tbuckley/cabot-search huggingface dataset:
Clinical outcomes and appropriate treatment strategies of locally advanced resectable cervical esophageal cancer.
Authors: Jun Miyakoshi, Yoshitaka Honma, Kazuki Yokoyama, Shun Yamamoto, Koshiro Ishiyama, Junya Oguma, Tairo Kashihara, Koji Inaba, Naoya Murakami, Hiroshi Igaki, Ken Kato, Hiroyuki Daiko
Journal: Journal of Clinical Oncology (2022)

313 Background: Due to its rare nature, no standard treatment based on the randomized controlled trials for locally-advanced resectable cervical esophageal cancer (rCEC) has been established. Prognostic factors of locally-advanced rCEC are not also well evaluated. When considering the treatment for rCEC, larynx preservation (LP) is an important issue, as well as the prolongation of survival. This study aimed to clarify the clinical outcomes and prognostic factors on locally-advanced rCEC, and the appropriate treatment strategies focused on both LP and long-term survival. Methods: We retrospectively reviewed the medical records of rCEC patients treated with surgery or definitive chemoradiotherapy (CRT) at our institute from 2010 to 2020. This retrospective study was approved by the institutional review board of NCCH (2017-229). Results: A total of 123 cases were extracted as subjects, treated with surgery in 53 and CRT in 70. 1/3/5-year PFS and OS in all subjects were 52/40/36% and 84/60/56%, respectively. Univariate analysis indicated that clinical tumor depth might be a prognostic factor (T1 vs. T≥2, hazard ratio [HR]: 2.30, p=0027. in PFS; HR: 2.86, p=0.046 in OS). In the subjects with ≥T3 lesion (N=95) who usually require laryngectomy, both PFS (31.0 vs. 7.0 months, HR: 0.50, p=0.013) and OS (not reached vs. 25.0 months, HR: 0.28, p=0.005) were better in subjects treated with surgical approach than with CRT. Focused on the cases with ≥T3 lesion and initially treated with induction chemotherapy (N=33), the surgical approach also showed better clinical outcomes than the CRT approach (median PFS: 19.0 vs. 8.0 months, HR: 0.37, p=0.007; median OS: not reached vs. 18.0 months, HR: 0.18, p=0.007). Especially, subjects treated with induction chemotherapy followed by larynx-preserving surgery achieved better outcomes. Conclusions: This study indicated that clinical depth might be a significant prognostic factor in rCEC. A chemo-selection approach using induction chemotherapy might be a good strategy to achieve LP and improve survival outcomes in locally-advanced rCEC.
Quantitative and Multiplex Detection of Extracellular Vesicle‐Derived MicroRNA via Rolling Circle Amplification within Encoded Hydrogel Microparticles
Authors: Dana Al Sulaiman, Nidhi Juthani, Patrick S. Doyle
Journal: Advanced Healthcare Materials (2022)

Abstract Extracellular vesicle‐derived microRNA (EV‐miRNA) represent a promising cancer biomarker for disease diagnosis and monitoring. However, existing techniques to detect EV‐miRNA rely on complex, bias‐prone strategies, and preprocessing steps, making absolute quantification highly challenging. This work demonstrates the development and application of a method for quantitative and multiplex detection of EV‐miRNA, via rolling circle amplification within encoded hydrogel particles. By a one‐pot extracellular vesicle lysis and microRNA capture step, the bias and losses associated with standard RNA extraction techniques is avoided. The system offers a large dynamic range (3 orders of magnitude), ease of multiplexing, and a limit of detection down to 2.3 zmol (46 × 10 −18 m ), demonstrating its utility in clinical applications based on liquid biopsy tests. Furthermore, orthogonal measurements of EV concentrations coupled with the direct, absolute quantification of miRNA in biological samples results in quantitative measurements of miRNA copy numbers per volume sample, and per extracellular vesicle.
Phase 1b expansion study of CX-5461 in patients with solid tumors and <i>BRCA2 </i>and/or <i>PALB2</i> mutation.
Authors: Jennifer J. Knox, Amit M. Oza, Diane M. Provencher, John Soong, Daniel McCormick, Jimmy Chen, Jenny Chen, Ariel Chang
Journal: Journal of Clinical Oncology (2022)

