tbuckley/cabot-search huggingface dataset:
A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumors.
Authors: Jordan Berlin, Ramesh K. Ramanathan, John H. Strickler, Deepa Suresh Subramaniam, Herbert Hurwitz, Yoon-Koo Kang, Tae-You Kim, Stacie Peacock Shepherd, Hao Xiong, Robert Hetman, Caroline Nickner, Matthew W. Dudley, Vincent L. Giranda, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

2574 Background: Veliparib (V; ABT-888), a potent, competitive poly (ADP-ribose) polymerase (PARP)-1 and -2 inhibitor enhances the activity of irrinotecan (IRI). This study seeks to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) of V in combination with bimonthly FOLFIRI. Methods: Solid tumorpatients (pts; ≤3 prior DNA-damaging regimens) were administered V BID (days 1-5; 15–19) and FOLFIRI in three parts (P) : (P1) IRI 150 mg/m2; (P2) IRI 180 mg/m2 with 5-FU 400 mg/m2 bolus; or (P3) IRI 180mg/m2. All regimens included folinic acid 400 mg/m2, immediately followed by 5-FU 46-hour continuous infusion. Dose escalation began with V 10 mg BID in P1 and 100 mg BID in P2 and P3. Two expansion cohorts were evaluated in gastric or colorectal cancer pts with no prior PARP inhibitor therapy. Results: 96 pts (median age 54.5 years; range, 24–77) were enrolled in cohorts from 10–300 mg BID V. Tumor types were: other (n=30); gastric (n=20); pancreatic (n=14); ovarian, breast, and colorectal (each, n=9). 88 pts discontinued: 83 due to progressive disease; 2 withdrew consent; and 3 other. Most common AEs (>40% pts) were diarrhea (61%), nausea (60%), neutropenia (59%), vomiting (48%), fatigue (47%), anemia and alopecia (each, 41%). Grade 3/4 AEs (>30 pts) were neutropenia (47%), nausea (38%), and diarrhea (34%). Four DLTs occurred: neutropenia (n=3; P1, 160 mg and 270 mg BID V; P2, 100 mg BID V); and gastritis and vomiting (P1, 270 mg BID V). 12 pts (gastric, n=3; ovarian, breast, pancreatic, and other, each n=2; colorectal, n=1) achieved a partial response and 1 (ovarian) a complete response. V exposure was approximately dose-proportional in combination with FOLFIRI. FOLFIRI PKs were comparable with or without V administration, indicating the lack of drug-drug interaction. Conclusions: V in combination with chemotherapy was generally well-tolerated without drug-drug interactions. Ovarian and breast cancer pts experienced the greatest anti-tumor activity with an objective response rate of 33% and 22%, respectively. The RPTD was 200 mg BID V with bimonthly FOLFIRI (IRI 150 or 180 mg/m2 without 5-FU bolus). This study supports further evaluation of V in combination with FOLFIRI in specific tumor types. Clinical trial information: NCT01123876.
Cost-effectiveness of <i>HLA-B*15:02</i> screening in Malaysia
Authors: C. Plumpton, D. Hughes
Journal: British Journal of Dermatology (2017)

The authors use a (published) local study to inform the parameter value for mortality (4.2%); significantly lower than is typically quoted for SJS/TEN (15%-50%) [3,4].It would perhaps have been interesting to see the impact of this parameter on cost-effectiveness, but also highlights that with improved recognition and diagnosis, that survival outcomes can be improved, which should be acknowledged in future economic evaluations.The findings of this evaluation highlight the importance of carrying out robust, population-specific economic analyses to best inform local evidence-based policy.
Fitness cost and benefit of antimicrobial resistance in Neisseria gonorrhoeae: Multidisciplinary approaches are needed
Authors: Magnus Unemo, Christian L. Althaus
Journal: PLoS Medicine (2017)

