tbuckley/cabot-search huggingface dataset:
Intragraft Blood Dendritic Cell Antigen-1–Positive Myeloid Dendritic Cells Increase during BK Polyomavirus–Associated Nephropathy
Authors: Ünsal Yapici, Jesper Kers, Ivana Slavujevic-Letic, Geurt Stokman, Joris J.T.H. Roelofs, Michiel C. van Aalderen, Jaap W. Groothoff, Onno J. de Boer, Karlijn A.M.I. van der Pant, Nike Claessen, Luuk B. Hilbrands, Frederike J. Bemelman, Ineke J.M. ten Berge, Sandrine Florquin
Journal: Journal of the American Society of Nephrology (2015)

Although both polyomavirus infection and T cell–mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions are treated with opposing therapeutic regimens. To gain more insight into the differences between antiviral and alloimmune responses, we performed a case-control study, in which we immunophenotyped the inflammatory infiltrates in renal biopsy specimens with BK polyomavirus–associated nephropathy (BKPyVAN) and specimens with TCMR. Compared with TCMR, BKPyVAN was diagnosed later after transplantation; therefore, BKPyVAN specimens showed more chronic damage than TCMR specimens showed. However, TCMR and BKPyVAN specimens had comparable levels of tubulointerstitial inflammation. Adjustment for confounders in various multivariable models revealed more blood dendritic cell antigen-1 + (BDCA-1 + ) myeloid dendritic cells (mDCs) present during BKPyVAN (odds ratio, 2.31; 95% confidence interval, 1.03 to 5.16; P =0.04) than during TCMR. Double immunostaining for SV40 and BDCA-1 showed that, during BKPyVAN, BDCA-1 + mDCs localized in proximity to the polyomavirus–infected tubular epithelial cells. We ensured that time of biopsy after transplantation was not a confounding factor by including additional specimens with late TCMR and protocol biopsy specimens matched for biopsy time. These additional specimens showed amounts of BDCA-1 + mDCs comparable with amounts in the early TCMR specimens. These results suggest that BDCA-1 + mDCs, known to be involved in the antiviral immune response during various viral infections, might have a pivotal role during BKPyVAN infection in the grafted kidney.
Bevacizumab plus FOLFOX7 as first line treatment in patients with advanced colorectal cancer
Authors: M. Oukkal, F. Kara, S. Difi, D. Bouzidi, K. Bentabak, A. Graba, N. Smail, N. Ait Kaci, R. Baba Ahmed, K. Bouzid
Journal: Journal of Clinical Oncology (2009)

e15092 Background: Bevacizumab a monoclonal antibody against vascular endothelial growth factor (VEGF) has shown in combination with chemotherapy a significant survival improvement in pts with advanced colorectal cancer (F. Kabbinavar JCO 2005 and H. Hurwitz NEJM 2004). In this study we investigated the safety and the efficacy of the addition of bevacizumab to FOLFOX7 regimen in pts with metastatic colorectal cancer. Methods: Inclusion criteria: Histological proven colorectal carcinoma, measurable disease at time of inclusion, no prior chemotherapy (adjuvant chemotherapy allowed), no CNS metastasis, no peripheral neuropathy, no other serious concomitant illness, ECOG PS ≤ 2, Urine dipstick of proteinuria &lt;2+, adequate renal and liver function, good bone marrow reserve and informed consent. Pts received bimonthly Oxaliplatin 130 mg/m 2 D1, Folinic acid 400 mg/m 2 D1, Fluorouracil 2400 mg/m 2 46 hours continuous infusion and Bevacizumab 5mg/kg D3 Results: From April 2005 to June 2007, 47 pts (M/F = 28/19, colon/rectum = 28/19) were enrolled in the study. Median age is 52,7 years old (32–74). They received 452 cycles, median=7 range (1–18). All pts were evaluable for toxicity and survival and 46 for responses. Complete response (CR) was achieved in 3 pts (6.6%), partial response (PR) in 28 pts (60.8%), stable disease in 4 pts (8.7%) and progressive disease in 11 pts (24%). The overall response rate (ORR=CR+PR) is 67.3%. Severe toxicity (CTC/NCI ¾ Grade) related to chemotherapy was neuropathy 5.3%, neutropenia 8.4%, anaemia 3.3%, thrombocytopenia 1.8%, vomiting 8.2%, diarrhoea 2.9%, stomatis 4.9% and allergy 0.7%. Toxicity related to Bevacizumab was bleeding CTCNCI grade 1 and 2 in 40.8%, hypertension grade 1 qnd 2 in 3.7% qnd grqde 3 in 0.2. proteinuria grade and 2 in 13.7%. 1 case of phlebitis and 1 case of Bevacizumab allergy Conclusions: Bevacizumab and FOLFOX7 combination is a promising treatment with high efficacy and safety profile for pts with advanced colorectal cancer No significant financial relationships to disclose.
Effect of late preterm birth on longitudinal lung spirometry in children
Authors: Sarah J. Kotecha, W. John Watkins, David Herrick, Shantini Paranjothy, Frank D. Dunstan, A. John Henderson, Sailesh Kotecha
Journal: European Respiratory Journal (2011)

