tbuckley/cabot-search huggingface dataset:
MARIANNE: A phase III, randomized study of trastuzumab-DM1 (T-DM1) with or without pertuzumab (P) compared with trastuzumab (H) plus taxane for first-line treatment of HER2-positive, progressive, or recurrent locally advanced or metastatic breast cancer (MBC).
Authors: P. A. Ellis, C. H. Barrios, Y. Im, M. Patre, F. Branle, E. A. Perez
Journal: Journal of Clinical Oncology (2011)

TPS102 Background: T-DM1 is a unique antibody-drug conjugate (ADC) composed of H, a stable thioether linker, and the highly potent cytotoxic agent DM1 (derivative of maytansine). In a randomized phase II trial, single-agent T-DM1 had comparable efficacy to H + docetaxel in the first-line treatment of HER2-positive locally advanced or MBC. P is the first HER2-directed dimerization inhibitor for the treatment of HER2-positive BC. T-DM1 and P bind to different epitopes on HER2, and have distinct mechanisms of action suggesting that the combination may result in more complete blockade of HER2. T-DM1 + P showed synergistic antitumor effects in preclinical models, and preliminary phase Ib/II trial results showed acceptable tolerability and promising efficacy in patients with MBC. Methods: MARIANNE BO22589 (trial registry #NCT01120184) is the first phase III study to evaluate the combination of a targeted antibody and an ADC for first-line MBC. This systemic chemotherapy-sparing combination has the potential to establish a new treatment paradigm by optimizing efficacy while minimizing toxicity. Patients are randomized 1:1:1 to each arm (T-DM1 arms are blinded for P; H + taxane arm is open-label): H + taxane (H 8 mg/kg loading dose, then 6 mg/kg + docetaxel 75 mg/m2 q3w, or H 4 mg/kg loading dose, then 2 mg/kg + paclitaxel 80 mg/m2 qw); T-DM1 (3.6 mg/kg) q3w + P (840 mg loading dose, then 420 mg) q3w; or T-DM1 + placebo. Key eligibility criteria include centrally-confirmed HER2-positive MBC and no history of cardiopulmonary dysfunction. The primary endpoint is progression-free survival by independent review facility. Secondary endpoints include safety, overall response rate, overall survival, duration of response and quality of life. Enrollment began in July 2010, and as of January 31, 2011, 141 patients have been recruited, well ahead of schedule. Target enrollment is 1092 patients across ~310 sites globally. The independent Data Monitoring Committee which assesses safety data has recently recommended continuation of the study without modification. Brisk completion of accrual and data analyses are eagerly awaited.
Non-invasive ventilation (NIV) in community-acquired pneumonia (CAP) and severe acute respiratory failure (ARF): Effectiveness and risk factors for failure and mortality
Authors: Andres Carrillo, Gumersindo Gonzalez-Diaz, Miquel Ferrer, Maria Elena Martinez-Quintana, Antonia Lopez-Martinez, Noemi Llamas, Maravillas Alcazar, Antoni Torres
Journal: European Respiratory Journal (2011)

Background:  The use of NIV for treating severe ARF due to CAP is controversial, and the risk factors for failure with this mode of ventilation are not well-known in these patients.   Methods:  Prospective observational study to assess the usefulness of NIV in patients with CAP and severe ARF. The primary end-point variable was to determine the success of NIV, defined as avoidance of endotracheal intubation and survival in the ICU and for at least 24 hours in the medical ward, in patients with CAP. We assessed predictors of NIV failure and hospital mortality in multivariate analyses.   Results:  We studied 184 consecutive patients with CAP and severe ARF; 102 (55%) patients had  de novo  ARF and 82 (45%) previous pulmonary or cardiac disease. NIV was successful in 116 (63%) patients. Hospital mortality was 10 (9%) in successfully treated patients and 37 (54%) in those who failed treatment (p 2 /FiO 2  ratio after 1 hour of NIV, and worsening of radiologic infiltrate 24 hours after admission. Likewise, independent predictors of hospital mortality were maximum SOFA during ICU stay, NIV failure and older age.   Conclusions:  Patients with CAP and severe ARF can be treated with NIV with a reasonable success rate. Successful NIV treatment is strongly related with improved outcome in these patients. Multi-organ failure and older age strongly predict both treatment failure and poor survival.
Antibodies against Defined Nerve Cell Components: Gangliosides
Authors: N A Gregson, C T Hammer
Journal: Journal of the Royal Society of Medicine (1980)

