel resistance in prostate cancer.
Organic anion transporters also mediate the drug–drug interaction between imipenem and cilastatin
Authors: Yanna Zhu, Xiaokui Huo, Changyuan Wang, Qiang Meng, Zhihao Liu, Huijun Sun, Aiping Tan, Xiaodong Ma, Jinyong Peng, Kexin Liu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

This study aimed to clarify that organic anion transporters (OATs) mediate the drug-drug interaction (DDI) between imipenem and cilastatin. After co-administration with imipenem, the plasma concentrations and the plasma concentration-time curve (AUC) of cilastatin were significantly increased, while renal clearance and cumulative urinary excretion of cilastatin were decreased. At the same time, imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1 (hOAT1)-HEK293 and human OAT3 (hOAT3)-HEK293 cells. Probenecid, p-aminohippurate, and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1- and hOAT3-HEK 293 cells, respectively. The uptakes of imipenem and cilastatin in hOAT1- and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells. Moreover, the Km values of cilastatin were increased in the presence of imipenem with unchanged Vmax , indicating that imipenem inhibited the uptake of cilastatin in a competitive manner. When imipenem and cilastatin were co-administered, the level of imipenem was higher compared with imipenem alone both in vivo and in vitro. But, cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1 (DPEP1) was silenced by RNAi technology in hOAT1- and hOAT3-HEK 293 cells. In conclusion, imipenem and cilastatin are the substrates of OAT1 and OAT3. OAT1 and OAT3 mediate the DDI between imipenem and cilastatin. Meanwhile, cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.
FT-2102, an IDH1m Inhibitor, in Combination with Azacitidine in Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Ayndrome (MDS): Results from a Phase 1 Study
Authors: Jorge E. Cortes, Justin Watts, Thomas Prebet, Gary J. Schiller, Sangmin Lee, Jay Yang, Eunice S. Wang, Shira Dinner, Paul Brent Ferrell, Will Donnellan, Brian A. Jonas, Andrew H Wei, Pau Montesinos, Montserrat Arnan Sangerman, Patrick Kelly, Ping Li, Jennifer Sweeney, Courtney Watson, Hesham Mohamed, Maria R. Baer
Journal: Blood (2018)
Phase 1 dose escalation study of copanlisib (BAY 80-6946) in combination with gemcitabine or gemcitabine-cisplatin in advanced cancer patients.
Authors: Richard D. Kim, Steven R. Alberts, Frank Gary Renshaw, Isabelle Genvresse, Stefanie Reif, Jennifer Kaplan, Juneko E. Grilley-Olson
Journal: Journal of Clinical Oncology (2014)

2610 Background: Copanlisib (BAY 80–6946) is a potent and reversible pan-class I PI3K inhibitor with significant activity against PI3K-δ and PI3K-α isoforms. We report the results of an open-label, Phase 1 study of copanlisib in combination with gemcitabine alone and with gemcitabine plus cisplatin in advanced cancer patients. Methods: On Treatment A, patients received gemcitabine at 1000 mg/m2 IV and 2 dose levels of copanlisib 0.6 mg /kg or 0.8 mg/kg IV on days 1, 8 and 15 of a 28-day cycle to determine whether the single agent maximum tolerated dose (MTD) of copanlisib (0.8mg/kg) was tolerable with the chemotherapy. On Treatment B, patients received cisplatin at 25 mg/m2 IV, gemcitabine 1000 mg/m2 IV and copanlisib IV on days 1 and 8 of a 21-day cycle at the MTD determined in Treatment A. The primary objective was to determine the safety, tolerability, and MTD of copanlisib in combination with gemcitabine and gemcitabine-cisplatin. Results: A total of 29 patients were treated with copanlisib. In Treatment A, 8 patients received copanlisib at 0.6 mg/kg and 8 at 0.8 mg/kg in combination with gemcitabine. There were no reported dose-limiting toxicities (DLTs) and the 0.8 mg/kg dose was the maximum tested dose. In Treatment B, 13 patients received copanlisib at 0.8 mg/kg with gemcitabine-cisplatin and no DLTs were observed. The most frequently observed drug-related adverse events reported in >20% of the patients were hyperglycemia, nausea, diarrhea, anemia, and fatigue. There were no treatment-related deaths. Pharmacokinetic evaluations showed comparable results across treatment groups indicating the absence of relevant PK interactions. Of the 2 patients enrolled in treatment schedule B with biliary tract cancer (BTC), one achieved a complete response (CR) and one a partial response (PR) according to RECIST criteria. An expansion cohort in patients with BTC with treatment schedule B is now ongoing, and one PR has been observed to date. Conclusions: The combination of copanlisib with gemcitabine alone or with gemcitabine plus cisplatin is generally well tolerated, with an early efficacy signal seen in patients with BTC. Clinical trial information: NCT01460537.
Image Gallery: Red coral vascular pattern as a new dermoscopic clue for clear cell acanthoma
Authors: A. Lobato‐Berezo, A. Vidal Navarro, R.M. Pujol
Journal: British Journal of Dermatology (2019)

