tbuckley/cabot-search huggingface dataset:
Robert Vaughan Clark
Authors: Andrew Clark
Journal: BMJ (2021)

Robert Vaughan Clark (“Robin”) was born in Alloa, Clackmannanshire, the son of a minister and a teacher. He was a day pupil at Dollar Academy.

He studied medicine at St Andrews University from 1951 to 1957 and, in April 1959, with Marnie, his wife of two weeks, began life as a medical officer with the Colonial Service in Sokoto and Zaria, Nigeria.

On returning to Glasgow, he gained further experience in several hospitals and, in 1963, achieved fellowship of the Royal College of Surgeons, Edinburgh.

In 1965, the family travelled to Nairobi; Robin to assist the formation of the Kenya School of Medicine in collaboration with Glasgow University. He also worked with the flying doctor service.

When he was a senior registrar in Glasgow, Robin was …
Abstract 4471: Long-Term Follow-Up After Deferral of Percutaneous Coronary Intervention (PCI) in Patients With Moderate Coronary Lesions and Borderline Fractional Flow Reserve Measurements
Authors: Takafumi Yamane, Koichi Tamita, Noriomi Kimura, Shunsuke Funakoshi, Kite Kim, Yoshimori An, Takeshi Kitai, Minako Katayama, Natuhiko Ehara, Makoto Kinoshita, Atushi Kobori, Shuichiro Kaji, Atushi Yamamuro, Tomoko Tani, Yutaka Furukawa
Journal: Circulation (2008)

Background: Many studies have demonstrated that deferral of percutaneous coronary intervention (PCI) on the basis of a myocardial fractional flow reserve (FFR) ≥0.75 is associated with a very low coronary event rate. However, some groups have empirically chosen the cut-off value of 0.80 rather than 0.75 for decision to defer PCI and the FFR measurement between 0.75 and 0.80 has been established as a grey zone. The aim of this study was to evaluate the long-term clinical outcomes of patients with moderate coronary lesions and FFR measurements between 0.75 and 0.80. Methods: The study included 125 anigiographically moderate coronary lesions (&gt;50% diameter stenosis by visual assessment) in 125 patients but in whom the PCI was deferred on the basis of an FFR ≥ 0.75. The FFR was calculated as the ratio of mean distal pressure divided by the proximal pressure during hyperemia. Patients were divided into two groups according to the result of FFR: ≥ 0.80 (n=99, group 1) and between 0.75 and 0.79 (n=26, group 2). We evaluated the long-term major adverse cardiovascular events (MACE) related and unrelated to the FFR-evaluated lesion. Results: During a follow-up period of 82 ± 29 months (mean ± SD), The Kaplan-Meier event-free survival curves showed that group 2 was poorer than group 1 in prognosis (p=0.0148). The incidence of MACE unrelated FFR-evaluated lesion in group 1 was equivalent to that in group 2 (p=0.96). Conclusions: In patients with moderate coronary lesions and borderline FFR measurements, deferral of PCI was associated with a higher rate of MACE related to the FFR-evaluated lesion. FFR cut-off point of 0.80 instead of 0.75 may be more appropriate for deferring PCI.
Unexpected gallbladder cancer as the source of some unknown primary cancers.
Authors: Xiaowei Zhang, Xin Liu, Zhiguo Luo, Xichun Hu, Qifeng WANG, Silong Hu, Liangping Zhou, Shiyu Jiang
Journal: Journal of Clinical Oncology (2021)

