tbuckley/cabot-search huggingface dataset:
A phase II study of docetaxel plus irinotecan (DOCIRI) in chemo-naïve patients with non small cell lung cancer (NSCLC)
Authors: P. Ziotopoulos, V. Chandrinos, N. Samaras, E. Mylonaki, J. Stergiou, E. Zachariadis, X. Tsiafaki, A. Agelidou, N. Ketepozidis, V. Georgoulias
Journal: Journal of Clinical Oncology (2004)

7267 Background: To evaluate the efficacy and tolerance of the docetaxel and irinotecan (DOCIRI) combination in chemo-naïve patients with advanced/metastatic NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC stage IIIB (pleural effusion or supraclavicular lymphadenopathy) and IV, with PS (WHO) 0–2, and measurable disease, were treated with irinotecan (200mg/m2) followed by docetaxel (80mg/m2) on day 1 every 3 weeks and G-CSF (150μg/m2) support (d2-d9). Results: Thirty-nine patients (IIIB n=12; IV n=27) with PS 0 (n=23), 1 (n=15) and 2 (n=1) were enrolled. A total of 173 cycles were administered (median 5cy/pt; range 1–9). Grade 3/4 neutropenia occurred in 4 pts (10%) and febrile neutropenia in 3 (8%). Grade 3/4 diarrhea occurred in 2% of the pts and grade 3/4 myalgias in 6%. Partial response (PR) was achieved (intention-to-treat) in 9 (23%) pts (95% c.i. 9.85–36.30%). Stable (SD) and progressive (PD) disease occurred in 10 (26%) and 20 (52%) pts, respectively. The median time to tumor progression was 3.0 months (range, 1–22.9) and the median survival 10.8 months (range 1.4–22.9). The 1-year survival was 42.3%.Conclusions: The combination DOCIRI is an active and well tolerated front-line chemotherapy regimen for patients with advanced/metastatic NSCLC. No significant financial relationships to disclose.
Abstract 133: Transcription Factor Early Growth Response 1 Promotes T-Type Calcium Channel Cav3.2 in Response to Hypertrophic Stimulation Through Evolutionary Conserved Promoter
Authors: Shao-Chun Hsu, Chien-Chang Chen
Journal: Circulation Research (2012)

Introduction: Although it is known that the Ca v 3.2 T-type calcium channel is predominantly expressed in the embryonic stage and re-expressed in adult hearts during the cardiac hypertrophy. What does regulate the reexpression of Ca v 3.2 in hearts? Hypothesis: Because the mRNA re-expression is mainly through the transcriptional regulation in the promoter or enhancer conserved in different species, we assessed to the hypothesis that the evolutionary conserved promoter (ECP) of Ca v 3.2 carries important binding sites for transcription factors that regulate its re-expression in the hypertrophic hearts. Methods and Results: In this study, the ECP is gotten by aligning Ca v 3.2 genes from different species. By fusing mouse ECP with the reporter gene firefly luciferase, we showed that the ECP drove high luciferase activity in the cells expressing endogenous Ca v 3.2 but not in the one without Ca v 3.2. To further validate ECP in vivo, Ca v 3.2 reporter mice were generated by fusing the Ca v 3.2 promoter with the reporter gene luciferase. ECP confers the reporter expressing as the endogenous Ca v 3.2 in the tissue distribution, development of hearts, and most importantly, the inducibility of hypertrophic stimuli. By injecting reporters driven by different truncated promoters followed with the trans-aortic banding (TAB) surgery, the hypertrophic regulatory elements are identified_ -41 to -81 relative to the transcription start site (TSS) of Ca v 3.2. At the end, we found the early growth response 1 (Egr1) is the important transcription factor to enhance Ca v 3.2 gene expression. Our EMSA data suggested that Egr1 can bind to three regions of the hypertrophic regulatory elements. Conclusion: In conclusion, transcription factor early growth response 1 (Egr1) regulates the reexpression of Ca v 3.2 T-type Calcium Channel in the cardiac hypertrophy.
Docetaxel plus carboplatin with or without levofloxacin prophylaxis in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): The APRONTA trial
Authors: W. Schuette, S. Nagel, L. Fischer von Weikersthal, S. Pabst, C. Schumann, T. Salm, K. Roscher, N. Dickgreber
Journal: Journal of Clinical Oncology (2009)