Introduction:  Rates of preterm birth have increased in most industrialised countries (Goldenburgh, R.L. et al. Lancet 2008; 371:75-84) but data on later lung function of late preterm birth is limited.   Aims and objectives:  To compare lung function at 8-9 and 14-17 years in a population-based cohort of children born at 25-32, 33-34 and 35-36 weeks gestation with similar aged children born at term (≥37 weeks gestation).   Methods:  From the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 14062), children who had spirometry at 8-9 (n=6712) and/or 14-17 (n=4513) years of age were divided into 4 groups: 25-32, 33-34, 35-36 and ≥37 weeks (term control) of gestation.   Results:  At 8-9 years of age, all spirometry measures (except FVC, in the 25-32 weeks gestation group) were significantly lower in both 25-32 and 33-34 weeks gestation groups compared to term controls (FEV 1 , mean z-score ± SD -0.461±0.876, -0.498±1.09 and 0.011±1.00 respectively). The 35-36 weeks gestation (FEV 1  0.008±0.908) and term groups had similar values. At 14-17 years of age, most spirometry measures in the 25-32 and 33-34 week gestation groups were not different from term controls except lower FEF 25-75  and FEF 25-75 /FVC in both 25-32 and 33-34 weeks gestation groups and lower FEV 1 /FVC in the latter group.   Conclusions:  Children born at 33-34 weeks gestation have significantly lower lung function values at 8-9 years of age similar to decrements observed in the 25-32 weeks group although most of these differences were reduced by 14-17 years of age.
Reliability and validity for the Vanderbilt Head and Neck Symptom Survey (VHNSS): A new tool to assess symptom burden in patients undergoing chemoradiation
Authors: B. A. Murphy, N. L. Wells, A. J. Cmelak, J. L. Netterville, B. B. Burkey, K. Z. Smith
Journal: Journal of Clinical Oncology (2004)

5569 Background: Head and neck cancer patients experience significant symptom burden related to tumor and its treatment. We undertook the development and validation of a tool designed to assess physical symptom burden in patients receiving chemoradiation. We report the initial results of testing for reliability and validity of this 27 item fixed format tool which uses a 0 to 10 numeric rating scale response format. Tool development has been reported previously. Methods: The VHNSS was administered to 186 patients enrolled on three trials: (1) 51 patients on a diet adaptation study, (2) 100 patients on a health care utilization study, and (3) 35 undergoing modified barium swallow. Results: The internal consistency was good for the total scale (.94) and the 12 item swallow subscale (.91). 86 patients completed the EORTC HN-35 and the PSS-HN. Overall the patterns suggest convergence between the appropriate EORTC subscales and the VHNSS total scale and swallow subscale. For example - EORTC swallow: total VHNSS (r = .76) and swallow subscale (r = .84). Convergence is also noted for the PSS-HN eat and diet items for the total and the swallow subscale. Differences in total and swallow scores were in the expected direction for the use of PEG tubes and the use of health care resources (p < .05). Construct validity of the swallow subscale was supported by correlation with an objective measure of swallow function. Conclusion: Preliminary results demonstrate reliability and construct validity for the newly developed VHNSS. Further testing is ongoing. No significant financial relationships to disclose.
Cisplatin (CDDP) plus oral vinorelbine (NVBO) as first-line treatment for advanced non-small cell lung cancer (NSCLC): Prospective analysis to improve the patient's convenience on day 8 NVBO administration
Authors: A. Sanchez, M. Provencio, A. Artal, M. Constenla, R. Garcia-Gomez, N. Viñolas, M. Domine, F. J. Perez, J. Gayo
Journal: Journal of Clinical Oncology (2009)