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern globally, compromising the treatment of gonorrhea and its severe sequelae [1][2][3].In response to emerging resistance to extended-spectrum cephalosporins (ESCs; cefixime and ceftriaxone), many countries introduced dual antimicrobial therapy for gonorrhea (mainly ceftriaxone plus azithromycin).Subsequently, resistance to the previous first-line treatment, cefixime, has decreased in many countries, including England [4,5].However, several imperatives remain: increased surveillance of AMR (ideally including treatment outcomes and prescribing), rapid point-of-care tests that can simultaneously detect gonococci and predict resistance to multiple antimicrobials, novel antimicrobials with new mechanisms of action, and, ideally, an effective gonococcal vaccine [1][2][3][4][5].Furthermore, improved understanding of the emergence, evolution, spread, and fitness of AMR in gonococci, which could predict future AMR scenarios and ideally mitigate them and inform public health practices, is also crucial but has received less attention.In a research study in the latest issue of PLOS Medicine, Xavier Didelot and colleagues [6] aimed to estimate the fitness cost and benefit of cefixime resistance in gonococci in men who have sex with men (MSM) in England, using mathematical modeling and Bayesian inference.They developed a stochastic compartmental model representing the natural history and transmission of cefixime-sensitive and cefixime-resistant gonococcal strains.The authors assumed that the resistant strain has a fitness cost that results in faster clearance from asymptomatic infection.The model was then fitted to data on the total number of diagnoses and incidence of cefixime-resistant gonorrhea from 2008 to 2014.Briefly, the investigators estimated that cefixime treatment of cefixime-resistant strains was unsuccessful in 83% (95% credible interval [CrI] 53%-99%) of cases, resulting in a potential fitness benefit of resistance.This benefit was counterbalanced by the fitness cost when 31% (95% CrI 26%-36%) of patients were treated with cefixime, and when >55% (95% CrI 44%-66%) of patients were treated with cefixime, the resistant strain had a net fitness advantage over the susceptible strain.The study concludes that a previously abandoned antimicrobial such as cefixime could be reintroduced for treatment of a minority of gonorrhea patients without raising resistance levels. Alternative hypothesesDidelot and colleagues' study [6] had important aims and represents a valuable addition to the sparse literature on gonorrhea modeling specifically related to AMR.A major limitation of the
TCT-807 Accuracy of the Society of Thoracic Surgeons (STS) Mortality and Stroke Risk Scores for Predicting Outcomes in Patients With Left Main Coronary Artery Disease Undergoing CABG Versus PCI: Insights From the EXCEL Trial
Authors: Daniel Thuijs, Robert Habib, Gregg Stone, Patrick Serruys, Joseph Sabik, A. Pieter Kappetein
Journal: Journal of the American College of Cardiology (2017)
GMC is criticised for failing to properly investigate case against cosmetic surgeon
Authors: Clare Dyer
Journal: BMJ (2017)

A cosmetic surgeon accused of improperly anaesthetising a patient and lying to cover it up has been exonerated on all charges by a medical practitioners tribunal, which also strongly criticised the conduct of the General Medical Council in bringing the case.

The tribunal also had harsh words for the “fundamentally flawed” original investigation of surgeon Annamalaikani Jeyapragash by Aspen Healthcare, owner of Highgate Private Hospital in north London, where he performed a bilateral breast implant change on “Patient A.” She later complained that she had awoken during the procedure despite requesting general anaesthetic.

Numerous witnesses called by the GMC against Jeyapragash were deemed “unreliable,” “evasive,” or not credible, including Patient A herself, the anaesthetist booked for the operation, the scrub nurse, the theatre manager, and an operating department practitioner, said the …
What’s hot that the other lot got
Authors: Rebecca F D’Cruz
Journal: Thorax (2017)

Weaning from mechanical ventilation is an ill-defined process. The 2007 International Consensus Conference (ICC) weaning definition is difficult to apply as it uses spontaneous breathing trials (SBT) which are not universally used and excludes tracheostomised patients and those who fail to wean or die. In this prospective, multinational observational study, Beduneau et al propose a weaning classification for utilisation in daily practice for all mechanically ventilated patients ( Am J Respir Crit Care Med 2017;195:772–83). 2709 intubated patients from 36 European intensive care units (ICUs) were observed until ICU discharge or day 60. The authors propose a classification based on weaning duration from first separation attempt (extubation or SBT in intubated patients or ≥24 hours spontaneous ventilation in tracheostomised patients). Group ‘no weaning’ (24%) had no separation attempt; group 1 (57%) weaned in  1 and <7 days (mortality 15%), group 3 (9%) had a weaning duration of ≥7 days (mortality 30%). Group 3 was divided into 3a (completed wean after ≥7 days, 62%) and …
Self-assembling peptide hydrogel enables instant epicardial coating of the heart with mesenchymal stromal cells for the treatment of heart failure
Authors: Yuki Ichihara, Masahiro Kaneko, Kenichi Yamahara, Marinos Koulouroudias, Nobuhiko Sato, Rakesh Uppal, Kenji Yamazaki, Satoshi Saito, Ken Suzuki
Journal: Biomaterials (2017)

Transplantation of mesenchymal stromal cells (MSCs) is an emerging therapy for the treatment of heart failure. However, the delivery method of MSC is currently suboptimal. The use of self-assembling peptide hydrogels, including PuraMatrix
Doxorubicin immunoliposomes targeting RON receptor tyrosine kinase: an alternative strategy for potential cancer therapy
Authors: Ming-Hai Wang, Sunny Guin
Journal: Cancer Research (2008)

