tbuckley/cabot-search huggingface dataset:
Trends in utilization and impact of concurrent chemotherapy with radiation therapy for elderly patients with newly diagnosed glioblastoma: A review of the National Cancer Data Base.
Authors: Jiayi Huang, Pamela Parker Samson, Stephanie Mabry Perkins, George Ansstas, Milan Chheda, Cliff Grant Robinson, Jian Li Campian
Journal: Journal of Clinical Oncology (2016)

2034 Background: To investigate the utilization and overall survival (OS) impact of concurrent chemotherapy in combination with radiation therapy (RT) for elderly glioblastoma (GBM) patients. Methods: Elderly patients (age > 70) with supratentorial and nonmetastatic GBM who received RT of 20-75 Gy with concurrent single-agent chemotherapy (chemoRT) or without (RT alone) during 2004-2012 were identified from the National Cancer Data Base (NCDB). RT fractionation was evaluated for those who received standard-fractionated RT (SFRT) or abbreviated hypo-fractionated RT (HFRT). Hazard ratios (HR) and 95% confidence intervals (CIs) were determined using Cox regression analysis. OS rates were determined using the Kaplan-Meier method and compared using the log-rank test. Propensity score analysis was performed to reduce selection bias in treatment allocation. Results: A total of 5,252 patients were identified (RT alone: n = 1389; chemoRT: n = 3863). There was increasing utilization of chemotherapy since 2004, which reached 80% per year after 2010 (including > 66% for the subset of age > 80). ChemoRT was associated with significantly better OS than RT alone (HR 0.76; 95% CI 0.71-0.81; P< .001) on multivariate analysis. Similar OS benefit was demonstrated with 1202 pairs of propensity-matched patients (HR 0.79, 95% CI 0.73-0.86; P< .001). For the entire cohort, OS was 33% at 1 year and 12% at 2 years with chemoRT, versus 15% at 1 year and 3% at 2 years with RT alone (P< .001). For the matched pair, OS was 26% at 1 year and 9% at 2 years with chemoRT, versus 16% at 1 year and 4% at 2 years with RT alone (P< .001). Five thousand and one-hundred fifty-two patients (98%) were evaluable for RT fractionation (SFRT: n = 4621; HFRT: n = 531). HFRT was used selectively for a minority of patients and increased slightly after 2010 (approximately 10% per year for age ≤ 80 and 20% for age > 80). Conclusions: Concurrent chemotherapy has been administered with RT for the majority of elderly GBM patients. Addition of chemotherapy to RT for elderly GBM patients significantly improved OS in routine clinical practice. HFRT utilization remains limited for elderly GBM patients.
Flipping the Script — A Patient-Centered Approach to Fixing Acute Care
Authors: Keith E. Kocher, John Z. Ayanian
Journal: New England Journal of Medicine (2016)

Though largely overlooked in health care reform efforts, the U.S. acute care system is plagued by inefficiency, fragmentation, and redundancy. Fundamentally, to fix acute care, we need to place patients at the center of the delivery system.
PTU-045 Diagnostic Utility of Single-User Peroral Cholangioscopy for Indeterminate Biliary Strictures in Sclerosing Cholangitis: Abstract PTU-045 Table
Authors: E Kalaitzakis, R Sturgess, H Kaltsidis, K Oppong, V Lekharaju, P Bergenzaun, P Vlavianos, H Sharma, D Westaby, G J Webster
Journal: Gut (2013)

