tbuckley/cabot-search huggingface dataset:
Prognostic factors for prolonged progression-free survival with high-dose chemotherapy with autologous stem-cell support for advanced breast cancer.
Authors: L J Ayash, C Wheeler, D Fairclough, G Schwartz, E Reich, D Warren, L Schnipper, K Antman, E Frei, A Elias
Journal: Journal of Clinical Oncology (1995)

PURPOSE With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS). METHODS From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepa, and carboplatin with autotransplantation. Data encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS. RESULTS The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (&gt; or = 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066). CONCLUSION We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach.
The effect of erythropoietin (EPO) on cyclooxygenase-2 (COX-2) and cytochrome-c (CYT-c) in the bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats
Authors: Drosos Tsavlis, Anna Tzoumaka, Georgia Kokaraki, Kokkona Kouzi-Koliakos, Ioannis Angomachalelis, Anastasia Tektonidou, Dimitrios Koutsonikolas, Evangelia Spandou
Journal: European Respiratory Journal (2011)

Purpose:  The enzymes COX-2 and CYT-c are known to be a part of the fibrotic pathway.EPO is a multiple functional cytokine with anti-inflammatory and anti-apoptotic properties. Aim of this study was to investigate the role of EPO on the expression of both enzymes in BLM- induced PF in rats.   Methods:  Fifty Wistar rats (300gr) were divided into five groups of 10 animals each:1)control animals,2)intratracheal (i.t) and intraperitoneal (i.p) injection of saline (0.5ml/kg),3)BLM hydrochloride (7.5mg/kg) i.t injection,4)BLM hydrochloride (7.5mg/kg) i.t injection followed by EPO i.p injection (2000 iu/kg),5)saline (0.5ml/kg) i.t injection followed by EPO i.p injection (2000 iu/kg). All rats were sacrified after 14 days.Immunohistochemical evaluation was performed for the expression of COX-2 and Cyt-c.A scale of 4 grades was used for the evaluation of the results: 0-25% (A),25-50% (B),50-75% (C),75-100% (D).   Results:  In groups 1,2 and 5, both COX-2 and CYT-c were expressed in the grade A (80%) and in the grade B (20%). In group 3,COX-2 was expressed in the high grades B (20%),C (60%) and D (20%),and CYT-c only in the two higher grades C (70%) and D (30%). In group 4,both enzymes were expressed only in the low grades A (80% and 70% respectively) and B (20% and 30% respectively). The expression of COX-2 and CYT-c took place in the high grades for BLM group and in the lower grades for BLM+EPO group (p   Conclusions:  BLM injection followed by EPO resulted in significant lower expression of COX-2 and CYT-c compared with BLM group. The protective mechanisms of EPO on PF must be further clarified.
A primitive hematopoietic cell is the target for the leukemic transformation in human Philadelphia-positive acute lymphoblastic leukemia
Authors: C. Cobaleda, N. Gutiérrez-Cianca, J. Pérez-Losada, T. Flores, R. Garcı́a-Sanz, M. González, I. Sánchez-Garcı́a
Journal: Blood (2000)
The renal handling of low molecular weight proteins
Authors: Thomas A. Waldmann, Warren Strober, R. Peter Mogielnicki
Journal: Journal of Clinical Investigation (1972)