Antisera have been raised in rabbits against the purified brain gangliosides GM 1 , GD 1a and GT 1b . The reactivity of these sera with a range of purified gangliosides has been examined by complement fixation and their specificities partially defined by absorptions with purified gangliosides.
Clinical profile of newly diagnosed patients of non small cell carcinima with epidermal growth factor receptor positivity on oral tyrosine kinase inhibitor therapy
Authors: Uthara Vijai Kumar, Vijai Kumar Ratnavelu, Bharat Vaswani
Journal: European Respiratory Journal (2013)

Lung cancer, of which Non-Small Cell Lung Cancer (NSCLC) is the most predominant form, can express activating mutations like Epidermal Growth Factor Receptor mutation that confer hypersensitivity to the tyrosine kinase inhibitors Geftinib and Erlotinib, oral chemotherapeutic agents, one of the many recent advances in management of NSCLC. Retrospective studies show that EGFR mutations were an independent predictor of response to treatment, progression free survival and overall survival in patients with NSCLC who were treated with Geftinib/ Erlotinib Objectives: To study the Clinical Profile of patients in a private hospital setting diagnosed with Non-Small Cell Carcinoma Lung with Epidermal Growth Factor Receptor (EGFR) mutation positivity. To assess Median Progression Free Survival (PFS), Objective Response Rate(ORR) and Overall Survival (OS) after Tyrosine Kinase Inhibitor therapy. MaterialsM No. 30; duration- January 1st 2010 to Feb 29th 2012. Patients visiting the Department of Pulmonary Medicine and diagnosed as Adenocarcinoma Lung with a positive mutation study were included in the study. Patient was started on oral tyrosine kinase inhibitor Tab. Gefitinib 250 mg once daily Follow up: Every 6 weeks; Results: Median age: 55 ; 76.67% of the study population were never smokers; the median PFS was 13.24 months; the objective response rate was 61.7% ; the median OS was 26.2 months Conclusions: EGFR mutation is more common in never smoker females who when treated with Tyrosine kinase inhibitor therapy show an increased PFS, OS and ORR when compared to previous studies.
Safety and feasibility of arterial embolization before endobronchial typical carcinoid tumors resection
Authors: Rachid Tazi Mezalek, Rosa Lopez Lisbona, Noelia Cubero, Juan Antonio Botero, Elena Escalante, Roger Barranco, Ester Alba, Juan Dominguez, Roger Llatjos, Jordi Dorca, Antoni Rosell
Journal: European Respiratory Journal (2013)

Purpose:  typical carcinoid tumors are low-grade malignant tumors with slow growth and high survival. The gold standard treatment is surgery. However, in some inoperable patients with endoluminal tumors, bronchial selective arterial embolization before rigid bronchoscopy could be useful as a complementary technique to avoid bleeding and ensure an accurate radical resection.   Materials and methods:  5 inoperable patients between 17 to 82 years with endoluminal carcinoid and significant bronchial obstruction have been treated endoscopically 24 h after embolization. Debulking was achieved with rigid bronchoscopy and YAP laser coagulation. Bronchial arterial embolization was performed with microcoils and PVA particles. Final pathologic diagnoses rendered 4 typical and one atypical carcinoid.   Results:  no inmediatly or short term complications after embolization have been registred. In all patients endoscopic treatment executed without significant bleeding, allowing a complete and accurate resection. A successful follow-up (2 to 22 months) was observed by CT and autofluorescence bronchoscopy.   Conclusions:  Arterial embolization of endobronchial carcinoid tumors is a feasible and safe method to avoid bleeding during rigid bronchoscopy ensuring an accurate endobronchial resection. Impact on recurrences and distant disease, should wait for a long term follow up in a multicenter study.
Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study
Authors: N. Benito, E. García-Vázquez, J.P. Horcajada, J. González, F. Oppenheimer, F. Cofán, M.J. Ricart, A. Rimola, M. Navasa, M. Rovira, E. Roig, F. Pérez-Villa, C. Cervera, A. Moreno
Journal: Clinical Microbiology and Infection (2015)

There are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2-63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made.
Long-Term Ingestion of Paracetamol and Liver Disease<sup>1</sup>
Authors: James Neuberger, M Davis, Roger Williams
Journal: Journal of the Royal Society of Medicine (1980)