e19096 Background: Severe neutropenia observed during chemotherapy (CT) is a clinical finding leading to treatment modification and, sometimes, life-threatening events. The results of a previous study with 180 p treated with IV vinorelbine plus CDDP as first-line treatment for advanced NSCLC could lead to consider not performing a blood count prior to day 8 vinorelbine administration for patients aged 70 years (y) or less who presented a good haematological tolerability profile during previous cycles (cy) in order to improve treatment convenience. The aim of this study is to prospectively validate these results with the combination of NVBO plus CDDP. Methods: Between October 2007 and September 2008, 31 chemo-naïve p with histologically confirmed stage IIIB/IV NSCLC were included. Treatment consisted of CDDP 75 mg/m 2 day 1 plus NVBO 80 mg/m 2 days 1 and 8, with a prior test of myelosensitivity at 60 mg/m 2 for the first cycle, every 21 days. Patient's characteristics were: Median age, 62 years (range 32–73); males, 93.5%; smokers, 38.7%; all PS 0–1; adenocarcinoma, 33.3% / squamous, 36.7%; stage IIIB, 14.8% / IV, 85.2%. Results: We analyzed 129 cy. NVBO administration on day 8 was cancelled in 3 cycles due to haematological events (2.3% [95% CI: 0.4%-6.6%]. The reported events were: 1 grade-2 neutropenia, 1 grade-4 neutropenia and 1 grade- 2 thrombocytopenia. Among 22 p evaluable for response, 10 p achieved partial response (overall response rate, 45.5% [95% CI: 24.4- 67.8]). Toxicity was mild with neutropenia WHO grade 3–4 observed in 2.1% cy (9.7% p), leukopenia grade 3 in 1.4% cy (6.5% p); 1 case of febrile neutropenia was reported. Grade-3 fatigue was observed in 6 cy (6 p), grade-3 nausea in 2 cy (2 p) and grade-3 vomiting in 2 cy (2 p). Conclusions: The findings of this study could lead to consider not performing a blood count prior to day 8 NVBO administration for patients aged 70 y or less who presented a good haematological tolerability profile during previous cycles in first-line treatment for advanced NSCLC. [Table: see text]
Leptomeningeal metastases: Results of different therapeutic approaches
Authors: M. de Wit, V. Lange-Brock, A. Kruell, C. Bokemeyer
Journal: Journal of Clinical Oncology (2007)

2047 Background: The aim of this study was to compare different treatment options for patients with leptomeningeal metastases (LM). Method: In this retrospective single center study all patients (n=135) between 1985 and 2005 diagnosed with leptomeningeal metastases (LM) showing malignant cells in the cerebrospinal fluid (CSF) were evaluated. Results: 135 patients, 80 females and 55 males, were treated for LM, 73 patients with solid tumors and 62 patients with hematological malignancies. Of the total 135 patients 28% received combined chemotherapy and intrathecal chemotherapy (ITC), 22% only ITC, 3% received only systemic chemotherapy, 28.5% radiochemotherapy and 1.5% radiotherapy only. 13% patients were treated with supportive therapy only and in 4% therapy could not be evaluated. Median overall survival (OS) was 2.5 months (3 days- 58.2 months). According to univariate analysis age &gt; 50 years and Karnofsky status &lt; 80 were predictors of poor survival. Response to therapy and application of systemic therapy were correlated with longer survival. In this study, time of survival varied considerably depending on the type of primary tumor. Univariate analysis of Kaplan-Meier plots revealed age &gt;50 years and Karnofsky performance status &lt;80 as therapy-independent predictors of poor survival. Positive prognostic factors were response to therapy as measured by malignant cell count in the CSF, and application of systemic chemotherapy alone or in combination with other therapy-modalities in the entire cohort. Difference through systemic therapy was extremely relevant for the two entities NHL (n=37) and breast cancer (BC) (n=35). The median OS was 4.4 months for NHL and 7.0 months for BC following systemic therapy compared to 1.8 months for NHL and 1.4 months for BC without systemic treatment thus demonstrating a significant better OS using systemic therapy. Conclusion: The results suggest that systemic chemotherapy has the main impact on improved survival in patients with LM and chemosensitive disease. Still the prognosis for patients with LM is poor and treatment is aimed at palliation of symptoms and preservation of neurologic function. Future randomized studies of therapies should include quality-of-life assessment and provide additional data on this important outcome. No significant financial relationships to disclose.
Osteonecrosis of the jaw (ONJ) in patients with renal cancer treated with bisphosphonates (BPs) and sunitinib or other targeted therapy (TT) agents: A multicenter survey.
Authors: V. Fusco, C. Porta, C. Paglino, A. Bedogni, G. Bettini, G. Saia, G. Campisi, M. Scoletta, A. Agrillo, A. Fasciolo
Journal: Journal of Clinical Oncology (2011)

