tbuckley/cabot-search huggingface dataset:
Double Contrast Barium Enemas – How Frequent are Reports Inconclusive and what Action is Taken?
Authors: GC Beattie, A Wray, RER Wright, WJ Campbell
Journal: Endoscopy (2004)

Introduction: Double contrast barium enema (DCBE) in combination with flexible sigmoidoscopy (FS) is an adequate means of visualizing the colorectum. Irrespective of financial implications of inconclusive investigations, clinicians are faced with the problem of ongoing management. The aim of this study was to evaluate actual numbers.
Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib
Authors: E Kastritis, M Gavriatopoulou, M Roussou, D Fotiou, D C Ziogas, M Migkou, E Eleutherakis-Papaiakovou, I Panagiotidis, N Kanellias, E Psimenou, E Papadopoulou, C Pamboucas, E Manios, H Gakiopoulou, A Ntalianis, A Tasidou, S Giannouli, E Terpos, M A Dimopoulos
Journal: Blood Cancer Journal (2017)

Abstract Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD ( n =59) or VCD ( n =42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD ( P =0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P =0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.
Sexual relationships between doctors and former patients
Authors: Gerald Freshwater
Journal: BMJ (2006)

Use of Google as a diagnostic aid Bias your searchEditor-Although Google can be a valuable aid in reaching diagnoses in rare conditions, 1 the problem faced in a busy, fast-paced clinic can be the abundance of lesser quality material on the web."Biasing" or directing your search by adding the name of an online clinical knowledge base such as Emedicine can lead you to quality information more quickly; you avoid sifting through dozens of unknown journals, personal webpages, blogs, or discussion forums containing your search terms.For example, by typing "pigmented lesion+buccal" into Google you will get 55 000 hits with a vast array of very different material.However, typing "pigmented lesion+buccal+emedicine" provides only 106 hits (accessed 12 November 2006), the first being a comprehensive Emedicine review on Peutz-Jeghers syndrome. 2You get similar results by adding "BMJ" to the end of your search; in this case the top hit is an ABC of oral health article.
Abstract 18895: A Novel Gene Involved in Severe Neonatal Cardiomyopathy
Authors: Johanna C Herkert, Rowida Almomani, Judith M Verhagen, Marja W Wessels, Aida M Bertoli-Avella, Marjon A van Slegtenhorst, Rob M Verdijk, Frederik A du Plessis, Ingrid M Frohn-Mulder, Erwin Brosens, Robert M Hofstra, Karin Y van Spaendonck-Zwarts, Angeliki Asimaki, Paul A van der Zwaag, Jasper J van der Smagt, Bert Timmer, Margriet van Stuijvenberg, Richard J Sinke, J. Peter van Tintelen, Ingrid M van de Laar, Jan D Jongbloed
Journal: Circulation (2015)

Cardiomyopathies (CMP) in children are heterogeneous disorders of cardiac muscle with a relatively high incidence in infancy (8/100.000) as compared to older children (0.7/100.000). Beyond infancy, CMP is the most important indication for heart transplantation and transplantation free survival at 5 years after initial diagnosis is only 54%. Mutations in over 65 genes encoding sarcomeric, cytoskeletal and calcium-metabolizing proteins, cell-signaling molecules, and mitochondrial enzymes have been shown to cause CMPs. This has led to new recommendations for diagnostic evaluation and family screening incorporating genetic testing. However, present (targeted/custom based) diagnostic tests do not represent the whole spectrum of genetic etiologies and are leading to a correct diagnosis in just a subset of pediatric CMP patients. We present four children from two consanguineous families of Dutch and Moroccan descent with severe neonatal onset of CMP, ranging from lethal cardiomegaly with reduced contractility in three to severe left ventricular hypertrophy that remained stable in one child. A combined approach using homozygosity mapping and exome sequencing in both families identified a homozygous splice site variant resulting in exon skipping in the Dutch family, and a homozygous nonsense mutation in the Moroccan family within the same gene. This novel disease causing gene is implicated in the early differentiation of cardiomyocytes. Both variants were confirmed with Sanger sequencing and absent in large control populations. Previously published studies in a knockout mouse model demonstrated the functional role of this gene in CMPs. Additionally, we investigated the effect of the homozygous splice site mutation on the expression of different proteins at myocardial cell-cell junctions and myofibrils. These results point towards a role in intercalated disk remodeling. Electron microscopy- and protein expression studies on heart tissue of the patients are ongoing. Our findings add a new autosomal recessive gene to the list of genes already implicated in pediatric CMP, underscoring its genetic heterogeneity. Furthermore, our study indicates that the application of exome sequencing can improve the diagnostic yield in pediatric CMP.
Survival data and toxicity profile in advanced non-small cell lung cancer (NSCLC) patients (PTS) treated within or outside controlled clinical trials.
Authors: Tiziana Vavala, Giulia Rovere, Simonetta Rapetti, Enrica Capelletto, Marina Longo, Matteo Giaj Levra, Benedetta Crida, Silvia Novello
Journal: Journal of Clinical Oncology (2012)

