tbuckley/cabot-search huggingface dataset:
OC-027 Defining Cancer Risk in Barrett’S Oesophagus using a 90-Gene Signature
Authors: S Varghese, R Newton, C S Ross-Innes, K K Krishnadath, P Lao-Sirieix, M O’Donovan, L Wernisch, J J Bergman, R C Fitzgerald
Journal: Gut (2013)

<h3>Introduction</h3> Barrett’s oesophagus (BE) has a highly variable outcome with 0.12–0.5% of patients per year progressing to oesophageal adenocarcinoma (EA). The histopathological grading of dysplasia is used to detect cancer risk in BE; however, considerable variability exists in the reporting of dysplasia. Molecular biomarkers that can detect BE patients with dysplasia would improve risk stratification in BE, enabling clinicians to focus on high risk patients requiring treatment and reduce endoscopic surveillance in the low risk group. The aim of this study was to identify and validate a gene expression signature as a biomarker that can objectively determine dysplastic status and thereby determine the risk of cancer progression. <h3>Methods</h3> Microarray gene expression profiling was done using 59 oesophageal samples with strict consensus diagnosis by expert pathologists (21 BE with no dysplasia, 10 BE with low grade dysplasia, 13 BE with high grade dysplasia and 8 EA). This data was used to identify a gene signature that separated non-dysplastic BE from high grade dysplasia. Gene expression data from publically available datasets were used to validate the signature. An independent set of 135 fresh frozen samples covering a spectrum of dysplastic Barrett’s stages and control tissue (40 BE with no dysplasia, 21 BE with low grade, 33 BE with high grade dysplasia, 32 EA and 9 duodenum) were used for validation using the high throughput 96:96 microfluidic Fluidigm® chip on the BioMark™ PCR system. <h3>Results</h3> A set of 90 genes was identified that separated BE with no dysplasia from BE with high grade dysplasia. This 90-gene signature was able to separate the remaining untrained samples on the microarray dataset (7 non-dysplastic, 10 low grade dysplasia and 8 EA). The signature also separated non dysplastic BE samples from EA samples on 2 external published datasets (p ≤ 0.0012). With the fresh frozen samples, the signature separated BE with no dysplasia from BE with dysplasia and EA with an area under the curve of 0.87 (95% CI, 0.80–0.93). Pathway analysis revealed that the RAN (RAs-related Nuclear protein) regulation pathway (p &lt; 0.0001) was the most significant pathway in this gene set. Furthermore, MYC was found to be the most significant transcription factor regulating at least 30% of these genes (p &lt; 0.0001). <h3>Conclusion</h3> The 90 gene-expression profile can reliably identify BE samples with dysplasia and cancer. This approach has the potential to provide robust risk stratification in BE samples as it overcomes the problems with variability in the reporting of dysplasia. <h3>Disclosure of Interest</h3> None Declared
Non-Financial Barriers to Care for Children and Youth
Authors: N. Halfon
Journal: Annual Review of Public Health (1995)

Public health and medical care interventions have produced dramatic changes in the health of children in the United States. Emerging new morbidities such as behavioral and learning disorders, and child abuse and neglect, highlight the lack of an integrated system of health. Children's developmental vulnerability, dependency, and unique morbidities have been underemphasized in the organization and delivery of health care. The Andersen and Aday model of health care utilization is used to describe financial and nonfinancial barriers to care for children that include family characteristics and organizational characteristics of the health system. Case studies of immunization delivery, children with chronic illness, and mobile populations of children reveal the mismatch between the health care system and children's basic health needs. Integrated service models for high-risk populations of children represent an essential mechanism for coordinating the delivery of medical, developmental, educational, and social services needed by children and families. Universal, coordinated public health and medical services of adequate scope and quality should be assured for children through market and health system reform.
In Reply
Authors: Paul L. Nguyen, Alphonse G. Taghian, Jay R. Harris
Journal: Journal of Clinical Oncology (2008)