e15182 Background: ONJ has been very rarely reported in patients (pts) suffering from bone metastases of renal cell cancer (RCC) treated with BPs, such as pamidronate (P) and zoledronic acid (Z). Recently reports of ONJ cases among cancer pts receiving TT agents (sunitinib, bevacizumab, sorafenib, etc) w/o BPs have been published, including few cases among RCC pts. TT agents have been consequently suspected to be a possible risk factor for ONJ. On December 2010, EMA (European Medicine Agency) issued two safety warnings about ONJ risk after sunitinib or bevacizumab treatment; in the "dear doctor" alert letters, manufacturers reported the following data about ONJ cases registered among patients treated on clinical trials or on post-marketing setting (in all types of cancer): 27 ONJ cases among 101.400 pts after sunitinib and 55 ONJ cases among 800.00 pts after bevacizumab worldwide. Methods: We conducted a limited survey, asking three Medical Oncology units and four referral Oral Medicine and Surgery centres (involved in ONJ tertiary care), in different regions of Italy, to look for ONJ and RCC in their database. Nineteen cases of ONJ in RCC pts have been found. Available details of oncologic and dental history have been collected so far of 16 pts; of further 3 cases data reporting authorization is ongoing. Results: Pts characteristics of 16 evaluated pts: sex: 13/3 M/F; median age 63 years (range 45-72). BP treatment: 13 Z, 1 P, 1 Z+P, 1 Ibandronate. BP treatment duration at the ONJ onset: 12 months (range 1-36). Latest TT treatment at the ONJ diagnosis time: sunitinib (13 cases), sorafenib (1), bevacizumab (1), deforolimus (1). Previous treatments: sorafenib (3), IL2, capecitabine. Site of ONJ: 9 in mandible, 4 in maxilla, 2 in both (1 unspecified). Possible risk factors or precipitating events, such as teeth extraction, oral surgery, dental implants, have been reported on 8/16 cases. Conclusions: Incidence of ONJ in RCC pts is largely underestimated in literature. In selected Italian centers, an unexpected rate of ONJ among RCC pts has been observed. We planned a new survey, enlarged to medical oncology units and oral care centers in all Italian regions.
STAINING TOXOPLASMA GONDII WITH FLUORESCEIN-LABELLED ANTIBODY
Authors: Morris Goldman
Journal: The Journal of Experimental Medicine (1957)

A new serologic test for antibodies to Toxoplasma is described, which is based upon inhibition of specific staining with fluorescent antibody. In performing the test, a mixture of the test serum and known fluorescein-labelled antiserum is added to a dried smear of toxoplasms for 1 hour at 37 degrees C. The smear is then rinsed and examined with a fluorescence microscope. Reduction in the brightness of fluorescence, as compared to that of a negative control slide, indicates the presence of antibody in the test serum. A comparison of the results of this test with those of the methylene blue dye test showed a strong parallelism between the two sets of results. On the other hand, the complement-fixation test for toxoplasmosis did not yield nearly as many positives as the inhibition test. The specificity of the new test was studied by comparing it with dye test results and clinical histories in human patients, and by testing a group of animals immunized with a variety of non-Toxoplasma antigens. No evidence of cross-reactions was obtained in the latter series. Some advantages and disadvantages of the inhibition test are discussed.
Neoadjuvant Radiotherapy Use in Locally Advanced Rectal Cancer at NCCN Member Institutions
Authors: Marsha Reyngold, Joyce Niland, Anna ter Veer, Dana Milne, Tanios Bekaii-Saab, Steven J. Cohen, Lily Lai, Deborah Schrag, John M. Skibber, William Small, Martin Weiser, Neal Wilkinson, Karyn A. Goodman
Journal: Journal of the National Comprehensive Cancer Network (2014)

Based on randomized data, neoadjuvant chemoradiotherapy has been incorporated into the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for stage II-III rectal cancer. Factors associated with nonadherence to evidence-based guidelines for neoadjuvant radiotherapy (RT) were examined at dedicated cancer centers. The prospective NCCN Oncology Outcomes Database for Colorectal Cancers was queried for patients with stage II-III rectal cancer who underwent a transabdominal surgical resection between September 2005 and June 2012. Multivariable logistic regression was used to identify factors associated with omission of RT. Among 1199 identified patients, 1119 (93%) received neoadjuvant RT, 51 (4%) did not receive RT, and 29 (2%) received adjuvant RT. Among 51 patients not receiving RT, only 19 (37%) were referred and evaluated by a radiation oncologist. On multivariable analysis, clinical factors associated with not receiving RT included a history of prior pelvic RT (adjusted odds ratio [aOR], 23.9; P=.0003), ECOG performance status of 2 or greater (aOR, 11.1; P=.01), tumor distance from the anal verge greater than 10 cm (aOR, 5.4; P=.009), age at diagnosis of 75 years or older (aOR, 4.43; P=.002), body mass index of 25 to 30 kg/m(2) and less than 25 kg/m(2) (aOR, 5.22 and 4.23, respectively; P=.03), and clinical stage II (aOR, 2.27; P=.02). No significant change was seen in RT use according to diagnosis year, nor was any correlation seen with distance to the nearest RT facility. Concordance with NCCN Guidelines for neoadjuvant RT is high among NCCN Member Institutions. After adjusting for clinical characteristics that increase the risk for RT toxicity, including history of pelvic RT and high comorbidity burden/low functional status, the authors found that non-obese patients of advanced age or those with more favorable clinical features were more likely to not receive RT.
The role of interstitial cells in the progression of renal diseases.
Authors: G A Müller, J Markovic-Lipkovski, J Frank, H P Rodemann
Journal: Journal of the American Society of Nephrology (1992)

