tbuckley/cabot-search huggingface dataset:
FUNCTIONAL MITRAL REGURGITATION WITHOUT SIGNIFICANT MITRAL VALVE TETHERING: A THREE-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY STUDY
Authors: Atsushi Hayashi, Takafumi Nagaura, Jun Yoshida, Satoshi Yamaguchi, Tetsuo Kamiyama, Florian Rader, Robert Siegel, Takahiro Shiota
Journal: Journal of the American College of Cardiology (2018)
GPs are opposed to pension scheme changes
Authors: Abi Rimmer
Journal: BMJ (2014)

GPs have voted to oppose changes to the NHS pension scheme that mean they will have to work longer and pay higher contributions.

Delegates at the BMA’s local medical committee (LMC) conference in York voted in favour of a motion saying that it was “unacceptable” to ask all GPs to work to the age of 68. The conference agreed that the pension lifetime allowance caps and taxation of pension growth …
The prognostic impact of a negative confirmatory biopsy in men on active surveillance for prostate cancer.
Authors: Keyan Salari, Dimitar V. Zlatev, David Kuppermann, Mark A. Preston, Douglas M. Dahl, Jason A. Efstathiou, Michael L. Blute, Anthony L. Zietman, Adam S. Feldman
Journal: Journal of Clinical Oncology (2018)

76 Background: Active surveillance (AS) is increasingly used in managing low-risk and favorable intermediate-risk prostate cancer. To mitigate the risk of unsampled higher risk disease, most institutional AS protocols call for a confirmatory prostate biopsy within 12-18 months following initial diagnostic biopsy. Here, we investigate whether the results of confirmatory biopsy impact the outcomes of men on AS. Methods: We retrospectively reviewed our institutional database of men enrolled in AS between 1997-2014 with a minimum follow-up of 6 months (n = 974). Biopsies with any prostate cancer were considered positive. Biopsies containing only benign prostatic tissue, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation (ASAP) were considered negative. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: At diagnosis, median age was 67 years (IQR 62-72) and median PSA was 5.1 ng/mL (IQR 3.9-6.8). The vast majority of patients had Gleason ≤6 (97%) and clinical stage T1 (92%) disease. With a median follow-up of 4.8 years, 702 (72%) patients underwent a confirmatory biopsy. 67% of confirmatory biopsies were positive for prostate cancer; 33% were negative (167 benign, 40 PIN, and 22 ASAP). Of the 702 patients, 33% progressed to treatment, with pathologic progression the most common reason (77%). Univariate predictors of progression to treatment included initial clinical stage ( P= 0.04), involvement of &gt; 20% of any core on diagnostic biopsy ( P &lt; 0.01), PSA density ≥0.15 ( P &lt; 0.001), and confirmatory biopsy status ( P &lt; 10 -14 ). In multivariate analysis, a negative confirmatory biopsy remained the strongest predictor of progression to treatment (HR 0.12 [95%CI 0.06-0.24], P &lt; 10 -8 ). Confirmatory biopsy status was not associated with risk of adverse pathology on RP, metastasis-free survival, disease-specific survival, or overall survival. Conclusions: A negative confirmatory biopsy is associated with a significantly lower rate of progression to treatment among men on AS. This may serve as a useful tool for prognostication and help determine the need for further repeat biopsies for men on AS.
Effect of a third-generation oncolytic herpes simplex virus on the growth of human hepatocellular carcinoma.
Authors: Richi Nakatake, Masaki Kaibori, Yusuke Nakamura, Hideyuki Matsushima, Tadayoshi Okumura, Yasushi Inou, Tomoki Todo, Masanori Kon
Journal: Journal of Clinical Oncology (2018)

