tbuckley/cabot-search huggingface dataset:
A pilot study of dose-dense (biweekly) carboplatin plus paclitaxel with or without trastuzumab as neoadjuvant treatment for breast cancer.
Authors: Teng Zhu, Guochun Zhang, XueRui Li, YanHui Liu, Fangping Xu, Jian Zu, Ning Liao, Kun Wang
Journal: Journal of Clinical Oncology (2014)

1062 Background: Dose-dense regimens have been shown to improve outcome when given as adjuvant therapy to patients with breast cancer compared with their three weekly counterparts. We investigated the efficacy and safety of dose-dense (biweekly) carboplatin and paclitaxel ± trastuzumab as neoadjuvant treatment in early breast cancer. Methods: Patients with tumor more than 2cm with or without node-positive breast cancer received treatment with 4 cycles of carboplatin area under the curve (AUC) 5 biweekly and paclitaxel 175mg/m2 biweekly, and biweekly trastuzumab 4mg/kg was added for human epidermal growth factor receptor 2 (HER2) positive status. All patients received primary prophylaxis (PP) with recombinant human granulocyte colony-stimulating factors (G-CSF) from day 2 to 3. Results: Between 01/2009-12/2013, one hundred and twenty-two patients enrolled. The overall pathologic complete response (pCR) rate was 40.1 %( 49 out of 122). The pCR rate was 4.5%(1 out of 22) in patients of Luminal A Subtype; 13.8% in patients of Luminal B(HER2-) Subtype; 50.0% (9 out of 18)in patents of Triple Negative Subtype; 64.0%(16 out of 25) in patients of Luminal B(HER2+) Subtype; 85.0%(18 out of 21) in patients of HER2+ Subtype. 89 of 122 (73%) completed all chemotherapy as planned; the remaining patients (27%) had treatment modifications for toxicity. The dose limiting toxicities resulting in treatment discontinuation included: grade 3/4 neutropenia, grade 3/4 anemia, grade 3/4 thrombocytopenia, and other grade 3 nonhematologic toxicity including bone pain, neuropathy, mucocitis etc. There were 29(23.8%) episodes of grade 3/4 neutropenia, 4(3.27%) episodes of grade 3/4 anemia, and 2 (1.64%) episodes of grade 3/4 thrombocytopenia and there were 3(2.45%) episodes of grade 3 neuropathy. Conclusions: Dose-dense neoadjuvant carboplatin plus paclitaxel±trastuzumab is feasible and the regimen is more effective in Luminal B(HER2+) Subtype, HER2+ Subtype and Triple Negative Subtype. Additional study about the postoperative follow-up of this regimen is warranted.
Costs and Benefits of Extended Endocrine Strategies for Premenopausal Breast Cancer
Authors: Janice S. Kwon, Gary Pansegrau, Melica Nourmoussavi, Geoffrey L. Hammond, Mark S. Carey
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: After completing 5 years of adjuvant tamoxifen, women with estrogen receptor (ER)–positive breast cancer benefit from 5 more years of endocrine therapy, either with tamoxifen or an aromatase inhibitor (AI). For premenopausal women, ovarian ablation (OA) would be required before starting an AI (OA/AI). According to the SOFT/TEXT studies, OA/AI improves 5-year disease-free survival compared with tamoxifen alone, suggesting that OA/AI could be superior to tamoxifen as extended endocrine therapy. The long-term costs and consequences of premature menopause from OA are unknown, but could be estimated through a cost-effectiveness analysis. Methods: A Markov chain Monte Carlo simulation model estimated the costs and benefits of 3 extended endocrine strategies in a hypothetical cohort of premenopausal women with ER-positive early breast cancer: (1) no further treatment; (2) tamoxifen for 5 years (extended tamoxifen); or (3) OA/AI for 5 years. Effectiveness was measured in years of life expectancy gain. Sensitivity analyses accounted for uncertainty surrounding various parameters. Monte Carlo simulation estimated the number of adverse events and deaths from each strategy in the US population over a 40-year period. Results: Extended tamoxifen yielded a higher average life expectancy gain than OA/AI (17.31 vs 17.06 years) at lower average cost ($3,550 vs $14,312). For 18,000 premenopausal ER-positive women, the simulation estimated 13,236, 12,557, and 11,338 deaths with no further treatment, extended tamoxifen, and OA/AI, respectively, but an additional 1,897 deaths from OA, for a total of 13,235 deaths associated with OA/AI. After 24.6 years of follow-up, more women are expected to die from OA/AI than extended tamoxifen. Conclusions: For premenopausal women with ER-positive cancer who have completed adjuvant tamoxifen, another 5 years of tamoxifen is the preferable extended endocrine strategy. The potential long-term health consequences of OA could affect overall survival when it precedes the use of an AI.
Abstract P167: CXCR4 Antagonism Is Equally Effective as Sirolimus in Reducing Neointima Formation After Arterial Injury Without Impairing Reendothelialization
Authors: Karim Hamesch, Pallavi Subramanian, Xiaofeng Li, Anna Thiemann, Kathrin Heyll, Klaus Dembowsky, Eric Chevalier, Christian Weber, Andreas Schober
Journal: Circulation Research (2011)

