tbuckley/cabot-search huggingface dataset:
EBUS-TBNA, EUS-FNA or EUS-B-FNA for mediastinal staging of lung cancer: A purpose of diagnostic algorithm
Authors: Simone Scarlata, Raffaele Antonelli Incalzi, Francesco Maria Di Matteo
Journal: European Respiratory Journal (2014)

To minimize the use of mediastinoscopy in lung cancer staging, EBUS-TBNA and EUS-FNA represent reasonable approaches. Several trials using a combination of both methods showed a higher diagnostic yield than each method alone. EUS complements the anterior mediastinal access of EBUS and most of the mediastinal lymph node stations, as well as the left adrenal gland, can be visualized and biopsied. Indeed, a growing evidence supports the value of a combination of both methods by use of one EBUS bronchoscope (EUS-B-FNA).  The combined EBUS/EUS-B-FNA seems to be significantly less time-consuming, cost saving, and as effective and safe as the use of two endoscopes for N staging. Indeed, this approach is associated with less clear US imaging and with some technical issues deriving from the reduced caliper of the EBUS scope and its lesser stiffness compared to the EUS probe, making the biopsy sample more challenging as well as with its limited ability to reach the stomach, to visualize and sample the left adrenal gland.  Based on this assumption, we developed a diagnostic algorithm (Figure 1) aiming at planning the choice of the ultrasound device before to proceed with the endoscopic examination.  We took into account the best potential approach enabling to correctly perform a complete N and M staging minimizing the risk of endoscopes overuse.  A confirmatory case-control study based on our hypothesis is needed.
A conditional contribution of mast cells to malignant pleural effusion
Authors: Anastasios D. Giannou, Zeljko Prijovic, Antonia Marazioti, Magda Spella, Chryssoula Kairi, Ioanna Giopanou, Vasilis Papaleonidopoulos, Dimitris Kardamakis, Ioannis Kalomenidis, Georgios T. Stathopoulos
Journal: European Respiratory Journal (2013)

Although mast cells (MC) have been identified in various tumors, their role remains controversial. We accidentaly identified MC in malignant pleural effusions (MPE) and solid tumors of humans and mice, hidden in conventional stains. In C57BL/6 mice, MPE-competent LLC lung and MC38 colon adenocarcinoma cells attracted MC, whether injected intrapleurally or subcoutaneously, in contrast to MPE-incompetent B16F10 melanoma cells. To this end, CCL2 was found to be a major tumor-derived MC chemoattractant, since CCL2-silenced LLC cells lost their ability for MC recruitment, a phenotype rescued by CCL2 overexpression in B16F10 cells. Intrapleural co-transplantation of bone marrow-derived MC with B16F10 cells enhanced MPE formation by these cells. MC-deficient mice (cKitWsh) were protected from LLC-, but not from MC38-induced MPE, indicating a conditional requirement for MC in MPE development. The protection of cKitWsh mice specifically from LLC-induced MPE was ablated by adoptive bone marrow transfer (BMT) of MC-competent wt donors and was transplantable to wt mice by cKitWsh BMT. This conditional protection was associated with osteopontin (SPP1) deficiency of LLC-triggered MPEs in cKitWsh hosts, indicating that MC can serve to supplement pleural SPP1 levels during MPE formation. To this end, MC38 cells produced more SPP1 than LLC cells in vitro, and incubation of naive MC with LLC- and MC38-, but not B16F10-conditioned media triggered de novo SPP1 elaboration. SPP1 silencing in MC38 cells rendered cKitWsh mice protected against MPE induction. Finally, imatinib mesylate treatment inhibited LLC-induced but not MC38-induced MPE, indicating a druggable and conditional requirement for MC in MPE.  Supported by ERC Grant.
Reduction of fatal complications from combined modality therapy in Hodgkin's disease.
Authors: P M Mauch, G P Canellos, D S Rosenthal, S Hellman
Journal: Journal of Clinical Oncology (1985)