e16177 Background: CUP (Cancer of Unknown Primary) represents a frequent cancer type causing incomparable difficulties in pathological diagnosis as compared to other tumor types. To explore and analyze the causes of CUP (Cancer of Unkown Primary) patients with misdiagnosis in patients after laparoscopic cholecystectomy with cholecystitis or cholecystolithiasis. Methods: 13 patients with CUP (Cancer of Unkown Primary) were recruited in this research, who accepted the multidisciplinary discussion of the CMUP (Cancer of Multiple or Unknown Primary) multidisciplinary team. Our team analyzed the clinical data and pathological characteristics of these patients, and tried to find the common characteristics of the CUP patients whose primary site is the gallbladder that has been already removed. Results: 13 patients were received laparoscopic cholecystectomy because of previously considered cholecystitis or cholecystolithiasis. The gallbladder is considered as the primary organ supported by the pathological features of the metastatic sites. Importantly, all these patients have local abdominal wall and/or local perigallbladder lymph node metastases. Among them, 3 cases were diagnosed as gallbladder cancer, and 1 case was considered as high-grade intraepithelial neoplasia after pathological consultation, which were recognized as benign disease. Among the 13 cases, 9 cases showed local thickening of the gallbladder wall by preoperative CT or B-ultrasound. The median recurrence time was 16.4 months (9-48 months). Of the 13 patients, 5 received radical resection again, and received GP (gemcitabine plus platinum) chemotherapy after surgery. Of the 8 patients who were unable to undergo radical surgery, 5 received first-line GP based chemotherapy, 2 received first-line PD-1 immunotherapy combined with anti-vascular targeted drugs, and 1 received tegafur monotherapy due to poor physical condition. Till now, these patients are still under follow-up. Conclusions: Unexpected gallbladder cancer is the source of some unknown primary cancers. For these patients with cholecystitis or cholecystolithiasis, B-ultrasound examination should not be performed alone, and CT or MRI examination should be performed when necessary. We should pay high attention to the patients with cholecystitis or gallstone thickening of the gallbladder wall or other high-risk gallbladder cancer. Before surgery, clinical data should be analyzed comprehensively, and rapid frozen examination should be performed on patients suspected of having cancer. In order to avoid misdiagnosis, we should pay attention to the principle of none tumor and avoid the risk of incision implantation. If unexpected gallbladder cancer is found, radical operation should be performed as soon as possible.
Obinutuzumab (G)-atezolizumab (atezo)-lenalidomide (len) for the treatment of relapsed/refractory (R/R) follicular lymphoma (FL): Final analysis of a phase Ib/II trial.
Authors: Nilanjan Ghosh, Gilles A. Salles, Izidore S. Lossos, Maria Lia Palomba, Amitkumar Mehta, Olivier Casasnovas, Don A. Stevens, Sudhakar Katakam, Andrea Knapp, Tina Nielsen, Franck Morschhauser
Journal: Journal of Clinical Oncology (2021)

7511 Background: G-len has promising activity and manageable toxicity in R/R FL (Morschhauser et al. 2019). We report the final analysis of an open-label, multicenter, Phase Ib/II trial (NCT02631577) that evaluated the immunomodulatory triplet G-atezo-len in pts with R/R FL. Methods: An initial 3+3 dose‐escalation to identify the Phase II len dose was followed by an expansion phase with G-atezo-len. Enrolled pts (aged ≥18 years) received induction with 6, 28-day cycles of G 1000 mg IV on Day [D] 1, 8, and 15 of Cycle [C] 1 and D1 of C2–6, atezo 840 mg IV on D1 and 15 of C2–6, and len 15/20 mg (dose escalation) or 20 mg (expansion) orally on D1–21 of C1–6. Responders received 24 months (mos) of maintenance with G 1000 mg D1 every 2 mos, atezo 840 mg D1–2 every mo, and len 10 mg D1–21 mos 1–12. The primary endpoint was complete response at end of induction by PET-CT assessed by Independent Review Committee (modified Lugano 2014 criteria; Morschhauser et al. ICML 2019). Exploratory endpoints described herein included progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Adverse events (AEs) were also assessed. Results: At the final analysis (October 7, 2020), 38 pts had completed the trial. Median age was 62 years, 26% had a high-risk FLIPI score, 45% were refractory to their last line of therapy, and 37% had progression of disease within 24 mos of their first-line of therapy (POD24). Median treatment duration was 26 mos (range: 0.4‒30). The 36-mo PFS rate for the overall population (median observation time, 35.9 mos; range: 3‒47) was 64% (95% CI, 45‒79), OS was 85% (95% CI, 70‒93), and median DOR was 38 mos (95% CI, 35‒NE). 36-mo PFS rates for the following subgroups are provided in the table: double refractory (rituximab and an alkylator); with/without POD24; minimal residual disease (MRD) +/-. In total, 32 pts (84%) had a Grade 3/4 AE (majority hematologic), and 18 (47%) had a serious AE. Five pts (13%) during induction and six pts (16%) during maintenance had an AE that led to discontinuation of any drug. Two fatal AEs were reported (1 merkel carcinoma, 1 sarcomatoid carcinoma; both unrelated to any study drug). The most common atezo AEs of special interest were hyperthyroidism (13%), hypothyroidism (11%), increased ALT and AST (both 8%), increased lipase (8%), and hepatocellular injury (5%). Conclusions: G-atezo-len is efficacious in pts with R/R FL, with data from the final analysis suggesting a potential for improved outcomes versus the G-len doublet. AEs were consistent with the safety profile of the individual drugs. Clinical trial information: NCT02631577. [Table: see text]
A single-arm phase II trial of palbociclib in combination with tamoxifen as first-line therapy for metastatic hormone receptor-positive breast cancer.
Authors: Oana Cristina Danciu, Kent Hoskins, Cristina I. Truica, Anne Hudson Blaes, Deimante Tamkus, Jatin Rana, Pavankumar Tandra, Lauren Green, Menggang Yu, Qianqian Zhao, Deborah Toppmeyer, Ruth O'Regan, Kari Braun Wisinski
Journal: Journal of Clinical Oncology (2021)