The present study was directed toward determining the role of the kidney in the metabolism of various classes of serum proteins and to define the urinary protein excretion patterns and the pathogenesis of disorders of protein metabolism in patients with proteinuria. To this end, the metabolic fates of a small protein, lambda-L chain (mol wt 44,000), and a protein of intermediate size, IgG (mol wt 160,000), were studied in controls and patients with renal disease. Controls metabolized 0.28%/hr of circulating IgG and 22.3%/hr of circulating lambda-L chain. All the IgG and 99% of the lambda-L chain was catabolized with the remaining lambda-L chain lost intact into the urine. The kidney was shown to be the major site of catabolism for small serum proteins. Three distinct disorders of protein metabolism were noted in patients with renal tubular disease and tubular proteinuria, glomerular disease (the nephrotic syndrome), and disease involving the entire nephrons (uremia), respectively. Patients with renal tubular disease had a 50-fold increase in the daily urinary excretion of 15-40,000 molecular weight proteins such as lysozyme and lambda-L chains. Serum IgG and lambda-L chain survivals were normal; however, the fraction of the over-all lambda-L chain metabolism accounted for by proteinuria was increased 40-fold whereas endogenous catabolism was correspondingly decreased. Thus, tubular proteinuria results from a failure of proximal tubular uptake and catabolism of small proteins that are normally filtered through the glomerulus. Patients with the nephrotic syndrome had a slight increase in lambda-L chain survival whereas IgG survival was decreased and the fraction of IgG lost in the urine was markedly increased. Here, abnormal glomerular permeability to proteins of intermediate size is the basic abnormality. Patients with uremia had a normal IgG survival but a four to 10-fold prolongation of lambda-L chain survival due to loss of entire nephrons, the major site of metabolism of these proteins. This results in an increase (up to 10-fold) in the serum concentration of lambda-L chain, lysozyme, and other small biologically active proteins, a phenomenon that may be of importance in causing some of the manifestations of the uremic syndrome.
High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.
Authors: W Siegert, J Beyer, I Strohscheer, H Baurmann, H Oettle, J Zingsem, R Zimmermann, C Bokemeyer, H J Schmoll, D Huhn
Journal: Journal of Clinical Oncology (1994)

PURPOSE This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.
Downstaging of hepatocellular cancer before liver transplant: Long‐term outcome compared to tumors within Milan criteria
Authors: Francis Y. Yao, Neil Mehta, Jennifer Flemming, Jennifer Dodge, Bilal Hameed, Oren Fix, Ryutaro Hirose, Nicholas Fidelman, Robert K. Kerlan, John P. Roberts
Journal: Hepatology (2015)

We report on the long-term intention-to-treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4-5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan-Meier's 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5-year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha-fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04).Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup.
Biomarkers with Predictive and Prognostic Function in Non–Small Cell Lung Cancer: Ready for Prime Time?
Authors: Charu Aggarwal, Neeta Somaiah, George R. Simon
Journal: Journal of the National Comprehensive Cancer Network (2010)

Lung cancer is the leading cause of cancer-related mortality in the United States. Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients with NSCLC present with locoregionally advanced or metastatic disease, for which response rates and median overall survival remain poor. Platinum-based chemotherapy is the mainstay of treatment for NSCLC in both adjuvant and metastatic disease. Personalized chemotherapy and targeted biologic therapy based on a tumor's histologic and molecular profile have already shown promise in optimizing efficacy. Various markers are currently being investigated for their ability to guide treatment decision-making and management. This article describes these predictive and prognostic markers and details their current role, benefit, and potential future use in the management of patients with NSCLC.
Obstructive sleep apnea syndrome in patient with primary open angle glaucoma
Authors: Ege Gulec Balbay, Oner Balbay, Murat Tunc, Harun Yuksel, Ali Nihat Annakkaya, Peri Arbak, Talha Dumlu
Journal: European Respiratory Journal (2011)

Introduction: It was claimed that obstructive sleep apnea syndrome (OSAS) aggravates or causes glaucoma by impaired optic nerve head blood flow or by directly damage to the optic nerve secondary to prolonged hypoxia. The objective of this study was to investigate the prevalence of OSAS in patient with primary open angle glaucoma (POAG).

Material and methods: The consecutive 21 POAG patients (12 female/ 9 male) attending the outpatient clinic of the department of Ophthalmology between July 2007 and February 2008 were included in this study. All of these patients underwent to Polysomnographic examination.

Results: The prevalence of OSAS was 33.3% in glaucoma patients (14.3% mild and 19% moderate). The age and the diameter of the neck in patients with OSAS were significantly greater than those with no OSAS. The adipose tissue thickness in triceps reached near significance in glaucomatous OSAS patients. Snoring was observed in all glaucoma cases with OSAS. Particularly, the prevalence of OSAS was significantly more common in glaucoma patients having the symptoms of habitual snoring, witnessed apnea than those of not. The prevalence of OSAS was also significantly increased with having major symptoms together.

