tbuckley/cabot-search huggingface dataset:
Comparison of Adverse Events for Endoscopic vs Percutaneous Biliary Drainage in the Treatment of Malignant Biliary Tract Obstruction in an Inpatient National Cohort
Authors: Sumant Inamdar, Eoin Slattery, Ramandeep Bhalla, Divyesh V. Sejpal, Arvind J. Trindade
Journal: JAMA Oncology (2015)

IMPORTANCE Nonsurgical biliary drainage in malignant biliary tract obstruction can be performed endoscopically by endoscopic retrograde cholangiopancreatography (ERCP) or by percutaneous transhepatic biliary drainage (PTBD).The published body of literature to support either approach is surprisingly sparse, is conflicting on the preferred approach, and is limited by small studies with heterogeneous groups.OBJECTIVE To evaluate the procedure-related adverse event rate with endoscopic vs percutaneous drainage in patients with malignant biliary tract obstruction.DESIGN, SETTING, AND PARTICIPANTS This was a retrospective analysis from the National Inpatient Sample (NIS) database from 2007 through 2009.Data analysis was performed in 2015.Patients from the NIS database are representative of the US population and are included from both community and tertiary care hospitals in the United States.MAIN OUTCOMES AND MEASURES Procedure-related adverse event rates.RESULTS A total of 7445 patients were included for ERCP and 1690 for PTBD.The overall adverse event rate was 8.6% for endoscopic drainage (640 events) and 12.3% for percutaneous biliary drainage (208 events) (P < .001).When analyzed by type of malignant neoplasm, ERCP was associated with a lower rate of adverse events compared with PTBD for pancreatic cancer (2.9% vs 6.2%; odds ratio [OR], 0.46 [95% CI, 0.35-0.61];P < .001)and cholangiocarcinoma (2.6% vs 4.2% OR, 0.62 [95% CI, 0.35-1.10];P = .10).For pancreatic cancer, endoscopic procedures were associated with a lower rate of adverse events regardless of the volume of percutaneous procedures performed by a center.For cholangiocarcinoma, centers that performed a low volume of percutaneous biliary drainage procedures were more likely to have adverse events compared with endoscopic procedures performed at the same center (5.7% vs 2.5%; OR, 2.28 [95% CI, 1.02-5.11];P = .04).In centers that performed a high volume of percutaneous drainage procedures, rates of adverse events were similar to those of endoscopic adverse events (3.5% vs 3.0%; OR, 1.18 [95% CI, 0.53-2.66];P = .68). CONCLUSIONS AND RELEVANCEOur results support the finding that endoscopic biliary drainage for malignant biliary obstruction is a first-line intervention.Endoscopic drainage is superior to percutaneous drainage, in regard to adverse event rate, for patients with pancreatic cancer.For patients with cholangiocarcinoma, endoscopic drainage is superior in centers that perform a low volume of percutaneous biliary drainage procedures.
Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors
Authors: Lukas J.A.C. Hawinkels, Amaya Garcia de Vinuesa, Madelon Paauwe, Marianna Kruithof-de Julio, Eliza Wiercinska, Evangelia Pardali, Laura Mezzanotte, Stijn Keereweer, Tanya M. Braumuller, Renier C. Heijkants, Jos Jonkers, Clemens W. Löwik, Marie-José Goumans, Timo L. ten Hagen, Peter ten Dijke
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Antiangiogenic therapy, mostly targeting VEGF, has been applied in cancer patients for the last decade. However, resistance to anti-VEGF therapy and/or no significant benefit as monotherapeutic agent is often observed. Therefore, new antiangiogenic strategies are needed. In the current study, we investigated the therapeutic effect of interfering with the bone morphogenetic protein (BMP)9/activin receptor–like kinase (ALK)1 signaling pathway by using an ALK1-Fc ligand trap. Experimental Design: We analyzed the potential antiangiogenic and antitumor effects of ALK1-Fc protein as monotherapy and in combination with chemotherapy in vivo in mouse models of melanoma, head and neck cancer, and invasive lobular breast carcinomas. ALK1-Fc sequesters BMP9 and 10 and prevents binding of these ligands to endothelial ALK1, which regulates angiogenesis. Results: Treatment of mice with ALK1-Fc strongly decreased the tumors' microvascular density in the three different mouse cancer models. However, this effect was not accompanied by a reduction in tumor volume. An immunohistochemical analysis of the tumor samples revealed that ALK1-Fc treatment increased the pericyte coverage of the remaining tumor vessels and decreased the hypoxia within the tumor. Next, we observed that combining ALK1-Fc with cisplatin inhibited tumor growth in the breast and head and neck cancer models more efficiently than chemotherapy alone. Conclusions: The addition of ALK1-Fc to the cisplatin treatment was able to enhance the cytotoxic effect of the chemotherapy. Our results provide strong rationale to explore combined targeting of ALK1 with chemotherapy in a clinical setting, especially in the ongoing phase II clinical trials with ALK1-Fc. Clin Cancer Res; 22(1); 96–106. ©2015 AACR.
Minimal important difference and clinical determinants of the 6-minute walk distance in lung cancer
Authors: Catherine Granger, Anne Holland, Ian Gordon, Linda Denehy
Journal: European Respiratory Journal (2014)