women while sparing unnecessary complications of an aggressive surgery in low-risk patients. 5f the data reported by Nguyen et al, most clinical interest is focused on the basal-like subtype because the updated treatment has not changed.In contrast, there are limitations for the other subtypes.The current standard targeted agents, trastuzumab for HER-2-positive disease 7,8 and aromatase inhibitors for postmenopausal women with ER/PR-positive disease 9 were not used.These newer therapies reduce local failure [7][8][9] and thus, data from the Nguyen report on these subtypes are of limited clinical utility.Basal-like subtype is characterized by lack of expression of HER-2/ER/PR (triple negative), aggressive behavior, limited or no efficacy of available targeted agents, and poor prognosis.These tumors are remarkably similar to tumors arising in BRCA1 mutation carriers. 10 Given that the patient subgroup with BRCA1 inherited mutations is thought to be associated with the highest risk of local failure and may benefit from aggressive surgery, 5,[11][12][13] it could be supposed that women with early-stage sporadic triple-negative tumors might also benefit from such an aggressive surgery for local control.However, at present, evidence is still insufficient to support this hypothesis, and long-term results from prospective, large-scale studies should be awaited to drawn rigorous conclusions.Although all types of recurrence (local, contralateral, or distant) are important, identification of high-risk patients for local failure still remains a dream.Pretreatment genetic testing allows identification of BRCA1/2 mutations carriers, who account for only a small fraction of high-risk patients. 14 The identification of the remaining high-risk patients among familial BRCA-negative patients and those patients with sporadic cancer (no breast cancer family history) is currently impossible.Novel genetic variants have already been identified by genomewide association studies, but they confer only a modest risk to breast cancer initiation. [15][6][17] Although several other new susceptibility gene variants will be detected by new larger genomewide association studies, the major challenge will remain the assessment of sophisticated interactions between these gene variants and environmental exposure.Future prospective, large-scale, population-based studies (familial BRCA and non-BRCA patients and sporadic patients with and without local failure) may lead to identification of combined genetic and environmental risk factors as predictive tools for accurate risk stratification and truly personalized local control.
Index of Subjects&lt;subtitle&gt;Volume 24 January 1960 • June 1960&lt;/subtitle&gt;
Journal: JNCI Journal of the National Cancer Institute (1960)

Index of Subjects: Volume 24 January 1960 • June 1960 Get access JNCI: Journal of the National Cancer Institute, Volume 24, Issue 6, June 1960, Pages 1455–1461, https://doi.org/10.1093/jnci/24.6.1455 Published: 01 June 1960
Editorial Board
Authors: Christos Mantzoros, Luigi Gnudi, Per-Olof Hasselgren, Young-Bum Boston, Giuseppe Matarese, Stergios Polyzos, Despina Sanoudou, Manuel Tena-Sempere, George Bray, La Kahn, James Field, Hilton Head, Jun-Ichi Abe, Carlos Houston, Mexico Aguilar-Salinas, Mexico City, A Demetrios, Arne Astrup, Vassilios Athyros, Salman Azhar, Rene Baudrand, Gerard Berry, Zachary Bloomgarden, New York, Sebastien Bouret, V Daniel Castracane, Theodore Ciaraldi, La Jolla, Daniela Cota, Kenneth Cusi, Maria Dalamaga, Louis Elsas, John Fain, Gregory Freund, Ghada El-Hajj, Aleksander Fuleihan, Julie Giwercman, Charles Boston, Dimitrios Glueck, Greece Thessaloniki, Fabio Grassi, George Grunberger, Bloomfield Hills, Oreste Gualillo, W Hardman, Steven Heymsfield, L Joo, Young Huh, Linda Jaffe, Washington Dc, Linong Ji, Madhu Kalia, Gregory Kaltsas, Masao Kaneki, Eun Kang, Niki Katsiki, Theodoros Kelesidis, Los Angeles, Abbas Kitabchi, Fredric Kraemer, Robert Kraemer, L Hammond, Vera Novak, M Boston, Kartal Nesrin, Michael Pagliassotti, Fort Collins, Kyong Soo, Nikos Perakakis, Catherine Postic, Kumaravel Rajakumar, Manfredi Rizzo, Alan Robinson, Neil Ruderman, Mario Saad, Ernst Brazil, Peter Boston, Jochen Seufert, James Sowers, Peter Stacpoole, Günter Stalla, Elliot Sternthal, Yu-Hua Boston, Robert Tseng, New Tuttle, Gerald York
Journal: Metabolism (2021)
Radiology of abdominal trauma
Authors: L. Love
Journal: JAMA (1975)