Conclusions: Although it was not provided an evidence for a cause-effect relationship in the present study, the high prevalence of OSAS in patients with POAG might put forward a different view of aspect to ophthalmologists. Further studies are required especially in large groups who had CPAP (Continuous positive airway pressure) therapy to explore the long term results of coincidence, relation and cross interaction of these two common disorders.
Identification of patients who are at high risk for locoregional breast cancer recurrence after conservative surgery and radiotherapy: a review article for surgeons, pathologists, and radiation and medical oncologists.
Authors: D H Clarke, A A Martinez
Journal: Journal of Clinical Oncology (1992)

PURPOSE Many retrospective reports have been published identifying risk factors for locoregional (LR) recurrence after breast conservation therapy (BCT). We review these reports, with the purpose of better enabling surgeons, pathologists, radiation oncologists, and medical oncologists to develop strategies for an individualized treatment approach. DESIGN AND RESULTS English-language retrospective and prospective randomized studies published in the 1980s were reviewed. Histopathologic predictors, young age, extent of conservative surgery (CS), lobular carcinoma, and the impact of adjuvant chemotherapy are all examined as reported risk factors for LR. CONCLUSIONS Recognition of these factors provides rationale for individualizing the extent of CS based on histopathologic features. In addition, the aggressiveness of radiotherapy (RT) should be dictated by the extent of CS and by identifiable prognostic factors. Strategies are presented for an individualized treatment approach based on a clear understanding of the prognostic factors for LR.
Early Prediction of Disease Progression in Small Cell Lung Cancer: Toward Model-Based Personalized Medicine in Oncology
Authors: Núria Buil-Bruna, Tarjinder Sahota, José-María López-Picazo, Marta Moreno-Jiménez, Salvador Martín-Algarra, Benjamin Ribba, Iñaki F. Trocóniz
Journal: Cancer Research (2015)

Predictive biomarkers can play a key role in individualized disease monitoring. Unfortunately, the use of biomarkers in clinical settings has thus far been limited. We have previously shown that mechanism-based pharmacokinetic/pharmacodynamic modeling enables integration of nonvalidated biomarker data to provide predictive model-based biomarkers for response classification. The biomarker model we developed incorporates an underlying latent variable (disease) representing (unobserved) tumor size dynamics, which is assumed to drive biomarker production and to be influenced by exposure to treatment. Here, we show that by integrating CT scan data, the population model can be expanded to include patient outcome. Moreover, we show that in conjunction with routine medical monitoring data, the population model can support accurate individual predictions of outcome. Our combined model predicts that a change in disease of 29.2% (relative standard error 20%) between two consecutive CT scans (i.e., 6-8 weeks) gives a probability of disease progression of 50%. We apply this framework to an external dataset containing biomarker data from 22 small cell lung cancer patients (four patients progressing during follow-up). Using only data up until the end of treatment (a total of 137 lactate dehydrogenase and 77 neuron-specific enolase observations), the statistical framework prospectively identified 75% of the individuals as having a predictable outcome in follow-up visits. This included two of the four patients who eventually progressed. In all identified individuals, the model-predicted outcomes matched the observed outcomes. This framework allows at risk patients to be identified early and therapeutic intervention/monitoring to be adjusted individually, which may improve overall patient survival.
Bronchiectasis in the children
Authors: Sevgi Pekcan, Tugba Yilmaz, Meltem Energin
Journal: European Respiratory Journal (2013)