e18103 Background: Even without well defined data, a common perception is that clinical trials inclusion improve outcomes in pts with cancer. We conducted a retrospective analysis, in a single institution, evaluating survival data and tolerability in advanced NSCLC pts treated with standard therapy or within phase II/III clinical trials. Methods: We analysed 300 consecutive pts treated at the Thoracic Oncology Unit at San Luigi Gonzaga Hospital from 2004, January the 1st to 2011, December 31 st having these characteristics: histo/cytological diagnosis of NCSLC, stage IV who received at least 3 chemotherapy cycles, minimum follow-up of 6 months. In this pts population 180 (60%) were enrolled in controlled clinical trials (T), while 120 (40%) were treated with standard therapy (S). Results: The most important differences between the two groups were about median age at the time of starting first line treatment (61.2 in group T vs 64 years in group S), pts older than 70 years (19% vs 27%, respectively) and ECOG/PS distribution (PS=2: 0 vs 9 pts, PS=1: 33 vs 53 pts, PS=0: 145 vs 60 pts in T and S group, respectively). Evaluating T and S population: 106 (59%) vs 43 (36%) pts were eligible for second line treatment and 45 (25%) vs 19 (16%) pts for third line treatment. Median OS was 16,3 in T population vs 14,4 months in S population and PFS was 7.1 vs 6.3 months respectively. Any relevant differences was seen between group T and S in terms of toxicity. Conclusions: This single institution retrospective analysis documented a trend of better outcome for pts enrolled in clinical trials compared to those treated with standard therapy (even without a statistical significance) with an higher percentage of pts reaching second and third line therapies. A larger multicenter prospective dedicated trial is needed to have further, more cleaned, data about this item.
A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers
Authors: Paul K. Paik, Ronglai Shen, Michael F. Berger, David Ferry, Jean-Charles Soria, Alastair Mathewson, Claire Rooney, Neil R. Smith, Marie Cullberg, Elaine Kilgour, Donal Landers, Paul Frewer, Nigel Brooks, Fabrice André
Journal: Clinical Cancer Research (2017)

Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in approximately 20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with antitumor activity in FGFR1-amplified SQCLC cell lines and patient-derived xenografts.Experimental Design: On the basis of these data, we performed a phase I study of AZD4547 in patients with previously treated stage IV FGFR1-amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8 ≥ 2) was determined by FISH. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, pharmacodynamics, and molecular analyses.Results: Fifteen FGFR1-amplified patients were treated. The most common related adverse events (AE) were gastrointestinal and dermatologic. Grade ≥3-related AEs occurred in 3 patients (23%). Thirteen patients were evaluable for radiographic response assessment. The overall response rate was 8% (1 PR). Two of 15 patients (13.3%) were progression-free at 12 weeks, and the median overall survival was 4.9 months. Molecular tests, including next-generation sequencing, gene expression analysis, and FGFR1 immunohistochemistry, showed poor correlation between gene amplification and expression, potential genomic modifiers of efficacy, and heterogeneity in 8p11 amplicon.Conclusions: AZD4547 was tolerable at a dosage of 80 mg oral twice a day, with modest antitumor activity. Detailed molecular studies show that these tumors are heterogeneous, with a range of mutational covariates and stark differences in gene expression of the 8p11 amplicon that likely explain the modest efficacy of FGFR inhibition in this disease. Clin Cancer Res; 23(18); 5366-73. ©2017 AACR.
Educational Performance of Children Born Prematurely
Authors: Craig F. Garfield, Krzysztof Karbownik, Karna Murthy, Gustave Falciglia, Jonathan Guryan, David N. Figlio, Jeffrey Roth
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Survivors of preterm birth often present with medical morbidities; however, variation in their long-term educational performance has not been well described. <h3>Objective</h3> To estimate the association between gestational age and 4 outcomes in school-aged children: readiness to enter kindergarten, scores on standardized tests in elementary and middle school, gifted status, and low performance. <h3>Design, Setting, and Participants</h3> In a retrospective cohort study, children born in Florida between 1992 and 2002 at 23 to 41 weeks' gestation who entered Florida's public schools between 1995 and 2012 were assessed for kindergarten readiness and tested in mathematics and reading in grades 3 through 8. Data analysis was performed from January 12, 2016, to March 1, 2017. <h3>Exposures</h3> Gestational age at birth. <h3>Main Outcomes and Measures</h3> Kindergarten readiness, scores on the Florida Comprehensive Achievement Test (FCAT), classified as gifted, and classified as low performance. <h3>Results</h3> A total of 1 527 113 singleton infants with gestational ages of 23 to 41 weeks born between 1992 and 2002 were matched to Florida public school records. Of these, 1 301 497 children were included in the analysis; 641 479 (49.3%) were girls. A total of 301 (65.0%) Florida children born at 23 to 24 weeks' gestation were designated as ready to start kindergarten. When the FCAT test scores were adjusted for potentially confounding maternal and infant variables, children born at 23 to 24 weeks' gestation performed 0.66 SD (95% CI, −0.73 to −0.59) lower compared with those born at full term. A total of 123 554 (9.5%) of all Florida-born public school students were considered gifted, including 17 (1.8%) of those born at 23 to 24 weeks' gestation. In comparison, 75 458 (5.8%) of all Florida-born public school students were low performing; 310 (33.5%) of these children had been born at 23 to 24 weeks' gestation. Kindergarten readiness, FCAT scores, and gifted status were positively related to gestational age, whereas low performance was inversely related to gestational age. <h3>Conclusions and Relevance</h3> Although gestational age has long been associated with poor educational performance, a sufficient proportion of children born near the limits of viability performed within expected school norms, warranting further investigation into how and why certain children are able to overcome the educational burdens that may follow preterm birth.
The Diagnostic Accuracy of FDG PET in the Detection of Recurrence of Colorectal Carcinoma and its Affect on Intention to Treat
Authors: JJ Sheehan, EVM Ward, CA Ridge, SE Harte, GJ Duffy, DE Malone, SJ Skehan
Journal: Endoscopy (2004)

Aim: This study retrospectively evaluated the clinical impact of PET in staging and management of colorectal liver metastases (CRCLM).
Correction
Authors: Francesco Bedogni, Azeem Latib, Federico De Marco, Agnifili Mauro, Jacopo Oreglia, Samuele Pizzocri, Roberto A. Latini, Stefania Lanotte, Anna Sonia Petronio, Marco De Carlo, Federica Ettori, Claudia Fiorina, Arnaldo Poli, Silvia Cirri, Stefano De Servi, Angelo Ramondo, Giuseppe Tarantini, Antonio Marzocchi, Rosario Fiorilli, Silvio Klugmann, Gian Paolo Ussia, Corrado Tamburino, Francesco Maisano, Nedy Brambilla, Antonio Colombo, Luca Testa
Journal: Circulation (2014)
Traction strategy with clips and rubber band allows complete en bloc endoscopic submucosal dissection of laterally spreading tumors invading the appendix
Authors: Erika Utzeri, Jérémie Jacques, Aurélie Charissoux, Jérôme Rivory, Romain Legros, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2017)

Endoscopic submucosal dissection (ESD) is now the reference method for en bloc resection of large colorectal neoplasia [1]. Nevertheless, appendix invasion is still considered a contraindication to resection because of the risk of perforation and the difficulty in finding the dissection space at the bottom of the appendix. We report on the case of a 72-year-old man referred for resection of a 4 cm granular laterally spreading tumor (LST) of the cecum ([Fig. 1], [Video 1]). The lesion had developed on the appendiceal orifice, invading it deeply.
Whole genome BAC array detects described and novel regions of alteration in oral tumors
Authors: Corisande S. Baldwin, Cathie Garnis, Lewei Zhang, Miriam P. Rosin, Calum Macaulay, Wan L. Lam
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1690 