IN 1970, trauma was the fourth leading cause of death, after heart disease, cancer, and stroke.<sup>1</sup>Of the 52 million US citizens injured annually, 110,000 die, while 11 million require hospitalization for one or more days, at a cost of $3 billion.<sup>2</sup> The role of radiology has steadily increased in importance in the diagnosis and management of abdominal trauma. A sequence of radiologic procedures is useful and should be varied according to the clinical manifestations; they are reviewed here. <h3>Scout-Film Studies</h3> Scout-film studies of abdomen and chest are extremely valuable in the initial detection of hemorrhage, extraluminal air, and mass effect of a hematoma that may displace bowel or viscera and enlarge organs. Associated skeletal and chest trauma may first be detected on these studies. The patient should be transported to the x-ray department while lying on his left side. Since it may take 10 to 15 minutes
Correction
Journal: BMJ (1966)

affected area, even when this area is a ringlike, hypopigmented, spontaneously healing lesion when first seen.I am sure many others must have noticed this phenomenon.Recently Whelan, Pugh, and MacFadzean" found that of six compounds examined, dapsone showed no in vitro activity against twelve strains of cultivable mycobacteria.Dr. Jopling himself, in a previous report on the mouse-footpad experiment of Pettit and Rees, wrote': " On this subject your reporter would like to sound a warning note, for he has a lepromatous patient who relapsed clinically and bacteriologically while under treatment with sulphone (given orally and parenterally) ; yet the response to D.D.S. was quite different when the patient's bacilli were injected into the footpads of mice."What has happened in the intervening period to change Dr. Jopling's doubt into certainty ?Surely, Sir, the belief that a leprosy patient resistant to sulphone has become so because he harbours a " sulphoneresistant strain of M. leprae " rests upon the assumption that there is a simple direct cause- and-effect relationship between lepra bacilli .and" leprosy."Such a relationship is still unproved.-Iam, etc.,
Efficacy and safety of nintedanib and docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): First interim results of the ongoing non-interventional study VARGADO (NCT02392455)
Authors: C. Grohe, W. Gleiber, S. Haas, H. Mueller-Huesmann, M. Schulze, J. Atz, R. Kaiser
Journal: Annals of Oncology (2018)

Background: Nintedanib (Vargatef®), an oral triple angiokinase inhibitor of VEGF-, PDGF- and FGF-receptors, is approved in the EU and other countries for treatment of locally advanced or metastatic NSCLC of adenocarcinoma histology in combination with docetaxel after 1st line chemotherapy. Data are scarce regarding efficacy and safety of nintedanib in NSCLC pts who had been pre-treated with ICIs. Methods: This interim analysis is part of this ongoing trial and included 22 treated pts with locally advanced or metastatic lung adenocarcinoma who received nintedanib and docetaxel in 3rd line following ICIs in 2nd line. Results: Median age was 58 years (range: 45 – 76); 15/22 pts (68.2%) were men, 9/22 pts (40.9%) were ECOG PS0/1, 4/22 pts (18.2%) had brain metastases, and 19/22 pts (86.4%) were current or former smokers. 1st line chemotherapy included pemetrexed (15/22 pts, 68.2%), carboplatin (12/22 pts, 54.6%), cisplatin (12/22pts, 54.6%), bevacizumab (6/22 pts, 27.3%), vinorelbine (4/22 pts, 18.2%), paclitaxel (2/22 pts, 9.1%), and docetaxel (1/22 pts, 4.4%). 2nd line treatment included nivolumab (17/22 pts, 77.3%) and pembrolizumab (5/22 pts, 22.7%). Under nintedanib and docetaxel, 7/12 pts (58.3%) showed a partial response, and 3/12 pts (25.0%) showed stable disease, resulting in a DCR of 83.3% (10/12 pts). Median PFS was 5.5 months (95%CI 1.9 – 8.7). Treatment emergent adverse events (TEAEs) grade ≥3, serious TEAEs, and TEAEs leading to discontinuation occurred in 13/22 pts (59.1%), 11/22 pts (50.0%), and 7/22 pts (31.8%), respectively. Conclusions: Nintedanib, in combination with docetaxel, showed clinically meaningful efficacy and an acceptable safety profile in a limited number of stage IIIB/IV lung adenocarcinoma patients following chemotherapy and ICIs. Larger studies are warranted to further explore the potential of nintedanib and docetaxel in this novel setting supporting anti-angiogenesis plus docetaxel as a subsequent therapeutic principle in patients progressing under ICI therapy. Clinical trial identification: NCT02392455. Legal entity responsible for the study: Boehringer Ingelheim Pharma GmbH & Co. KG. Funding: Boehringer Ingelheim Pharma GmbH & Co. KG. Disclosure: W. Gleiber: Membership on an advisory board. J. Atz, R. Kaiser: Employee of Boehringer Ingelheim Pharma GmbH & Co KG. All other authors have declared no conflicts of interest.
Rapid sequence variation of the hypervariable region of hepatitis C virus during the course of chronic infection
Authors: M Kurosaki
Journal: Hepatology (1993)