<h3>Introduction</h3> Single-user peroral cholangioscopy (SOC) has been reported to be useful in the differential diagnosis of indeterminate biliary lesions, but its diagnostic utility in sclerosing cholangitis(SC) has not been evaluated. <h3>Methods</h3> Fifty-one consecutive patients with sclerosing cholangitis(47 primary SC; 4 IgG4-related cholangitis), who underwent 54 attempted SOC procedures due to indeterminate biliary strictures, in 4 UK and 1 Swedish tertiary referral centres in 2008–2012, were retrospectively enrolled. Brush cytology or SOC-directed biopsies were obtained as clinically indicated. The operating characteristics of SOC for detecting cancer were calculated using a composite reference standard (incl. surgical confirmation, tissue sampling, follow-up). For each SOC procedure in SC, another one attempted due to an indeterminate biliary stricture in patients without SC in the same centre and calendar year was randomly selected as control. <h3>Results</h3> The SpyglassTM cholangioscope could be successfully inserted in the bile duct less frequently in SC compared to controls(83% vs 96%, p = 0.05), but the two groups did not differ in the mucosal visualisation success rate(93% vs 94%). SOC-directed biopsies were more commonly performed in SC vs controls (83% vs 61%, p = 0.02) but the rate of adequate samples did not differ significantly (67% vs 77%, p = 0.2). The sensitivity, specificity and accuracy of SOC with/without tissue sampling for cancer diagnosis were similar in the 2 groups(intention-to-diagnose; table). The SOC diagnosis rate of malignant lesions was also similar in SC vs controls (50% vs 55%, p &gt; 0.05). Adverse events were more common in SC, mainly due to an increased frequency of cholangitis (table). No severe adverse events were observed. Data are presented as medians (IQR) and percentage as appropriate. The 95% confidence intervals of operating characteristics are reported. <sup>*</sup>p ≤ 0.05. <h3>Conclusion</h3> In experienced hands, SOC is equally accurate in cancer diagnosis in SC and patients with single biliary strictures. SOC may be of particular use in the assessment of SC, in which differentiating benign from malignant strictures remains particularly challenging. However, cholangioscope insertion may be hampered by bile duct narrowing and cholangitis is more common following SOC in SC. <h3>Disclosure of Interest</h3> None Declared
Patient safety concerns were chief reason for strike suspension, says BMA
Authors: Susan Mayor
Journal: BMJ (2016)

The BMA’s cancellation of next week’s five day strike by junior doctors in England was primarily due to warnings from trainees, senior doctors, and NHS managers that the safety of patients would be put at greater risk than in previous strikes, because of the strike’s longer duration and the shorter notice given by the BMA of the action.

The BMA said in a statement on Monday 5 September that although it had provided more than the legally required seven days’ notice NHS England said that it needed more time to plan for escalated action.1

The BMA’s Junior Doctors Committee called the strike on Wednesday 31 August, giving the NHS 12 days to prepare for full withdrawal of junior doctors’ labour between 8 am and 5 pm for five consecutive weekdays from 12 to 16 September. Previous strikes each lasted for a maximum of 48 hours and gave longer notice.2 …
LP46 : Occult HBV is highly prevalent in patients with intrahepatic cholangiocarcinoma and it is detected as both free episomal and integrated DNA
Authors: T. Pollicino, C. Musolino, G. Tripodi, M. Lanza, G. Raffa, C. Saitta, S. Benfatto, C. Beninati, G. Navarra, P. Invernizzi, D. Alvaro, G. Raimondo
Journal: Journal of Hepatology (2015)
Secondary Infection in Patients With Sepsis
Authors: Daniel A. Sweeney, Andre C. Kalil
Journal: JAMA (2016)

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
N‐myc downstream‐regulated gene 2 inhibits human cholangiocarcinoma progression and is regulated by leukemia inhibitory factor/MicroRNA‐181c negative feedback pathway
Authors: Jiabei Wang, Changming Xie, Shangha Pan, Yingjian Liang, Jihua Han, Yaliang Lan, Jing Sun, Keyu Li, Boshi Sun, Guangchao Yang, Huawen Shi, Yuejin Li, Ruipeng Song, Xirui Liu, Mingxi Zhu, Dalong Yin, Huanlai Wang, Xuan Song, Zhaoyang Lu, Hongchi Jiang, Tongsen Zheng, Lianxin Liu
Journal: Hepatology (2016)

