tbuckley/cabot-search huggingface dataset:
Patients’ experience of colonoscopy in the English Bowel Cancer Screening Programme
Authors: Alex Ghanouni, Andrew Plumb, Paul Hewitson, Claire Nickerson, Colin Rees, Christian von Wagner
Journal: Endoscopy (2016)

<b>Background and study aims:</b> Understanding patients' experience of screening programs is crucial for service improvement. The English Bowel Cancer Screening Programme (BCSP) aims to achieve this by sending out questionnaires to all patients who undergo a colonoscopy following an abnormal fecal occult blood test result. This study used the questionnaire data to report the experiences of these patients. <b>Patients and methods:</b> Data on patients who underwent colonoscopy between 2011 and 2012 were extracted from the BCSP database. Descriptive statistics were used to summarize key questionnaire items relating to informed choice, psychological wellbeing, physical experience, and after-effects. Multilevel logistic regression was used to test for associations with variables of interest: sex, age, socioeconomic status, colonoscopy results, and screening center performance (adenoma detection rate, cecal intubation rate, proportion of colonoscopies involving sedation). <b>Results:</b> Data from 50 858 patients (79.3 % of those eligible) were analyzed. A majority reported a positive experience on items relating to informed choice (e. g. 95.7 % felt they understood the risks) and psychological wellbeing (e. g. 98.3 % felt they were treated with respect). However, an appreciable proportion experienced unexpected test discomfort (21.0 %) or pain at home (14.8 %). There were few notable demographic differences, although women were more likely than men to experience unexpected discomfort (25.1 % vs. 18.0 %; <i>P</i> < 0.01) and pain at home (18.2 % vs. 12.3 %; <i>P</i> < 0.01). No associations with center-level variables were apparent. <b>Conclusions:</b> Colonoscopy experience was generally positive, suggesting high satisfaction with the BCSP. Reported pain and unexpected discomfort were more negative than most other outcomes (particularly for women); measures to improve this should be considered.
The association between <i>PTEN</i> expression and survival in patients (pts) with advanced non-small cell lung cancer (NSCLC) treated with erlotinib.
Authors: T. A. Hensing, M. J. Fidler, F. Wong, A. Polish, W. Watkin, S. Basu, K. A. Kaiser-Walters, M. Pool, J. Coon, P. Bonomi
Journal: Journal of Clinical Oncology (2010)

7552 Background: In pts with NSCLC, somatic activating mutations in the EGFR gene are associated with sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKI). Loss of PTEN expression is associated with deregulation of the Akt/PKB pathway. PTEN loss as measured by gene expression, gene copy number or protein expression, has been associated with poorer survival in pts treated with EGFR TKIs. The objective of this study was to evaluate potential relationships between PTEN expression, and other EGFR and downstream biomarkers in pts with stage IV NSCLC treated with erlotinib. Methods: We performed a retrospective analysis of pts treated with erlotinib (any line) for NSCLC. Adequate paraffin embedded tissue for performance of molecular assays was required for inclusion in our study. Tumor specimens from 123 pts were analyzed by immunhistochemistry (IHC) for expression of PTEN and other biomarkers. In addition, fluorescence in situ hybridization (FISH) for EGFR gene and chromosome 7 copy number and EGFR mutational analyses were performed. The results of the PTEN analysis are reported here. IHC staining frequency and intensity of all tumor cells were estimated on a scale of 0-4. For the analysis, IHC expression was dichotomized into 2 levels: detected (+1 to +4) and undetected (0). Results: PTEN expression data was obtained from 115 pts. 84/115 pts (73%) had PTEN+ tumors. There was no difference in characteristics between PTEN+ and PTEN− pts (overall, female 38%, never smoker 17%, squamous 10%). Median PFS was 2.9 vs. 2.0 months (mo) (PTEN+ vs PTEN−, p = 0.129). OS was prolonged in PTEN+ pts (8.51 vs. 4.04 mo, p = 0.057). In a multivariate cox proportional hazards model that included clinical factors (smoking, histology and gender), PTEN expression was the only factor significantly associated with improved OS (p = 0.046, HR 0.57, 95% CI 0.283-1.99). Conclusions: These data support the relationship between PTEN loss and resistance to treatment with EGFR TKIs in pts with NSCLC. Additional cases are being evaluated for PTEN expression by IHC and FISH analysis is underway to examine the relationship between PTEN and PIK3CA gene copy numbers and survival in this patient population. No significant financial relationships to disclose.
Episodic dyscontrol and family dynamics
Authors: H T Harbin
Journal: American Journal of Psychiatry (1977)