321 Background: Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 replicates efficiently and selectively in tumor cells, kills tumor cells without damaging the surrounding normal tissues, and induces host immune responses specific to tumor cells. Here we investigated the antitumor effects of T-01 on HCC. Methods: The cytopathic activities of T-01 were tested at different multiplicities of infection in 14 human and one murine hepatoma cell lines in vitro. In mouse various xenograft models, HuH-7, KYN-2, PLC/PRF/5 and HepG2 human cells and Hepa1-6 murine cells were used to investigate the in vivo efficacy of T-01. Results: T-01 was cytotoxic to 13 cell lines (in vitro), including 10 human HCCs, two human hepatoblastomas, and one murine hepatoma. In mouse xenograft models of subcutaneous, orthotopic, and peritoneal tumor metastasis in athymic mice (BALB/c nu/nu), the growth of tumors formed by the HCC cell lines HuH-7, KYN-2, and PLC/PRF/5 as well as those formed by the hepatoblastoma cell line HepG2 was inhibited by T-01 compared with that of mock-inoculated tumors. In a bilateral Hepa1-6 subcutaneous tumor model in C57BL/6 mice, the growth of tumors inoculated with T-01 was inhibited and, in the contralateral tumors without T-01, T-01 also significantly reduced tumor growth compared with mock-infected tumors. T-01 infection significantly enhanced antitumor efficacy via T cell-mediated immune responses. Conclusions: These results demonstrate that a third-generation oncolytic HSV-1 may serve as a novel treatment for patients with HCC.
How to care for survivors of torture
Authors: Caroline Jewels, Helen Maguire, Brian Fine, Carol Cheal
Journal: BMJ (2004)

All doctors in the United Kingdom can expect to see patientsat some stage in their career who have been tortured. <b>Caroline Jewels</b>, <b>Helen Maguire</b>,<b>Brian Fine</b>, and <b>Carol Cheal</b> discuss how to identify and support survivors of torture
Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study
Authors: Silvia Paggi, Giuseppe Mogavero, Arnaldo Amato, Emanuele Rondonotti, Alida Andrealli, Gianni Imperiali, Nicoletta Lenoci, Giovanna Mandelli, Natalia Terreni, Francesco Conforti, Dario Conte, Giancarlo Spinzi, Franco Radaelli
Journal: Endoscopy (2018)

Abstract Background Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI). Methods Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI–WLI group) and vice versa (WLI–LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate. Results Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI–WLI and 24.7 % in WLI–LCI). At per-polyp analysis, double inspection of the right colon in the LCI–WLI and WLI–LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively (P &lt; 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI – WLI group and in 13 of 300 patients (4.3 %) in the WLI – LCI group (P = 0.01). Conclusions LCI could reduce the miss rate of neoplastic lesions in the right colon.
Sixteen-year percutaneous renal mass ablation trends: Results from the Ablation of Renal Masses Outcomes Registry (ARMOR).
Authors: Aaron Wilhelm Palmer Maxwell, Francois H. Cornelis, Grayson L. Baird, Marwah Jihad, Dharam Patel, Elizabeth Hurtado, Jeremy C. Durack
Journal: Journal of Clinical Oncology (2018)

620 Background: Existing data suggest that percutaneous renal mass ablation offers favorable rates of disease control with lower cost and fewer complications relative to surgical interventions. Despite increasing utilization, little is known about changes in practice patterns and patient selection over time as new technologies have emerged and indications for renal ablation have been refined. Methods: Institutional review board approval was granted with a waiver of informed consent to review data from the multinational Ablation of Renal Masses Outcomes Registry (ARMOR), which is composed of adult ablation patients with biopsied renal masses. Patient demographics, ablation modality, timing of renal biopsy, malignancy rate, method of anesthesia, and type of imaging guidance from 2001-2016 were reviewed. Analyses were conducted using generalized mixed modeling assuming normal or binary distribution with sandwich estimation, where observations were nested within participating institutions. Variables were modeled over time using SAS/GLIMMIX with significance set at α = 0.05. Results: Data from 768 patients at eleven institutions were available for review. Average patient age was 67.7±11.7 years (male:female, 1.9:1), which remained unchanged throughout the study period. Radiofrequency ablation (RFA) was the most commonly utilized modality from 2001-2007 but decreased thereafter, with cryoablation favored from 2008-2012. By 2016, RFA, microwave (MWA), and cryoablation were all used with relative equipoise, though a significant trend toward increased MWA utilization was found beginning in 2010 (OR: 1.28; p = 0.004). A significant increase in the frequency of same-day biopsy was observed relative to pre-ablation biopsy (OR: 1.16; p = 0.003) alongside a trend toward increasing rates of benign histology (p = 0.08). Use of CT guidance and general anesthesia increased by 4% and 5%, respectively. Conclusions: ARMOR data illustrate fluctuating practice patterns, with increasing use of microwave ablation technology. Growing utilization of concurrent renal mass biopsy and ablation may be contributing to the observed trend toward increased rates of ablation for benign tumors.
Fitness to practise procedures do not discriminate against ethnic minority and non-UK doctors, say researchers
Authors: Abi Rimmer
Journal: BMJ (2015)