Increasing evidence supports a role for N-myc downstream-regulated gene 2 (NDRG2) deregulation in tumorigenesis. We investigated the roles and mechanisms of NDRG2 in human cholangiocarcinoma (CCA) progression. In the present study, expression of NDRG2, microRNA (miR)-181c and leukemia inhibitory factor (LIF) in human CCA and adjacent nontumor tissues were examined. The effects of NDRG2 on CCA tumor growth and metastasis were determined both in vivo and in vitro. The role of the NDRG2/LIF/miR-181c signaling pathway in cholangiocarcinogenesis and metastasis were investigated both in vivo and in vitro. The results showed that human CCA tissues exhibited decreased levels of NDRG2 and increased levels of miR-181c and LIF compared with nontumor tissues. NDRG2 could inhibit CCA cell proliferation, chemoresistance, and metastasis both in vitro and in vivo. We found that NDRG2 is a target gene of miR-181c, and the down-regulation of NDRG2 was attributed to miR-181c overexpression in CCA. Furthermore, miR-181c can be activated by LIF treatment, whereas NDRG2 could inhibit LIF transcription through disrupting the binding between Smad, small mothers against decapentaplegic complex and LIF promoter. Down-regulation of NDRG2 and overexpression of miR-181c or LIF are significantly associated with a poorer overall survival (OS) in CCA patients. Finally, we found that a combination of NDRG2, miR-181c, and LIF expression is a strong predictor of prognosis in CCA patients.These results establish the counteraction between NDRG2 and LIF/miR-181c as a key mechanism that regulates cholangiocarcinogenesis and metastasis. Our results elucidated a novel pathway in NDRG2-mediated inhibition of cholangiocarcinogenesis and metastasis and suggest new therapeutic targets, including NDRG2, LIF, miR-181c, and transforming growth factor beta, in CCA prevention and treatment. (Hepatology 2016;64:1606-1622).
lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome
Authors: D Ronchetti, M Manzoni, L Agnelli, C Vinci, S Fabris, G Cutrona, S Matis, M Colombo, S Galletti, E Taiana, A G Recchia, S Bossio, M Gentile, C Musolino, F Di Raimondo, A Grilli, S Bicciato, A Cortelezzi, P Tassone, F Morabito, M Ferrarini, A Neri
Journal: Blood Cancer Journal (2016)

Abstract Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA molecules with an important emerging role in cancer. To elucidate their potential pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and clinically heterogeneous neoplasia, we investigated lncRNAs expression in a prospective series of 217 early-stage Binet A CLL patients and 26 different subpopulations of normal B-cells, through a custom annotation pipeline of microarray data. Our study identified a 24-lncRNA-signature specifically deregulated in CLL compared with the normal B-cell counterpart. Importantly, this classifier was validated on an independent data set of CLL samples. Belonging to the lncRNA signature characterizing distinct molecular CLL subgroups, we identified lncRNAs recurrently associated with adverse prognostic markers, such as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1 mutations. In addition, correlation analyses predicted a putative lncRNAs interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able to distinguish three different prognostic groups in our series of early-stage patients. Overall, our study provides an important resource for future studies on the functions of lncRNAs in CLL, and contributes to the discovery of novel molecular markers with clinical relevance associated with the disease.
Novel antioxidant capability of titanium induced by UV light treatment
Authors: Takeshi Ueno, Takayuki Ikeda, Naoki Tsukimura, Manabu Ishijima, Hajime Minamikawa, Yoshihiko Sugita, Masahiro Yamada, Noriyuki Wakabayashi, Takahiro Ogawa
Journal: Biomaterials (2016)
PD-L1 and HER2 expression in gastric cancer (GC) patients (pts) using cell-free RNA (cfRNA).
Authors: James Yu Chang Shen, Joshua Usher, David Samberg, Toshiyuki Ishiba, Kathleen Danenberg, Heinz-Josef Lenz, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2016)

