tbuckley/cabot-search huggingface dataset:
The impact of <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (<sup>18</sup>F-FDG-PET) on the decision-making process in breast cancer patients: The experience of Bologna’s S.Orsola-Malpighi Hospital
Authors: F. Sperandi, S. Fanti, R. Franchi, A. Martoni
Journal: Journal of Clinical Oncology (2006)

10588 Background: 18 F-FDG-PET is rapidly spreading “technology” in oncology. Its appropriate use and the clinical settings in which it can modify decision-making need to be defined. Methods: All the requests for 18 F-FDG-PET issued by the Medical Oncology Unit are submitted to internal audit. The aim is to evaluate the impact of the information deriving from the test on the subsequent therapeutic strategy in breast cancer patients (pts). From July 2002 to July 2005, 195 18 F-FDG-PET examinations were performed in 110 pts. Pt series have been subdivided according to disease stage or clinical setting: Group 1) NED during the follow-up 23 (11.8%); Group 2) suspected first recurrence 52 (26.7%) (included 20 cases with an isolated elevation of CA15.3 and/or CEA serum levels); Group 3) overt metastases: a) single lesion 10 (5.1%), b) multiple lesions with suspected disease progression 26 (13.3%), c) re-evaluation of non-progressive metastatic disease 84 (43.1%). Results: Overall, 18 F-FDG-PET was positive in 112 (57.4%) cases: in Groups 1), 2), 3a), 3b) and 3c) positivity was 13%, 63.5%, 60%, 73.1% and 60.7%, respectively. As concerns those pts with an isolated marker serum level increase during the follow-up, 18 F-FDG-PET was positive in 13 (65%) cases. Overall, the result of 18 F-FDG-PET determined a therapeutic strategy change in 79 (40.5%) cases. This change consisted in a decision to start or re-start anti-tumor medical treatment in 46 (58.2%), to perform or exclude surgery or radiotherapy with a potentially radical purpose in 10 (12.7%), to continue follow-up or to stop treatment in 23 (29.1%). The change of strategy according to Groups 1), 2), 3a), 3b) and 3c) was 13%, 75%, 90%, 61.5% and 14.3%, respectively. Conclusions: A “clinical” approach to the use of 18 F-FDG-PET in breast cancer pts allows us to change the decision-making in about 40% of pts. Clinical situations in which 18 F-FDG-PET is more useful are in cases of suspected recurrence and oligometastatic disease. No significant financial relationships to disclose.
Excess Ventilation in Chronic Obstructive Pulmonary Disease–Heart Failure Overlap. Implications for Dyspnea and Exercise Intolerance
Authors: Alcides Rocha, Flavio F. Arbex, Priscilla A. Sperandio, Aline Souza, Ligia Biazzim, Frederico Mancuso, Danilo C. Berton, Bruno Hochhegger, Maria Clara N. Alencar, Luiz E. Nery, Denis E. O’Donnell, J. Alberto Neder
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

An increased ventilatory response to exertional metabolic demand (high [Formula: see text]e/[Formula: see text]co2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure.We aimed to determine the mechanisms underlying high [Formula: see text]e/[Formula: see text]co2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients.Twenty-two ex-smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection.Regardless of the chosen metric (increased [Formula: see text]e-[Formula: see text]co2 slope, [Formula: see text]e/[Formula: see text]co2 nadir, or end-exercise [Formula: see text]e/[Formula: see text]co2), ventilatory inefficiency was closely related to PcCO2 (r values from -0.80 to -0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise PcCO2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between-group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting PaCO2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional PcO2. The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05).Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased "wasted" ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease-heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea.
Do the Criteria for Endoscopic Evaluation of Anaemia Need to be Broadened?
Authors: G Cullen, AR Aftab, G Courtney
Journal: Endoscopy (2006)