Fitness to practise procedures do not discriminate against black and minority ethnic (BME) doctors or doctors who qualified outside the UK, but there is a need for “greater clarity and transparency” in these procedures, researchers have concluded.1

The researchers reviewed decisions made by the General Medical Council as part of fitness to practise procedures. They aimed to identify “instances of bias or discriminatory practice, and …
Lyc-55716: A novel small-molecule RORγ agonist immuno-oncology agent: Rationale for tumor selection and clinical evaluation of gastric and esophageal carcinoma in phase 2a expansion.
Authors: Garry Alan Weems, Xiao Hu, Xikui Liu, Hongxiu Li, Madhumita Bogdan, Yilin Gao, Brian Fox, H. Jeffrey Wilkins, Laura Carter
Journal: Journal of Clinical Oncology (2018)

67 Background: Type 17 effector T cell differentiation and function are regulated by the master transcription factor retinoic acid receptor–related orphan receptor γt (RORγ). Synthetic RORγ agonists, which modulate immune cell gene expression to enhance effector functions and decrease Treg and checkpoint pathways, have shown promise as mono- and combination therapy in syngeneic tumor models. Translational and bioinformatics assessments were performed during Phase 1 testing of the investigational RORγ agonist LYC-55716 to support inclusion of patients with gastric carcinoma (GC) and esophageal carcinoma (EC) in a Phase 2a expansion of clinical trial LYC-55716-1001 (NCT02929862). Methods: Transcriptional profiling of murine and human T cells treated ± RORγ agonists identified a gene signature. Using The Cancer Genome Atlas (TCGA), and other public datasets, data on GC and EC patients were evaluated to determine: (a) RORγ and RORγ-inducing cytokine expression; (b) signature genes associated with RORγ biology, surrogate biomarkers for endogenous RORγ ligands, and correlations with prognosis; (c) tumor microenvironment (TME) immune profiles. Results: Expression: In TCGA RNA sequencing data analysis, 50%-70% of GC and EC samples expressed moderate to high levels of RORγ, indicating infiltration of Type 17 T cells into the tumors. Furthermore, genes that support expression of RORγ were highly expressed in ~75% of GC and EC tumors. Biology: TCGA data showed that GC and EC tumors express low levels of sterol efflux genes, suggesting low levels of endogenous agonists in the TME. In analysis of public datasets, expression of the RORγ target gene IL17A correlated with a favorable prognosis for EC. In addition, some of the other RORγ signature genes also correlated with good prognosis in GC and EC. Immune profile: TCGA showed infiltration of T cells and a high mutational burden in GC and EC, which are positively associated with efficacy of immunotherapy. Conclusions: Bioinformatics assessments of RORγ expression, biology, and tumor immune profiles support the inclusion of GC and EC patients in an ongoing Phase 2 clinical trial of LYC-55716.
ANALYSIS OF THE INITIAL UNITED STATES EXPERIENCE WITH THE BIOTRACE TEMPO TEMPORARY PACING LEAD IN TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR) AND OTHER CARDIAC PROCEDURES
Authors: Tamim Nazif, Carlos Sanchez, Brian Whisenant, John Forrest, Steven J. Yakubov, Paul Grossman, Arash Arshi, Daniel Menees, Juan Terre, James Orford, Martin B. Leon, Susheel K. Kodali, Stanley Chetcuti
Journal: Journal of the American College of Cardiology (2018)
Comprehensive genomic profiling of appendiceal adenocarcinoma.
Authors: Kanwal Pratap Singh Raghav, Jonathan M. Loree, Keith F. Fournier, Kenna Rael Shaw, Melissa W. Taggart, Wai Chin Foo, Aurelio Matamoros, Amir Mehdizadeh, Shahab U. Ahmed, Jennifer L. Guerra, Paul F. Mansfield, Richard Eldon Royal, Michael J. Overman, Cathy Eng
Journal: Journal of Clinical Oncology (2018)