A total of 464 pathologically staged IA through IIIB Hodgkin's disease patients were evaluated for the risk of developing acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, or a fatal infection after treatment with radiation therapy (RT) alone, initial combined radiation therapy and chemotherapy (CMT), or RT with MOPP administered at relapse. Patients received a standard six cycles of MOPP, and additional maintenance chemotherapy was not administered. Patients receiving total nodal irradiation (TNI) and MOPP chemotherapy have an 11.9% actuarial risk of developing a fatal complication at ten years, as compared to a 0.8% risk for lesser field irradiation and MOPP (P = .005). The risk with RT alone is 0.6%. Patients 40 years of age or older have a greater risk for complications. These data report a low risk for fatal complication with CMT when less than TNI is administered and when maintenance chemotherapy is not used.
Safety Data Analyses for First-Line Pemetrexed Plus Carboplatin (Pem + Cb) in Nonsquamous Non-Small Cell Lung Cancer (Ns-Nsclc)
Authors: I. Okamoto, W. Schuette, T. Stinchecombe, J. Rodrigues Pereira, J. Liu, B. San Antonio, W. John, J. Chen, R. Zinner
Journal: Annals of Oncology (2014)
Irritative respiratory simptoms and ventilatory function to workers exposed to man made mineral fibres
Authors: Micaela Margineanu, Eugenia Danulescu, Felicia Gradinariu, Carmen Croitoru, Madalina Ipate
Journal: European Respiratory Journal (2012)

We conducted a case-control study of 43 subjects who use Man Made Mineral Fibres (MMMF) to isolate cookers: 25 male and 18 female, aged 29-55, average of exposure 17.7± 4.1 years and a matched control group. Clinical, respiratory, skin and eye symptoms were recorded by questionnaire, pulmonary functional tests (PFT); MMMF mean concentration in the workplace air was measured.  Prevalence of chronic respiratory symptoms in exposed workers was insignificantly higher (32% vs. 21%).  Significantly higher prevalence was found for irritative simptoms of the upper airways (r=0.32, p  Our data suggest interactive influence of workplace exposure to MMF in development of irritative anomalies of the upper airways with predominantly smaller airways affecting.
Pregnancy outcome and its relationship to progression of renal failure in autosomal dominant polycystic kidney disease.
Authors: A B Chapman, A M Johnson, P A Gabow
Journal: Journal of the American Society of Nephrology (1994)

The effect of pregnancy on renal disease has not been defined in autosomal dominant polycystic kidney disease (ADPKD). Therefore, fetal and maternal complication rates in ADPKD women as compared with those in unaffected family members (NADPKD) were assessed. Two hundred thirty-five ADPKD and 108 NADPKD women with 605 and 244 pregnancies, respectively, were studied. Overall, fetal complication rates were similar between ADPKD and NADPKD women (32.6 versus 26.2%). Fetal complications were more common in ADPKD women when they were older than 30 yr. Increased fetal prematurity rates were found in preeclamptic ADPKD women as compared with normotensive ADPKD women (28 versus 10%; P < 0.01). More maternal complications occurred in ADPKD as compared with NADPKD women (35 versus 19%; P < 0.001), with preexisting hypertension being the most important risk factor for a maternal complication to occur. Normotensive ADPKD women who developed preeclampsia were more likely to develop chronic hypertension as compared with those without preeclampsia (89 versus 58%; P < 0.01). Hypertensive ADPKD women with four or more pregnancies had lower creatinine clearances than age-adjusted hypertensive ADPKD women with fewer than four pregnancies (49 +/- 5 versus 66 +/- 3 mL/min per 1.73 m2; P < 0.01). Therefore, normotensive ADPKD women usually have successful, uncomplicated pregnancies. However, hypertensive ADPKD women are at high risk for fetal and maternal complications and measures should be taken to prevent the development of preeclampsia in these women.
Delay in Presentation after Myocardial Infarction
Authors: Alexander G Heriot, Stephen J Brecker, D John Coltart
Journal: Journal of the Royal Society of Medicine (1993)