Introduction: The 6-Minute Walk Distance (6MWD) is the most commonly used measure of functional capacity in NSCLC, however the minimal important difference (MID) has not been established for this population. Aims: To identify: 1) the MID of the 6MWD in NSCLC and 2) the relationship between 6MWD, demographic and disease-related factors. Method: Fifty-six participants (34 male, mean age 65±10years) with stage I-IV NSCLC completed the 6MWD prior to treatment and 10weeks later. No exercise intervention occurred. Additional measures included the European Organization for the Research and Treatment of Cancer questionnaire (EORTC QLQ-C30), Eastern Cooperative Oncology Group Scale (function) and questionnaires (physical activity levels, symptoms and mood). MID was calculated using anchor and distribution based methods. The QLQ-C30 physical function domain was used as the anchor to determine if patients were clinically changed. Results: The mean decline in 6MWD in participants classed as 'deteriorated' was 60m compared to 16m in participants classed as 'not-deteriorated' (p=0.01). The received operating curve indicated a cut-off value for clinically relevant change to be 42m (95%CI 6-75) (area under curve 0.66, 95%CI 0.51-0.81). Distribution based methods indicated an MID between 22m (95%CI 18-26) and 32m (95%CI 20-42) using standard error of the measurement and effect size respectively. A shorter 6MWD correlated with worse function (r=0.42, p=0.001), lower physical activity (r=0.56, p<0.005) and more dyspnea (r=0.44, p=0.001). Conclusion: The MID of the 6MWD in NSCLC is between 22m and 42m. This is similar to the MID previously established for other chronic respiratory disease populations.
LSC 2013 abstract - Apoptotic, inflammatory and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung
Authors: Agnes Boots, Damien van Berlo, Verena Wilhelmi, Maja Hullmann, Thomas Kulbusch, Aalt Bast, Roel Schins, Catrin Albrecht
Journal: European Respiratory Journal (2013)

There is increasing concern about the toxicity of inhaled multi walled carbon nanotubes (MW-CNT). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulates and induction of apoptosis in these cells has been considered to contribute to fibrosis development.  We have investigated the apoptotic, pro-inflammatory and fibrotic potential of two samples of MW-CNT, characterized by a contrasting average tube length and entanglement/agglomeration.  The damaging effects of two MW-CNTs with different properties (average length of respectively 13 and 5 µm and diameter of 40-100 or 30 nm) have been investigated  in vivo  via pharyngeal aspiration in C57Bl6/J mice and  in vitro  in RAW 264.7 macrophage-like murine cells. Main endpoints included toxicity, apoptosis, production of reactive oxygen species (ROS) and cytokines, gene expression and Masson9s Trichrome staining.  Both nanotubes caused granuloma and apoptosis in the mouse lungs. However, the long sample induced a more pronounced inflammatory and pro-fibrotic response as indicated by increased collagen deposition, mRNA expression of matrix metalloproteinase-8 and serum level of monocyte chemotactic protein-1. Interestingly, apoptosis was merely localized in the granulomatous foci.  In vitro , neither of the samples induced apoptosis whereas both nanotube types triggered ROS formation and only the longer sample induced toxicity.  Our study reveals that the inflammatory, apoptotic and fibrogenic effects of MW-CNT in mouse lung can vary considerably depending on their composition. The  in vitro  analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard.
Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors.
Authors: L B Saltz, J Kanowitz, N E Kemeny, L Schaaf, D Spriggs, B A Staton, R Berkery, C Steger, M Eng, A Dietz, P Locker, D P Kelsen
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the maximum-tolerable dose (MTD) of fluorouracil (5FU) when given with fixed doses of leucovorin and irinotecan (CPT-11), to define the dose-limiting toxicities of this combination, and to evaluate the effect of 5FU on the pharmacokinetics of CPT-11. PATIENTS AND METHODS CPT-11, leucovorin, and 5FU were administered in repeated 6-week cycles that consisted of weekly treatment with all three drugs for 4 consecutive weeks followed by a 2-week break. On day 1 of treatment, CPT-11 alone was given by 90-minute infusion, and pharmacokinetic sampling was performed over 24 hours. Leucovorin and 5FU were administered by brief intravenous injection on day 2. On days 8, 15, and 22, CPT-11 infusion was immediately followed by leucovorin and then 5FU. A second 24-hour pharmacokinetic sampling was performed on day 8, which permitted comparison of the pharmacokinetics of CPT-11 with and without 5FU. For the second 6-week cycle, leucovorin was administered first, followed by 5FU and then CPT-11, and a third pharmacokinetic sampling was performed. RESULTS Forty-two patients were entered onto this trial. The CPT-11 dose was initially fixed at 100 mg/m2. Leucovorin was fixed at 20 mg/m2. 5FU doses of 210, 265, 340, 425, and 500 mg/m2 were studied. When the 500-mg/m2 dose of 5FU was found to be tolerable, this was then maintained and CPT-11 was escalated to 125 and then 150 mg/m2. This final CPT-11 dose exceeded the MTD. Neutropenia was the major dose-limiting toxicity. Diarrhea was common, but was rarely dose-limiting. Coadministration of 5FU had no substantial effect on the pharmacokinetics of CPT-11 or SN-38. Among the 38 patients with colorectal cancer, six partial responses (PRs) were seen in this predominantly 5FU-refractory patient population. CONCLUSION 5FU does not substantially affect the metabolism of CPT-11 to its active metabolite, SN-38. The combination of CPT-11125 mg/m2, 5FU 500 mg/m2, and leucovorin 20 mg/m2 is feasible and tolerable on this schedule.
Cumulative Incidence of Cancer Among Persons With HIV in North America
Authors: Michael J. Silverberg, Bryan Lau, Chad J. Achenbach, Yuezhou Jing, Keri N. Althoff, Gypsyamber D'Souza, Eric A. Engels, Nancy A. Hessol, John T. Brooks, Ann N. Burchell, M. John Gill, James J. Goedert, Robert Hogg, Michael A. Horberg, Gregory D. Kirk, Mari M. Kitahata, Philip T. Korthuis, William C. Mathews, Angel Mayor, Sharada P. Modur, Sonia Napravnik, Richard M. Novak, Pragna Patel, Anita R. Rachlis, Timothy R. Sterling, James H. Willig, Amy C. Justice, Richard D. Moore, Robert Dubrow
Journal: Annals of Internal Medicine (2015)