Renal interstitial fibrosis (RIF) is frequently associated with distinct inflammatory and noninflammatory glomerular diseases. RIF is mainly responsible for a decline of excretory renal function and therefore influences the prognosis of several renal diseases. The resident interstitial cells of the kidney, which play a major role in causing RIF, are different renal fibroblasts, which respond to a variety of cytokines released by various cell types. Immunohistochemical analysis of human renal biopsies with different glomerulopathies revealed that CD2+ T lymphocytes are the major cells infiltrating the renal interstitium. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/HLA-DP antigens, often associated with an aberrant expression of the intercellular adhesion molecule 1, was observed on proximal tubular epithelial cells, indicating that these cells may play an important role in local immune responses and probably function as antigen-presenting cells. Furthermore, it has been shown by Northern blot analysis that renal epithelial cells in culture express interleukin 6, platelet-derived growth factor and granulocyte-macrophage colony stimulating factor. Cell cultures established from renal biopsies revealed the presence of the three mitotic fibroblast types (MF I through MF III) and the three postmitotic types (PMF IV through PMF VI). The frequencies of the various progenitor fibroblasts MF I, MF II, and MF III differed significantly in cultures established from kidneys with (FKIF cells) and without RIF (NKF cells). In comparison to NKF cells, FKIF cells are characterized by the expression of a "new" protein, called "FIBROSIN," which seems to be specific for FKIF cells.(ABSTRACT TRUNCATED AT 250 WORDS)
A phase I trial of weekly topotecan and carboplatin in potentially platinum sensitive ovarian and peritoneal carcinoma
Authors: M. Smrekar, R. E. Buller, P. Haba, C. Visser, P. G. Rose
Journal: Journal of Clinical Oncology (2004)

5147 Background: Topotecan is an active second-line agent for ovarian cancer but combinations with carboplatin have been limited by myeolsuppression. Weekly topotecan has been associated with less myelosuppression and moderate activity. We performed a phase I trial of weekly topotecan and carboplatin in potentially platinum sensitive ovarian and peritoneal carcinoma. Methods: Patients with evaluable potentially platinum sensitive ovarian or peritoneal carcinoma with PS 0–2, normal bone marrow, renal and hepatic function were eligible. Patients with a creatinine clearance of <50 cc/min by Jelliffe were excluded. Carboplatin at an AUC of 4 and in subsequent patients at an AUC of 5 with topotecan 2.0 mg/m2 was administered IV on day 1 each over 30 minutes. Topotecan at 2.0 mg/m2 was administered on days 8 and 15 provided the day of therapy ANC was ≥1,500/mcl and platelet count ≥100,000/mcl. Cycles were prescribed every 21 days. Dose escalation of topotecan was planned at 0.5 mg/m2 increments to a maximum of 4 mg/m2/week. Results: Thirteen patients were enrolled with 64 (median 5) every 21 day courses have been administered. With carboplatin at an AUC of 4, dose limiting toxicity was seen with topotecan at the starting dose of 2.0 mg/m2 and further escalation of topotecan was not possible. Since the dose limiting toxicity was neutropenia, the dose of carboplatin was elevated to an AUC of 5. This was tolerated with topotecan on day 1 and 8, but the day 15 dose was held on 43/64 (85%) of treatments due to inadequate neutrophil and/or platelet counts. Weekly topotecan on day 1 and 8 was well tolerated but in all but one patient, when day 15 topotecan was administered delays in subsequent therapy occurred. Responses have been seen in 7 of 10 evaluable patients. Conclusion: Carboplatin at an AUC of 5 in combination with topotecan at a dose of 2.0 mg/m2 on day 1and 8 is tolerable and active in potentially platinum sensitive ovarian or peritoneal carcinoma. A phase II study is planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline