tbuckley/cabot-search huggingface dataset:
Abstract P5-15-04: Oncotype DX cost effectivity to a Brazilian public hospital
Authors: C Cabello, RN de Andrade, TF Cabello, S Teixeira, LS da Costa, S Ramalho
Journal: Cancer Research (2019)

Abstract Introduction: The Oncotype DX was associated to 14% of adjuvant chemotherapy administration to Hormonal Receptor positive (HR+) and HER2 negative, T1N0 or T2N0 breast cancer patients at Tailor X trial recently published (RS&amp;gt;25) Objective: To describe the adjuvant chemotherapy administration to a Brazilian public hospital for HR+ HER2 negative, T1N0 or T2N0 breast cancer patients. And the estimate the cost effectivity of Oncotype DX in our low income scenary. Materials and Methods:This retrospective cross-sectional study was conducted at the Oncology Division of the Women's Hospital - CAISM of the State University of Campinas (UNICAMP), Brazil. All patient data were found from the hospital records from 2007 to 2009. It was included T1N0 and T2N0 HR+/HER2 negative breast cancer patients. Patients submitted to neoadjuvant treatment were excluded. We calculate the final cost of different types of chemotherapy used and the potential impact to oncotype DX introduction in this scenary. Results: It was found 109 patients records. 66% (72/109) had received adjuvant chemotherapy. 35% (38/109) had AC (X6), 29% (32/109) had CMF (X6) and 2% (2/109) had AC-T (X4). The total cost for chemotherapy scheme were; AC (X6) US$ 346,9; CMF (X6), US$300,6; ACT (X4), US$395,9. The total cost of chemotherapy was US$ 23.596,83 to 72 patients. If we consider 14% (15/109) of adjuvant chemotherapy associate to a Oncotype DX use (Tailor X RS&amp;gt;25), It would reduce adjuvant chemotherapy administration to 15 patients. The chemotherapy cost would be US$ 4588,27. In our scenary, It could save US$ 19.008,56. Nevertheless, the Oncotype Dx cost to Brasil is US$ 3.200,00 for each test. To 109 patients the total cost would be (109 X US$ 3.200,00) US$ 348.800,00. Therefore, the total cost for Oncotype DX program plus adjuvant chemotherapy for our patients would be US$ 348.800,00 + US$ 4.588,27= US$ 353.388,27. While in the real situation we had spent US$ 23.596,83. The total estimate cost would be 15 times more. Conclusion: At the moment, because of the assay high cost and the low cost of the adjuvant chemotherapy to HR+, HER2 negative T1N0 and T2N0, It would be difficult to consider Oncotype DX cost-effective to Brazilian public heath system. Even considering many advantages to spare chemotherapy to this population. Citation Format: Cabello C, de Andrade RN, Cabello TF, Teixeira S, da Costa LS, Ramalho S. Oncotype DX cost effectivity to a Brazilian public hospital [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-04.
Successful removal of impacted large bile duct stones using electrohydraulic lithotripsy with an ultraslim endoscope after Billroth II gastrectomy
Authors: Kazuyuki Matsumoto, Hironari Kato, Shigeru Horiguchi, Daisuke Uchida, Takeshi Tomoda, Shinichiro Muro, Hiroyuki Okada
Journal: Endoscopy (2019)

The diagnostic and therapeutic effectiveness of combined double-balloon endoscopy (DBE) using a short endoscope and peroral direct cholangioscopy with an ultraslim endoscope for altered gastrointestinal anatomy has been demonstrated [1] [2] [3] [4] [5]. This method offers the following advantages over mother–baby cholangioscopy for bile duct stone treatment: single-operator use, wide working channel, favourable cost performance, and high image resolution. We treated impacted large bile duct stones using electrohydraulic lithotripsy (EHL) and an ultraslim endoscope in a patient who had undergone Billroth II gastrectomy.
Abstract P1-12-13: Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer
Authors: E Healy, X Pan, S Beyer, I Washington, J Bazan, J White
Journal: Cancer Research (2019)

