tbuckley/cabot-search huggingface dataset:
Postviral Syndrome-How can a Diagnosis be Made? A Study of Patients Undergoing a Monospot Test
Authors: S J Bowman, J Brostoff, S Newman, J F Mowbray
Journal: Journal of the Royal Society of Medicine (1989)

Eighty-nine of 150 patients having a Monospot test filled out a questionnaire about their illness, and the General Health Questionnaire. They completed a follow-up questionnaire 6 months later. Twelve (8%) had a positive Monospot. Twenty-eight of 83 serum samples tested (34%) were positive for VP1 enteroviral antigen. Forty of the patients had a self limiting illness, 13 had a definite diagnosis (excepting glandular fever), 14 had a possible postviral syndrome, 10 had recurrent sore throats/flu, and 12 had a chronic non-specific illness. Patients with a specific diagnosis were less likely to complain of aching muscles/joints, sore throat, tiredness or loss of concentration. Their GHQ scores were lower, although this just failed to reach significance (P = 0.08), and they scored significantly lower on the somatic symptoms subscale (P = 0.022). Overall 72% scored above the GHQ threshold for 'psychological caseness' which is higher than in other studies. Sixty-five per cent of the sample questioned at 6 months felt that their illness started with a viral infection. The methodological problems involved in making a diagnosis of postviral syndrome are discussed.
Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib
Authors: S K Kumar, B LaPlant, V Roy, C B Reeder, M Q Lacy, M A Gertz, K Laumann, M A Thompson, T E Witzig, F K Buadi, C E Rivera, J R Mikhael, P L Bergsagel, P Kapoor, L Hwa, R Fonseca, A K Stewart, A Chanan-Khan, S V Rajkumar, A Dispenzieri
Journal: Blood Cancer Journal (2015)

Abstract This phase 2 trial was designed to evaluate ixazomib, an orally bioavailable proteasome inhibitor, in patients with myeloma who have limited prior exposure to bortezomib. Thirty-three patients with relapsed multiple myeloma were enrolled. Ixazomib was given at 5.5 mg weekly for 3 of 4 weeks. Dexamethasone was added for lack of a minor response (MR) by end of cycle 2 or lack of a partial response (PR) by end of cycle 4 or for disease progression at any time. Median age was 69 years; patients had a median of two prior therapies (range 1–7). A grade 3 or 4 adverse event considered at least possibly related to drug was seen in 19 (59%) and 6 (19%) patients, respectively. The most common adverse events were thrombocytopenia, fatigue, nausea and diarrhea. Dexamethasone was initiated in 22 (67%) patients, 17 for not reaching the desired response and 5 for progression. Response (⩾PR) to single agent was seen in five patients within four cycles of therapy including three patients with PR, one patient with complete response (CR) and one patient with stringent CR. Six additional patients with either an MR (2) or SD (4) achieved a PR after addition of dexamethasone, translating to an overall response rate of 34%.
The cancer anorexia-cachexia syndrome.
Authors: K A Nelson, D Walsh, F A Sheehan
Journal: Journal of Clinical Oncology (1994)

PURPOSE To review the research related to the anorexia-cachexia syndrome in patients with cancer, with attention to the etiology and symptomatic treatment. DESIGN A comprehensive literature review using MEDLINE. RESULTS AND CONCLUSION The anorexia-cachexia syndrome is a common problem in advanced cancer. Although many possible etiologies have been investigated, the cause has not been determined. Appropriate clinical evaluation is necessary to identify those patients who may respond to available, symptomatic treatments.
Effective endoscopic holmium laser lithotripsy in the treatment of a large impacted gallstone in the duodenum
Authors: Vincenzo Mirante, Helga Bertani, Giuseppe Grande, Mauro Manno, Angelo Caruso, Santi Mangiafico, Rita Conigliaro
Journal: Endoscopy (2015)