1056 Background: Palbociclib is a CDK4/6 inhibitor used to treat metastatic hormone receptor-positive (HR+) breast cancer (MBC) in combination with endocrine therapy. Tamoxifen is an effective treatment for HR+ MBC, with different toxicity profile compared with aromatase inhibitors (AI) and fulvestrant. Preclinical data demonstrated synergy for the combination of tamoxifen and palbociclib, being effective in a model of acquired tamoxifen resistance. Methods: We conducted an open-label, single-arm, multicenter phase II trial of palbociclib in combination with tamoxifen in patients with HR+/HER2 - advanced BC, with no prior therapy for MBC. Ovarian suppression was recommended for pre-menopausal women, but not required. Primary objective was progression free survival. Secondary objectives: objective response rate (CR or PR) based on RECIST 1.1 or MDA Criteria (for patients with bone only disease); safety and tolerability (using CTCAE v4); clinical benefit rate (CR, PR or SD lasting min 24 weeks); 2-year overall survival. Correlative objectives: proteomic analysis of plasma exosomes to identify mechanisms of primary and secondary resistance to tamoxifen/palbociclib. Results: Between 6/30/2016 and 7/02/2019, we enrolled 49 patients (47 evaluable): 23 pts with de-novo metastatic disease and 24 pts with recurrent BC (12 pts were on adjuvant treatment with AI at time of recurrence and 12 pts on surveillance). As of 1/5/21 data cut-off, 7 pts were still on treatment. Median follow-up time was 24 months (range 8-42). Median age was 60 (range 39-82). The median PFS was 14.6 months with 95% CI (7-41) for pts with de-novo MBC and 6 months (2-12) for pts with recurrent BC. The ORR was 30% overall, 39% for pts with de novo MBC, 21% for pts with recurrent BC. CBR was 64% overall, 78% for pts with de novo MBC and 50% for pts with recurrent BC. CBR was 65% for white pts and 55% for African American pts. Best response per RECIST1.1: 14 pts (34%) had PR, 18 pts (44%) had SD, 9 pts (22%) had PD. All 6 pts with bone only disease had SD. The most common drug related grade ≥ 3 AE was neutropenia (51%), transient and manageable by dose modifications, no cases of febrile neutropenia. Four patients developed thromboembolic events (1 grade 2, 2 grade 3, 1 grade 4). One patient died while on treatment from PD. Conclusions: The combination of palbociclib and tamoxifen showed tolerable, expected safety profile. This may be an alternative approach for selected patients in first line treatment of HR+ MBC, especially those who are intolerant to AI, although this small study indicates a lower PFS. Clinical trial information: 02668666 .[Table: see text]
Automated identification of immune related adverse events in oncology patients using machine learning.
Authors: Wenxin Xu, Alexander Gusev, Stefan Groha, Osama E. Rahma, Deborah Schrag, Toni K. Choueiri, Kenneth L. Kehl
Journal: Journal of Clinical Oncology (2021)