Thrombolytic therapy reduces mortality in acute myocardial infarction (AMI), giving maximal benefit with early treatment. In the UK delayed presentation after AMI may reduce the advantages of thrombolysis. To assess this, 103 patients presenting with AMI to two London Hospitals were interviewed to determine the length and cause of delay from onset of chest pain to arrival at hospital. Forty-nine per cent of patients took longer than 2 h to arrive at hospital, and 21% took longer than 4 h. Patients who contacted their general practitioner (GP) had a significantly prolonged time delay (160 mins; 65-730: median; range) compared to those who went directly to hospital by ambulance (82 mins; 15-395; P < 0.0005), or on their own (90 min; 15-855; P < 0.005). Patients calling their GP took a similar duration to decide to seek help [decision time (30 min versus 25 mins) P = NS], but significantly longer to reach hospital once the decision was made (110 min versus 56 min; P < 0.0001), than those proceeding directly to hospital. Believing the pain was cardiac in origin significantly shortened decision time (15 min versus 45 min; P < 0.05), as did knowledge of the existence of thrombolysis (15 min versus 50 min; P < 0.05) and lack of prior cardiac symptoms (18 min versus 42 min; P < 0.05). Only 14% were aware of thrombolysis. Rank correlation confirmed that decision and total delay time were age independent. Delays of this magnitude may compromise the efficiency of thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: Olivier Humbert, Jean-Marc Riedinger, Céline Charon-Barra, Alina Berriolo-Riedinger, Isabelle Desmoulins, Véronique Lorgis, Salim Kanoun, Charles Coutant, Pierre Fumoleau, Alexandre Cochet, François Brunotte
Journal: Clinical Cancer Research (2015)

To investigate the value of the metabolic tumor response assessed with (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC).Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (ΔSUVmax) were assessed using FDG-PET.The pCR rate was 42%. High Ki-67 proliferation index (P = 0.016), negative EGFR status (P = 0.042), and high ΔSUVmax (P = 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P = 0.043) and high ΔSUVmax (OR, 7.1; P = 0.014) were independent predictors of pCR. Using a threshold at -50%, tumor ΔSUVmax predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low ΔSUVmax and positive EGFR status could predict non-pCR with an accuracy of 92%.It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials. Clin Cancer Res; 21(24); 5460-8. ©2015 AACR.
Critical balance of TNF-a signaling in newborn mice undergoing mechanical ventilation
Authors: Tina Gimm, Melina Kossert, Markus Koschlig, Cristina M. Alvira, Harald Ehrhardt, Anne Hilgendorff
Journal: European Respiratory Journal (2014)