The author describes characteristics of patients, primarily adolescents, who suffer from episodic violent behavior and their relations with their families. Typical family patterns include overly close alliances by the adolescent with one or both parents and transmission by parents of inconsistent values regarding aggression. Family therapy is the preferred treatment approach; treatment should be active, should initially focus on ways of handling dyscontrol episodes, and should emphasize that the patient is responsible for his or her actions.
Paraproteinemic keratopathy as the presenting sign of hematologic malignancy
Authors: Tova E. Mannis, Gabriel N. Mannis, Emily G. Waterhouse, Anthony J. Aldave, Jennifer Rose‐Nussbaumer
Journal: American Journal of Hematology (2016)

Three years prior to her initial Hematology evaluation, a 53-year-old woman with no significant medical history presented to her local ophthalmologist for a routine eye examination. Slit lamp examination was remarkable for multiple circular anterior stromal deposits with intervening clear spaces, mostly concentrated peripherally (Image 1A,B). Over the course of 3 years, the number of anterior stromal deposits nearly doubled, but they remained outside of the visual axis and the patient maintained excellent visual acuity. After genetic testing excluded an inherited TGFBI corneal dystrophy, she was referred to Hematology for further evaluation. Slit lamp examination showing multiple, circular, peripherally located anterior corneal stromal deposits (A). Optical coherence tomography of the cornea shows deposits (arrows) with intervening clear spaces (B). Peripheral blood smear at 20× (C) and 100× (D), showing a mild lymphocytosis composed of small- to medium-sized mature lymphocytes with occasional smudge cells. On initial visit, history and physical examination were unremarkable. Laboratory testing showed a mild, lymphocyte-predominant leukocytosis with a total white blood cell count of 12.4 × 109/L and an absolute lymphocyte count of 7.39 × 109/L. Peripheral blood smear (Image 1C,D) revealed a mild lymphocytosis composed of small- to medium-sized mature lymphocytes with occasional smudge cells. Serum protein electrophoresis/immunofixation electrophoresis revealed a 0.4g/dL IgG kappa paraprotein with normal light chains and immunoglobulins. Peripheral blood flow cytometry demonstrated a CD5+, CD23+, mature B-cell lymphoproliferative disorder. FISH testing and staging CT scans were unremarkable. The diagnosis of Rai stage 0 chronic lymphocytic leukemia with paraproteinemic keratopathy was made. Corneal immunoglobulin deposition—otherwise known as paraproteinemic or immunotactoid keratopathy—has been described most commonly in the setting of plasma cell dyscrasias, particularly in patients with monoclonal gammopathy of unknown significance and multiple myeloma 1-4. However, paraproteinemic keratopathy can be associated with any systemic disorder that causes paraproteinemia, including lymphomas, leukemias, and some autoimmune conditions.
CHAPTER 1: Hemodialysis Adequacy in Adults
Authors: Kailash Jindal, Christopher T. Chan, Clement Deziel, David Hirsch, Steven D. Soroka, Marcello Tonelli, Bruce F. Culleton
Journal: Journal of the American Society of Nephrology (2006)

### Recommendations



1.  All hemodialysis patients should have regular global assessments of dialysis adequacy. (Grade D, opinion) Assessment of hemodialysis adequacy should include urea clearance, volume control, blood pressure, mineral metabolism, and clinical symptoms. (Grade C) 