Of 45 patients with chronic active hepatitis, 17 had taken paracetamol before the onset of symptoms. There were no significant differences, however, between the two groups in abnormalities of liver function tests, nor in ease of control after paracetamol withdrawal and institution of immunosuppressive therapy. The patient who had taken more than 5 g/week was studied in greater detail, but after a challenge dose of 1 g paracetamol there was no rise in serum aminotransferases and the pattern of excretion of paracetamol metabolites was normal. A critical review of the previously published reports failed to uncover any convincing evidence that paracetamol is an initiating factor in the development of chronic active hepatitis, although it may, at therapeutic levels, cause a toxic hepatitis in those individuals at risk.
Molecular epidemiology of Pseudomonas aeruginosa in intensive care units over a 10-year period (1998-2007)
Authors: M. Cuttelod, L. Senn, V. Terletskiy, I. Nahimana, C. Petignat, P. Eggimann, J. Bille, G. Prod'hom, G. Zanetti, D.S. Blanc
Journal: Clinical Microbiology and Infection (2010)
Abstract 4361: The Hemodynamic Significance of Non-culprit Coronary Artery Stenoses Can Be Reliably Evaluated With FFR During the Acute Phase of Acute Coronary Syndromes
Authors: Argyrios Ntalianis, Jan-Willem Sells, Giedrius Davidavicius, Nob Tanaka, Olivier Muller, Catalina Trana, Emanuele Barbato, Guy R Heyndrickx, William Wijns, Nico H Pijls, Bernard De Bruyne
Journal: Circulation (2009)
The Development of a Model for the Homing of Multiple Myeloma Cells to Human Bone Marrow
Authors: Mitsuyoshi Urashima, Benjamin P. Chen, Shirley Chen, Geraldine S. Pinkus, Roderick T. Bronson, Douglas A. Dedera, Yasutaka Hoshi, Gerrard Teoh, Atsushi Ogata, Steve P. Treon, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (1997)
Higher frequency of neuroleptic-induced dystonia in mania than in schizophrenia
Authors: H A Nasrallah, C M Churchill, G A Hamdan-Allan
Journal: American Journal of Psychiatry (1988)

In a study of 135 schizophrenic and 46 manic male patients treated with neuroleptics, a significantly higher proportion of the manic patients (26.1%) than of the schizophrenic patients (5.9%) developed acute dystonia. This suggests a higher vulnerability to acute extrapyramidal symptoms in mania.
The reasons for late diagnosis of nephrotuberculosis
Authors: Denis Kholtobin, Ekaterina Kulchavenya
Journal: European Respiratory Journal (2011)

Introduction:  In fact nephrotuberculosis (NTB), like any other infectious disease, potentially can be cured by chemotherapy. But this statement is valid only for early diagnosis; actually more than 60% new-revealed patients are diagnosed late, in cavernous stage, when surgery is indicated.  The aim of study was to identify the reasons for late diagnosis of NTB.   Material and methods:  167 patients with nephrotuberculosis were enrolled in study. History cases were detailed analyzed to determine clinical features, previous therapy and a level of kidney destruction in time of diagnosis tuberculosis.   Results:  11 (6.6%) had acute onset like pyonephrosis, and were operated without previous therapy. Diagnosis was verificated after surgery. Other 156 had chronic NTB with clinical features specific for chronic pyelonephritis and cystitis. 59 (37.8%) were revealed in small-destructive stage of nephrotuberculosis - papillitis. 47 patients among them (79.7%) were treated with optimal antimicrobials, that means drugs don9t influence on Mycobacterium tuberculosis (nitrofurantoin, gentamycin, amoxicillin, cephalosporins). Average time of correct diagnosis in this group was 4.7 months. 97 patients in cohort (62.2%) had cavernous NTB. The main reason was prescription to 75.3% amycacin, rifampicin and fluorquinolons that disguised, changed clinical features of NTB and resulted in long time of diagnostic – on average 27.4 months.   Conclusion:  Nephrotuberculosis often mimics at chronic pyelonephritis and cystitis. Using amycacin, rifampicin and fluorquinolons for therapy these diseases before excluding of NTB resulted in late diagnoses cavernous forms of NTB. Probably this statement is actual for region with severe epidemic situation, like Siberia.
EVALUATION OF SAFETY AND GENE EXPRESSION WITH A SINGLE DOSE OF PGM169/GL67A ADMINISTERED TO THE NOSE AND LUNG OF INDIVIDUALS WITH CYSTIC FIBROSIS: THE UK CF GENE THERAPY CONSORTIUM "PILOT STUDY''
Authors: Jane C. Davies, G. Davies, N. Voase, S. Hyde, A. Innes, Christopher Boyd, David Porteous, T. Higgins, U. Griesenbach, D. Gill, E. W. F. W. Alton
Journal: Thorax (2009)
The effect of regular brisk walking on quality of life and lung function in partially controlled adult asthmatics
Authors: Davis Paul, P. Mithun
Journal: European Respiratory Journal (2013)