Rationale:  Neonatal chronic lung disease (CLD), occurring after mechanical ventilation with O 2  rich gas (MV-O 2 ), is characterized by an increase in lung inflammation and apoptosis involved in the development of impaired alveolar and vascular development. Since lung lavage from preterms developing CLD exhibit increased expression of tumor necrosis factor (TNF)-a,we hypothesized, that its absence will ameliorate apoptosis and histologic changes induced by MV-O 2  in a neonatal mouse model of the disease.   Methods:  5-6 days old TNF-a knock-out (TNF-a -/- ) and wild-type (TNF-a +/+ ) mice received MV with 40%O 2  at 180 breaths/min; controls spontaneously breathed 40%O 2 . After 8h, lungs were harvested for histologic, mRNA and protein analysis.  In vitro , primary pulmonary myofibroblasts (MFB) were isolated from unventilated newborn TNF-a -/-  and WT mice and subjected to mechanical stretch (Flexcell ® ) as well as cytokine exposure.   Results:  Contrary to our hypothesis, the pulmonary inflammatory response was significantly elevated in ventilated TNF-a -/- as compared to WT mice accompanied by an increased influx of monocytes. Furthermore, apoptosis was significantly increased in the lungs of ventilated TNF-a -/-  mice. These differences potentially resulted from a significant increase in pulmonary TGF-b signaling in TNF-a -/-  mice following MV-O 2 .  In vitro  analysis revealed an elevated apoptotic response to TGF-s in MFB from TNF-a -/-  mice in contrast to WT pups. Histological changes were similar in both groups.   Conclusion:  The findings indicate a critical balance of pulmonary TNF-a and TGF-b signaling in the developing lung and underline the importance of both pathways in the development of CLD following MV-O 2 .
The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids
Authors: Jingyuan Fu, Marc Jan Bonder, María Carmen Cenit, Ettje F. Tigchelaar, Astrid Maatman, Jackie A.M. Dekens, Eelke Brandsma, Joanna Marczynska, Floris Imhann, Rinse K. Weersma, Lude Franke, Tiffany W. Poon, Ramnik J. Xavier, Dirk Gevers, Marten H. Hofker, Cisca Wijmenga, Alexandra Zhernakova
Journal: Circulation Research (2015)

Rationale: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host–microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. Objectives: To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. Methods and Results: We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. Conclusions: Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins.
Ewing's sarcoma and primitive neuroectodermal tumor in adults: are they different from Ewing's sarcoma and primitive neuroectodermal tumor in children?
Authors: M W Verrill, I R Judson, C L Harmer, C Fisher, J M Thomas, E Wiltshaw
Journal: Journal of Clinical Oncology (1997)

To determine whether age at diagnosis influences the behavior of Ewing's sarcoma and primitive neuroectodermal tumor (PNET).We reviewed the clinical features, treatment, and outcome of 59 consecutive patients with Ewing's sarcoma and PNET treated on the Adult Sarcoma Unit at our institution from 1980 to 1995.The 37 male and 22 female patients had a median age of 24 years. Lower limb was the most common primary tumor site. Fifteen patients had nonmetastatic tumor less than 100-mL volume, 27 had nonmetastatic disease greater than 100-mL volume, and 17 had evidence of metastatic disease at presentation. The origin of the primary tumor was soft tissue in 28 cases, bone in 30, and uncertain in one. The Kaplan-Meier estimate of 5-year overall survival (OS) in all patients was 38% and of progression-free survival (PFS), 27%. When patients with metastatic disease at presentation were excluded, these figures increased to 52% and 34%, respectively. Bulk of disease at presentation and response to primary treatment were statistically highly significant predictors of both PFS and OS. Age and tissue of origin of the tumor did not influence outcome.The behavior of Ewing's sarcoma and PNET in adults is no different from its behavior in children. We feel the way forward in the treatment of adults with Ewing's sarcoma and PNET is for them to be included in the current multicenter trials of multidisciplinary treatment directed at children.
Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis
Authors: Rafael Kramann, Susanne V. Fleig, Rebekka K. Schneider, Steven L. Fabian, Derek P. DiRocco, Omar Maarouf, Janewit Wongboonsin, Yoichiro Ikeda, Dirk Heckl, Steven L. Chang, Helmut G. Rennke, Sushrut S. Waikar, Benjamin D. Humphreys
Journal: Journal of Clinical Investigation (2015)