The chemokine receptor CXCR4 is crucial in neointima formation which is a problem after stent implantation. Drug-eluting stents reduce the restenosis risk but delayed re-endothelialization promotes late stent thrombosis. We compared CXCR4 antagonism with sirolimus treatment in preventing neointima formation after arterial injury in mice. Apolipoprotein E -/- mice after carotid wire injury were given a CXCR4 antagonist (POL5551 (P), a Protein Epitope Mimetic (PEM)) or sirolimus (n=6-8/group). The drugs were administered continuously (P: 2 and 20 mg/kg/d; sirolimus: 1.25 mg/kg/d; osmotic pumps) or intermittently (P: 20 mg/kg; IP, once daily) for 28 days. The neointimal area, smooth muscle cell (SMC) content, macrophage content, and endothelial coverage were quantified by planimetry from injured arteries stained with Elastica van Giesson, or after immunostaining for α-smooth muscle actin, Mac-2, and von Willebrand Factor, respectively. Peripheral Sca-1 + /Lin - smooth muscle progenitor cells (SPCs) were measured by flow cytometry. Treatment with sirolimus as well as with a continuous (C) or intermittent (I), high (H) or low (L) dose (D) of POL5551 (P) reduced the neointimal area compared to corresponding vehicle (Sirolimus: 69%, CHD-P: 70%, CLD-P: 63%, IHD-P: 53%). The relative neointimal content of macrophages increased by sirolimus application (70%). In contrast, the macrophage content decreased by CHD-P and IHD-P application (57% and 37%, respectively). However, CLD-P application did not alter the macrophage content. Sirolimus, CHD-P, and IHD-P highly diminished the neointimal SMC content (78%, 85%, and 67%, respectively), while CLD-P treatment did not. SPC increase in the circulation 1 day post injury was prevented by sirolimus, CHD-P, and IHD-P, but not by CLD-P. The endothelial coverage was not reduced by P, but significantly by sirolimus (14%). In conclusion, CXCR4 antagonism by POL5551 is equally effective as sirolimus in reducing neointima formation after arterial injury in mice. It might be more beneficial than sirolimus because it does not impair re-endothelialization and leads to a more stable lesional phenotype. These results indicate that POL5551 might be a promising alternative for restenosis prevention after stent implantation.
Midwife led debriefing to reduce maternal depression
Authors: J M Bland, J. Lumley, R. Small
Journal: BMJ (2000)

Editor—I should like to comment on the randomised controlled trial of midwife led debriefing to reduce maternal depression by Small et al.1 The first randomised clinical trial was of a drug treatment, streptomycin for pulmonary tuberculosis,2 which has provided the model for clinical trials ever since. In a drug trial we are not usually concerned with who is giving the drug because the effect of the drug itself is being measured. The treatment is impersonal, and we should be justified in assuming that the effect of a drug given by one person will be the same as it would be given by another.