TPS622 Background: BRCA and PALB2 proteins play important roles in the maintenance of genomic stability as they are essential for error-free repair of double-stranded DNA breaks, while deficiency of these proteins promotes error-prone DNA repair, chromosomal instability and carcinogenesis. Inherited mutations in BRCA genes predispose to various early onset cancers. Poly(ADP-ribose) polymerase inhibitors (PARPi) inducing synthetic lethality in tumors with homologous recombination (HR)-mediated DNA repair deficiencies have been approved for treatment in patients with germline BRCA-mutated metastatic pancreatic adenocarcinoma. Unfortunately, resistance to PARPi associated with multiple mechanisms can be observed over time, suggesting a prominent unmet need for the development of new treatment options. CX-5461, a G-quadruplex stabilizer, employs an alternative mechanism in destabilizing the DNA replication fork to promote DNA damage resulting in cancer cell lethality in HR-deficient (HRD) tumors, thus represent a promising therapeutic strategy for patients with defects in HR-repair. Methods: A prior phase I dose escalation study has been completed for CX-5461 (CCTG IND.231, NCT02719977) but additional safety data are required to define the chronic tolerable dose for phase 2 trials. Therefore, a phase Ib expansion trial was designed for two doses preselected from our previous phase I trial to determine the final recommended phase II dose (RP2D) by evaluating safety, tolerability and objective response rate in a more selected population. This trial will enroll patients in two cohorts; the main cohort recruiting patients with pancreatic, breast, ovarian or prostate cancer with germline BRCA2 and/or PALB2 mutation, and an exploratory cohort recruiting ovarian cancer patients with BRCA1 and/or other HRD-associated mutations. Major eligibility criteria include documented evidence of pathogenic or likely pathogenic germline mutation in BRCA2 and/or PALB2 for main cohort patients, documented evidence of pathogenic or likely pathogenic germline mutation or a clinically actionable somatic mutation in BRCA1 and/or other HRD-associated mutation for exploratory cohort. Patients with non-adenocarcinoma histology of pancreatic cancer, known photosensitivity disorders of the skin, or patients with ophthalmological conditions will not be enrolled. An initial 16 eligible patients for the main cohort and 10 eligible patients for the exploratory cohort will be enrolled in parallel to receive CX-5461 at 250mg/m2, delivered via IV infusion on Day 1 and Day 8 of a 28-day cycle. Upon completion of the initial arms with no safety concerns, another two arms will open to enroll an additional 16 patients for the main cohort and 10 patients for the exploratory cohort to receive CX-5461 at 325mg/m2 of the same dosing schedule. Clinical trial information: NCT04890613.
REGINA: A phase II trial of neoadjuvant regorafenib (Rego) in combination with nivolumab (Nivo) and short-course radiotherapy (SCRT) in intermediate-risk, stage II-III rectal cancer (RC).
Authors: Giacomo Bregni, Chiara Senti, Elena Acedo Reina, Paraskevas Gkolfakis, Luigi Moretti, Ana Veron, Pieter Demetter, Gabriel Liberale, Javier Carrasco, Karen Paula Geboes, Yeter Gokburun, Marc Peeters, Marc Van Den Eynde, Jean-Luc Van Laethem, Philippe Vergauwe, Marc E. Buyse, Amélie Deleporte, Alain Hendlisz, Francesco Sclafani
Journal: Journal of Clinical Oncology (2022)