Abstract Objectives: Upper extremity dysfunction (UED) is a known side effect of breast cancer treatment. It is unclear, however, to what degree radiation contributes to this morbidity. We aimed to characterize the level of UED using patient-reported outcomes (PROs) prior to, during, and after treatment with radiation for breast cancer. Our secondary aims were to evaluate the association of UED with pain scores. Methods: This is a single-institution, prospective, longitudinal cohort study of patients treated with radiation for breast cancer. The validated patient-reported outcome measure, Quick Disabilities of the Arm, Shoulder and Hand (QD) was used to capture UED prior to radiation, at the end of radiation, and 1 month following the completion of radiation. Pain scores were also collected at these intervals using the numeric pain reporting scale (NPRS) from 0 (no pain) to 10 (worst pain). Results: Forty-four patients were enrolled on this study and 43 (97.7%) had completed radiation at the time of analysis. Thirteen patients (29.5%) were treated with mastectomy, axillary lymph node dissection and regional nodal irradiation in the supine position. The other 31 (70.5%) patients underwent lumpectomy and sentinel lymph node biopsy. Of these patients, 26 (83.9%) were treated in the prone position and 30 (96.8%) received whole breast irradiation. Median time from surgery to radiation was 69 days (range 35 – 212 days), 76 days for mastectomy and 68 days for lumpectomy. Median time from start to end of radiation was 38 days for mastectomy and 28 days for lumpectomy. Pre-treatment median QD score prior to radiation was 12.5 (11.4 for lumpectomy, 15.9 for mastectomy), 9.1 at the end of radiation (9.1 for lumpectomy, 18.2 for mastectomy), and 2.4 at 1 month after radiation (2.3 for lumpectomy, 2.5 for mastectomy). Median NPRS scores at pre-treatment, post-treatment and 1 month follow-up were 1, 1, and 1 for lumpectomy and 0, 1, 0 for mastectomy patients, respectively. Conclusion: In this initial pilot study with 1 month of follow up, patient-reported UED as demonstrated by QD scores were higher pre-radiation and decreased by one month after. This likely reflects recuperation after surgical procedure. Median average pain scores were low at all time points. Further evaluation of UED over time to characterize the long-term effect of radiation and correlation with quality of life and other clinical factors is planned. Citation Format: Healy E, Pan X, Beyer S, Washington I, Bazan J, White J. Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-13.
Exosomal Transport of Hepatocyte‐Derived Drug‐Modified Proteins to the Immune System
Authors: Monday O. Ogese, Rosalind E. Jenkins, Kareena Adair, Arun Tailor, Xiaoli Meng, Lee Faulkner, Bright O. Enyindah, Amy Schofield, Rafael Diaz‐Nieto, Lorenzo Ressel, Gina L. Eagle, Neil R. Kitteringham, Chris E. Goldring, B. Kevin Park, Dean J. Naisbitt, Catherine Betts
Journal: Hepatology (2019)

Idiosyncratic drug‐induced liver injury (DILI) is a rare, often difficult‐to‐predict adverse reaction with complex pathomechanisms. However, it is now evident that certain forms of DILI are immune‐mediated and may involve the activation of drug‐specific T cells. Exosomes are cell‐derived vesicles that carry RNA, lipids, and protein cargo from their cell of origin to distant cells, and they may play a role in immune activation. Herein, primary human hepatocytes were treated with drugs associated with a high incidence of DILI (flucloxacillin, amoxicillin, isoniazid, and nitroso‐sulfamethoxazole) to characterize the proteins packaged within exosomes that are subsequently transported to dendritic cells for processing. Exosomes measured between 50 and 100 nm and expressed enriched CD63. Liquid chromatography–tandem mass spectrometry (LC/MS‐MS) identified 2,109 proteins, with 608 proteins being quantified across all exosome samples. Data are available through ProteomeXchange with identifier PXD010760. Analysis of gene ontologies revealed that exosomes mirrored whole human liver tissue in terms of the families of proteins present, regardless of drug treatment. However, exosomes from nitroso‐sulfamethoxazole‐treated hepatocytes selectively packaged a specific subset of proteins. LC/MS‐MS also revealed the presence of hepatocyte‐derived exosomal proteins covalently modified with amoxicillin, flucloxacillin, and nitroso‐sulfamethoxazole. Uptake of exosomes by monocyte‐derived dendritic cells occurred silently, mainly through phagocytosis, and was inhibited by latrunculin A. An amoxicillin‐modified 9‐mer peptide derived from the exosomal transcription factor protein SRY (sex determining region Y)‐box 30 activated naïve T cells from human leukocyte antigen A*02:01–positive human donors. Conclusion: This study shows that exosomes have the potential to transmit drug‐specific hepatocyte‐derived signals to the immune system and provide a pathway for the induction of drug hapten‐specific T‐cell responses.
Gambling and public health: we need policy action to prevent harm
Authors: Heather Wardle, Gerda Reith, Erika Langham, Robert D Rogers
Journal: BMJ (2019)