Aims: Oesophagogastroduodenoscopy (OGD) and colonoscopy are routine investigations for iron deficiency anaemia (IDA). We aimed to identify the incidence of significant GI pathology in patients with normochromic normocytic anaemia (NNA) and normal haematinic values.
Evaluation of Liver Iron Deposition in Transfusion-Dependent Patients By Dual-Energy CT
Authors: Hironori Kobayashi, Norihiko Yoshimura, Takayuki Katagiri, Takashi Ushiki, Kyoko Fuse, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko
Journal: Blood (2016)
Prenatally Diagnosed Trisomy 21
Authors: Elizabeth V. Schulz
Journal: JAMA Pediatrics (2017)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Patient Outcomes Following Neoadjuvant Chemoradiotherapy in Rectal Carcinoma
Authors: D Fanning, RS Prichard, G Roche-Nagle, J Deasy, D McNamara
Journal: Endoscopy (2006)

Background: Neo-adjuvant chemo-radiotherapy is accepted as the best standard of care for patients who present with advanced (T3 or T4) rectal tumours. It has been shown to reduce the overall five-year recurrence rate by 6% and to improve the five year survival to 68%. However, the associated morbidity and mortality of such treatment has yet to be fully elucidated.
Abstract 150: FAK/Pyk2 Inhibitor Prevents Mitochondrial Ca <sup>2</sup> + Overload and Cardiac Injury during Adrenergic Stimulation.
Authors: Jin O-Uchi, Bong Sook Jhun, Stephen Hurst, Shey-Shing Sheu
Journal: Circulation Research (2013)

Introduction: Proline-rich tyrosine kinase 2 (Pyk2) and focal adhesion kinase (FAK) are abundantly expressed in cancer cells. In addition, these kinases are the potent therapeutic targets for cancer treatment and currently several selective FAK/Pyk2 inhibitors are in clinical trials. Recent study revealed that Pyk2 is also highly expressed in heart tissue and significantly activated during human heart failure. We have recently reported that α 1 -adrenoceptor (α 1 -AR) stimulation accelerates mitochondrial Ca 2+ uptake through Pyk2-dependent phospholylation of mitochondrial Ca 2+ uniporter (MCU). However, the roles of Pyk2 in cardiac mitochondrial physiology and pathophysiology have not been well established. Hypothesis: Persistent adrenergic signaling activates cell death signaling via Pyk2-dependent MCU activation and mitochondrial Ca 2+ overload. Methods: Using H9C2 cardiac myoblasts, mitochondrial Ca 2+ and reactive oxygen species (ROS) were measured using mitochondrial matrix-targeted Ca 2+ -sensitive inverse pericam and MitoSOX, respectively. Mitochondrial permeability transition pore (mPTP) activity was observed by measuring the amount of cytochrome c in cytosol by Western blotting or by monitoring the release of GFP-tagged mitochondrial protein, Smac-GFP using confocal microscopy. Results: Pyk2 was not only expressed in cytosol, but also in cardiac mitochondria. α 1 -AR agonist phenylephrine activated mitochondrial Pyk2 and enhanced mitochondrial Ca 2+ uptake via Pyk2-dependent MCU phosphorylation. In addition, persistent α 1 -AR stimulation increases ROS, activity of mPTP. These effects were abolished by co-expression of dominant-negative MCU or kinase-dead Pyk2, suggesting that Pyk2-dependent MCU activation followed by mitochondrial Ca 2+ overload are critical for this mechanism. Moreover, pretreatment of a potent FAK/Pyk2 inhibitor PF-431396 also effectively inhibited α 1 -AR-mediated ROS generation and mPTP activation. Conclusion: FAK/Pyk2 inhibitor prevents mitochondrial Ca 2+ overload, oxidative stress and mitochondrial injury under persistent adrenergic stimulation. Thus, Pyk2 may become a novel potent therapeutic target for preventing cardiac cell injury and death during heart failure.
Pathologists’ diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study
Authors: Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To quantify the accuracy and reproducibility of pathologists' diagnoses of melanocytic skin lesions. <b>Design</b>&nbsp;Observer accuracy and reproducibility study. <b>Setting</b>&nbsp;10 US states. <b>Participants</b>&nbsp;Skin biopsy cases (n=240), grouped into sets of 36 or 48. Pathologists from 10 US states were randomized to independently interpret the same set on two occasions (phases 1 and 2), at least eight months apart. <b>Main outcome measures</b>&nbsp;Pathologists' interpretations were condensed into five classes: I (eg, nevus or mild atypia); II (eg, moderate atypia); III (eg, severe atypia or melanoma in situ); IV (eg, pathologic stage T1a (pT1a) early invasive melanoma); and V (eg, ≥pT1b invasive melanoma). Reproducibility was assessed by intraobserver and interobserver concordance rates, and accuracy by concordance with three reference diagnoses. <b>Results</b>&nbsp;In phase 1, 187 pathologists completed 8976 independent case interpretations resulting in an average of 10 (SD 4) different diagnostic terms applied to each case. Among pathologists interpreting the same cases in both phases, when pathologists diagnosed a case as class I or class V during phase 1, they gave the same diagnosis in phase 2 for the majority of cases (class I 76.7%; class V 82.6%). However, the intraobserver reproducibility was lower for cases interpreted as class II (35.2%), class III (59.5%), and class IV (63.2%). Average interobserver concordance rates were lower, but with similar trends. Accuracy using a consensus diagnosis of experienced pathologists as reference varied by class: I, 92% (95% confidence interval 90% to 94%); II, 25% (22% to 28%); III, 40% (37% to 44%); IV, 43% (39% to 46%); and V, 72% (69% to 75%). It is estimated that at a population level, 82.8% (81.0% to 84.5%) of melanocytic skin biopsy diagnoses would have their diagnosis verified if reviewed by a consensus reference panel of experienced pathologists, with 8.0% (6.2% to 9.9%) of cases overinterpreted by the initial pathologist and 9.2% (8.8% to 9.6%) underinterpreted. <b>Conclusion</b>&nbsp;Diagnoses spanning moderately dysplastic nevi to early stage invasive melanoma were neither reproducible nor accurate in this large study of pathologists in the USA. Efforts to improve clinical practice should include using a standardized classification system, acknowledging uncertainty in pathology reports, and developing tools such as molecular markers to support pathologists' visual assessments.
Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with pancreatic ductal adenocarcinoma (PDA).
Authors: Nathan Bahary, Jie He, Mark Bailey, Shan Zhong, Gerald Li, Lauren Young, Aatur D. Singhi, Phil Stephens, Siraj Mahamed Ali, Gaurav Singal, Alexa Betzig Schrock, Jon Chung, Jeffrey S. Ross, Vincent A. Miller, Ben George
Journal: Journal of Clinical Oncology (2017)