When we carry out trials of more personal treatments, however, as in the trial by Small et al, we should be aware that the treatment given by one operator might not be the same as that given by another. Surgeons are not all equally skilful, for example. So if we were to carry out a trial comparing two surgical techniques the surgeons would be a non-random sample from the wider population of surgeons. This might not be too bad if each surgeon carried out both techniques because there would be some sort of balance. If different groups of surgeons carried out each technique this would not be so. We could randomise surgeons to treatments, but this would probably be difficult to achieve. We could, and I think should, take surgeon variation into account—for example, by multilevel modelling.3 The inevitable result would be to make confidence intervals wider and P values bigger, as happens when cluster randomised trials are analysed correctly.4

In the trial by Small et al the situation is even more complicated. The intervention is debriefing by a midwife—a very personal intervention. It is easy to believe that the individual skills of midwives in this complex task vary greatly. Clearly, the mothers in this trial are a sample from which we want to draw some conclusions about mothers in general. But surely the midwives are a sample too. We are asking whether debriefing by midwives is helpful. The two midwives here have somehow to represent the effectiveness of midwives everywhere. It may be that these particular midwives are not very good at debriefing rather than that debriefing is ineffective. Half of us are below average, after all.

It is difficult to see how we could analyse the trial to take the midwife variation into account as such variation exists only in one arm. Although stratification by midwife is mentioned, the midwife's intervention is received by women in only one arm of the trial. Stratification therefore cannot allow for variation between midwives.

I cannot criticise researchers for not applying a statistical technique yet to be invented, or at least to be noticed by myself. Medical research is in its infancy. There are many unanswered questions and, I suspect, many that are yet to be asked. We do not really know how to do it yet. It will be an interesting challenge to find out.
Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population
Authors: Emi Oishi, Tomoyuki Ohara, Satoko Sakata, Masayo Fukuhara, Jun Hata, Daigo Yoshida, Mao Shibata, Toshio Ohtsubo, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya
Journal: Circulation (2017)

Several observational studies have reported that higher visit-to-visit blood pressure variability is a risk factor for cognitive impairment and dementia. However, no studies have investigated the association of day-to-day blood pressure variability assessed by home blood pressure measurement with the development of dementia.A total of 1674 community-dwelling Japanese elderly without dementia, ≥60 years of age, were followed up for 5 years (2007-2012). Home blood pressure was measured 3 times every morning for a median of 28 days. Day-to-day systolic (SBP) and diastolic blood pressure variabilities, calculated as coefficients of variation (CoV) of home SBP and diastolic blood pressure, were categorized into quartiles. The hazard ratios and their 95% confidence intervals of the CoV levels of home blood pressure on the development of all-cause dementia, vascular dementia (VaD), and Alzheimer disease (AD) were computed with a Cox proportional hazards model.During the follow-up, 194 subjects developed all-cause dementia; of these, 47 had VaD and 134 had AD. The age- and sex-adjusted incidences of all-cause dementia, VaD, and AD increased significantly with increasing CoV levels of home SBP (all P for trend <0.05). These associations remained unchanged after adjustment for potential confounding factors, including home SBP. Compared with subjects in the first quartile of CoV levels of home SBP, the risks of the development of all-cause dementia, VaD, and AD were significantly higher in those in the fourth quartile (hazard ratio=2.27, 95% confidence interval=1.45-3.55, P<0.001 for all-cause dementia; hazard ratio=2.79, 95% confidence interval=1.04-7.51, P=0.03 for VaD; hazard ratio=2.22, 95% confidence interval=1.31-3.75, P<0.001 for AD). Similar associations were observed for CoV levels of home diastolic blood pressure. Meanwhile, home SBP levels were significantly associated with the risk of VaD but not with the risks of all-cause dementia and AD. There was no interaction between home SBP levels and CoV levels of home SBP on the risk of each subtype of dementia.Our findings suggest that increased day-to-day blood pressure variability is, independently of average home blood pressure, a significant risk factor for the development of all-cause dementia, VaD, and AD in the general elderly Japanese population.
PTH-005 Trends in endoscopy for acute upper gastrointestinal bleeding: outcomes from a four year informatics audit of a single centre
Authors: S Mumtaz, N Bhala, E ward, R Boulton
Journal: Endoscopy (2017)