5744   The RON receptor tyrosine kinase is overexpressed in various epithelial cancers and implicated in cancer malignant phenotypes. These features provide the pathogenic basis to use RON as a therapeutic target and to develop effective drugs for experimental cancer therapy. We hypothesized that an antibody-targeted delivery of doxorubicin-loaded immunoliposomes provides effective and specific intracellular drug delivery, leading to increased cytotoxicity against RON overexpressing cancer cells. RON-specific immunoliposomes, designated as Zt/Dox-ILs, were prepared with standard procedures followed by insertion of Fab fragments derived from a RON specific antibody Zt/c1. As evident in fluorescent cell surface binding studies, Zt/Dox-ILs specifically interacted with breast cancer T-47D cells with high sensitivity and affinity. A 4-fold increase in fluorescence-binding intensity was achieved in comparison with control immunoliposomes constructed with normal IgG Fab fragment. A significant increase in T-47D cell internalization of Zt/Dox-ILs was also observed. Results from analysis of drug cytotoxicity revealed that upon internalization, doxorubicin, released from Zt/Dox-ILs, exerts cytotoxic effects on T-47D cells at an IC50 value of 1.8 mcg/ml. This value is comparable to those induced by free doxorubicin and is much lower to those induced by control immunoliposomes. In conclusion, Zt/Dox-ILs specifically binds to RON-expressing breast cancer cells leading to increased drug internalization and effective cellular cytotoxicity. Thus, targeted RON immunoliposomes represent a novel approach for potential cancer therapy in the future.
Carboplatin hypersensitivity reactions (HSR) in carboplatin retreatment for recurrent ovarian cancer.
Authors: Roisin Eilish O'Cearbhaill, David Michael Hyman, William P. Tew, Alexia Iasonos, Nicholas A Cangemi, Carol Aghajanian, Katherine M. Bell-McGuinn, Vicky Makker, Martee Leigh Hensley, Jason A. Konner, Rachel N. Grisham, Katherine Diaz-Macinnis, Paul Sabbatini, David R. Spriggs
Journal: Journal of Clinical Oncology (2015)

5572 Background: The reported risk of HSR during carboplatin retreatment is 18-44% and increases with repeated carboplatin exposure. We aimed to prospectively study the effect of an extended incremental infusion of carboplatin on the rate of HSR. Methods: Eligible patients (pts) with recurrent ovarian cancer were consented to an IRB-approved phase II randomized study from 01/2011-01/2015. Pts were randomly assigned 1:1 to standard 30-minute or an incremental 3-hour (1% in 1st hour, 9% in 2nd hour and 90% in 3rd hour) carboplatin infusion. Pts were stratified for concomitant taxane. Based on historical estimates the study was powered to detect a reduction in HSR from 20% to 5% with the extended infusion. All pts were prescribed premedication with montelukast 10 mg nocte x 3 days, dexamethasone 20 mg the night before and morning of, as well as famotidine 20 mg (or ranitidine) and diphenhydramine 50 mg (or hydroxyzine) prior to carboplatin. Pts were deemed evaluable for the study endpoint if they completed ≥ 5 cycles of carboplatin-based treatment or had carboplatin HSR. CTCAE criteria were used. Results: A total of 143 pts with recurrent ovarian cancer were enrolled. Median age was 62 years (35-82). 104 pts (52 in each arm) were evaluable for the study endpoint. Among these pts, 72 (69%), 27 (26%), 2 (1.9%) and 3 (2.9%) pts had 1, 2, 3 and 4 prior platinum-based regimens, respectively. 27 pts (26%) received carboplatin single agent and the remainder a platinum-doublet (46 liposomal doxorubicin, 24 gemcitabine, 7 paclitaxel). There were 15 HSR (14% of pts); 9 HSR in standard arm (9/52, 17%) and 6 HSR in the extended arm (6/52, 12%). There was 1 grade 3 HSR in the extended arm. No pt required hospitalization or epinephrine for HSR. The other 14 HSR were grade 1 or 2. HSR occurred on cycle #1 (1 pt); #2 (5 pts); #3 (4 pts); #4 (2 pts); #5 (2 pts) and #6 (1 pt). 2/9 HSR pts in standard arm were able to complete therapy with an extended infusion without further HSR. Conclusions: We did not demonstrate a statistically significant reduction in carboplatin HSR with use of an extended carboplatin infusion. However, the relatively low frequency of severe HSR in both arms suggests there may be a role for prophylactic premedication prior to carboplatin retreatment. Clinical trial information: NCT01248962.
TCT-508 Impact of incomplete revascularization in either diabetic and non-diabetic patients presenting with STEMI and multi-vessel disease
Authors: Dominika Klimczak, Mariusz Tomaniak, Maria Tovar, Joost Daemen, Jeroen Wilschut, Peter de Jaegere, Felix Zijlstra, Nicolas Van Mieghem, Roberto Diletti
Journal: Journal of the American College of Cardiology (2017)
TCT-847 Everolimus-eluting bioresorbable scaffold for the treatment of coronary in-stent restenosis: immediate and 12 months clinical results
Authors: Ivan Gomez-Blazquez, Victor Jimenez Diaz, Saleta Fernandez-Barbeira, Guillermo Bastos Fernández, Antonio De Miguel Castro, Jose Antonio Baz Alonso, Alberto Ortiz Saez, Andres Iñiguez
Journal: Journal of the American College of Cardiology (2017)
Politiche nazionali di prevenzione della resistenza antimicrobica - la situazione in 17 paesi europei alla fine del 2000
Authors: H Therre
Journal: Eurosurveillance (2001)