Each year, there are ∼300,000 cases of oral squamous cell carcinoma (OSCC) world-wide. Most cases are not diagnosed or treated until the advanced stages of disease. As a result, patients have a poor prognosis with a 5-year survival rate of just 50%. However, if diagnosed at the pre-malignant stages, prognosis and survival rates improve. Identification of novel genetic alterations in oral dysplasias and tumors will provide novel targets for early diagnosis and treatment. LOH studies on OSCC have identified the earliest genetic alterations to occur on chromosome 9p, followed by 3p and than 17p. However, LOH is not designed to distinguish copy number amplifications from deletions and the resolution is limited. Similarly, conventional CGH, although able to distinguish between copy number increases and decreases, also provides limited resolution. Here, we present a new genome-wide approach to fine-map these alterations with ∼80kb resolution in order to identify novel genes involved in OSCC. OBJECTIVE : The objective of this study is to detect novel regions of alteration in OSCCs using our high resolution human whole genome BAC array CGH technology in order to elucidate the genetic mechanisms underlying OSCC. METHODS: In this study we utilized a BAC array comprised of 32,433 mostly over-lapping BAC clones spanning the entire human genome. DNA from each BAC clone was PCR-amplified and spotted in triplicate onto two glass slides. Tumor DNA, extracted from OSCC specimens and normal reference DNA was labeled with cyanine-dyes, co-hybridized onto whole genome BAC array slides, and scanned for each dye to determine the hybridization signal intensity ratios for each loci. The data was plotted to reveal copy number amplification and deletions across all chromosomes in the human genome. RESULTS: We profiled OSCC using our human whole genome BAC arrays. Alignment of the profiles from each sample revealed recurrent alterations on multiple chromosome arms. Previously reported alterations such as those on 3p and 8q and novel genetic alterations were identified. CONCLUSION : Genome profiling OSCCs using our human whole genome BAC array revealed copy number alterations of novel and known regions. Further expression analysis will elucidate the biological mechanisms underlying OSCC progression. This work was supported by funds from Genome Canada/BC, CIHR and NICDR.
Platelet Reactivity in Hemophilia a. Flow Cytometry Study to Detect the Hemorragic Phenotype
Authors: Antonia Melero-Amor, Faustino García Candel, David García, Paola Romecin, David Iyu, Valentin Cabañas-Perianes, Raúl Pérez, Jose-Enrique O´Connor, Jose M Moraleda, Noemí Marín, Miguel Blanquer Blanquer
Journal: Blood (2016)
Abstract 16652: Inhibition of Prolyl Hydroxylase as a Novel Therapeutic Target for Hif-Mediated Sdf-1 Activation and Stem Cell Homing in the Ischemic Heart
Authors: Santhosh Ghadge, Maximilian Doppelhammer, Thi Van Pham, Sarah Kühlenthal, Wolfgang-Michael Franz, Marc-Michael Zaruba
Journal: Circulation (2013)

Objective:  Recently published data from our lab indicate that stabilization of the cardiac SDF-1/CXCR4 axis preserves myocardial function and attenuates ischemic cardiomyopathy. After acute myocardial infarction the critical homing factor SDF-1 is only upregulated for 48-72 hours in a HIF-1α dependent manner limiting the targeting of stem cells to ischemic myocardium. To overcome this caveat we aimed to activate SDF-1 expression by stabilization of HIF-1α through inhibition of prolyl hydroxylase with the ratio to increase CXCR4+ stem cell migration.   Methods:  To evaluate the effects on HIF-1α mediated SDF-1 expression, genetically tagged SDF1-EGFP mice were subjected to optimal doses (80mg/kg i.p.) of the prolyl hydroxylase Inhibitor dimethyloxalylglycine (DMOG). To track the fate of CXCR4+ cells, genetically tagged CXCR4-EGFP BAC reporter mice were utilized. FACS and immunhistochemical analyses of CXCR4+ bone marrow, peripheral blood, and heart cells were analyzed under normoxaemic and ischemic conditions with and without DMOG.   Results:  SDF1-EGFP reporter mice treated with DMOG showed robust induction of SDF-1 in the heart. FACS of transgenic CXCR4-EGFP hearts revealed that CXCR4+ was most frequently expressed on CD11b+ monocytes, and to a less amount on angiogenic CD31+ , CD34+, c-kit+, and Flk1+ cells, as well as stem cell populations like ACC133+ and Lin-/c-kit+/Sca-1+. After myocardial ischemia these cell populations were upregulated. A subpopulation of CXCR4-EGFP+ cells co-expressed CD31 in capillaries. Treatment with DMOG revealed a robust upregulation of CXCR4+ cell populations in the ischemic heart, predominantly of angiogenic CXCR4+/CD11b+ monocytes. Further analysis of the latter showed expression of Sca1+, CD86+, CD206+ and F4/80+. DMOG treatment leads especially to upregulation of the CD206+ subpopulation in the infarcted hearts in favor of repair mechanisms.  In conclusion  , our data suggest that CXCR4 is highly expressed on angiogenic and stem cells in the ischemic myocardium. Proly hydroxylase inhibitors may be a novel promising therapeutic target for HIF-1α mediated SDF-1 activation to increase stem cell homing and myocardial repair.
Hispanic Ethnicity Is Associated with Younger Age at Presentation and Worse Survival in AML
Authors: Karine Antonovna Darbinyan, Daniel Helbig, Junaid Saleh Esa, Anjali Budhathoki, Swati Goel, Aditi Shastri, Murali Janakiram, Noah Kornblum, Olga Derman, Kira Gritsman, Ulrich Steidl, Amit Verma, Ira Braunschweig, Ioannis Mantzaris
Journal: Blood (2016)
β-Catenin Is a Candidate Therapeutic Target for Myeloid Neoplasms with del(5q)
Authors: Liping Li, Yue Sheng, Wenshu Li, Chao Hu, Nupur Mittal, Kaoru Tohyama, Amber Seba, You-Yang Zhao, Howard Ozer, Tongyu Zhu, Zhijian Qian
Journal: Cancer Research (2017)

Deletion of the chromosome 5q [del(5q)] is one of the most common cytogenetic abnormalities observed in patients with de novo myelodysplastic syndromes (MDS) and therapy-related MDS or acute myeloid leukemia (t-MDS/tAML). Emerging evidence indicates that activation of the Wnt/β-catenin pathway contributes to the development of myeloid neoplasms with del(5q). Whether β-catenin is a potential therapeutic target for myeloid neoplasms with del(5q) has yet to be evaluated. Here, we report that genetic deletion of a single allele of β-catenin rescues ineffective hematopoiesis in an Apc haploinsufficient mouse model, which recapitulates several characteristic features of the preleukemic stage of myeloid neoplasms with a -5/del(5q). In addition, loss of a single allele of β-catenin reversed the defective self-renewal capacity of Apc-haploinsufficient hematopoietic stem cells and reduced the frequency of apoptosis induced by Apc haploinsufficiency. Suppression of β-catenin by indomethacin or β-catenin shRNA reduced proliferation and survival of human leukemia cell lines with del(5q) but not of control leukemia cell lines in vitro; β-catenin inactivation also inhibited leukemia progression in vivo in xenograft mice reconstituted with del(5q) leukemia cell lines. Inhibition of β-catenin also stunted growth and colony-forming abilities of primary bone marrow cells from del(5q) AML patients in vitro Overall, our data support the idea that β-catenin could serve as a therapeutic target for the treatment of myeloid neoplasms with del(5q). Cancer Res; 77(15); 4116-26. ©2017 AACR.
Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity
Authors: Andrea Emanuelli, Aurora P. Borroni, Liat Apel-Sarid, Pooja A. Shah, Dhanoop Manikoth Ayyathan, Praveen Koganti, Gal Levy-Cohen, Michael Blank
Journal: Cancer Research (2017)

Abstract DNA topoisomerase IIα (Topo IIα) ensures genomic integrity and unaltered chromosome inheritance and serves as a major target of several anticancer drugs. Topo IIα function is well understood, but how its expression is regulated remains unclear. Here, we identify the E3 ubiquitin ligase Smurf2 as a physiologic regulator of Topo IIα levels. Smurf2 physically interacted with Topo IIα and modified its ubiquitination status to protect Topo IIα from the proteasomal degradation in dose- and catalytically dependent manners. Smurf2-depleted cells exhibited a reduced ability to resolve DNA catenanes and pathological chromatin bridges formed during mitosis, a trait of Topo IIα–deficient cells and a hallmark of chromosome instability. Introducing Topo IIα into Smurf2-depleted cells rescued this phenomenon. Smurf2 was a determinant of Topo IIα protein levels in normal and cancer cells and tissues, and its levels affected cell sensitivity to the Topo II–targeting drug etoposide. Our results identified Smurf2 as an essential regulator of Topo IIα, providing novel insights into its control and into the suggested tumor-suppressor functions of Smurf2. Cancer Res; 77(16); 4217–27. ©2017 AACR.