Back ground  The impact of brisk walking on health related quality of life (HRLQ) and FEV1 of asthmatic patients is not well studied  Aim  To assess improvement in FEV1 and HRLQ following regular brisk walking  Methods  This is a prospective interventional study conducted in 100 partially controlled asthmatic, randomized in to exercise group(EG) and control group(CG). Basic FEV1 and HRLQ total scores were assessed by spirometry and Asthma Quality of Life Questionnaire (AQLQ). Patients in EG were subjected to brisk walking for 30 minutes/day for 6 months. Both groups were followed up regularly. FEV1 & AQLQ reassessed at 1st & 6th months  Results  There were 40 patients in each group who completed study. Ages were between 18-40 years. Mean base line FEV1 in the EG was 63.1± 12.0(CG = 63.9 ±11.5), after 1st month it was 69.8 ±6.9 (CG = 66.6± 6.6) and 6th month it was 72.7 ± 5.9(CG = 67.7±5.5).The change in FEV1 after 1st month in the EG was 6.7 ± 10.12 % (CG= 2.7% ± 8.0) p value 0.06 and in 6 months was 9.6 ±11.6 %( CG = 3.9± 8.5%) p value 0.014. Base line total HRLQ scores in EG was 136±27.3 (CG =136±26.5), after 1st month it was 169.7± 23.5 (CG= 153.7±21.9) and after 6 months it was 200.9±8.4 (CG =169.7± 23.5). The mean improvement in the 1st month for EG was 33.7±19.4 (CG = 16.9±14.5) & in the 6th month it was 64.9±26.2 (CG was 30.7±19.3).The increment in the total HRLQ scores were much higher in the EG when compared to CG, after 1 as well as 6 months (p value   Conclusion  Brisk walking for 6 months in partially controlled asthmatic improved HRLQ & FEV1  Reference  1) Sian Turner et al. Respiration 81:302–310; 2011.
Response to hyperventilation in a group of patients with panic disorder
Authors: J M Gorman, J Askanazi, M R Liebowitz, A J Fyer, J Stein, J M Kinney, D F Klein
Journal: American Journal of Psychiatry (1984)

Twelve patients with DSM-III diagnoses of panic disorder and four normal volunteers were studied during hyperventilation of room air and increased ventilation stimulated by 5% CO2. Patients also underwent sodium lactate infusion. Eight of the patients had a panic attack during sodium lactate infusion, seven during CO2 inhalation, and three during room-air hyperventilation. Since CO2 increases the firing of the locus ceruleus, and since sodium lactate infusion is known to increase cerebral CO2, these findings are consistent with other evidence implicating the locus ceruleus in panic anxiety.
Start mammography at age 45, US guideline recommends
Authors: Jacqui Wise
Journal: BMJ (2015)

New guidelines from the American Cancer Society have raised the recommended age for starting regular breast cancer screening from 40 to 45 years in women with an average risk of breast cancer. However, women should still have the opportunity to choose to begin yearly mammography as early as age 40, said the updated guidelines published in JAMA .1

Women aged 55 or older should move from screening yearly to screening every two years, although they should still have the opportunity to be screened yearly, the guidelines said. The guidelines did not recommend a particular …
Extension of the Legionella pneumophila sequence-based typing scheme to include strains carrying a variant of the N-acylneuraminate cytidylyltransferase gene
Authors: M. Mentasti, A. Underwood, C. Lück, N.A. Kozak-Muiznieks, T.G. Harrison, N.K. Fry
Journal: Clinical Microbiology and Infection (2013)
Vaccines and medicines for the world's poorest
Authors: S. C Arya
Journal: BMJ (2000)