1551 Background: Immune related adverse events (irAEs) are a major cause of morbidity among cancer patients treated with immune checkpoint inhibitors (ICIs). irAEs are difficult to identify systematically, which represents a major barrier to the conduct and reproducibility of irAE research. Automated approaches would facilitate cohort identification and understanding of risk factors for irAEs following ICI therapy. Methods: Patients treated with one or more ICIs at a single tertiary cancer center were identified. Patients who received ICIs outside the clinical trial context were used as a development cohort. For each date containing clinical documentation, proxy outcomes expected to correlate with grade 2+ irAEs including irAE related diagnosis codes, key laboratory values, prescriptions for topical and systemic steroids, and irAE keywords were extracted. Intermediate machine learning models were trained to predict the presence of each proxy outcome using structured and unstructured patient data. We used clinical trial irAEs extracted from adverse event tables found in the electronic health record as the “gold standard” outcome for a final training and evaluation cohort. A logistic regression model was used to combine predictions from each intermediate model and generate an overall probability score for each irAE type on a given encounter date. Ten-fold cross-validation was used to evaluate the final machine learning model on a held-out sample of clinical trial patients. Encounter level models were evaluated for predicting the onset of a given irAE on a given date, and patient level models for predicting irAE onset within 6 months of ICI initiation. Results: We identified 3,765 patients treated with ICIs off-trial and 1106 patients treated on ICI clinical trials. Among trial patients, overall incidence of any grade 2+ irAE was 21%. The combined irAE models were able to predict prospective gold standard irAE labels with accurate discrimination at both the encounter and patient level (Table). Conclusions: Machine learning models can identify irAEs among cancer patients in an automated manner, which may facilitate research to mitigate toxicities and optimize clinical outcomes. Validation of these methods in an external institutional cohort is underway.[Table: see text]
Dissemination of validated health literacy videos: A tailored approach.
Authors: Shannon M. Blee, Margie D. Dixon, Viraj A. Master, Rebecca D. Pentz
Journal: Journal of Clinical Oncology (2021)

e18505 Background: Previously, we showed that chemotherapy and precision medicine terminology are remarkably difficult for patients to understand. Therefore, we developed short, animated videos explaining key terminology and demonstrated that they significantly improved understanding. These videos, though effective and published, including freely downloadable, will only be helpful if appropriately disseminated. In the past, even after a video-based educational tool for prostate cancer was proven effective for improving patient comprehension, no dissemination plan was implemented due to copyright issues. Therefore, in order to propel these validated health literacy videos from the academic community into clinic workflow, we aimed to determine the best dissemination method at two different hospitals with disparate populations just six miles apart: an underserved, inner-city hospital and a higher SES hospital. Methods: The dissemination interview was developed in collaboration with an expert Intervention Development, Dissemination, and Implementation team. The draft was cognitively tested with physicians and staff who were not oncologists and finalized. With consent, interviews were conducted with both Winship Cancer Institute and Grady Memorial Hospital providers (GMH). All interviews were audio recorded, transcribed and analyzed using a semantic content analysis method. Results: Eleven providers at GMH and 22 providers at Winship were interviewed, reaching saturation of themes. 72% (n = 8) of the GMH providers felt that the best place for patients to view the videos was in the clinic, compared to 27% (n = 6) of the Winship providers. 68% (n = 15) of the Winship providers stated an app would be the most useful format, compared to 27% (n = 3) at GMH. All agreed that it would be useful for the patient’s family or caregiver to view the videos (GMH = 100%, Winship = 72%), that translation of the videos to Spanish would be beneficial (GMH = 90%, Winship = 63%), and that a nurse would be best to introduce the videos (GMH = 81%, Winship = 68%). Conclusions: Educational materials explaining complicated oncology treatment terminology enhance patient-centered care, yet without proper dissemination these crucial educational tools may never reach the intended patient population. The hospitals examined in this study served significantly different patient populations and the dissemination recommendations were quite different. Providers believed that the underserved patients needed the videos accessible in the clinic whereas providers serving higher SES patients thought that a web-based app, requiring a smart device or internet access, was more appropriate. Our study shows that it is crucial to ensure that educational materials are accessible to all populations, not just those with more means. Without a location-specific dissemination plan, educational tools may only further exacerbate disparities, rather than alleviate them.
Abstract 8795: Cardiac Cachexia is Associated with Abnormal Liver Metabolism and Pro-Inflammatory Responses in a Rat Model of Heart Failure
Authors: Takao Kato, Tetsuo Shioi, Shinichiro Niizuma, Tsuneaki Kawashima, Junji Okuda, Akira Kawamoto, Yodo Tamaki, Yoshitaka Iwanaga, Tomoyoshi Soga, Toru Kita, Takeshi Kimura
Journal: Circulation (2011)