TPS226 Background: Despite recent improvements, management of locally advanced rectal cancer (LARC) remains challenging, and many patients (pts) still experience recurrence. In preclinical models, combining Rego with an anti-PD-1 inhibitor led to superior tumour growth suppression as compared with either treatment alone. In a phase I clinical trial, remarkable results were reported for the combination of Rego and Nivo in advanced MSS colorectal cancer. This synergistic effect is thought to be secondary to the anti-angiogenic effects of Rego and its potential to reduce TAMs, promote M1 macrophage conversion, and down-regulate expression of immunosuppressive factors. Building on these data, we designed a trial of Rego-Nivo with standard SCRT in the neoadjuvant setting of RC. Methods: REGINA is an academic, multicentre, single-arm, phase II trial sponsored by Institut Jules Bordet. Eligible patients are treated according to the following plan: induction phase (Nivo 240 mg IV D1&amp;15, and Rego 80 mg PO D1-14), SCRT (D22-26), consolidation phase (Nivo 240 mg IV D29,43&amp;57, and Rego 80 mg PO D29-49), and surgery (7-8 weeks after SCRT). Key eligibility criteria include age ≥18 years, ECOG PS ≤1, adenocarcinomas below the peritoneal reflection, intermediate-risk, stage II-III tumour (ie, cT3/T4aNany or cT1-2N+, no involvement/threatening of the mesorectal fascia, no involvement of lateral pelvic lymph nodes) irrespective of microsatellite instability status. The primary endpoint is pathological complete response (pCR). Secondary endpoints include, among others, toxicity, compliance to treatment, pathological tumour regression grade, event-free survival, and overall survival. Subjects will be followed for recurrence and survival for 5 years after end of treatment visit. The study follows a Simon’s two-stage design (null hypothesis pCR = 12%, alternative hypothesis pCR = 24%; α= 5%, β= 20%) with a maximum of 60 pts to be enrolled. A safety interim analysis is planned after the first 6 pts have completed treatment. Serial collection of tumour, blood, and stool samples is mandatory at pre-specified time points for exploratory correlative biomarker analyses. The trial is planned to be run at 8-10 centres across Belgium. Study recruitment started in Q1 2021 and is anticipated to complete in Q3 2023. The study is funded by Bayer. Clinical trial information: NCT04503694.
Book Review Principles and Practice of Radiation Oncology Second edition. Edited by Carlos A. Perez and Luther W. Brady. 1544 pp., illustrated. Philadelphia, J.B. Lippincott, 1992. $195. ISBN 0–397–51162–0 . Levitt and Tapley's Technological Basis of Radiation Therapy: Practical clinical applications Second edition. Edited by Seymour H. Levitt, Faiz M. Khan, and Roger A. Potish. 414 pp., illustrated. Philadelphia, Lea and Febiger, 1992. $75. ISBN 0–8121–1466–3 .
Authors: Karen Chayt Marcus
Journal: New England Journal of Medicine (1992)
Neurology, Minneapolis
Journal: JAMA (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Reverse Remodeling With Left Ventricular Assist Devices
Authors: Daniel Burkhoff, Veli K. Topkara, Gabriel Sayer, Nir Uriel
Journal: Circulation Research (2021)

This review provides a comprehensive overview of the past 25+ years of research into the development of left ventricular assist device (LVAD) to improve clinical outcomes in patients with severe end-stage heart failure and basic insights gained into the biology of heart failure gleaned from studies of hearts and myocardium of patients undergoing LVAD support. Clinical aspects of contemporary LVAD therapy, including evolving device technology, overall mortality, and complications, are reviewed. We explain the hemodynamic effects of LVAD support and how these lead to ventricular unloading. This includes a detailed review of the structural, cellular, and molecular aspects of LVAD-associated reverse remodeling. Synergisms between LVAD support and medical therapies for heart failure related to reverse remodeling, remission, and recovery are discussed within the context of both clinical outcomes and fundamental effects on myocardial biology. The incidence, clinical implications and factors most likely to be associated with improved ventricular function and remission of the heart failure are reviewed. Finally, we discuss recognized impediments to achieving myocardial recovery in the vast majority of LVAD-supported hearts and their implications for future research aimed at improving the overall rates of recovery.
Direct Cholangioscopy
Authors: C. S. Shim, H. Neuhaus, K. Tamada
Journal: Endoscopy (2003)

Since it was first advocated by Takada et al. in 1974 [1], percutaneous transhepatic cholangioscopy (PTCS) has been utilized to manage a variety of biliary tract disorders. Percutaneous lithotomy using PTCS has become one of the most important nonsurgical forms of treatment for hepatolithiasis. The diagnostic and therapeutic efficacy of PTCS has been widely accepted, and clinical applications for this procedure have expanded to provide more precise preoperative diagnosis of biliary malignancy and to treat difficult biliary stenoses or gallstones using improved and less invasive instruments. PTCS has also been used in the management of diverse biliary tract disorders, including biliary neoplasms, calculi, strictures (benign and malignant), and evaluation of biliary-enteric anastomoses. PTCS appears to be of particular benefit in managing poor surgical candidates with diffuse intrahepatic stones.
Seventh Annual San Diego Residents' Radiology Review Course
Journal: JNCI Journal of the National Cancer Institute (1987)

Seventh Annual San Diego Residents' Radiology Review Course JNCI: Journal of the National Cancer Institute, Volume 78, Issue 2, February 1987, Page 397, https://doi.org/10.1093/jnci/78.2.397-e Published: 01 February 1987
Effectiveness of a nicotine patch in helping people stop smoking: results of a randomised trial in general practice. Imperial Cancer Research Fund General Practice Research Group.
Authors: David Mant, Godfrey Fowler, Peter Burke, Andrew Chivers, John Clements, Martin Dawes, Ian Eastwood, David Ebbs, Rickman Godlee, Richard Harrington, Karen Kearley, Neil Maclennan, Janet Murray, Mary Nichols, Helen Van Oss, David Stem, Richard Stevens, David Thurston, Robin Wilson
Journal: BMJ (1993)