Chronic kidney disease is characterized by interstitial fibrosis and proliferation of scar-secreting myofibroblasts, ultimately leading to end-stage renal disease. The hedgehog (Hh) pathway transcriptional effectors GLI1 and GLI2 are expressed in myofibroblast progenitors; however, the role of these effectors during fibrogenesis is poorly understood. Here, we demonstrated that GLI2, but not GLI1, drives myofibroblast cell-cycle progression in cultured mesenchymal stem cell-like progenitors. In animals exposed to unilateral ureteral obstruction, Hh pathway suppression by expression of the GLI3 repressor in GLI1+ myofibroblast progenitors limited kidney fibrosis. Myofibroblast-specific deletion of Gli2, but not Gli1, also limited kidney fibrosis, and induction of myofibroblast-specific cell-cycle arrest mediated this inhibition. Pharmacologic targeting of this pathway with darinaparsin, an arsenical in clinical trials, reduced fibrosis through reduction of GLI2 protein levels and subsequent cell-cycle arrest in myofibroblasts. GLI2 overexpression rescued the cell-cycle effect of darinaparsin in vitro. While darinaparsin ameliorated fibrosis in WT and Gli1-KO mice, it was not effective in conditional Gli2-KO mice, supporting GLI2 as a direct darinaparsin target. The GLI inhibitor GANT61 also reduced fibrosis in mice. Finally, GLI1 and GLI2 were upregulated in the kidneys of patients with high-grade fibrosis. Together, these data indicate that GLI inhibition has potential as a therapeutic strategy to limit myofibroblast proliferation in kidney fibrosis.
No reason to doubt standard of prenatal diagnosis
Authors: J. M Hahnemann, L. O Vejerslev
Journal: BMJ (1996)

France pasteurisation of raw milk cheeses is not feasible for cultural, social, and economic reasons."To me, the managing director of a cheesemonger, this strikes right at the heart of the mat- ter.Pasteurisation is not the obvious answer it might seem.Good cheese can be made from pasteurised milk.Exceptional cheeses can be made only from raw milk: the flavours are so much more alive and vibrant.Pasteurised cheeses always have a dull, subdued character.Not only that, but raw milk cheeses retain more calcium and vitamins and so provide a healthier diet.It is thought that the calcium helps to lower the amount of cholesterol absorbed into the body, thus minimising the risk of cardiovascular disease.Raw milk cheeses probably also harbour fewer pathogeus than pasteurised milk cheeses, thus making them "safer."Finally, it was Louis Pasteur himself who said, "I would rather that a child ate bread which had been dragged through the dirt than to grow up on an over sterile diet."The correct answer is to ensure that the quality of the milk is good.Pasteurisation should be seen as a last resort-an admission of failure of good hygiene-leading to poorer quality, less nutritious cheeses with a greater risk of contamination by pathogens after their production.
Are D-dimers requested appropriately in the emergency department? A retrospective audit
Authors: Alexia Williams, Andy Ashton
Journal: European Respiratory Journal (2011)

Introduction: Venous thrombo-embolism (VTE) is commonly encountered in the emergency department (ED). Due to the potential severity of a missed diagnosis and the particularly varied presentation of PE, there has been an increasing reliance on D-dimers in the ED. The British Thoracic Society (BTS) suggest this is potentially leading to over-investigation of patients for possible PE (British Thoracic Society. Thorax 2003; 58: 470-484).

Aims and objectives: This audit aimed to establish whether BTS guidelines were followed when D-dimers were requested in the ED, and whether D-dimers were requested appropriately by reviewing indication for the test, co-morbidities and documented end diagnosis.

Methods: A retrospective analysis of patients with positive D-dimers performed in ED or the acute medical unit in January 2010. 147 case notes were reviewed with a view to Well's score documentation; indication for request; further investigation for venous thrombo-embolism; end diagnosis.

Results: Of the 147 patients, 90 had a D-dimer performed for possible PE, 47 for possible DVT. Only two patients had a Well's score documented at any point during their hospital admission. Although 100% patients with D-dimer performed for possible DVT had further investigation, only 51% of patients with a D-dimer requested for possible PE went on to have any further investigation for PE, leading to an end diagnosis of PE in eight. The modal diagnosis in the patients reviewed was pneumonia.

Conclusions: Overuse of D-dimer testing in our ED leads to over-investigation of patients resulting in unnecessary radiation exposure. Guidelines for the use of D-dimer testing together with bedside testing will be implemented.