4128 Background: PDA is a lethal and increasingly common malignancy and tissue samples for genomic characterization may be limited. As PDA has a high and consistent frequency of KRAS, p53 and CDKN2A mutations it serves as a robust indication to test the utility of ctDNA in accurately characterizing genomic alterations (GA). A prior study suggested significant differences between ctDNA and tissue base profiling but assays were not conducted on the same platform (PMID27833075). We undertook this study to see whether ctDNA could recapitulate the known genomic hallmarks of tumor based profiling. Methods: Hybrid-capture based genomic profiling of 62 genes (FoundationACT) was performed on ctDNA from 78 pts with advanced PDA with samples received in the course of clinical care. The fraction of ctDNA in the blood was estimated using the maximum somatic allele frequency (MSAF) for each sample. Frequencies of alterations in these common drivers were then compared to those seen in tumors of pts who underwent comprehensive genomic profiling (CGP) tissue testing performed on the same core platform, FoundationOne, and The Cancer Genome Atlas (TCGA). Results: Pt characteristics: Median age 65 (range, 47-88); Female (33) /Male (45). FoundationACT results show that 53/78 (68%) cases had MSAF &gt;0 (56%-78%%, 95% CI). ≥1 GA was reported in 81% of the cases with evidence of ctDNA in the blood. The most common GA detected by FoundationACT (based on cases with evidence of ctDNA in blood) vs FoundationOne were in KRAS (59% vs 89%, p&lt; 0.0001), TP53 (69% vs.74%, p=0.19), and CDKN2A (14% vs.45%). Other detected clinically relevant GA detected by FoundationACT included: BRCA1, ERBB2, NF1, PIK3CA. Conclusions: This study demonstrates significant differences between the established driver oncogenic alterations for PDA, as assessed by ct DNA and tissue based genomic profiling which are unlikely to be explained by differences in assay, but rather novel cancer biology. At present use of ctDNA genomic profiling in PDA should not routinely replace tissue based genomic characterization. [Table: see text]
Peculiarities of postoperative dynamics of biochemical indices of the liver function depending on the character of focal masses and volume of liver resection
Authors: Saidrakhim Lukmonov, Umid Allazarov, Uktam Kurbankulov, Oybek Usmanov, Muzaffar Ismailov, Kurbanbay Madatov
Journal: Annals of Oncology (2017)
Identifying factors to predict benefit from bevacizumab in progressive glioblastoma multiforme (GBM).
Authors: Jack Patrick Gleeson, Abdullah Alhusaini, Philip O'Halloran, Emily Harrold, Niamh M. Keegan, Nabeeha Eltag Karadawi, Emin Mammadov, Dalia Kamel, Keith Egan, Susan Molloy, Bryan T Hennessy, Oscar S. Breathnach, William Grogan, Patrick G. Morris
Journal: Journal of Clinical Oncology (2017)