Gallstone ileus is caused by the passage of one or more large gallstones (at least 2.5 cm in size) in the gastrointestinal tract through a bilioenteric fistula. It accounts for 1 % to 4 % of all cases of mechanical small-bowel obstruction [1] [2]. The obstructing gallstone is usually impacted in the terminal ileum, rarely the duodenum [1]. Computed tomography generally reveals mechanical bowel obstruction, pneumobilia, and an ectopic stone in the intestinal lumen (Rigler's triad) [3]. Although surgery is considered the gold standard treatment, a less invasive endoscopic approach is advisable in high risk patients [4].
Abstract LB-045: Detection of keratin fusions in oral squamous cell carcinoma
Authors: Jim Jinn-Chyuan Sheu
Journal: Cancer Research (2015)

Abstract Keratin cytoskeleton proteins form intermediate filaments in epithelial cells to regulate cell shape, mobility, membrane trafficking and cellular signaling. Although keratin-6 (K6) and -14 (K14) are highly expressed in certain squamous cell carcinomas and have been suggested as tumor markers, molecular mechanisms of how keratins contribute to cancer development still remain elusive. Here, we demonstrated novel K6-K14 chimeras in oral squamous cell carcinomas (OSCCs) by pair-ended transcriptome sequencing and subsequent validation by fluorescence in situ hybridization and junction site mapping. Two unique fusion types (type-1 and type-2) were identified with a total of 23 in-frame fusion variants verified in OSCCs. Clinical screening confirmed high detection rate of K6-K14 fusions in tumor samples: 33% for type-1 and 25% for type-2. Notably, K6-K14 fusions could be only detected in tumor lesions at late carcinoma stage, but not the ones at early stages, suggesting potential benefits of K6-K14 fusions in promoting aggressive tumors. Functional domain analyses revealed a potent role involved in EMT and metastasis. Citation Format: Jim Jinn-Chyuan Sheu. Detection of keratin fusions in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-045. doi:10.1158/1538-7445.AM2015-LB-045
Nivolumab for metastatic renal cell carcinoma (mRCC): Results of a randomized, dose-ranging phase II trial.
Authors: Robert J. Motzer, Brian I. Rini, David F. McDermott, Bruce G. Redman, Timothy Kuzel, Michael Roger Harrison, Ulka N. Vaishampayan, Harry A. Drabkin, Saby George, Theodore F. Logan, Kim Allyson Margolin, Elizabeth R. Plimack, Ian Waxman, Alexandre Lambert, Hans J. Hammers
Journal: Journal of Clinical Oncology (2014)

5009 Background: Nivolumab, a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, restores T-cell immune activity and showed objective responses in mRCC in a phase I trial (NEJM 366:2443). This phase II trial (NCT01354431) assesses three nivolumab doses in mRCC patients (pts) pretreated with agents targeting the VEGF pathway. Methods: Pts with clear-cell mRCC (≥1 agent targeting VEGF pathway; ≤3 prior systemic therapies) were randomized (blinded 1:1:1) to nivolumab 0.3, 2 or 10 mg/kg IV Q3W until progression or toxicity. The primary objective was to evaluate the dose-response relationship measured by progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR) and safety assessment. Results: All pts (N=168) received prior systemic therapy (70% received ≥2) including VEGFR TKIs (98%), mTOR inhibitors (38%) and immunotherapy (24%). 25% were MSKCC poor risk. All had >16 months of follow-up. No dose-response relationship was noted for PFS (stratified trend test, P=0.9). PFS and ORR were similar across doses (Table). For 0.3 mg/kg, median duration of response was 15.7 months and median OS was 18.2 months; for other doses medians were not reached. Across doses 19/35 responders (54%) had objective responses lasting >12–20+ months. Rates of grade 3–4 related adverse events (AEs) were ≤17% for all doses (Table). There was no grade 3–4 pneumonitis. For 0.3, 2 and 10 mg/kg, 1 (2%), 6 (11%) and 4 (7%) pts, respectively, had treatment-related AEs that led to discontinuation. Conclusions: Antitumor activity was observed with nivolumab in this pretreated mRCC population including objective responses of long duration. No dose-response relationship for PFS was noted and the safety profile was acceptable. Median OS was 18.2 months for the 0.3 mg/kg dose and was not reached for 2 or 10 mg/kg; updated OS will be presented. Clinical trial information: NCT01354431. 0.3 mg/kg n=60a 2 mg/kg n=54 10 mg/kg n=54 Median PFS, months (80% CI) 2.7 (1.9, 3.0) 4.0 (2.8, 4.2) 4.2 (2.8, 5.5) ORR, n (%) 12 (20) 12 (22) 11 (20) Median OS, months (80% CI) 18.2 (16.7, NR) NR NR Treatment-related AE, n (%) Grade 3–4 44 (75) 3 (5) 36 (67) 9 (17) 42 (78) 7 (13) a Safety analysis included 59 treated pts; CI=confidence interval; NR=not reached.
Determining the manner in which patients with Duchenne muscular dystrophy start non-invasive ventilation
Authors: Christopher Edwards, Philip Davies, Scott Davidson
Journal: European Respiratory Journal (2014)