8047 Background: Elderly pts receiving chemotherapy are more likely to have febrile neutropenia and infection than younger pts. Prophylactic fluoroquinolone during chemotherapy reduces the rate of infection and hospitalization vs placebo. The effect of prophylactic treatment with the fluoroquinolone, levofloxacin, on infection rates and survival during docetaxel plus carboplatin therapy was assessed in elderly pts with advanced NSCLC. Methods: In this randomized, double-blind, placebo-controlled Phase III study, eligible pts were aged ≥65 years with previously untreated, histologically/cytologically proven stage IIIB/IV NSCLC, and normal cardiac, renal, hepatic, and hematologic function. Active infection or antibiotics 72 hours before inclusion was not permitted. A planned sample size of 192 pts was considered sufficient for analysis. Pts were randomized to docetaxel (75 mg/m 2 IV, Day 1) plus carboplatin (AUC 6 IV, Day 1) q3w, plus placebo or levofloxacin (500 mg po, once daily) on Days 5–11. Primary endpoint was grade 3/4 infection rate or systemic antibiotic therapy of grade 1/2 infection rate. Secondary endpoints were progression free-survival and overall survival. Between-group comparisons were performed using Fisher's exact test. Results: 192 pts (median age 70 years; ECOG PS 0/1/2 in 36%/55%/9%) were randomized to docetaxel plus carboplatin and levofloxacin (n=99) or placebo (n=93); 5 pts received no treatment and were excluded from the ITT population. Rate of grade 3/4 infection was 27.5% (95% CI: 19.3–39.0%) with levofloxacin vs 36.7% (95% CI: 27.1–48.0%) with placebo. Median progression-free survival (PFS) for patients in the levofloxacin arm was 165 days compared with 121 days in the placebo arm (p=0.22). Median overall survival was comparable between groups (307 vs 314 days, respectively; p=0.28). Conclusions: Levofloxacin prophylaxis reduces the rate of grade 3/4 infection compared with placebo. [Table: see text]
BAL markers of alveolar/capillary abnormality in IPF
Authors: Ermanno Puxeddu, Alessia Comandini, Paola Rogliani, Assunta Porretta, Francesco Cavalli, Cesare Saltini
Journal: European Respiratory Journal (2012)

Several lines of evidence suggest that alveolar-capillary abnormalities, including increased alveolar septal capillary density and pulmonary veno-occlusive disease,are characterizing feature of IPF and may play a role in its progression.This study assess altered capillary permeability,abnormal intra-alveolar coagulation and alveolar hemorrhage as markers of alveolar/capillary abnormality.  Methods: Bronchoalveolar lavage (BAL) samples from 62 subjects (53 IPF patients and 14 healthy volunteers) were evaluated for α2-macroglobulin (α2-M) and fibrinogen D-dimer (D-d) concentration by ELISA.D-d levels were comparatively assessed in blood as well.The numbers of haemosiderin laden macrophages were measured by Perls9 stain and the intensity thereof assessed by the Golde score.  Results: IPF patients had markedly increased α2-M levels (mean 10000 vs 50 ng/ml, p 59) the D-d concentration (125 vs 17 p  Conclusions: leak of α2-M,intra-alveolar hemorrage and coagulation,indicate that alveolar-capillary abnormalities are important in the pathogenesis and progression of pulmonary fibrosis, and likely pulmonary hypertension in IPF.
Pemetrexed (A)/platinum for patients with advanced malignant peritoneal mesothelioma (AbM)—The Bielefeld experience
Authors: M. Karthaus, F. Frieler, N. Vasquez, K. Grader, N. Pfeil, A. Plahl, K. Tagizadeh, M. Trapp, D. Metzner
Journal: Journal of Clinical Oncology (2006)