OBJECTIVE--To assess the effectiveness of 12 weeks' treatment with a 24 hour transdermal nicotine patch in helping heavy smokers to stop smoking; also to assess the value of a specially written support booklet about smoking cessation and patch use compared with a simple advice pamphlet. DESIGN--Double blind placebo controlled randomised trial with a 2 x 2 factorial design. SETTING--19 general practices in Oxfordshire. SUBJECTS--1686 heavy smokers aged 25-64 (mean cigarette consumption 24/day; mean duration of smoking 25 years). MAIN OUTCOME MEASURE--Sustained cessation for the last four weeks of the 12 week treatment period, confirmed by saliva cotinine estimation (226/262 cases; 86.3%) or expired carbon monoxide concentration (36/262; 13.7%). Patients lost to follow up (155/1686; 9%) were assumed to have continued to smoke. RESULTS--Cessation was confirmed in 163 patients (19.4%) using the nicotine patch and 99 patients (11.7%) using the placebo patch (difference 7.6% (95% confidence interval 4.2% to 11.1%); p < 0.0001). There was no significant advantage in using the more detailed written support material. The most important adverse effect of the patch was local skin irritation, which occurred in 15.8% (133/842) and 5.1% (43/844) of patients using the nicotine and placebo patches respectively, was graded as severe in 4.8% (40) and 1.1% (nine), and was stated as a reason for withdrawal from the trial in 9.5% (80) and 2.8% (24). CONCLUSION--Nicotine patches are effective in a general practice setting with nursing support, but the extent to which this effect is sustained cannot be assessed until the results of longer term follow up are known.
Treatment of hepatocellular carcinoma with tyrosine kinase inhibitors: Real-world outcomes from the West of Scotland.
Authors: Gregory Naylor, Alistair McLaren, Janet Graham, T.R. Jeffry Evans
Journal: Journal of Clinical Oncology (2022)

390 Background: Sorafenib, lenvatinib and regorafenib have proven efficacy in patients with HCC in randomised clinical trials. First line sorafenib significantly improves overall survival (OS) and disease control rates vs. placebo (SHARP) whilst lenvatinib (REFLECT) is non-inferior to sorafenib in terms of OS. Second line regorafenib improves OS versus placebo (RESORCE). Real world outcomes are often inferior to randomised controlled trial data. Consequently we investigated the outcomes of real world patients with HCC treated with multi-kinase inhibitors in our regional tertiary-referral centre. Methods: All patients with advanced HCC treated with sorafenib, lenvatinib or regorafenib as monotherapy from 4 December 2015 to 16 September 2020 were included. The Information Governance (Caldicott) guardian approved access to patients records. Median OS (mOS) and treatment duration (mDoT) were calculated using Kaplan-Meier estimate; baseline patient characteristics and information on dosing regimen, dose interruptions and modifications, were also collected. Results: The SHARP trial achieved mOS and mDoT of 10.7 and 5.3 months. 26% required dose reductions and 44% dose interruptions. Our patients achieved mOS of 7.98 and mDoT 2.62 months; 35% required a dose reduction and 48% a dose interruption. Mean daily dose (MDD) was not given in SHARP but was 663.8mg in REFLECT; 728mg sorafenib was achieved in West of Scotland (WOS). In REFLECT, lenvatinib patients had mOS and mDOT of 13.6 and 5.7 months; our patients had a mOS of 9.55 and mDoT of 3.68 comparatively. 37% and 40% had dose reductions and interruptions in REFLECT vs. 50% and 44% in WOS. Our patients had a MDD of 10.9 mg (12mg/day) and 6.88mg (8mg/day) lenvatinib vs. 10.5mg and 7.0mg in REFLECT. In RESORCE, mOS and mDOT of 10.6 and 3.6 months was acheived in regorafenib patients vs. 9.52 and 3.42 months in WOS. 68% needed drug interruption or reduction vs. 53% in WOS and MDD of regorafenib was 144·1mg vs. 148.3mg in our population. Conclusions: Consistent with other real world experiences our data demonstrate reduced mOS and mDoT times compared to trials. This is despite maintaining good dose intensity. On average, mOS was 2.6 months less in our population vs. trial data. This may be explained by etiological differences of underlying liver disease or treatment of less highly selected patients. Our patients tended to be older, have poorer PS and Child Pugh scores compared with trials. Our data lack control arms, preventing interpretation of whether improved survival outcomes over placebo are maintained. Interestingly our data mirror the results of REFLECT where lenvatinib treatment was maintained for longer periods compared to sorafenib, despite higher numbers of dose interruptions. Our data also confirm that observed within RESORCE where, remarkably, patients treated with second line regorafenib achieved mOS similar to those treated in the first line setting.
Paraneoplastic Cerebellar Syndrome Presented as Cerebellar Hypermetabolism in a Patient With Occult Breast Carcinoma
Authors: Jan Booij, Judit A. Adam, Maaike S. van Eerde, Irene M. Bronner
Journal: Clinical Nuclear Medicine (2022)