Introduction: Non-invasive ventilation (NIV) has been shown to improve the quality and quantity of life for DMD patients. However, very little is written about what triggers the commencement of NIV in these patients.  Aims: To determine the manner in which long term non-invasive ventilation is commenced in children with Duchenne Muscular Dystrophy (DMD).  Methods: A notes review of patients in the West of Scotland with Duchenne Muscular Dystrophy who have been commenced on non-invasive ventilation in the last 10 years.  Results: 19 patients were commenced on ventilation during the study period. The average age at starting ventilation was 17.5 years. 13 patients were started electively, based on an assessment of overnight ventilation, lung function and / or symptoms. All of the patients started electively were commenced on NIV by a respiratory consultant on a general respiratory ward, except one, who was commenced on NIV at home.  6 patients (32%) were started during an acute admission. Two of these were commenced NIV on the general respiratory ward by a respiratory consultant, the remainder were started on PICU. Four acute admissions were precipitated by pneumonia, one due to food aspiration, and one had an out of hospital cardiorespiratory arrest.  Conclusion: It is becoming increasingly common for patients with Duchenne muscular dystrophy to commence NIV electively. However, over the period study just under one-third started NIV during an acute admission.  There is the potential to increase the number of DMD patients commenced on NIV electively. However, the unpredictable nature of acute infections means that some patients will inevitably be commenced on NIV in a non-elective fashion.
Inhibitors of the stromal protease fibroblast activation protein attenuate tumor growth in vivo
Authors: Kalyani Narra, Hyung Ok Lee, Anthony Lerro, Jacquelyn Valvardi, Olumayowa Azeez, Michael I. Jesson, Nazneen Aziz, Barry Jones, Jonathan D. Cheng
Journal: Cancer Research (2006)

4382  Fibroblast activation protein (FAP) is a serine protease that is selectively expressed on tumor stromal fibroblasts in a vast majority of epithelial cancers. We have previously shown that FAP overexpression enhances tumor growth and suggested a possible therapeutic role for functional inhibition of FAP activity (Cancer Res 62:4767–4772, 2002). PT-100 and PT-630 are boronic dipeptides, which competitively inhibit dipeptidyl peptidases including FAP and DPP-IV/CD26 with Ki in the nanomolar range. PT-100 treatment has been shown to decrease tumor size and cause tumor regression and rejection in a variety of animal tumor models (Cancer Res 64: 5471–5480, 2004). Its mechanism of action is complex, as it not only inhibits FAP enzymatic activity but also has been shown to have immunomodulatory effects including upregulation of cytokine and chemokine expression. PT-630 inhibits FAP enzymatic activity to a similar degree as PT-100, but without invoking a cytokine response. Therefore, we investigated the effects of PT-630 and PT-100 in animal models that have strong FAP expression. HT-29 xenografts induce stromal FAP expression in the tumor fibroblasts without any detectable expression on the colorectal cancer cells themselves. In addition HEK293 cells transfected with FAP were also tested as an epithelial FAP overexpression animal model. PT-100 and PT-630 when administered orally to mice inoculated subcutaneously with either HT-29 or HEK-FAP cells, significantly inhibited tumor growth when compared to saline treated controls. Both PT-100 and PT-630 decreased tumor volume in the HT-29 and HEK-FAP xenografts by approximately 50%. Immunocapture of FAP and DPP-IV from the tumors showed significantly decreased enzymatic activity in PT 100 and PT 630 treated xenografts indicating that FAP activity is suppressed in vivo. A dose related response for PT-630 was also suggested. We therefore demonstrate that PT-100 and PT-630 inhibit tumor growth of HT-29 and HEK-FAP xenografts. In addition, PT-100 and PT-630 attenuate enzymatic activity in vivo in a dose dependent manner. Given that PT-630 has minimal immunomodulatory effects, this suggests that the antitumor activity seen in these animal models may be mediated by the inhibition of FAP at the tumor microenvironment.
Metastasis‐associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients
Authors: Andri Lederer, Pia Herrmann, Daniel Seehofer, Manfred Dietel, Johann Pratschke, Peter Schlag, Ulrike Stein
Journal: Hepatology (2015)

Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis‐associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen‐activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n = 76) and ICC (n = 80) using real‐time quantitative reverse‐transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue ( P &lt; 0.001). Klatskin tumor patients with a history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence ( P = 0.005). Uni‐ und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease‐free survival (DFS; P = 0.001 and P &lt; 0.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389‐5.555; P = 0.004). Conclusion: Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an important diagnostic tool and might be a candidate for targeted therapy. (H epatology 2015;62:841–850)
Managing Systemic Light-Chain Amyloidosis
Authors: Raymond L. Comenzo
Journal: Journal of the National Comprehensive Cancer Network (2007)

Amyloidosis is a rare disease in which a specific protein is deposited as aggregated interstitial fibrils that can compromise organ function and lead to death. Immunoglobulin (Ig) light-chain amyloidosis (AL), caused by the monoclonal gammopathy of a plasma cell dyscrasia, is the most common type. A hereditary type is also caused by mutant transthyretin and other proteins. Rarely, a patient with amyloid has both a monoclonal gammopathy and a hereditary protein. In AL, circulating monoclonal Ig light chains can be measured with the free light-chain (FLC) assay and provide a target for therapy to eliminate the underlying plasma cell dyscrasia while supporting the patient's organ function. Amyloid deposits can be resorbed and organ function restored if the amyloid-forming precursor FLC is eliminated. For patients with limited organ involvement, intravenous melphalan in doses from 100 to 200 mg/m 2 with autologous stem cell support (SCT) is an effective approach and, when followed at 3 months post-SCT with adjuvant thalidomide and dexamethasone for persistent plasma cell disease, has a 1-year hematologic response rate of 77%. Monthly oral melphalan and dexamethasone for 1 year can also be effective therapy for patients too sick for SCT (67% response rate). Hematologic complete responses are usually durable and result in long-term survival and a variable degree of organ recovery. For patients with advanced cardiac involvement, the prognosis remains guarded even with treatment. Drugs effective in multiple myeloma are usually active in AL, depending on side effects. New agents such as bortezomib and lenalidomide have shown promising activity, and novel antibody-based approaches for imaging amyloid and accelerating removal of deposits are being actively investigated.
Psychosocial adjustment among women with breast cancer stages I and II: six-year follow-up of consecutive patients.
Authors: M Omne-Pontén, L Holmberg, P O Sjödén
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate, in a long-term follow-up study of consecutive patients (N = 99), the impact of surgery--breast-conserving treatment (BCT) versus mastectomy (MT)--on psychosocial adjustment among women with breast cancer, pTNM stage I/II. PATIENTS AND METHODS Semistructured interviews were conducted at a median of 6 years (range, 5.8 to 8.1) after primary surgery. Sixty-six women were available for the long-term follow-up study. Twenty-six women had been treated with BCT and 40 with MT. RESULTS No statistically significant differences were found between the two groups concerning psychosocial adjustment, as measured by the Social adjustment Scale (SAS). In general, the levels of maladjustment were lower than at 13 months postoperatively, but 10% still showed maladjustment. Sixty percent of the women were unwilling to show themselves naked, and 22% felt that they had become less attractive because of the surgical treatment. In an explorative part of the interview, 68% of the women complained about how they had been informed of the diagnosis. A tendency toward a significant difference was found in the relation between previous maladjustment and a negative experience at the time of diagnosis (P = .07). CONCLUSION Few data are available on long-term follow-up results with regard to psychosocial adjustment among women after breast cancer surgery. This study provides the important information that there are no differences in patient psychosocial adjustment that can be ascribed to the type of surgery at 6-year follow-up evaluation.
Six minute walk test in children, adolescents and young adults with and without cystic fibrosis
Authors: Fabíola Meister Pereira, Maria Angela Ribeiro, Adyléia Dalbo Toro, Gabriel Hessel, Antonio Fernando Ribeiro, José Dirceu Ribeiro
Journal: European Respiratory Journal (2011)

Background: The six minute walk test (6MWT) analyses tolerance to submaximal effort. It's important to compare Cystic Fibrosis (CF) patients with healthy controls to better understand their responses to physical exercise.