Knowledge can flow from developing to developed countriesEditor-I am pleased that this issue of the BMJ explores the many aspects of research in developing countries.The first thing that comes to mind on this issue is how developed countries can teach developing countries, but few people realise that the flow of knowledge can sometimes be reversed.Developed countries can learn and benefit from research in developing countries, particularly from research on infectious diseases and alternative treatments.More international travel has led to a resurgence of infectious diseases and to a rapid spread to developed countries of diseases that used to be exclusive to the developing world.The emergence of HIV infection has warned us about the global threat of new infections, which are more likely to start in developing countries. 1 Research and surveillance on infectious diseases are most effectively done in areas where the diseases are common.Early communication and attention to this epidemiological information from developing countries can prevent potential global disasters.The different needs and healthcare settings in developing countries often stimulate new treatment methods, some of which can be more cost effective than established practices in developed countries.Directly observed therapy, short term (DOTS) for tuberculosis was shown to be effective in Africa and Asia in the early 1950s and has been the standard method of treatment in Hong Kong since then.It was only in 1993 that the US Centers for Disease Control recommended it be considered for all patients with tuberculosis. 2Earlier adoption of this research evidence might have prevented some of the deaths and multiple drug resistance associated with tuberculosis in many developed countries in recent years.Traditional medical practices in developing countries can be a treasure box of alternative or complementary treatments for people in developed countries.Research on the effectiveness of acupuncture has made it a standard treatment in many developed countries.Qing hao su, a Chinese herbal medicine, has been proved to be an effective and safe treatment for malaria. 3 Trials of many Chinese herbal medicines for the treatment of HIV infection and cancer are currently under way.The lack of advanced technology and sophisticated equipment may limit the quality and scope of some research in developing countries, but a lot of knowledge can be acquired through careful observations and innovative ideas, which do not need a lot of money.Mutual exchange is a more satisfying process than one-way transfer of knowledge and resources.Developed countries will get more in return for their investments in research in developing countries if they are more receptive to findings from these countries.
High prevalence of genetically-determined mannose binding lectin deficiency in young children with invasive pneumococcal disease
Authors: C. MuÑoz-Almagro, C. Bautista, M.T. Arias, R. Boixeda, E. del Amo, C. Borrás, N. Armiger, L. Garcia, G. Sauca, L. Selva, M.F. de Sevilla, P. Ciruela, J.C. Yebenes, R. Pallares, F. Lozano
Journal: Clinical Microbiology and Infection (2014)
Behavior of Borderline Tumors With Particular Interest to Persistence, Recurrence, and Progression to Invasive Carcinoma: A Prospective Study
Authors: Gerardo Zanetta, Sonia Rota, Stefania Chiari, Cristina Bonazzi, Giorgio Bratina, Costantino Mangioni
Journal: Journal of Clinical Oncology (2001)

Borderline tumors account for 10% to 20% of epithelial ovarian tumors, and their prognosis is outstanding; nevertheless, a mortality of up to 20% has been reported, particularly in earlier reports. There is a lack of information about the actual mortality and the rate of progression into invasive carcinoma in large and prospectively accrued populations.All women with borderline ovarian tumors undergoing primary surgery in our department or referred within 3 months from surgery performed elsewhere from 1982 to 1997 were prospectively accrued and observed.We studied 339 women (83.4% stage I, 7.9% stage II, and 8.5% stage III). The median age at diagnosis was 39 years. A total of 150 women underwent radical surgery, and 189 underwent fertility-sparing surgery. After surgery, 13 women had macroscopic residual disease. With a median follow-up of 70 months, 317 women are alive with no clinical disease (eight with documented subclinical persistence of implants), three are alive with clinical disease, two died of disease, 10 died of other reasons, and seven women have been lost to follow-up. The recurrence of disease was higher after fertility-sparing surgery (35 of 189 cases) than after radical surgery (seven of 150 cases); nevertheless, all but one woman with recurrence of borderline tumor or progression to carcinoma after conservative surgery were salvaged. We observed seven progressions (2.0%) into invasive carcinoma, five in serous tumors (2.4%), and two in mucinous tumors (1.6%). The disease-free survival is 99.6% in stage I patients, 95.8% in stage II, and 89% in stage III.The survival of patients with borderline tumors is higher than previously described in some retrospective studies. Conservative surgery is safe and may be proposed to several patients with early and disseminated disease after thorough discussion of all therapeutic options. Progression to carcinoma is approximately 2% and may be observed in both mucinous and serous tumors.