4151 Background: AbM is a very rare and aggressive neoplasm of the peritoneum. Treatment data of AbM are commonly case reports. A is approved for pleural mesothelioma (MPM) with rare data however regarding AbM. Methods: We evaluated efficacy and safety data of A (500 mg/m 2 ) +DDP (75 mg/m 2 ) or carboplatin (AUC 5) in AbM prospectively. Ctx was given d1 and repeated on d22 for 6 cycles or disease progression. Folic acid 400 μg po/d and vitamin B12 1000 μg i.m. qw 9 wks was administered to prevent AE . Study endpoints were best response (CR/PR), time to progression (TTP), survival and safety. Results: 89 consecutive mesothelioma pts were observed from 12/2002 until 12/2005 in a German single center institution. Four pts (1 AbM, 1 MPM, 2 MPM+AbM) were excluded due to renal impairment (n = 1) or death prior to Ctx (n = 3). AbM was diagnosed in 22 pts (16 epitholoid, 1 sarcomatoid, 5 other), while 5 additional pts had mesothelioma on both sites of the diaphragma. Efficacy data are available in 19 pts with AbM and 5 pts with AbM + MPM. Initial combination was with DDP in 21 pts treated with AbM. DDP was given in 3 and carboplatin combination in 2 pts with MPM + AbM. A was administered a median of 6 cycles in AbM (range 1–33). Toxicity (WHO &gt; III/IV) was nausea (n = 4) and neutropenia (n = 4). Up to 12/05 death has been reported in 8 out of 22 pts with AbM, and in 3 of 5 pts with AbM + MPM. Mean survival was 13,65 months (range 1 to 35+ months) in AbM. Benefit for AbM was 77% with objective RR in 36%. Mean TTP was 11,54 months (range 0 to 35+) in AbM vs 15,4 months with MPM + AbM with a mean survival of 13,65 months (range 0 to 35+) and 22,3 months (range 0 to 35+) in the latter group. Conclusions: Pemetrexed with platinum is well tolerated and has substantial activity for malignant peritoneal mesothelioma. Further trials are warranted to prove this hopeful concept of pemetrexed based therapy for advanced AbM. [Table: see text] No significant financial relationships to disclose.
Recurrent Richter’s Transformation Presenting With a Penile Ulcer
Authors: Tarek Yamany, Bobby Y. Reddy, Sameera Husain, Marc E. Grossman
Journal: JAMA Dermatology (2016)

melanocytic nevus in a patients with EBS, malignant potential of EB nevi has been reevaluated, and active surveillance of EB nevi in patients with EBS is warranted. 1 Examination of melanocytic nevi is recommended every 6 months, along with biopsy and histopathologic examination of any suspicious changes. 2 Given EB nevi's striking baseline resemblance of melanoma, clinical evaluation is challenging.As EB nevi tend to be large, have a rapid, continuous growth phase, and occasionally regress over time, regular histopathologic evaluation of the nevi seems impractical, especially in pediatric patients who may not tolerate large, frequent biopsies. 3,4 Even the histopathologic evaluation of EB nevi continues to be a challenge for the clinician, as blistering conditions can lead to pseudomelanomatous features that simulate melanomas. 1,3 With the use of melanoma gene expression markers, smaller biopsy samples can differentiate malignant transformations from benign lesions with high sensitivity and specificity. 5 Employing such gene expression markers can be especially helpful in cases of atypia seen on histopathologic examination because the markers can aid in distinguishing pseudomelanomatous changes from true malignant transformations.With the use of melanoma markers in combination with traditional histopathologic analysis, clinicians may also identify subtler changes of a malignant transformation earlier, ultimately leading to decreased morbidity and mortality of patients.
The detection of bone marrow involvement by lymphoma using magnetic resonance imaging.
Authors: A F Shields, B A Porter, S Churchley, D O Olson, F R Appelbaum, E D Thomas
Journal: Journal of Clinical Oncology (1987)