To evaluate the clinical significance of sequence variations in the hypervariable region of hepatitis C virus during the course of chronic infection, we performed pairwise comparison of the predominant nucleotide sequences. Hepatitis C virus RNA was extracted from two plasma samples obtained from 12 chronically infected Japanese patients over approximately 1 yr. Complementary DNA containing the hypervariable region was amplified by means of reverse transcription–polymerase chain reaction and was directly sequenced for determination of predominant sequences. In all 12 individuals, the predominant sequence of the hypervariable region at the second time point differed from that at the first time point, and significant sequence variation was observed during this short period. A high proportion of these nucleotide substitutions (90%) resulted in changes of predicted amino acid sequences, indirect evidence of in vivo positive selection for these variants. There appeared to be an important difference in the rate of nucleotide sequence variation of the hypervariable region between four patients with flare-ups of their ALT levels (1.54 to 2.24 × 10-−1/genome site/yr) and eight patients with quiescent courses (0.13 to 1.21 × 10−1/genome site/yr). These results demonstrate that rapid sequence variations of the hypervariable region of predominant virus population take place during the natural course of chronic hepatitis C virus infection. These sequence variations seem to occur as an adaptive response of hepatitis C virus to evade host immunity and may play a major role in the establishment of persistent infection and in the occasional flare-up of hepatitis. (HEPATOLOGY 1993;18:1293–1299.)
Ether Cystitis
Authors: Roger E. Nellans
Journal: JAMA (1985)

CHEMICAL cystitis has been reported and thoroughly documented following therapy with cyclophosphamide,<sup>1,2</sup>analgesics,<sup>3</sup>and methicillin sodium<sup>4,5</sup>and following turpentine ingestion<sup>6</sup>; however, cystitis due to ether has been the subject of only one previous report. Lebowitz and Effman<sup>7</sup>reported two cases of severe chemical cystitis that developed after ether was used to dissolve Foley catheter balloons that would not deflate. One child had an uneventful recovery, but the other required permanent urinary diversion because of increasing hydroureteronephrosis, vesicoureteral reflux, and a contracted bladder. The initial clinical course in both of these cases was very similar to the one we describe. <h3>Report of a Case</h3> A 30-year-old woman with no previous history of urologic problems underwent uneventful laparoscopy and dilatation and curettage for an infertility evaluation in November 1981. A Foley catheter was left in place postoperatively; however, there was difficulty in deflating the water-filled balloon at
Editorial Board
Authors: James Field, Samuel Soskin, Beverly Hills, Garfield Duncan, Salman Azhar, Palo Alto, Hisham Barakat, George Bray, Jorge Calles-Escandon, José Caro, M Charles, George Chrousos, Bernard Bethesda, St Davis, Leslie Louis, Frederick Degroot, Mario Derubertis, Atlanta Digirolamo, William Ga, Louis Duckworth, John Elsas, Kenneth Fain, San Feingold, Andrew Francisco, New Frantz, Gregory York, Saul Freund, Henry Cleveland, New Ginsberg, Charles York, Jane Glueck, Abbas Cleveland, Fredric Kitabchi, Stanford Kraemer, Nelly Mauras, James May, Donald Mcnamara, Glenn Mortimore, Maria New, New York, Michael Pagliassotti, Ft Collins, William Pandak, Alan Richmond, Los Robinson, Stanton Angeles, Peter Segal, Richard Stacpoole, Marc Durham, John Tucson
Journal: Metabolism (2005)
SURGERY ONE HUNDRED YEARS AGO. AN HISTORICAL STUDY
Authors: GEORGE FISCHER
Journal: JAMA (1897)

<h3>XVII.—DISEASES OF THE HEAD AND FACE.</h3> In affections of the<i>tongue</i>Richter made use of the following principles: Large cross cuts, if they could be gotten at, were immediately sewed; small wounds, or if situated far back, were left untouched, but the patient's mouth was tied up to prevent all motion. Serious hemorrhages were stopped by the hot iron, also by compression or ice. According to Job von Meekren, for glossitis it was necessary to make two deep incisions about two inches in length. Cancer of the tongue was extirpated with a curved scissors and a pair of hooked nippers, then the wound was cauterized, which was also done in case of a relapse. Symptoms against the operation were indicated by the swollen glands under the jaw and the impossibility to remove every particle of the cancer. In case of serious macroglossia a portion of the tongue was cut away
Nilotinib versus imatinib in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd 4-year (y) update.
Authors: Richard A. Larson, Andreas Hochhaus, Giuseppe Saglio, Dong-Wook Kim, Saengsuree Jootar, Philipp D. Le Coutre, Josy Reiffers, Ricardo Pasquini, Stuart L. Goldberg, Richard E. Clark, Charisse N. Kemp, Xiaolin Fan, Hans D. Menssen, Timothy P. Hughes, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2013)