Background: Cancer is increasingly common among persons with HIV. Objective: To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. Design: Cohort study. Setting: North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. Participants: 86 620 persons with HIV and 196 987 uninfected adults. Measurements: Cancer type–specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. Results: Cumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (−9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate. Limitation: Secular trends in screening, smoking, and viral co-infections were not evaluated. Conclusion: Cumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation. Primary Funding Source: National Institutes of Health.
Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer.
Authors: N C Choi, R W Carey, W Daly, D Mathisen, J Wain, C Wright, T Lynch, M Grossbard, H Grillo
Journal: Journal of Clinical Oncology (1997)

PURPOSE The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival. METHODS Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score &gt; or = 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation. RESULTS Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade &gt; or = 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotherapy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2,3, and 5 years, respectively, with a median follow-up time of 48 months. Pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (NO) in 24% (10 of 42), and to stage 0 (TONO) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04). CONCLUSION Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC.
Abstract 2323: Protection of Diabetic Heart with Glutaredoxin Gene Therapy
Authors: Istvan Lekli, Subhendu Mukherjee, Diptarka Ray, Narasimman Gurusamy, Dipak Das
Journal: Circulation (2008)

Glutaredoxin-1 [Grx1], a redox regulator of thioredoxin superfamily has been implicated in myocardial ischemia reperfusion injury. Diabetes is a well-recognized cardiovascular risk factor. Grx1 has been shown to protect the heart from ischemia reperfusion induced injuries. The present study examined whether Grx1 gene therapy could render the diabetic hearts resistant to ischemia reperfusion injury. Diabetes was induced with streptozotocin, and after the diabetes was confirmed, male C57B1/J6 mice were assigned to one of the two groups and open heart surgery was performed. The mice received an intra-myocardial injection of 109 p.f.u. adenovirus encoding Grx1 or injected with empty vector or adenovirus with LacZ. Three days later, the animals were sacrificed and isolated hearts were subjected to 30 min ischemia followed by 2 hours of reperfusion. Ventricular function was examined, and myocardial infarct size and cardiomyocyte apoptosis were determined. Hemodynamic parameters of the Grx1 overexpressed hearts exhibited improved function compared to those treated with either empty vector or LacZ. Grx1 overexpressed hearts also exhibited reduced myocardial infarct size and cardiomyocyte apoptosis. We examined the protein level of ASK1 and the activation of its downstream target JNK, P38MAPK and the level of procaspase 3 as well as the activities of Akt, and c-Src. Grx1 gene therapy inhibited the phosphorylation of c-Src, as well as suppressed the activities of the ASK1 and JNK indicating a reduction of overall death signal. Grx1 overexpression restored the procaspase 3 level. Akt phosphorylation was significantly higher compared to control hearts. The expression of phase II enzyme heme oxygenase-1 was higher after GRX1 gene therapy. Interestingly thioredoxin (Trx)-1 and Trx-2 protein levels were also slightly higher after GRX-1 treatment. The results of this study indicate cardioprotection with Grx1 gene therapy in diabetic hearts as evidenced by improved post ischemic cardiac performance, reduction of myocardial infarct size and cardiomyocite apoptosis as well as significant reduction of ischemia-reperfusion induced death signal.
A Comparison of Three Approaches to Patient Care Appraisal Based on Chart Review
Authors: JERZY E. HENISZ, PHILLIP B. GOLDBLATT, HULDA R. FLYNN, VIVIAN GARRISON
Journal: American Journal of Psychiatry (1974)