Da un'indagine condotta tra gli Stati Membri dell'Unione Europea e la Norvegia risulta che in tutti i paesi tranne due, al dicembre 2000, era in atto una sorveglianza nazionale sui microrganismi resistenti agli antibiotici. In Italia, Irlanda, e Scozia, i sistemi sono stati avviati recentemente (rispettivamente, nel 1998, 1999 e 1999). Inoltre, ad eccezione dell'Irlanda e Scozia, tutti i paesi hanno un sistema nazionale di raccolta di dati sul consumo di antibiotici, in particolare dal 2000 in Austria, Italia e Lussemburgo. Alcuni di questi sistemi sono stati avviati dopo il 1998, quando sono state pubblicate le raccomandazioni della conferenza europea The Microbial Threat tenutasi a Copenhagen. Inoltre, da allora sono state adottate una serie di altre misure preventive: campagne educative rivolte alla popolazione in Inghilterra e Galles, Irlanda e Francia, creazione di comitati specificamente incaricati di fare la sorveglianza sul consumo in Italia o sulla prevenzione della resistenza in Belgio e in Irlanda, pubblicazione di raccomandazioni sul buon uso di antibiotici in Austria e in Finlandia, ecc.
Renal Sympathetic Denervation Protects the Failing Heart Via Inhibition of Neprilysin Activity in the Kidney
Authors: David J. Polhemus, Rishi K. Trivedi, Juan Gao, Zhen Li, Amy L. Scarborough, Traci T. Goodchild, Kurt J. Varner, Huijing Xia, Frank W. Smart, Daniel R. Kapusta, David J. Lefer
Journal: Journal of the American College of Cardiology (2017)
TCT-606 Operator volume is not associated with mortality following Percutaneous Coronary Intervention: insights from the British Cardiovascular Intervention Society registry
Authors: William Hulme, Matthew Sperrin, Nick Curzen, Tim Kinnaird, Mark de Belder, Peter Ludman, Chun Shing Kwok, Christopher Gale, Evan Kontopantelis, Mamas Mamas
Journal: Journal of the American College of Cardiology (2017)
Abstract 12509: Initial Reports on the Safety of Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke Patients Taking Novel Oral Anticoagulants (NOACs)
Authors: Ying Xian, Jerome J Federspiel, Adrian F Hernandez, Barbara Lytle, Lee H Schwamm, Deepak L Bhatt, Eric E Smith, Gregg C Fonarow, Eric D Peterson
Journal: Circulation (2015)