7052^ Background: In the 3-y follow-up (f/u) of ENESTnd, NIL demonstrated superior rates of molecular response and reduced progression to accelerated phase/blast crisis (AP/BC) vs IM. Here, we report results with a minimum f/u of 4 y. Methods: 846 adults with newly diagnosed Philadelphia chromosome–positive CML-CP were randomized to receive NIL 300 mg twice daily (BID; n = 282), NIL 400 mg BID (n = 281), or IM 400 mg once daily (QD; n = 283). Results: NIL continued to demonstrate higher rates of major molecular response (MMR; ≤ 0.1% BCR-ABL IS ), MR 4 (≤ 0.01% IS ), and MR 4.5 (≤ 0.0032% IS ) vs IM (Table). No new progressions have occurred on treatment on any arm since the 2-y analysis. NIL had significantly lower rates of progression to AP/BC on treatment (n = 2, 3, and 12 on NIL 300 mg BID, 400 mg BID, and IM, respectively) and when including f/u after discontinuation (n = 9, 6, and 19 on NIL 300 mg BID, 400 mg BID, and IM, respectively) and higher overall survival (OS) vs IM. By 4 y, half as many pts acquired new BCR-ABL mutations on study with NIL vs IM (n = 12, 11, and 22 on NIL 300 mg BID, 400 mg BID, and IM, respectively). Since the 3-y analysis, 2 new mutations (1 pt with T315I on NIL 300 mg BID; 1 pt with F317L on IM) were reported. Safety profiles of both drugs were consistent with previous ENESTnd analyses. By 4 y, peripheral arterial occlusive disease (PAOD) events were reported in 4 and 5 pts in the NIL 300 mg BID, and 400 mg BID arms, respectively. No pt in the IM arm had a PAOD event. Conclusions: ENESTnd 4-y data continue to demonstrate the superiority of NIL over IM for achieving deeper responses with lower risk of progression, supporting the use of NIL as frontline therapy in CML-CP. Clinical trial information: NCT00471497. [Table: see text]
Firearm Laws, Patients, and the Roles of Psychiatrists
Authors: Donna M. Norris, Marilyn Price, Thomas Gutheil, William H. Reid
Journal: American Journal of Psychiatry (2006)

Objective: Persons with mental illness and/or substance abuse are frequently perceived by the public to be dangerous. This has resulted in an increase in state legislation restricting their ability to purchase, possess, register, obtain licensure, retain, and/or carry a firearm of any sort. The purpose of this article is to educate clinicians about the impact of firearms statutes and restrictions for their patients. Many state statutes mandate that treating psychiatrists report such gun possession to state justice or police departments. Psychiatrists may also have a statutory role in an appeals process. Method: The firearms statutes of the 50 states, the District of Columbia, and Puerto Rico and the Federal National Firearms Act were surveyed, with particular attention paid to the ability of persons with mental illness and/or alcohol or substance abuse to obtain firearms. The results were tabulated. Results: These statutes are not uniform. They vary in their definition of mental illness, the type and duration of gun restriction, reporting practices, the confidentiality of medical information, and the immunity of clinician reporters and appeals processes. Conclusion: Clinicians would be wise to familiarize themselves with the provisions of the relevant statutes in their particular states. This will allow them to identify the consequences to their firearm-possessing patients, understand their own roles and obligations—if any—and better consider potential clinical and ethical issues for particular patients.
Today's esophagologist, autocastrated
Authors: E. D. Palmer
Journal: JAMA (1974)

DIRECT inspection of diseased tissues is the most generally helpful of diagnostic efforts. Years ago, the clinician found that proper management of many gastrointestinal problems requires direct inspection of the appropriate mucosal and serosal surfaces via endoscopy. After many years of serious effort to achieve effective mucosal visualization throughout the whole gastrointestinal tract, from top to bottom, the goal has now almost been reached. Anybody who reads a journal or goes to a meeting knows that these days the mucosal panorama from lips to Treitz' arch is open to view in almost any adult patient, whenever the clinician feels a need for the diagnostic information it can give. The question of whether the patient with gastrointestinal disease fares better these days, now that pangastrointestinal fiberoptic endoscopy has become so popular, cannot be answered as yet. Advances in medical instrumentation have never automatically meant advances in therapeutic effectiveness, but if eventually