e15539 Background: In clinical practice, the majority of tumor biology information comes from an initial specimen. The ability to assess changes across time can direct treatment selection. Liquid biopsies of cell-free DNA (cfDNA) released into the bloodstream by tumor are currently under investigation as a surrogate for tissue biopsies. However, cfDNA lacks the ability to assess gene amplification, and may not reflect rapid dynamic changes; cfRNA fills this gap. In this study, HER2 and PD-L1 expression from metastatic GC pts using cfRNA was assessed. Methods: Blood samples from 16 GC pts (median age 52 (26-72), 11 male) were collected (4 pts had multiple collections). 11 pts were on platinum containing first-line therapy; 4 on second line therapy with ramucirumb with or without paclitaxel, and one pt was on best supportive care after failure of 3 lines of therapy. Three of the HER2 positive pts were on trastuzumab, one on second line therapy with no HER2 agent. Plasma was fractionated, and cfRNA was extracted and reverse transcribed to cDNA using random hexamers. Relative expressions of PD-L1 and HER2 versus beta-actin were analyzed using qRT-PCR. Results: PD-L1 was detected in 50% (8/16) of pts; HER2 in 43.8% (7/16). A total of 4 pts (25%) had no detectable levels of PD-L1 or HER2 by cfRNA, while a total of 3 (18.8%) had detectable levels of both genes. 75% (3/4) of pts with HER2 in tissue (assessed by IHC and/or FISH) were positive in cfRNA. 72.8% (7/11) of pts with negative HER2 in tissue were negative in cfRNA. Dynamic changes were found in expressions of HER2 and PD-L1 over time under different therapies. Of the 11 pts negative for HER2 in tissue, 3 were positive in the subsequent blood draws. No statistically significant difference was observed in the relative gene expressions of PD-L1 and HER2 measured across same pts (p = 0.5830, Wilcoxon Sign-Rank). Conclusions: While loss of HER2 in GC after receipt of trastuzumab is documented, our data suggest that chemotherapy may result in the advent of HER2 expression. Our data also support introduction of PDL1 under treatment pressure. In this heterogeneous population discordant HER2 results may be a reflection of tumor evolution. We plan to assess the clinical utility of these findings in a large cohort.
Use of a pretreatment systems pathology model to predict the likelihood of disease progression in patients treated with primary radiotherapy.
Authors: M. J. Donovan, F. Khan, G. Fernandez, V. Bayer-Zubek, P. C. Albertsen
Journal: Journal of Clinical Oncology (2010)

4651 Background: We previously developed a systems pathology model using pretreatment clinical and biopsy tissue metrics to predict disease progression (DP) in patients treated with radical prostatectomy and followed for a median of 8 years. Utilizing our existing model we sought to demonstrate feasibility for predicting outcome in patients treated with external beam radiotherapy (EBRT) and followed for a similar time frame. DP was defined as castrate PSA rise, systemic metastasis and or death of disease. We also wanted to assess performance of prognostic models developed without clinical variables (i.e. PSA and biopsy Gleason). Methods: 52 patients from a 72 EBRT cohort had complete clinical, morphometric and immunofluorescent (IF) biomarker feature data for inclusion in multivariate models. The mean age was 68 yrs, mean PSA 14.31, 36% biopsy Gleason score (BGS) <=6, 40% BGS 7 and 67% T1c. Biopsy H&E morphometry, and quantitative IF biomarker data was generated as previously described (Donovan et al., J Urol., 2009). Performance was based on the concordance index (CI), sensitivity and specificity. Results: The current pretreatment biopsy model performed with a CI 0.79, sensitivity 0.91 and specificity 0.60, for predicting DP within 8 years. Two new additional models were also developed; Model 1.contained the BGS, PSA and two H&E morphometric features with a predictive accuracy CI of 0.86, sensitivity 0.83 and specificity 0.88. Model 2 was developed without clinical variables and contained one morphometric feature and one IF feature, the relative area of Ki67 positive tumor epithelial nuclei. The model performed with a CI 0.82, sensitivity 0.75 and specificity 0.84. Conclusions: A previously developed pretreatment systems pathology model appears to accurately predict disease progression for patients post-EBRT. A model constructed without clinical variables may provide the necessary objective tools for developing future treatment algorithms. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aureon Aureon
Immunotherapy Gone Viral: Bortezomib and oHSV Enhance Antitumor NK-Cell Activity
Authors: Carter M. Suryadevara, Katherine A. Riccione, John H. Sampson
Journal: Clinical Cancer Research (2016)