A 47-year-old woman presented with an acute cerebellar syndrome. Neither cerebellar atrophy nor an infarction or tumor was shown on MRI. A diagnostic CT demonstrated enlarged axillary lymph nodes, but no primary tumor. Puncture of these nodes showed non-small cell carcinoma. 18F-FDG PET/CT imaging was performed and suggested an occult breast carcinoma, which was confirmed by pathological examination. It also showed cerebellar hypermetabolism, consistent with a PCS (paraneoplastic cerebellar syndrome). This case shows that 18F-FDG PET imaging may be of value in patients in which a PCS is considered clinically, particularly in patients suspicious for an occult malignancy.
Changes in COVID-19 Vaccine Hesitancy Among Black and White Individuals in the US
Authors: Tasleem J. Padamsee, Robert M. Bond, Graham N. Dixon, Shelly R. Hovick, Kilhoe Na, Erik C. Nisbet, Duane T. Wegener, R. Kelly Garrett
Journal: JAMA Network Open (2022)

<h3>Importance</h3> COVID-19 has disproportionately affected Black individuals in the US; however, vaccination rates among Black individuals trail those among other racial groups. This disparity is often attributed to a high level of vaccine hesitancy among Black individuals, but few studies have examined changes in vaccine hesitancy over time. <h3>Objectives</h3> To compare changes in vaccine hesitancy between Black and White individuals in the US and to examine mechanisms that might help explain the observed differences. <h3>Design, Setting, and Participants</h3> This survey study used 7 waves of data collected using a panel design. A total of 1200 English-speaking adults in the US were recruited from a nonprobability online panel to construct a census-matched sample. Participants were contacted monthly between December 9, 2020, and June 16, 2021. <h3>Main Outcomes and Measures</h3> The main outcome of interest was self-reported vaccination intention, measured on a 6-point scale (where 1 indicates extremely unlikely and 6 indicates extremely likely). Beliefs about the safety, effectiveness, and necessity of COVID-19 vaccines were measured on a 5-point Likert scale, with higher scores denoting greater agreement. <h3>Results</h3> The baseline data included 1200 participants (693 women [52.0%; weighted]; 921 White individuals [64.0%; weighted], 107 Black individuals [12.2%; weighted]; weighted mean [SD] age, 49.5 [17.6] years). The survey participation rate was 57.0% (1264 of 2218). Black and White individuals had comparable vaccination intentions in December 2020, but Black individuals experienced larger increases in vaccination intention than White individuals relative to baseline in March 2021 (<i>b</i> = 0.666;<i>P</i> &lt; .001), April 2021 (<i>b</i> = 0.890;<i>P</i> &lt; .001), May 2021 (<i>b</i> = 0.695;<i>P</i> &lt; .001), and June 2021 (<i>b</i> = 0.709;<i>P</i> &lt; .001). The belief that the vaccines are necessary for protection also increased more among Black than White individuals in March 2021 (<i>b</i> = 0.221;<i>P</i> = .01) and April 2021 (<i>b</i> = 0.187;<i>P</i> = .04). Beliefs that the vaccines are safe and effective (<i>b</i> = 0.125;<i>P</i> &lt; .001) and necessary (<i>b</i> = 0.405;<i>P</i> &lt; .001) were positively associated with vaccination intention. There was no evidence that these associations varied by race. <h3>Conclusions and Relevance</h3> This survey study suggests that the intention of Black individuals to be vaccinated was initially comparable to that of White individuals but increased more rapidly. There is some evidence that this increase is associated with changes in beliefs about the vaccine. Vaccination rates continue to be lower among Black individuals than White individuals, but these results suggest that this might be less likely the result of vaccine hesitancy than other factors.