Prevention of harms related to gambling requires investment in population based approaches, say Heather Wardle and colleagues ### Key messages In 2017 the gambling regulator for Great Britain, the Gambling Commission, described problem gambling as a public health concern (box 1)3 and emphasised the need to increase protection from harm.4 In 2018 the Faculty of Public Health released a position paper arguing for the introduction of harm prevention measures, underpinned by legislation, targeted at the whole population.5 The Labour Party recently shared plans for a radical overhaul of legislation to reduce the harms associated with "Britain's hidden epidemic."6 Box 1 ### Gambling behaviour in Great Britain12RETURN TO TEXT
How to make the most of your surgical placement
Authors: Frank Acquaah, Thomas Goldsmith, Scarlett McNally
Journal: BMJ (2017)

A placement in surgery offers you an opportunity to observe a range of surgical procedures and to follow patient journeys from admission to recovery.

Surgery is a fast paced, high pressured area of medicine where the need for perfection can make for a tense, but exciting, environment. A placement in a surgical department can be an intimidating experience at first, but it is a great opportunity to brush up on your anatomy, see how elective and emergency cases present, observe an operation, and follow a patient’s journey from admission to postoperative recovery.

This article gives an overview of what to expect from the different areas of a general surgery department and provides advice on what to focus on during your placement and how you can assist the team.

During a surgical rotation your time will be split between the ward, outpatient clinic, being on call, and the operating theatre.

### On the ward

The team on a typical surgical ward consists of foundation doctors, core surgical trainees, specialist registrars, consultants, specialty and associate specialist doctors, and other allied healthcare workers—for example, nurses, physiotherapists, and dietitians.

To begin with, it is a good idea to shadow the foundation doctor, who manages the ward patients by identifying those who are unwell and escalating concerns to senior members of the team.

A daily ward round is usually done by a registrar, and more formal consultant rounds take place once or twice a week, where management plans for patients are written or revised.

You can help by offering to scribe during a ward round, noting down patients’ most recent observations and investigation findings as well as recording the latest examination findings and management plan. Surgical ward rounds can be fast paced because of the number of patients that must be seen, so you need to keep up while …
Abstract P6-13-04: Estrogen-alone based hormone replacement therapy (HRT) reduces breast cancer (BrCa) incidence and mortality whereas estrogen plus progestin Provera based HRT increases both BrCa incidence and BrCa mortality: A comparative analysis of Women's Health Initiative trials
Authors: J Ragaz, H Qian, H Wong, KS Wilson, S Shakeraneh, JJ Spinelli
Journal: Cancer Research (2019)

Abstract OBJECTIVE: To quantitate breast cancer incidence (BrCa-I) and mortality (BrCa-M) outcome differences between the two Women's Health Initiative (WHI) HRT trials,1,2 the ratio of hazards was calculated for estrogen-alone based hormone replacement therapy (E-HRT) vs. placebo (P), and E + progestin Provera (ProgProv) combination HRT vs. P trials. METHODS: Hazard ratios (HR) of BrCa-I and BrCa-M and 95% confidence intervals (CI) were obtained from both WHI HRT trials. Subsequently, to compare BrCa outcomes between E-HRT vs. E + ProgProv, the ratios of HRs between the trials (HR1/HR2) were estimated separately for i. BrCa-I all women, ii. BrCa-I low Gail score (Gail score &amp;lt;1.75*), and iii. BrCa-M. The 95% CI was derived through logarithmic transformation of the 95% CI originally reported. RESULTS: Outcome Comparison, the two WHI HRT randomized trials. Ratio of Hazards, BrCa Incidence and BrCa mortality E-HRT vs. P, HR1 (95% CI)E-HRT + ProgProv vs. P, HR2 (95% CI)HR1/HR2 (95% CI)pBrCa-I All Woman10.77 (0.62-0.95)1.25 (1.07-1.46)0.62 (0.47-0.80)0.0004BrCa-I Low Gail Score* (Gail score &amp;lt;1.75)10.65 (0.50-0.86)1.24 (1.01-1.51)0.53 (0.38-0.74)0.0002BrCa-M20.55 (0.33-0.92)1.44 (0.97-2.15)0.38 (0.20-0.75)0.004*Gail score &amp;lt;1.75; HRs calculated from Reference 1, Figure 3 CONCLUSIONS: Our calculations show that the different outcomes between the two WHI HRT trials, estimated as ratio of hazards, are highly significant on statistical basis, both for BrCa incidence and for BrCa mortality. These findings highlight the potential carcinogenic impact of ProgProv and the major public health benefits of HRT based on E alone. REFERENCES: 1. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. The Lancet Oncology 2012;13:476-86. 2. Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials. JAMA 2017;318:927-38. Citation Format: Ragaz J, Qian H, Wong H, Wilson KS, Shakeraneh S, Spinelli JJ. Estrogen-alone based hormone replacement therapy (HRT) reduces breast cancer (BrCa) incidence and mortality whereas estrogen plus progestin Provera based HRT increases both BrCa incidence and BrCa mortality: A comparative analysis of Women's Health Initiative trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-13-04.
Abstract P2-08-44: Not presented
Authors: C Allemand, MF Calvo, AC Valerio, MC Riggi, F Corrao, R Orti, A Wernicke, L Zamora, MC Paez, C Lorusso
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Allemand C, Calvo MF, Valerio AC, Riggi MC, Corrao F, Orti R, Wernicke A, Zamora L, Paez MC, Lorusso C. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-44.
Early nasal microbiota and acute respiratory infections during the first years of life
Authors: Laura Toivonen, Kohei Hasegawa, Matti Waris, Nadim J Ajami, Joseph F Petrosino, Carlos A Camargo Jr, Ville Peltola
Journal: Thorax (2019)