2.  The
B 형 만성간염 환자에서 라미부딘의 치료효과와 YMDD 돌연변이형의 검출
Authors: 김미성(Mi Sung Kim), 채희복(Hee Bok Chae), 최기원(Ki Won Choi), 이태원(Tae Won Lee), 박선미(Seon Mee Park), 윤세진(Sei Jin Youn), 배석철(Suk Chul Bae)
Journal: Clinical and Molecular Hepatology (2001)

Background/Aims: Recipients, at 13 months after administration of daily doses of 100 mg of lamivudine, were likely to have the highest rate of HBeAg seroconversion (32%); the greatest suppression of HBV DNA (98% reduction at week 52); and the highest rate of sustained normalization of ALT levels (72%). In a 1-year trial of lamivudine for chronic hepatitis B patients, the incidence of YMDD mutations was known to be about 14%. We intend to determine the incidence of YMDD mutations and the correlation between the mutation of the virus and the clinical characteristics of the patient. Methods: Between Feb. 1999 and Sept. 2000 we conducted a prospective study. Patients received 100 mg of lamivudine per day orally for at least 9 months. The average period of follow-up was 15 months. The patients enrolled in this study were composed of 20 chronic hepatitis B patients and 3 liver cirrhosis patients. The male to female ratio was 18:5. The average age of the patients was 40 years. The HBV DNA was extracted from the initial serum and the serum on abnormal ALT level, and then PCR was done. Finally we sequenced a 459-bp fragment and analyzed which samples had YMDD mutation or did not. Results: (1) The genetic mutations in the YMDD locus occurred in 3 of the 23 patients (13%), two patients exhibited YIDD mutation, and one patient exhibited 3WDD at 24, 52, 48 weeks of therapy respectively. (2) During the 3 months of treatment, serum ALT levels returned to normal in 13 of the 23 patients (56%). The HBV DNA disappearance rate at 3 and 8 months was 63% and 84% respectively. The 8 of 19 patients who lost the HBV DNA during lamivudine treatment experienced the breakthrough at about 13 months (the range' 8-27 months). 4 patients experienced HBeAg seroconversion during the treatment period (17%). Conclusions: The mutations in the YMDD motif, especially the YIDD type, may aggravate the clinical outcome of the patients. We concluded that the treatment duration should be prolonged with these patients.
P-185 Randomized phase III trial of nab-paclitaxel (nab-P) plus gemcitabine (Gem) vs Gem alone as adjuvant therapy for patients with resected pancreatic cancer: APACT
Authors: M. Tempero, D. Cardin, A. Biankin, D. Goldstein, M. Moore, E. O'Reilly, P. Philip, H. Riess, T. Macarulla, L. Yung, M. Li, B. Lu
Journal: Annals of Oncology (2015)
Safety and antitumor activity of 3-weekly anti-EpCAM antibody adecatumumab (MT201) in combination with docetaxel for patients with metastatic breast cancer: Results of a multicenter phase Ib trial
Authors: M. Sebastian, C. Hanusch, M. Schmidt, N. Marschner, D. Oruzio, C. Wolf, C. Reinhardt, W. Eiermann, D. Rüttinger, M. Schuler
Journal: Journal of Clinical Oncology (2009)