Background: Intravenous tissue plasminogen activator (IV tPA) improves outcomes in ischemic stroke when given early; however, there is limited information on the safety of giving IV tPA to those already on a novel oral anticoagulants (NOACs, dabigatran, rivaroxaban, and apixaban). Given this, the current stroke guidelines warn against use of IV tPA in patients on a NOAC. Methods: We analyzed data from 42,887 ischemic stroke patients treated with IV tPA within 4.5 hours from 1,289 Get With The Guidelines-Stroke hospitals between October 2012 and March 2015. Results: A total of 1751 patients treated with tPA were receiving one of the oral anticoagulants prior to admission (warfarin with INR&lt;1.7 1500, dabigatran 87, rivaroxaban 129, and apixaban 35). Patients taking oral anticoagulants were older (median 79, 74, 71 for warfarin, any NOACs, and no oral anticoagulant, respectively), had more comorbid conditions, and more severe strokes (median NIHSS 13, 12, and 9). Compared with those not on any oral anticoagulant (3.9%), the unadjusted symptomatic intracranial hemorrhage (sICH) rates were higher in warfarin (4.9%) and NOAC (4.8%) patients. These differences were not statistically significant after adjusting for potential confounders in multivariable logistic regression model: adjusted odds ratio 0.85 (95 CI 0.66-1.10) for warfarin and 0.92 (0.51-1.65) for NOACs. Life-threatening or serious systemic hemorrhage, in-hospital mortality, discharge to hospice, and modified Rankin Score at discharge were similar among those on vs not on an oral anticoagulant (Table). Patients receiving NOACs appeared to have higher likelihood of discharge home and being able to ambulate independently at discharge, although the number of NOACs receiving tPA is small and may reflect potential treatment selection. Conclusion: This preliminary experience supports the potential safety of giving IV tPA to selected patients with acute ischemic stroke who were receiving chronic NOACs therapy.
A retrospective analysis for thromboembolic events associated with multikinase inhibitors
Authors: Kenta Nio, Kenji Tsuchihashi, Hitoshi Kusaba, Tomoyasu Yoshihiro, Shuji Arita, Hiroshi Ariyama, Takeshi Arita, Keita Odashiro, Koichi Akashi, Eishi Baba
Journal: Annals of Oncology (2017)
Surto de sarampo em adolescentes, Bélgica,1996
Authors: K De Schrijver
Journal: Eurosurveillance (1996)

O sarampo e uma doenca aguda altamente contagiosa caracterizada por febre, tosse, coriza, conjuntivite, eritema maculopapular e enantema patognomonico (manchas de Koplik). Dez por cento dos casos complicam-se de otite media ou broncopneumonia e a encefalite ocorre em 1 de cada 1000 casos. As complicacoes ocorrem mais frequentemente com o aumento da idade. Desde 1989, nos Estados Unidos morreram tres em cada 1000 casos notificados (1).
Tendenze evolutive delle infezioni da Salmonella Typhimurium multiresistente in Norvegia
Authors: O Alvseike, T Leegaard, P Aavitsland, J Lassen
Journal: Eurosurveillance (2002)

Questo articolo riporta l'andamento della Salmonella Typhimurium multiresistente isolata da campioni umani in Norvegia dal 1998 al 2000. Il primo caso si e verificato nel 1990. La maggior parte delle infezioni da Salmonella Typhimurium multiresistente contratte in Norvegia erano dovute al fagotipo DT104. Pertanto dovremmo attenderci un aumento delle infezioni primarie e secondarie se i ceppi con fagotipo DT104 e fenotipo ACSSuT diventano endemici.
Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality
Authors: Christian Jansen, Philipp Möller, Carsten Meyer, Carl Christian Kolbe, Christopher Bogs, Alessandra Pohlmann, Robert Schierwagen, Michael Praktiknjo, Zeinab Abdullah, Jennifer Lehmann, Daniel Thomas, Christian P. Strassburg, Eicke Latz, Sebastian Mueller, Martin Rössle, Jonel Trebicka
Journal: Hepatology (2017)

Transjugular intrahepatic portosystemic shunt (TIPS) efficiently treats complications of portal hypertension. Liver and spleen stiffness might predict clinically significant portal hypertension. This prospective study investigated liver stiffness in patients receiving TIPS regardless of indication. Of 83 included patients, 16 underwent transient elastography immediately before and 30 minutes after TIPS (acute group), while 67 received shear wave elastography of liver and spleen 1 day before and 7 days after TIPS (chronic group) and were followed further. In blood samples obtained before TIPS from cubital, portal, and hepatic veins, levels of several interleukins (IL1b, IL6, IL8, IL10, IL18) and interferon‐gamma were analyzed. In 27 patients (5 acute, 22 chronic), it resulted in an increase in liver stiffness of >10%. In 56 patients, liver stiffness decreased or remained unchanged (<10%). Importantly, spleen stiffness measured by shear wave elastography decreased in all patients (chronic group). None of the clinical or laboratory parameters differed between patients with increase in liver stiffness and those without. Of note, patients with increased liver stiffness showed higher overall and/or hepatic venous levels of proinflammatory cytokines at TIPS and higher incidence of organ failure and worse survival after TIPS. C‐reactive protein values and increase of >10% in liver stiffness after TIPS were the only independent predictors of mortality in these patients. Conclusion: This study demonstrates that the presence of systemic inflammation predisposes patients to develop increased liver stiffness after TIPS, a predictor of organ failure and death. (NCT03072615) (Hepatology 2018;67:1472‐1484).