Introduction: Cachexia, namely body wasting, is a common complication in heart failure (HF). Although neurohumoral and immune abnormalities are associated with the condition, the mechanism by which the imbalance of catabolism and anabolism occurs is not known. Hypothesis: We assessed the hypothesis that the liver is important in the pathogenesis of cardiac cachexia, since the liver plays a critical role in systemic metabolic regulation. Methods: We analyzed markers of cachexia in Dahl salt-sensitive rats fed a high salt diet which develop hypertension and, subsequently, HF. Dahl rats fed a low salt diet were used as a control. Glucose uptake of the liver was estimated using 18 F-deoxyglucose ( 18 FDG). The amount of metabolites in glycolysis and the Krebs cycle was measured employing metabolome analysis. Results and Conclusion: The body weight of HF rats was decreased compared with control rats (354±9 vs. 425±13 g, n=6, p&lt;0.05). Food intake was reduced compared with controls by 29% (p&lt;0.05). Blood sugar and insulin levels were decreased by 34 and 54%, respectively (p&lt;0.05). Blood retinol binding protein (RBP), a hepatic protein, was decreased by 53% (p&lt;0.05). The blood levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased. These results indicate that Dahl rats serve as a model of cardiac cachexia. Despite the apparent fasting condition, blood free fatty acid levels were decreased by 53% (p&lt;0.05) and triglyceride (TG) levels were increased 2.0-fold (p&lt;0.05). Next, we analyzed the livers of HF rats. 18 FDG uptake was increased 1.7-fold (p&lt;0.05). The concentrations of some metabolites in the glycolytic pathway increased, and those in the Krebs cycle decreased. Gene expression related to lipogenesis increased and the TG content of the liver increased 1.8-fold (p&lt;0.05). Gene expressions of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2, key enzymes in lipogenesis, increased 3.1- and 1.9-fold, respectively (p&lt;0.05). The protein levels of SREBP-1c and SREBP-2 also increased. The gene and protein expressions of TNF-α and IL-1β increased in the liver. In conclusion, cardiac cachexia was associated with abnormal lipogenesis and proinflammatory responses in the liver, which might act as a maladaptive response in HF.
The effect of enzymes on the in vitro degradation behavior of Mg alloy wires in simulated gastric fluid and intestinal fluid
Authors: Yue Zhang, Jian Cao, Xianli Wang, Huan Liu, Yi Shao, Chenglin Chu, Feng Xue, Jing Bai
Journal: Bioactive Materials (2021)

With an upsurge of biodegradable metal implants, the research and application of Mg alloys in the gastrointestinal environment of the digestive tract have been of great interest. Digestive enzymes, mainly pepsin in the stomach and pancreatin in the small intestine, are widespread in the gastrointestinal tract, but their effect on the degradation of Mg alloys has not been well understood. In this study, we investigated the impacts of pepsin and pancreatin on the degradation of Mg-2Zn alloy wires. The results showed that the pepsin and pancreatin had completely different even the opposite effects on the degradation of Mg, although they both affected the degradation product layer. The degradation rate of Mg wire declined with the addition of pepsin in simulated gastric fluid (SGF) but rose with the addition of pancreatin in simulated intestinal fluid (SIF). The opposite trends in degradation rate also resulted in completely different degradation morphologies in wires surface, where the pitting corrosion in SGF was inhibited because of the physical barrier effect of pepsin adsorption. In contrast, the adsorption of pancreatin affected the integrity of magnesium hydrogen phosphate film, causing a relatively uneven degraded surface. These results may help us to understand the role of different digestive enzymes in the degradation of magnesium and facilitate the development and clinical application of magnesium alloy implanted devices for the digestive tract.