e13515 Background: Bevacizumab (BEV) has demonstrated activity in GBM, but the benefits have not been clearly defined in prospective randomised phase III trials. Some patients continue BEV for extended periods but little is known about predictors of clinical benefit. It has been suggested that a less intensive dose schedule might offer similar benefits. Methods: In a retrospective analysis of a National Neuro-Oncology centre database we examined biomarkers of BEV benefit on overall survival (OS), including age at diagnosis, time from diagnosis to BEV start, MGMT methylation and IDH-1 status. We compared those who derived clinical benefit (OS of ≥6-months) to those with limited clinical benefit (OS &lt;6 months). At our Institution, there is variable practice between Neuro-Oncologists in terms of BEV dose schedule. In this homogeneous patient population, we examined whether OS was similar for patients who received standard BEV dosing (10mg/kg q 2wks or 15mg/kg q 3wks) or reduced intensity BEV (5mg/kg q 2wks or 7.5mg/kg q 3wks). Results: Between January 1 st 2010 and Dec 31 st 2016, 170 patients received BEV for progressive GBM. Median OS was 5.5 months (Range: 0.5-54). OS was 42%, 18% and 2% at 6-, 12- and 24-months, respectively. No significant predictors of clinical benefit were identified (table). Importantly, median OS was similar for patients who received standard (N=94) vs. reduced intensity (N=76) BEV (5.2 vs. 5.6mo respectively), p=0.74. Conclusions: In this large cohort of patients, we did not identify predictors of benefit from BEV. OS was similar in patients who received standard or reduced intensity BEV. Given the cost of BEV, these results have important implications for value in cancer care. [Table: see text]
Co-circulation of multiple subtypes of enterovirus A71 (EV- A71) genotype C, including novel recombinants characterised by use of whole genome sequencing (WGS), Denmark 2016
Authors: Sofie E Midgley, Astrid G Nielsen, Ramona Trebbien, Mille W. Poulsen, Peter H Andersen, Thea K Fischer
Journal: Eurosurveillance (2017)

In Europe, enterovirus A71 (EV-A71) has primarily been associated with sporadic cases of neurological disease. The recent emergence of new genotypes and larger outbreaks with severely ill patients demonstrates a potential for the spread of new, highly pathogenic EV-A71 strains. Detection and characterisation of these new emerging EV variants is challenging as standard EV assays may not be adequate, necessitating the use of whole genome analysis.
A phase 2 single-arm study with tremelimumab at an optimized dosing schedule in second-line mesothelioma patients.
Authors: Luana Calabrò, Aldo Morra, Ester Fonsatti, Ornella Cutaia, Carolina Fazio, Riccardo Danielli, Diana Giannarelli, Maresa Altomonte, Anna Maria Di Giacomo, Michele Maio
Journal: Journal of Clinical Oncology (2014)