298 Background: Appendiceal adenocarcinomas (AAs) are orphan tumors. Little is known about their molecular profile limiting understanding of their biology and development of novel targeted therapies. The purpose of this study was to delineate the molecular landscape of AAs. Methods: We performed a retrospective review of AAs patients (pts) who were evaluated at MD Anderson Cancer Center between October 2012 and April 2017 and underwent next-generation sequencing (NGS) with internal or external assays (at least 45 genes) using either tumor tissue specimens or peripheral blood for circulating cell-free DNA (cfDNA). The primary outcome was to assess the prevalence of genomic alterations (GAs) in AAs. We then performed comparative exploratory analyses of GAs using TCGA colorectal cancer (CRC) sequencing. Results: A total of 78 patients were identified of which 57 (73%) and 18 (23%) underwent tissue based and ctDNA based sequencing, respectively (3 cases had both). At least 1 GA was found in 61 (78%) of AA specimens, with a mean (SD) of 2.8 (1.6) GAs per case. Of these 44 (72%) had ≥ 2 GAs and 31 (51%) had ≥ 3 GAs. The most frequent GAs were KRAS (38 [62%]), TP53 (22 [36%]), GNAS (17 [28%]), SMAD4 (11 [18%]), PIK3CA (10 [16%]), APC (9 [15%]), ATM (8 [13%]), BRAF (5 [8%]), KIT (5 [8%]), NRAS (3 [5%]) and MET (3 [5%]). GNAS mutations frequently co-occurred with KRAS mutations (42% v 5%, OR 14.3, P &lt; 0.001). No GA was associated with grade, mucinous histology or overall survival (OS). Besides these mutations, we also found unusual cases with targetable mutations such as ALK, EGFR, MET, IDH1 and ERBB2. In our comparative analyses, mutations in KRAS (p = 0.009), TP53 (p = 0.020), GNAS (p &lt; 0.001) and APC (p &lt; 0.001) genes were significantly different from CRC whereas there was no difference in prevalence of PIK3CA, SMAD4 and ATM genes. Conclusions: To date, our analysis of one of the largest cohorts of AAs, demonstrate a majority of AAs harbor at least 1 GAs. Although treatment paradigms in AAs are extrapolated from CRC, the molecular profile of these tumors differs significantly. Molecular characterization of these rare tumors is a necessary first step towards discovery of opportunities for use of targeted therapies in these patients.
Effect of outside referrals to a tertiary care liver tumor board on diagnostic testing and initial curative therapy.
Authors: Yapei Zhang, Jennifer Arango, Jeffrey Weinreb, Tamar Hamosh Taddei
Journal: Journal of Clinical Oncology (2018)

259 Background: Hepatocellular carcinoma (HCC) is a complex and unique cancer. Arriving at the optimal treatment plan is best accomplished by a multidisciplinary tumor board (MDTB). We hypothesized that patients referred from outside institutions to our tertiary care center for MDTB review may face disparities in diagnosis and treatment. Methods: We performed chart review of incident HCC cases presented from 2/1/13-2/1/16 at an American College of Surgeons accredited MDTB that convenes weekly at a tertiary care, university-affiliated hospital. We examined variables such as demographics, originating institution, liver disease etiology, location of index imaging, date of first tumor board presentation, diagnostic method (imaging, biopsy, tumor board consensus), BCLC stage at diagnosis, initial treatment, and time to treatment. Results: 167 cases of HCC were referred from 37 outside institutions (outside cases); 127 cases originated from our institution (internal cases). The two groups were comparable in gender distribution, liver disease etiology, and BCLC stage at tumor board presentation. Compared to internal cases, outside cases were diagnosed less often by imaging (47% vs. 77%, p &lt; 0.000001) and more often by biopsy (38% vs. 17%, p &lt; 0.001) or MDTB consensus (16% vs. 6%, p &lt; 0.05). When stratified by BCLC stage, this difference in diagnostic method persisted in early and mid-staged patients (Stages 0, A, B), but not in advanced staged patients. Outside cases were also more likely to receive tumor biopsy (33% vs. 9%, p &lt; 0.05) and less likely to receive initial curative therapy (resection, ablation, transplantation) (22% vs. 32%, p &lt; 0.05). There was no significant difference in time to treatment. Conclusions: Despite similar demographics and disease profiles compared to patients from our tertiary care center, patients referred from outside facilities for MDTB review more often required biopsies or MDTB consensus to diagnose HCC, and were less likely to receive curative therapy. Differences in HCC diagnostic imaging protocols across institutions may help explain these results. Further study will help identify disparities in receipt of curative therapy.
99mTc-MDP SPECT-CT and Ultrasound in the Diagnosis and Staging of Thyroid Metastasis From Osteosarcoma
Authors: Wolfgang Roll, Matthias Weckesser, Monika Pöppelmann, Manfred Schiborr, Michael Schäfers, Kambiz Rahbar
Journal: Clinical Nuclear Medicine (2018)