<h3>Introduction</h3> Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency with persistent mortality rates. in the UK, National Institute of Clinical Excellence (NICE) recommends offering Oesophagogastroscopy (OGD) within 24 hours to patients presenting with a stable AUGIB. We audited our emergency OGD practice against these national standards as part of the informatics programme at our hospital to assess trends and otcomes. <h3>Method</h3> As part of prospective work, a retrospective audit was carried out over four years (2011–2014) for all patients undergoing an OGD for AUGIB at the Queen Elizabeth Hospital Birmingham. This serves a catchment population of around 7 50 000 including regional liver, renal and caridac transplant centres. We included patients presenting to Emergency Department with AUGIB (Acute) and those who had AUGIB as an in-patient (IP) Electronic data were accessed and analysed for time trends and 28 days mortality <h3>Results</h3> From 2011 to 2014, 1791 urgent OGDs were performed for patients presenting with AUGIB. The results are summarised in the table below. <h3>Conclusion</h3> This large-scale informatics audit shows that the time taken from referral to endosocopy for urgent OGD for AUGIB has improved over 4 years in accordance with NICE guidance. Whilst there was a 33% (p&lt;0.01) reduction in the mean time to OGD over four years, the trends in demographics, risks aetiology and mortality outcomes have remained similar in this time period. <h3>Reference</h3> . https://www.nice.org.uk/guidance/cg141 <h3>Disclosure of Interest</h3> None Declared
ナノゲル‐ペプチド縮合体による皮内薬剤輸送;テモポルフィンの特異的および効果的輸送
Authors: Zabihi Fatemeh, Wieczorek Sebastian, Dimde Mathias, Hedtrich Sarah, G Borner Hans, Haag Rainer
Journal: Journal of Controlled Release (2016)
Antibody–Drug Conjugates for Cancer Treatment
Authors: John M. Lambert, Anna Berkenblit
Journal: Annual Review of Medicine (2018)

The concept of exploiting the specific binding properties of monoclonal antibodies as a mechanism for selective delivery of cytotoxic agents to tumor cells is an attractive solution to the challenge of increasing the therapeutic index of cell-killing agents for treating cancer. All three parts of an antibody-drug conjugate (ADC)-the antibody, the cytotoxic payload, and the linker chemistry that joins them together-as well as the biologic properties of the cell-surface target antigen are important in designing an effective anticancer agent. The approval of brentuximab vedotin in 2011 for treating relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, and the approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive metastatic breast cancer, have sparked vigorous research in the field, with >65 ADCs currently in clinical evaluation. This review highlights the ADCs that are approved for marketing, in pivotal clinical trials, or in at least phase II clinical development for treating both hematologic malignancies and solid tumors.
THE CROWD GOES WILD: THE DISSEMINATION OF CONCUSSION RISK INFORMATION ON TWITTER IN RESPONSE TO THE REMOVAL OF HEADGEAR IN MEN'S BOXING AT THE OLYMPIC GAMES
Authors: Carly McKay, Keith Stokes
Journal: British Journal of Sports Medicine (2017)