The authors tested a three-level approach to auditing charts of psychiatric patients (review by clerks, research assistants, and clinical consultants) against two other methods. There were no significant differences among the three methods in scores of adequacy of patient care and adequacy of documentation. While the authors suggest the need for more research in the area of assessing quality of patient care, they believe that research assistants and other nonclinician reviewers can make a contribution to peer review.
Protein disulfide isomerase–endoplasmic reticulum resident protein 57 regulates allergen-induced airways inflammation, fibrosis, and hyperresponsiveness
Authors: Sidra M. Hoffman, David G. Chapman, Karolyn G. Lahue, Jonathon M. Cahoon, Gurkiranjit K. Rattu, Nirav Daphtary, Minara Aliyeva, Karen A. Fortner, Serpil C. Erzurum, Suzy A.A. Comhair, Prescott G. Woodruff, Nirav Bhakta, Anne E. Dixon, Charles G. Irvin, Yvonne M.W. Janssen-Heininger, Matthew E. Poynter, Vikas Anathy
Journal: Journal of Allergy and Clinical Immunology (2015)
Prevalence and pattern of pulmonary infections among HIV/AIDS adults patients admitted to a tertiary care hospital, Dubai, United Arab Emirates, 2009-2010
Authors: Layla Al-Dabal, Samar Badreddin, Ali Abro, Nadeem Younis Javeed
Journal: European Respiratory Journal (2011)

Background: The prevalence of HIV in UAE in estimated to be   Methods: Data was collected longitudinally as patients were admitted to IDU and included demographics, CD4, viral load, chest X-Ray, sputum microscopy/culture, AFB staining/culture and first line DST. CT chest and FOB were used in few selected cases.  Results: Between January 2009 and January 2011, 97 adult patients with HIV/AIDS were admitted to our unit. 45 patients had abnormal chest X-ray and non specific respiratory symptoms (46.39%), mostly presenting with cough (93%). We identified 19/45 (42.2%) patients with active pulmonary TB, 14/45 (31.1%) patients with CAP and 4/45 (8.8%) patients with PJP. No confirmed diagnosis was made in 8/45 (17.7%) patients, out of whom 6 patients died within 48-72 hours of admission. No patient was receiving ART or prophylaxis at the time of pulmonary infection. 29/45 patients had CD4   200/μL (31.7%, range 248-579). 14/18 (77.7%) patients with pulmonary tuberculosis had CD   Conclusions: Pulmonary TB was most frequently diagnosed illness followed by CAP. In patients with AIDS and TB, chest x ray shows a pattern of primary infection and sputum positivity was comparable to HIV infected and immunocompetent subjects.
Autoimmune disorders in allergen immunotherapy, allergic rhinitis, and non-allergic patients
Authors: Daina B. Esposito, Linda Nelsen, Jennifer C.L. Hawes, Crystal N. Holick, Jennifer Maloney, Vinay Mehta, Daniel Mines, Gillian Pianka, Stephan F. Lanes
Journal: European Respiratory Journal (2014)

Background:  Allergic rhinitis (AR) is the most common allergic disease. Allergen immunotherapy (AI) is the only available treatment that modifies the allergic process instead of suppressing symptoms. Whether AI or AR patients have an increased incident rate (IR) of autoimmune disorders is unknown.   Objectives:  Compare IRs of autoimmune disorders in AI, AR, and non-AR patients.   Methods:  This retrospective cohort study included members of the HealthCore Integrated Research Database SM  age ≥5 years (01Jan2004-30Sep2011). Cohorts included patients with neither AR nor AI, specialist-diagnosed AR patients unexposed to AI, and AI patients with AR. We calculated IR ratios (IRRs) and their 95% confidence intervals.   Results:  The cohorts included 1,582,205 non-AR, 1,723,956 AR, and 109,157 AI patients.   Conclusions:  Many autoimmune disorders are more commonly diagnosed in AR than non-AR patients.