We used magnetic resonance (MR) to image the bone marrow of 31 patients with lymphoma. Images were obtained of the femoral, pelvic, and vertebral marrow with a 0.15 tesla imaging system using a T1-weighted spin echo sequence (TR600/TE 40). With this pulse sequence, normal marrow produces a high intensity signal that reflects the presence of marrow fat (short T1 relaxation time). We previously reported MR imaging of patients with leukemia in relapse and found a diffusely and symmetrically decreased marrow signal intensity due to the replacement of normal marrow fat by cellular material with a long T1. Unlike leukemia, patients with lymphomatous marrow involvement often had patchy, often discrete, areas of low signal intensity, representing focal marrow infiltration. Five of six patients in this study with lymphoma detected by histologic examination also had marrow lesions seen on MR. An additional four patients had marrow lesions detected by MR that were not detected on initial marrow biopsies; two of these had marrow involvement proven on subsequent biopsies, one had disease isolated to the vertebrae that was never pathologically documented, and one had progression of disease in the marrow documented by MR without biopsy confirmation. These results indicate that marrow involvement with lymphoma can be detected by MR imaging and that MR can complement bone marrow biopsy.
Protein identification of two allergens of boletus edulis causing occupational asthma
Authors: Daniel Alvarez-Simon, Maria-Jesus Cruz, Carlos Castillo, Beatriz Lara, Xavier Munoz
Journal: European Respiratory Journal (2013)

BACKGROUND:  Boletus edulis , a highly valued edible mushroom, has been implicated in occupational asthma. While  Boletus edulis  allergens have occasionally been characterized using immunoblotting, to our knowledge their proteins have not been identified to date. The aim of this present study was to further identify these allergens using a proteomics approach.   METHODS:  A crude extract of  Boletus edulis  proteins was separated by SDS-PAGE and immunoblotting was then performed with the use of a serum from a patient with occupational asthma to  Boletus edulis  confirmed by a positive specific inhalation challenge. Protein identification was performed with DeNovo sequencing using PEAKS Studio 5.3 software (Bioinformatics Solutions Inc.). Briefly, the  Boletus edulis  protein bands separated by one-dimensional SDS-PAGE were excised from the gel and digested with trypsin according to standard protocols. The tryptic peptides were analyzed with a maXis UHR-Qq-TOF mass spectrometer (Bruker Daltonics, Bremen, Germany) and subsequently sequenced using both the DeNovo and the Spider Homology Search tools from the PEAKS Studio 5.3 software.   RESULTS:  Immunoblotting performed with the  Boletus edulis  powder extract showed two IgE-binding bands at approximately 17 and 55 kDa. The mass spectrometry identified a 16 kDa band as a fungal fruit body lectin and a 46 kDa band as a protein of the glycoside hydrolase family.   CONCLUSIONS:  Although few cases of OA due to inhalation of  Boletus edulis  have been described to date, its prevalence may well be increasing due to its wide use in the food industry. The sequencing of the proteins responsible may be a first step forward in the design of future therapeutic strategies.
Pay in the NHS: who earns what?
Authors: John Appleby
Journal: BMJ (2015)

Prominent leukoaraiosis is common in the clinical routine setting. In addition to microatheroma and hypertensive small vessel disease (lipohyalinosis), a large number of rare but clinically relevant differential diagnoses have to be considered. A man in his 60s presented with left pontine infarction and subsequent rapidly deteriorating leukoaraiosis associated with dementia. Standard non-invasive examination did not enable the correct diagnosis to be obtained. A brain biopsy sample revealed a combination of diffuse infiltrating and intravascular large B cell central nervous system (CNS) lymphoma, which has not previously been described in literature. Despite immediate treatment with state of the art chemotherapy, the patient died 3 months after the onset of symptoms. Diffuse infiltrating and intravascular primary CNS lymphoma is a rare cause of rapidly progressive leukoencephalopathy and stroke mediated by neoplastic microvessel occlusion and inflammatory tissue damage. This report intends to increase awareness among neurologists and other stroke physicians about this disease in order to accelerate diagnosis and initiation of treatment.
Q fever outbreak in Cheltenham, United Kingdom, in 2007 and the use of dispersion modelling to investigate the possibility of airborne spread
Authors: A Wallensten, P Moore, H Webster, C Johnson, G van der Burgt, G Pritchard, J Ellis-Iversen, I Oliver
Journal: Eurosurveillance (2010)