The classification of thyroid nodules in children is often difficult, especially in pretreated patients with metastatic disease. In osteosarcoma patients, Tc-MDP SPECT/CT is used for primary and follow-up staging. Bone and soft tissue metastases can be revealed because of Tc-MDP imaging of osteoid-producing metastases. We present Tc-MDP SPECT-CT, CT, and ultrasound images of a highly suspicious calcified thyroid lesion in a 17-year-old boy with osteosarcoma. High uptake in Tc-MDP SPECT-CT provides diagnosis of thyroid metastasis of osteosarcoma, which was proven by histopathology.
Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis
Authors: Salman Siddiqui, Aarti Shikotra, Matthew Richardson, Emma Doran, David Choy, Alex Bell, Cary D. Austin, Jeffrey Eastham-Anderson, Beverley Hargadon, Joseph R. Arron, Andrew Wardlaw, Christopher E. Brightling, Liam G. Heaney, Peter Bradding
Journal: Journal of Allergy and Clinical Immunology (2018)
Impact of tumor size on survival outcome in metastatic renal cell carcinoma patients (mRCC) treated with targeted therapy.
Authors: Wanling Xie, Renzo DiNatale, A. Ari Hakimi, Frede Donskov, Camillo Porta, M. Neil Reaume, Naveen S. Basappa, Aaron Richard Hansen, Brian I. Rini, Benoit Beuselinck, Georg A Bjarnason, Sandy Srinivas, James Brugarolas, Sun Young Rha, Lori Wood, Aly-Khan A. Lalani, Dominick Bosse, Audrey Duquette, Daniel Yick Chin Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2018)

667 Background: Recent research suggested that patients (pts) with small renal masses (4cm or less) were at low risk of disease recurrence after surgery. The impact of tumor size on survival in mRCC patients treated with targeted therapy (TKI) is unclear. Methods: Two cohorts were identified from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Cohort 1 pts had initial nephrectomy for M0 RCC and subsequently developed metastasis during follow-up. Cohort 2 pts presented with de novo metastasis with or without cytoreductive nephrectomy. Cox regression was performed to assess the associations of primary tumor size (≤4 vs &gt; 4cm) and overall survival (OS) on first line TKI, adjusted for histology, sarcomatoid features, tumor stage, number of metastasis, IMDC risk groups and age at TKI initiation. Results: 4089 pts with mRCC treated with first line TKI had primary tumor size data available. Patient characteristics were generally balanced between tumor size groups (≤4 vs &gt; 4cm), except pts with ≤4cm tumors were more likely to have single metastasis (29% vs 18%, p = 0.001) and less likely to have IMDC poor risk (32% vs 39%, p = 0.04) in pts from cohort 2. For pts from cohort 1, tumor size at initial nephrectomy did not impact OS after TKI initiation (p = 0.689). However, in pts presenting with de novo metastasis (cohort 2), small primary tumors were associated with improved OS after TKI initiation, but only in T1-2 tumors (Table). Conclusions: Tumor size impacts survival outcome with targeted therapy in mRCC patients presenting with de novo metastasis and T1-2 disease. This may need to be taken in consideration in clinical trial designs. [Table: see text]
Less than 70% of GP training places are filled in some areas
Authors: Abi Rimmer
Journal: BMJ (2014)

The fill rate for GP training places is lower than 70% in some areas of England, figures from Health Education England (HEE) have shown. 

The figures for the August 2014 intake of GP trainees, collected at the end of May, showed that 11% of training places remained unfilled across the United Kingdom. In England 2630 places of the total 2946 had been filled, representing an 89% fill rate. The corresponding figure the previous year was 2738 posts from a total of 2761, representing a 99% fill …