AIM:  The aim of this retrospective study was to define the general characteristics, underlying causative factors and treatment of bronchiectasis patients.   METHODS:  The study was performed in Medical Faculty of Meram. One hundred consecutive children, diagnosed with bronchiectasis were included in the study. General characteristics and underlying causes were recorded from the medical records.   RESULTS:  Males made up 58%, females 42% of the patients. Mean age of the patients was 9.81 ±4.40 years at diagnosis, patients had been followed 2.13±1.18 years on average. In 46%, parents of the patients were relatives. At least one other family member had been diagnosed with similar disease in 17% of the patients. Chronic cough was the most common symptom. In 71% of the patients, an underlying etiology was identified, postinfectious bronchiectasis was the most common (23%), followed by immundeficiencies (22%), primary ciliary dyskinesia (13%). The percentages of affected lobes were as follows: left lower lobe, 62%, right lower, 40%; middle, 39%; lingula, 33%; right upper, 20%; and left upper, 20%. 18% of the patients required surgery. The surgical intervention was unilateral lobectomy in 11, bilateral lobectomy in 5 and left pnomonectomy in 2 of the patients. There was no improvement in weight and height percentiles.   CONCLUSION:  Infections account for the majority of cases of bronchiectasis seen in our study. Otosomal resesif diseases as immunodeficiency and primary ciliary dyskinesia followed infections. Chronic productive purulent respiratory secretions and persistent crackles should raise the possibility of bronchiectasis in children and these symptoms should recognize bronhiectasis to pediatricans.
Appropriateness of endoscopic surveillance recommendations in organised colorectal cancer screening programmes based on the faecal immunochemical test
Authors: Manuel Zorzi, Carlo Senore, Anna Turrin, Paola Mantellini, Carmen Beatriz Visioli, Carlo Naldoni, Priscilla Sassoli de’ Bianchi, Chiara Fedato, Emanuela Anghinoni, Marco Zappa, Cesare Hassan
Journal: Gut (2015)

To assess the appropriateness of recommendations for endoscopic surveillance in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT).74 Italian CRC screening programmes provided aggregated data on the recommendations given after FIT-positive colonoscopies in 2011 and 2013. Index colonoscopies were divided into negative/no adenoma and low- risk, intermediate-risk and high-risk adenomas. Postcolonoscopy recommendations included a return to screening (FIT after 2 years or 5 years), an endoscopic surveillance after 6 months or after 1 year, 3 years or 5 years, surgery or other. We assessed the deviation from the postcolonoscopy recommendations of the European Guidelines in 2011 and 2013 and the correlation between overuse of endoscopic surveillance in 2011 and the process indicators associated with the endoscopic workload in 2013.49 704 postcolonoscopy recommendations were analysed. High-risk, intermediate-risk and low-risk adenomas, and no adenomas were reported in 5.9%, 19.3%, 15.3% and 51.5% of the cases, respectively. Endoscopic surveillance was inappropriately recommended in 67.4% and 7%, respectively, of cases with low-risk and no adenoma. Overall, 37% of all endoscopic surveillance recommendations were inappropriate (6696/17 860). Overuse of endoscopic surveillance was positively correlated with the extension of invitations (correlation coefficient (cc) 0.29; p value 0.03) and with compliance with post-FIT+ colonoscopy (cc 0.25; p value 0.05), while it was negatively correlated with total colonoscopy waiting times longer than 60 days (cc -0.26; p value 0.05).In organised screening programmes, a high rate of inappropriate recommendations for patients with low risk or no adenomas occurs, affecting the demand for endoscopic surveillance by a third.
CREWS - A validation pilot
Authors: Phyllis Murphie, Margaret Gall, Helen Coles, Jane Gysin, Stuart Little, Paul Rafferty
Journal: European Respiratory Journal (2012)

A previous pilot of a Community Respiratory Early Warning System (CREWS) measuring signs/symptoms with telehealth support to assess its impact on self management skills, early recognition of deterioration and subsequent health care utilisation were positive. A further validation study in 20 patients with severe COPD has now been conducted.  2 withdrew consent and 5 died due to the severity of COPD during the evaluation. 13 were invited to complete an evaluation that consisted of a visual analogue scale of their experience of using the CREWS with 1 being not useful and 5 being very useful. 3 were no longer using the CREWS although reported benefit initially in terms of recognising deteriorating health and made contact with the respiratory service. Results from the remaining 10 are reported.  100% of respondents reported the CREWS as useful /very useful. On ease of use 70% reported it very easy, 20% fairly easy and 10% easy to use the tool. 90% of respondents are still using the tool.  Conclusion: These responses validate the use of CREWS. It has the potential to assist in early recognition of exacerbations, improve self management skills and thus reduce hospital admission rates and will be tested in a larger population.