Oncolytic viruses, proteasome inhibitors, and natural killer (NK)-cell immunotherapy have all been studied extensively as monotherapies but have never been evaluated in combination. Synergetic treatment of oncolytic virus-infected glioblastomas with a proteasome inhibitor induces necroptotic cell death to enhance NK-cell immunotherapy, prolonging survival against human glioblastoma. Clin Cancer Res; 22(21); 5164-6. ©2016 AACRSee related article by Yoo et al., p. 5265.
Frequent occurrence of therapeutically reversible cmv-associated encephalopathy during radiotherapy of the brain.
Authors: Nicole Lydia Goerig, Benjamin Frey, Klaus Korn, Bernhard Fleckenstein, Klaus M Ueberla, Manuel A Schmidt, Arnd Doerfler, Tobias Engelhorn, Ilker Eyupoglus, Paul F Ruehle, Florian Putz, Sabine Semrau, Udo S Gaipl, Rainer Fietkau
Journal: Journal of Clinical Oncology (2016)

e13507 Background: Neurological decline during radio(chemo)therapy of the neurocranium is often attributed to disease-progression or side-effects of radiotherapy. Diagnosis of opportunistic neurotropic infections such as cytomegalovirus-(CMV)-infections is uncommon, even though high-grade gliomas and some brain metastases are known to contain CMV-particles. Methods: 50 patients requiring whole-brain-radiotherapy for brain-metastases (n = 27) or local radio(chemo)therapy of the brain for high-grade gliomas (n = 23) were observed in the prospective observational GLIO-CMV-01-study, aiming to determine whether and at which frequency radiotherapy of the brain was associated CMV-reactivation coinciding with encephalitis-like deterioration. Magnet-resonance-images and blood samples were obtained before, halfway through and at the end of radiotherapy. MRIs were screened for disease-progression or increased intracranial pressure. Blood was tested for anti-CMV-IgM, anti-CMV-IgG and CMV-DNA. Results: 32/50 (64%) patients were positive for anti-CMV-IgG before radio(chemo)therapy. 15 of those 32 (48%) developed viremia during or up to 28 days after treatment. 13 of those 15 (87%) required treatment for CMV-associated-encephalopathy. None of the patients negative for anti-CMV-IgG developed viremia, suggesting a reactivation rather than a primary infection. In the endangered group of anti-CMV-IgG+ patients, age > 65 (p = 0.004) and the amount of dexamethasone taken during radio(chemo)therapy (p = 0.004) were associated with an increased risk for CMV-associated-encephalopathy. 150 days after the start of radio(chemo)therapy survival was 74% (14/19) (no encephalopathy) versus 54% (7/13) (encephalopathy) (OR 0.42, CI 95% 0.03-1.86, p = 0.25). Conclusions: CMV-reactivation frequently causes encephalopathy during radio(chemo)therapy of the brain. The unexpected high incidence of this infection makes it highly clinically relevant for every treating physician.
Upsurge in Cases of Cutaneous Leishmaniasis in Syria
Authors: M.J. Friedrich
Journal: JAMA (2016)

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
Sexual harassment and bullying in UK surgery: no room for complacency
Authors: Scarlett McNally
Journal: BMJ (2016)

All surgeons need to guard against the effects of unconscious bias

A 2014 General Medical Council survey of 50 000 junior doctors in the United Kingdom found that about 8% had experienced bullying, with no significant difference between the sexes.1 Thus such incidents would seem to be much less common than among the nearly 50% of Royal Australasian College of Surgeons fellows, trainees, and international medical graduates who have reported discrimination, bullying, or sexual harassment. Any bullying, though, even 8%, is unacceptable.

Why are conditions better for surgeons working in the UK than in Australia in this regard? Firstly, we have had training programmes for decades with a bureaucratic but intense schedule of scrutiny. Every trainer has to justify any failure of a trainee to progress. Australia’s training programme was introduced only in 2007, so most trainers there did not follow a structured training programme themselves, and trainees have not benefited from the same …