We describe the investigation of an outbreak of Q fever in the town of Cheltenham, England. The outbreak was detected in June 2007, and prospective and retrospective case finding identified 30 confirmed or probable human cases. The investigation identified windborne spread of Coxiella burnetii from nearby sheep farms as the most likely source of infection. A telephone survey was conducted to identify risk practices at local farms. Subsequently the atmospheric dispersion model NAME was used to identify whether air from the identified farms with high risk practices had been carried into Cheltenham town centre during the risk period. Three high risk farms were identified and the modelling showed that air from all of these farms was carried over Cheltenham in the estimated risk period. The investigation resulted in an information campaign to farmers and production of improved advice for livestock farmers on reducing the risks of transmitting Q fever to humans.
Assessment of uterus, bone, serum lipids, and hormones in postmenopausal breast cancer patients treated with TAS-108, a novel steroidal antiestrogen: Results of a randomized phase II study
Authors: T. Nakayama, H. Inaji, H. Iwata, N. Yamamoto, Y. Sato, Y. Tokuda, K. Aogi, S. Saji, T. Ikeda, S. Noguchi
Journal: Journal of Clinical Oncology (2009)

1120 Background: TAS-108, a novel steroidal antiestrogen, has demonstrated a favorable safety profile, including lower agonistic activity on uterus than tamoxifen and supportive effect on bone in preclinical studies. The potential tissue-specific effect of TAS-108 was investigated in postmenopausal breast cancer patients included in a randomized phase II study. (The clinical efficacy and safety results were presented at the 31 st San Antonio Breast Cancer Symposium). Methods: Postmenopausal women aged 20–80 years with hormone receptor-positive metastatic breast cancer were eligible for this study and treated with oral TAS-108 (40, 80, or 120 mg/day) once a day. Endometrial thickness (ET) was measured by ultrasonography. The change in Bone Mineral Density (BMD) at lumber spine was assessed by dual energy X-ray absorptiometry. Hormone levels, bone metabolism markers, and serum lipid parameters were also measured at regular intervals. Wilcoxon signed-rank test was used to assess the significance of changes or percentage changes from baseline. Results: Ninety one patients with a median age of 62 years (range 44–80) were included in the analysis population. TAS-108 did not cause significant endometrial thickening (median baseline ET 3.3 mm, last point ET 3.6 mm; n = 36). In particular, after at least 1 year of treatment in 13 cases, no clinically significant increase in ET was found. No change was observed in median BMD (+0.74%; n = 20). Serum carboxy-terminal telopeptide of type I collagen (I CTP) levels remained unchanged although the decrease in osteocalcin levels was significant (p = 0.019; n = 49) in patients without bone metastasis. Median triglyceride levels significantly decreased from 104.0 to 85.0 mg/dl (p = 0.000) after 4 weeks of treatment, while there were no changes in other lipid parameters. An increase in sex hormone-binding globulin and testosterone levels were observed. Conclusions: TAS-108 may have no harmful effects within these parameters and could be used safely. However, further study in a greater number of cases is needed to identify the effect of the long-term use of TAS-108 on the uterus and bone. [Table: see text]
First-line chemotherapy with planned sequential administration of gemcitabine (G) followed by docetaxel (D) in elderly advanced non-small-cell lung cancer (NSCLC) patients: A multicenter phase II study
Authors: E. Vasile, C. Tibaldi, A. Antonuzzo, R. Di Marsico, G. Tartarelli, A. Fabbri, M. Lo Dico, E. Mazzoni, M. Andreuccetti, A. Falcone
Journal: Journal of Clinical Oncology (2008)