Objective: To evaluate patients with CF submitted to 6MWT and compare them to a control group (CG).

Methods: Transversal, prospective study comprising patients from a Brazilian CF reference centre. 6MWT was applied in a group of CF patients and in healthy controls accordingly to ATS guidelines and repeated after 30 minutes of rest. Respiratory frequency (RF), heart rate (HR), oxygen saturation (SpO2), dyspnea index, nutritional status and spirometry values were analyzed. Patients on pulmonary exacerbation were excluded from the research. Spearman's correlation and ANOVA for repeated measures were used, p<0.05.

Results: Fifty-five CF patients and 185 healthy individuals participated (12.2±4.3 and 11.3±4.3 years, respectively). CG walked a greater distance than the CF patients in both tests (610.3±53.4m x 547.2±80.6m and 616.2±58.0m x 552.2±82.1m; p<0.0001). Walked distance correlated with age, weight and height. Both groups achieved similar distances in both tests, although CF patients had better performance in the first test. Learning effect was not seen. The ICC calculated between the two tests was 0.81 and 0.77 (CF and CG, respectively). The SpO2 maintained stable during the test, with an increase in HR and RF (p< 0.0001) in all individuals.

Conclusion: CF patients presented functional impairment when compared to control group. Repeating 6MWT may represent an unnecessary effort for patients with chronic pulmonary disease.
<i>Escherichia coli</i>O111:H8 Outbreak Among Teenage Campers—Texas, 1999
Authors: D. Bergmire-Sweat, L. Marengo, P. Pendergrass, K. Hendricks, M. Garcia, R. Drumgoole, T. Baldwin, K. Kingsley, B. Walsh, S. Lang, L. Prine, T. Busby, L. Trujillo, D. Perrotta, A. Hathaway, B. Jones, A. Jaiyeola, S. Bengtson
Journal: JAMA (2000)
Patient comfort score at bronchoscopy
Authors: Alina Ionescu, Katie Pink
Journal: European Respiratory Journal (2011)

The aim of this study was to assess the patient comfort score immediately after bronchoscopy (by nursing staff and patient) and later on at follow up (by patient) in a teaching hospital.   Subjects and methods:  One hundred and four consecutive patients (62 male, mean (SD) age 63.2 (15.6)) were included and complete data was analysed for 96. The indication for bronchoscopy was radiological suspicion of lung cancer (39), haemoptysis (25), slowly resolving pneumonia (18), radiological picture of interstitial lung disease (16), cough (4) and mediastinal lymphadenopaty (2).  The nurses used a patient comfort score (1- mild to 4-severe) and a sedation score (1-awake, 2-sedated). While in recovery and then again at follow up appointment (7-14 days later) the patients were asked to describe their comfort score (1-mild to 4-severe). Patients received Midazolam for sedation (1-7 mg i.v.) and local anaesthetic Lignocaine 2%.  Data was analysed in Spss and corelation coefficients; Chi square Kruskal Wallis used.   Results:  The comfort score by nurses correlated with the score by patient in recovery (p= 0.006) and at follow up (p=0.03). The two patient scores correlated (p0.001, Pearson9s 0.51). No difference in the comfort scores was found when the grade of the operator, dose of Midazolam, type of local anaesthetic, specimens taken, patient9s position or the recovery sedation score were taken into account.  To conclude, the patient comfort score assessed by nursing staff is a good indicator of the patient9s own perception of their discomfort at bronchoscopy. The patient perceived comfort score is not different after the sedation effect of Midazolam wares off compared to the score assessed immediately after the bronchoscopy.