Dear Editor, A 68-year-old man developed a cutaneous lesion at the site of a previous needle aspiration for a liver biopsy, performed some years before. Examination revealed a 6-mm, crusted papule on his right hypochondrium (a). Dermoscopy revealed multiple long-branched, round-ending vessels coming together in the centre, along with a peripheral collarette scale. The composition of a symmetrical, three-lobulated vascular pattern resembled a red coral (b, d).1 Histopathology showed parakeratosis, psoriasiform acanthosis, neutrophilic exocytosis and pale keratinocytes after periodic acid–Schiff staining.2 Highly vascularized dermal papillae were seen with intense epidermal and dermal red-blood-cell extravasation that correlated with the dermoscopic image (c). The diagnosis of clear cell acanthoma was made. This new dermoscopic vascular pattern might help in the challenging clinical diagnosis of these lesions.
24-hour urinary steroid metabolites as predictors of response to chemotherapy in metastatic adrenocortical carcinoma (mACC).
Authors: Mehran Afshar, Helen Clarke, Irina Bancos, Weibke Arlt, Emilio Porfiri
Journal: Journal of Clinical Oncology (2014)

e15625 Background: Adrenocortical carcinoma is very rare with an estimated incidence of 0.5-2 new cases/million/year. Patients with aggressive disease necessitating chemotherapy often fare poorly, and due to the limited number of cases, there is a paucity of data regarding their treatment outcomes. Recent novel methodology has shown the usefulness of urine metabolomic analysis as a tool for differentiating ACC from adrenocortical adenoma. We hypothesise that the same methodology can be utitlised as a tool to assess response to chemotherapy Methods: We retrospectively reviewed electronic and paper case notes of all patients treated with chemotherapy for mACC at our institution from 2006 to 2013. Results of 24 hour urine metabolomics including pregnenediol (5PD), 5-Pregnenetriol (5PT), and tetrahydro-11-deoxyxortisol (THS) were reviewed where available. Steroid metabolite excretion was compared to results from the reference cohort (n=147) from Arlt et al. 2011, and computed determined likelihoods for ACC were calculated at different times through treatment with chemotherapy. Results: 19 patients were identified (8 female, 11 male) with a median age of 53 (range:25-77). 8 patients were alive at time of analysis. 13 patients (68%) were treated with etoposide/doxorubicin/cisplatin (EDP) as first line chemotherapy, with the remainder receiving streptozocin. The median number of cycles received was 3, with 4 patients (21%) going on to receive 2ndline treatment with Gemcitabine/Capecitabine. The median PFS was 3.5 months (range:0.4-9.9). 3 patients had 24 hour urine metabolomics data available prior to, during and after chemotherapy. In these 3 patients, the 3 compounds 5PD, 5PT and THS were found to correlate with response to chemotherapy and progression, with computer determined likelihood scores for ACC changing clearly in concordance with clinical and radiographic response and progression on chemotherapy. Conclusions: We present a cohort of patients who have received chemotherapy for metastatic ACC, and show a potential utility for 24 hour urine metabolomics as a predictive tool for response. The authors suggest further prospective analyses are required to validate this finding.
Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis
Authors: Murray B Urowitz, Robert L Ohsfeldt, Ronald C Wielage, Kari A Kelton, Yumi Asukai, Sulabha Ramachandran
Journal: Annals of the Rheumatic Diseases (2019)

Objectives The study (206347) compared organ damage progression in patients with systemic lupus erythematosus (SLE) who received belimumab in the BLISS long-term extension (LTE) study with propensity score (PS)-matched patients treated with standard of care (SoC) from the Toronto Lupus Cohort (TLC). Methods A systematic literature review identified 17 known predictors of organ damage to calculate a PS for each patient. Patients from the BLISS LTE and the TLC were PS matched posthoc 1:1 based on their PS (±calliper). The primary endpoint was difference in change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score from baseline to 5 years. Results For the 5- year analysis, of 567 (BLISS LTE n=195; TLC n=372) patients, 99 from each cohort were 1:1 PS matched. Change in SDI score at Year 5 was significantly lower for patients treated with belimumab compared with SoC (−0.434; 95% CI –0.667 to –0.201; p&lt;0.001). For the time to organ damage progression analysis (≥1 year follow-up), the sample included 965 (BLISS LTE n=259; TLC n=706) patients, of whom 179 from each cohort were PS-matched. Patients receiving belimumab were 61% less likely to progress to a higher SDI score over any given year compared with patients treated with SoC (HR 0.391; 95% CI 0.253 to 0.605; p&lt;0.001). Among the SDI score increases, the proportion of increases ≥2 was greater in the SoC group compared with the belimumab group. Conclusions PS-matched patients receiving belimumab had significantly less organ damage progression compared with patients receiving SoC.
Soft and elastic hydrogel-based microelectronics for localized low-voltage neuromodulation
Authors: Yuxin Liu, Jia Liu, Shucheng Chen, Ting Lei, Yeongin Kim, Simiao Niu, Huiliang Wang, Xiao Wang, Amir M. Foudeh, Jeffrey B.-H. Tok, Zhenan Bao
Journal: Nature Biomedical Engineering (2019)