1009 Background: The fully human IgG1 antibody adecatumumab (MT201) binds to the epithelial cell adhesion molecule (EpCAM), which is expressed in over 90% of breast cancers and has been associated with poor prognosis. Data from a previous phase II study in metastatic breast cancer (MBC) indicated that single agent MT201 could prolong progression-free survival in a subset of patients with high EpCAM expression. This study tested safety and tolerability of MT201 treatment in combination with standard docetaxel. Methods: Relapsed or primary refractory, EpCAM-positive MBC patients were treated with docetaxel (100 mg/m 2 q21d) in combination with MT201 (dose levels 180 mg/m 2 , and 550 mg/m 2 q21d). A loading dose of 100 mg/m 2 and 300 mg/m 2 , respectively, was administered on day 1 and 7. Patients were grouped into high- and low-level EpCAM expression. Primary objectives were safety and tolerability; anti-tumor activity according to RECIST was a secondary objective. Results: A total of 22 patients with a median of 3 prior chemotherapy lines were enrolled. Most frequent grade 3/4 adverse events (AE) in all patients were leucopenia (90%), neutropenia (77%), lymphopenia (68%), and diarrhea (23%). No evidence for aggravation of grade 3/4 toxicities typically associated with docetaxel was found. The dose level 550 mg/m 2 q21d has been determined as MTD in combination with 100 mg/m 2 q21d docetaxel. The overall response rate (CR/PR; RECIST) and clinical benefit rate (CR/PR and SD&gt;24wks) in all evaluable patients was 24% and 41%, respectively. Patients with high EpCAM expression showed a response rate of 43%, whereas patients with low EpCAM expression had a response rate of 10%. Median time-to-progression (TTP) in all evaluable patients was 165 days. Conclusions: Combining MT201 with docetaxel for the treatment of MBC appears to be safe and feasible. The DLT of this combination were short and manageable episodes of grade 3 diarrhea. The response rate and TTP observed in this heavily pre-treated population is encouraging and warrant further development of MT201/chemotherapy combinations in patients with tumors of high EpCAM target level. [Table: see text]
Use of targeted therapy in cancer patients in the end-of-life period.
Authors: Alysson Wann, David M. Ashley, Mustafa Khasraw
Journal: Journal of Clinical Oncology (2014)

129 Background: There is limited data on the use of these targeted therapies in patients at the end of life. This study reviews the pattern of use of targeted and potentially futile, toxic and costly therapies at the end of life at an Australian cancer centre. Methods: A retrospective single-centre review covering 12 month period of patients who died &lt; 3 months of starting a targeted agent. We extracted demographics, types of cancers, types of therapy, median age and lines of prior therapy. Results: 478 patients were on targeted therapies during this period. 54 patients, (11.3%) died &lt; 3 months. Of those, the median age was 69 years, men 65%, women 35%. 27 had haematological malignancies (mostly lymphoma and multiple myeloma), 21 had solid tumours (mostly colon and lung cancer). Ten agents were represented with erlotinib, bevacizumab, and rituximab having higher total number of deaths and none on transtuzumab. Treatment lines were first in 64.8%, second in 20.4% and 14.8% had &gt; 2 lines of treatment. Performance status was only documented in 9.3% at start and 11.1% at end of treatment. Symptoms at the start of treatment that can be used to track improvement were only documented in 25 patients (46.3%). Gender, type of cancer, age was found to have no influence on death &lt; 3 months of targeted treatment. Unfortunately we were unable to extract QoL data. Conclusions: In this small single centre descriptive study, the use of targeted therapy in the end of life population was common, mostly in first line treatment. No factors have shown correlation with dying &lt; 3 months of targeted therapies. There is a need to better document performance status and QoL data and also to analyse indicators of when it is appropriate to cease targeted therapies.
Alpha 2-adrenoceptors determine the response to nitric oxide inhibition in the rat glomerulus and proximal tubule.
Authors: S C Thomson, V Vallon
Journal: Journal of the American Society of Nephrology (1995)