19092 Background: Single-agent chemotherapy (G or vinorelbine) is currently a standard treatment for elderly advanced NSCLC patients. The combination of G+D was active but not well tolerated in this subset (Hainsworth et al, Clin Lung Cancer 2003). Modified schedule of D (37.5 mg/m2 on day 1 and 8 every 3 weeks) was active and well tolerated in pre-treated elderly advanced NSCLC patients (Tibaldi et al, Clin Lung Cancer, 2006). Aim of this study was to evaluate the activity and the toxicity of a sequential regimen of G followed by D in elderly advanced NSCLC patients. Methods: Chemo-naïve elderly patients (> 70 years old) with histologically or cytologically confirmed stage IIIB (positive pleural effusion or metastatic supraclavear lymph nodes) or IV NSCLC and a performance status (PS) 0–2 were treated with G 1200 mg/m2 on Day 1 and 8 every 3 weeks for 3 cycles followed by, in case of non-progressive disease, D 37.5 mg/m2 on Day 1 and 8 every 3 weeks for further 3 cycles. Results: Fifty-six patients were enrolled into the study: 46 male and 10 women; 7 PS 0, 38 PS1, 11 PS2; median age was 76 years (range 70–84). The median number of major comorbidities was 2. Toxicity was mild; afebrile grade 3 neutropenia was observed in 3 patients (5.4%) and grade 3 thrombocytopenia in 2 patients (3.6%); non-haematological grade 3–4 toxicities were: fatigue in 5 patients (8.9%), and diarrhoea and mucositis in 2 patients each (3.6%). According to intention-to-treat analysis, the objective response rate was 16.0% (95% C.I. 7.6%-28.3%); 23 patients (41.0%) had stable disease and 24 patients (43%) had progressive disease. Five patients who had a stable disease after three courses of G obtained a conversion to partial response by D. Median time to progression was 4.8 months (95% C.I 3.6–6.0 months) and median duration of survival was 8.0 months (95% C.I 5.6–10.5 months). The 1-year survival rate was 34%. Conclusion: Sequential chemotherapy with G and D seems a well-tolerated and effective regimen in elderly advanced NSCLC patients. No significant financial relationships to disclose.
Oral mucosal adverse events with chlorhexidine 2 % mouthwash in ICU
Authors: Nienke L. Plantinga, Bastiaan H. J. Wittekamp, Kris Leleu, Pieter Depuydt, Anne-Marie Van den Abeele, Christian Brun-Buisson, Marc J. M. Bonten
Journal: Intensive Care Medicine (2016)
Assessing the progression of renal disease in clinical studies
Authors: A S Levey, J J Gassman, P M Hall, W G Walker
Journal: Journal of the American Society of Nephrology (1991)

Many clinical studies of the effects of low-protein and low-phosphorus diets on the course of chronic renal disease have used the rate of decline in renal function to assess the rate of progression. In this report, data from the feasibility phase of the Modification of Diet in Renal Disease Study were used to analyze methods used in other studies. The focus is particularly on the effects of duration of follow-up and of regression to the mean. The findings are summarized as follows. (1) During the mean follow-up period of 14.1 months, rates of decline in glomerular filtration rate, creatinine clearance, and the reciprocal of the serum creatinine concentration were highly variable among individuals, and mean rates of decline were slow. (2) Precision of estimates of individual rates of decline in renal function were relatively low and improved with increasing duration of follow-up. (3) Correlations between rates of decline in creatinine clearance and the reciprocal of the serum creatinine concentration with glomerular filtration rate in individuals were significant but weak and became stronger with increasing duration of follow-up. (4) After entry into the study, mean rate of decline in the reciprocal of the serum creatinine concentration became less negative. The change predicted simply from regression to the mean was 68.4% of the observed change.(ABSTRACT TRUNCATED AT 250 WORDS)