7531 Background: We reported encouraging clinical activity of tremelimumab (treme), a fully human IgG 2 monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4, at 15 mg/kg q3 months (mos), in second-line malignant mesothelioma (MM) patients (pts). Durable partial responses in 2 pts, 31% disease control, 10.7 mos median overall survival (OS), and 1- and 2-y survivals of 48% and 37% were observed (Lancet Oncol, 2013). These findings and pharmacokinetic studies in melanoma pts, led us exploring the activity and safety of treme at an optimized dosing schedule in MM pts in the MESOT-TREM-2012 study (ClinicalTrials.gov Id NCT01655888). Methods: MM pts progressing on a first-line platinum-based regimen received treme at 10 mg/kg i.v. on day 1, q4 weeks (wks) for 6 doses (induction phase), followed by q12-week dosing (maintenance phase), until progressing disease (PD) or severe toxicity. Primary endpoint was objective response (OR) rate; among secondary were DCR, OS, and safety. Tumor assessment per immune-related (Ir) RECIST Criteria was done at screening and q12 wks. Adverse events (AEs) were collected according to the CTC v3.0. Results: From July 2012 to July 2013, 29 MM pts, 20 males and 9 females, median age 65 (42-78) years, 11 stage III and 18 stage IV, ECOG performance status 0-1 (23 pts) or 2 (6 pts), were treated. Nineteen pts had a good EORTC prognostic score; 21 pts had epithelioid histotype, 6 biphasic, 1 sarcomatoid, and 1 undefined. As of Jan 2014, all pts received at least 1 dose of treme (median 6, range 1-10). The study met its primary endpoint since at a median follow-up of 14.5 mos 4 irPR were observed. Eleven pts had stable disease of median duration 7.7 mos (range 2.6-16.6+), and the irDCR was 51.7%. Median OS was 11.3 mos (95% CI: 5.6-17.0). Grade 1-2 and 3 treatment-related AEs occurred in 89.6% and 3.4% of pts, respectively; no grade 4 AEs occurred. Most common treatment-related AEs were gastrointestinal (65.5%), dermatologic (48.2%), and fever (34.4%). Conclusions: At an optimized dosing schedule treme continues to show clinical activity and an acceptable safety profile in MM pts. A phase 2b global trial is ongoing. Clinical trial information: NCT01655888.
Comprehensive molecular profiling of Japanese patients with gastric adenocarcinoma.
Authors: Masanori Terashima, Rie Makuuchi, Yuichiro Miki, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Keiichi Hatakeyama, Keiichi Oshima, Shunpei Ohnami, Kennichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi
Journal: Journal of Clinical Oncology (2015)

e15045 Background: Gastric cancer is well known as having heterogeneous features. Recently, The Cancer Genome Atlas (TCGA) research network had proposed a new classification scheme based on the molecular profile of the tumor. However, the genomic profiling of gastric cancer in Asian patients is still unknown. We started a comprehensive molecular profiling study that analyzes genome and transcriptome of tumor obtained from cancer patients admitted to Shizuoka Cancer Center. We already had evaluated more than 1,000 samples from various type of cancer. Among them, 32 gastric cancer patients were analyzed. Methods: Fresh surgically resected tumor samples and peripheral blood were obtained and whole-exome sequencing (Ion Proton, Life Technologies) and gene expression profiling (DNA microarray, Agilent Technologies) were performed. Results: At least one genomic alteration was observed in all patients. Single nucleotide variants (SNVs) of TP53 were observed in 31% of the patients. Multiple SNVs in known mutation sites were observed in 56% of the patients. Over expression of FGFR, EGFR and ERBB2 were observed in 16%, 13% and 9% of the patients, respectively. PDL-1 expression was observed in 31%, however, mutations of PI3KCA were observed only in 6%. These genomic profiling was different between the histologic types, and appears to be classified into following six types; 1. Tumor positive for EBV, 2. MSI and with low expression of MLH1, 3. Undifferentiated type of tumor with solely TP53 mutation, 4. Undifferentiated type of tumor with overexpression of various oncogenes and PD-L1, 5. Differentiated type of tumor with TP53 mutation and decreased expression of tumor suppressor genes, 6. Differentiated type of tumor with various oncogenes overexpression. Conclusions: Molecular profile of Japanese gastric cancer appears to be different from US esophagogastric cancer. The high incidence of PD-L1 expression in Japanese may suggest better response to PD-L1 targeted therapy.