Arginine-derived nitric oxide exerts control over the processes of glomerular filtration and tubular reabsorption. The tonic influence of nitric oxide over both of these is eliminated by renal denervation. The hypothesis that the renal nerves function, in this regard, via the activation of alpha 2-adrenoceptors was tested by renal micropuncture. The physical determinants of glomerular filtration and proximal tubular reabsorption were assessed in Munich-Wistar rats before and during the administration of the nitric oxide synthase inhibitor NG-monomethyl L-arginine (L-NMMA). In one set of studies, the systemic infusion of the alpha 2-agonist B-HT 933 rendered nephron GFR, nephron plasma flow, and proximal reabsorption sensitive to reduction by L-NMMA after renal denervation. In a second set of studies, the infusion of the alpha 2 receptor antagonist, yohimbine, to rats with renal nerves intact was found to suppress the effects of L-NMMA on nephron plasma flow and proximal reabsorption. The effects of L-NMMA on nephron GFR and nephron plasma flow, afferent and efferent arteriolar resistances, and proximal reabsorption correlated with the level of underlying alpha 2-adrenergic activity. The activation of renal alpha 2-adrenoceptors increases the influence of arginine-derived nitric oxide in the glomerulus and proximal tubule.
Intensive Glycemic Control in Type 2 Diabetes Mellitus—A Balancing Act of Latent Benefit and Avoidable Harm
Authors: Rene Rodriguez-Gutierrez, Kasia J. Lipska, Rozalina G. McCoy
Journal: JAMA Internal Medicine (2016)

This Teachable Moment provides an example of how patient-centered care and shared decision-making require a comprehensive and transparent discussion between patient and physician of known risks, benefits, costs, and burden of available and reasonable treatment options.
Application of Quantitative 8tereology to the Evaluation of Phenotypically Heterogeneous Enzyme-Altered Foci in the Rat Liver2
Authors: H. A. Campbell, Yuan-Ding Xu, Marie H. Hanigan, H. C. Pitot
Journal: JNCI Journal of the National Cancer Institute (1986)

Quantitative stereologic relationships are applied in this report to the evaluation of F344 rat liver foci where the tissue sections exhibit congruent enzyme-altered areas of the several different phenotypes as well as enzyme-altered areas within a larger area of another enzyme alteration, that is, a "focus within a focus.' Quantitation of both the numbers and volume occupied by each of the phenotypes of the enzyme-altered foci was accomplished by the unique logic described in this report. The application of this logic to four representative experimental protocols with the use of three phenotypic markers demonstrated all possible congruent phenotypes as well as a small number of "foci within foci.' The variance of the quantitation of the experimental data was shown to depend on the number of focal transections identified in the sections, the number of sections examined, and the distribution of phenotypic alterations among foci.
Evaluation of risk for development of myeloproliferative disorders, myelodysplastic syndromes, or acute leukemias with long-term eculizumab therapy in paroxysmal nocturnal hemoglobinuria (PNH) patients
Authors: J. Schubert, N. S. Young, L. Luzzatto, R. A. Brodsky, G. Socié, R. P. Rother, S. A. Rollins, P. Hillmen
Journal: Journal of Clinical Oncology (2007)

7087 Background: PNH is a rare bone marrow failure disorder defined by stem cell clones with somatic mutations in the PIG-A gene. These mutations result in peripheral blood cells deficient in GPI-anchored proteins including complement inhibitors CD55 and CD59. Chronic lysis of PNH RBCs leads to severe anemia, life-threatening thrombosis, debilitating fatigue, and impaired quality of life. Previous studies have indicated an increased frequency of myeloproliferative disorders, MDS, and acute leukemias in PNH. In a previous retrospective analysis of 1,760 PNH patients, 6.8% developed either myeloid or lymphoid disorders and 1% developed acute leukemias. Eculizumab (Soliris) is a humanized antibody that prevents terminal complement activation. Long-term eculizumab treatment has been evaluated in 195 PNH patients (&gt;250 patient years of exposure) and shown to significantly restore the endogenous PNH RBC clone resulting in improved anemia, as well as significant improvements in thrombosis, fatigue, and quality of life. Methods: Leukocyte clone sizes were assessed at baseline and 26 weeks for patients receiving eculizumab in the Phase III clinical trials (TRIUMPH and SHEPHERD) using flow cytometry. The frequency of MDS and leukemia was calculated as a percentage of the eculizumab-treated patients across all eculizumab trials. Results: PNH leukocyte clone size did not increase with eculizumab treatment (median 96.1% at baseline vs 95.5% at week 26; P=0.80, signed rank test) suggesting that inhibition of terminal complement does not destroy or result in the proliferation of PNH leukocyte clones. Additionally, the frequency of new MDS (1/195 patients, 0.5%) and CMML (1/195 patients, 0.5%) during the treatment period was not increased over that expected. The single case of CMML occurred in a patient previously diagnosed with and was attributed to high grade myelodysplasia. Conclusions: To date, eculizumab treatment of PNH patients does not increase the risk for the development of myeloproliferative disorders, MDS or acute leukemias. Patients on eculizumab will continue to be followed in a Global PNH Safety Registry. No significant financial relationships to disclose.
Novel pre-mRNA splicing of intronically integrated HBV generates oncogenic chimera in hepatocellular carcinoma
Authors: Yung-Tuen Chiu, John K.L. Wong, Shing-Wan Choi, Karen M.F. Sze, Daniel W.H. Ho, Lo-Kong Chan, Joyce M.F. Lee, Kwan Man, Stacey Cherny, Wan-Ling Yang, Chun-Ming Wong, Pak-Chung Sham, Irene O.L. Ng
Journal: Journal of Hepatology (2016)

Hepatitis B virus (HBV) integration is common in HBV-associated hepatocellular carcinoma (HCC) and may play an important pathogenic role through the production of chimeric HBV-human transcripts. We aimed to screen the transcriptome for HBV integrations in HCCs.
Phase II trial of paclitaxel and cisplatin in women with advanced breast cancer: an active regimen with limiting neurotoxicity.
Authors: C Wasserheit, A Frazein, R Oratz, J Sorich, A Downey, H Hochster, A Chachoua, J Wernz, A Zeleniuch-Jacquotte, R Blum, J Speyer
Journal: Journal of Clinical Oncology (1996)

PURPOSE A phase II study of paclitaxel and cisplatin in patients with advanced breast cancer was performed to determine the objective response rate and make further observations about the toxicity of this regimen. PATIENTS AND METHODS Patients were required to have histologically proven adenocarcinoma of the breast with no more than one chemotherapeutic treatment for advanced disease. Treatment consisted of paclitaxel 200 mg/m2 administered as a 24-hour intravenous (i.v.) infusion followed by cisplatin 75 mg/m2 i.v. Patients received granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously on day 3 until WBC recovery. Cycles were repeated every 21 days. Patients continued to receive therapy until disease progression or unacceptable toxicity. RESULTS Forty-four patients entered the trial. Forty-two patients were assessable for response. Nineteen patients (43%) had no prior chemotherapy and 41 had no chemotherapy for metastatic disease. The median number of cycles administered per patient was five (range, one to seven). There were five complete responses (CRs) (11.9%) and 17 partial responses (PRs) (40.5%), with an overall response rate of 52.4% (95% confidence interval [CI], 36.4% to 68.0%). Nine patients had stage III disease. The response rate for this group was 66.7% (95% CI, 33.0% to 92.5%), with three CRs and three PRs. Among 35 patients with stage IV disease, there were two CRs and 14 PRs, with an overall response rate of 48.5% (95% CI, 30.8% to 66.5%). Overall, the median response duration was 10.6 months. Thirty patients (68%) developed transient grade 4 neutropenia. Cumulative neuropathy was the major dose-limiting toxicity. After five cycles of chemotherapy, 96% of patients had at least grade 1 neurotoxicity and 52% had at least grade 2 neurotoxicity. One patient had a toxic death after cycle 1 of therapy. CONCLUSION The combination of paclitaxel and cisplatin as first-line chemotherapy for women with advanced breast cancer is an active regimen. However, the cumulative neurotoxicity was significant and dose-limiting in the majority of patients.