Background Boxing headgear has previously been mandatory at the Olympic Games but was removed from men's competition in 2016, citing evidence that it increases concussion risk. Objective To describe the dissemination of concussion information on social media in response to headgear removal during Olympic competition. Design Cross-sectional media analysis. Setting User-generated content posted on the social networking site Twitter during the 2016 Olympic Summer Games. Participants Twitter users posting relevant content between 5th-21st August, 2016. Assessment of Risk Factors Twitter data (“tweets”) were extracted and coded as either for (supporting) or against (opposed to) headgear removal, and to indicate the user's belief that headgear prevents or increases the risk of concussion. Main Outcome Measurements The total number of tweets and the number of users reached were extracted. Pearson chi 2 was used to assess the effect of concussion risk beliefs on the type of disseminated message (e.g., personal opinion versus evidence-based). Results 646 tweets were captured, reaching ∼13.2 million Twitter users. Concussion was mentioned in 91 (14.1%) cases; increased laceration risk after headgear removal was referenced in 100 (15.5%). External links were included in 219 tweets (33.9%), comprising scientific publications/resources (n=27, 12.3%), news articles (n=141, 64.4%), and blog/opinion sites (n=51, 23.3%). Only 277 tweets were framed as either for (n=121, 43.7%) or against (n=156, 56.3%) headgear removal. Of these, 64 (45.4%) indicated that headgear increases concussion risk, whereas 77 (54.5%) suggested that it prevents concussions. Users who believed that headgear prevents concussions were more likely to base this on personal opinion (n=66, 85.7%) than those believing it increases risk (n=41, 64.1%) (x 2 =8.95, p=0.003). Conclusions Personal opinion and news articles were the most commonly disseminated concussion information sources, leading to conflicting positions on the counterintuitive removal of boxing headgear. These findings have implications for real-time knowledge translation strategies during intervention implementation across contexts.
PTH-024 The role of probe confocal laser endomicroscopy with image enhanced endoscopy in characterisation and endoscopic resection of dysplastic lesions in inflammatory bowel diseasepatients
Authors: M Iacucci, X Gui, S Ghosh
Journal: Endoscopy (2017)

<h3>Introduction</h3> Detection, characterisation and therapeutic management of dysplastic lesions during surveillance colonoscopy in inflammatory bowel disease (IBD) can be a challenge. The recent SCENIC consensus has introduced a new terminology and concept "endoscopically resectable" when the distinct margins of a lesion could be identified. New endoscopic techniques and skills are required to recognise the margins reliably and assess the surrounding mucosa to plan endoscopic removal. We report our experience of the use of probe confocal endomicroscopy (pCLE) combined with electronic virtual (VCE) and dye chromoendoscopy (DCE) for management of challenging dysplastic lesions. <h3>Method</h3> IBD patients underwent surveillance colonoscopy using high definition (HD)-iSCAN (Pentax, Japan) VCE and DCE in combination with pCLE (Cellvizio,France). pCLE was applied following injection of fluorescein 5% 10 ml to assess the histological features of the lesion, the margins and the mucosa surrounding the colonic lesion. Biopsies eventually proved dysplasia or SSA of the colonic lesions. The study was approved by the Conjoint Health Services Research Ethics Board of the University of Calgary. All patients gave informed consent. <h3>Results</h3> Seven patients with IBD and disease duration of ≥8 years (mean age 55 years; 6 male, UC=4 CD=3) were prospectively included. They underwent surveillance colonoscopy using HD–iSCAN (Pentax EC-3940Fi; Japan). When a colonic lesion was detected, selective iSCAN -VCE was performed with or without DCE (five out of seven had DCE) with methylene blue 1% to characterise the surface, vascular pattern and the margins of the lesion. Each of the 7 patients had non polypoid colonic lesions, 4 were sessile (Paris Is) and 3 flat (IIa/IIb).All dysplastic lesions were diagnosed by pCLE and confirmed by histology. Four of them were amenable to endoscopic therapy and were successfully removed using endoscopic mucosal resection (EMR) en-block or piecemeal technique. Interestingly, one patient with multiple scattered 'pseudopolyps' had a 8 mm sessile pseudopolypoid lesion with a suspicious areas of SSA in the midst that was confirmed by pCLE. The endoscopic, endomicroscopic and histological findings of all the lesions were described in Table <h3>Conclusion</h3> This case series highlights the first successful use of pCLE in combination with VCE and DCE to predict, characterise and treat colonic neoplasia in IBD. pCLE may be an additional tool to aid the endoscopist in therapeutic management by deciding endoscopic resectability versus colectomy. <h3>Disclosure of Interest</h3> None Declared
ROS産生およびTRPM2Ca~2+流入の抑制による表面コーティングペプチドによるマクロファージにおけるランタニドナノ結晶誘導インフラマソーム活性化の阻害【Powered by NICT】
Authors: Yao Han, Zhang Yunjiao, Liu Liu, Xu Youcui, Liu Xi, Lin Jun, Zhou Wei, Wei Pengfei, Jin Peipei, Wen Long-Ping
Journal: Biomaterials (2016)