Background Emerging evidence shows that airway microbiota may modulate local immune responses, thereby contributing to the susceptibility and severity of acute respiratory infections (ARIs). However, there are little data on the longitudinal relationships between airway microbiota and susceptibility to ARIs in children. Objective We aimed to investigate the association of early nasal microbiota and the subsequent risk of ARIs during the first years of life. Methods In this prospective population-based birth-cohort study in Finland, we followed 839 healthy infants for ARIs from birth to age 24 months. Nasal microbiota was tested using 16S rRNA gene sequencing at age 2 months. We applied an unsupervised clustering approach to identify early nasal microbiota profiles, and examined the association of profiles with the rate of ARIs during age 2–24 months. Results We identified five nasal microbiota profiles dominated by Moraxella , Streptococcus , Dolosigranulum , Staphylococcus and Corynebacteriaceae , respectively. Incidence rate of ARIs was highest in children with an early Moraxella -dominant profile and lowest in those with a Corynebacteriaceae -dominant profile (738 vs 552/100 children years; unadjusted incidence rate ratio (IRR), 1.34; 95% CI 1.16 to 1.54; p &lt; 0.001). After adjusting for nine potential confounders, the Moraxella -dominant profile-ARI association persisted (adjusted IRR (aIRR), 1.19; 95% CI 1.04 to 1.37; p = 0.01). Similarly, the incidence rate of lower respiratory tract infections (a subset of all ARIs) was significantly higher in children with an early Moraxella -dominant profile (aIRR, 2.79; 95% CI 1.04 to 8.09; p = 0.04). Conclusion Moraxella -dominant nasal microbiota profile in early infancy was associated with an increased rate of ARIs during the first 2 years of life.
Which specialty should I choose?
Authors: Caroline Elton
Journal: BMJ (2014)

Dear Caroline

I’m in my last year at medical school and still haven’t got a clue what specialty to choose. Two years from now I’ll be in my foundation year 2 and I’ll have to decide which career pathway I want to pursue. The trouble is that I have enjoyed all my attachments and got really good feedback across the board. What do you advise?

Anon, final year medical student, Cardiff University

Last weekend I was coming back from a conference in Oxford and rushed in to Marks & Spencer to grab some lunch. Faced with a huge array of sandwiches, wraps, and salads, I felt a growing annoyance that too much choice made the decision harder. Of course, choosing a specialty is a rather more weighty decision than sandwich selection—but the general principle still holds that breadth of choice can make a …
Abstract P6-05-08: LINC02273 interacts with hnRNPL and promotes metastasis through directly activating AGR2 in breast cancer
Authors: B Xiu, Y Chi, W Ji, Q Zhang, J Wu
Journal: Cancer Research (2019)

Abstract The prognosis of breast cancer patients with metastasis is still poor even improved by current treatment modalities. Unveiling new biomarkers and molecular mechanisms that underlie metastasis are of vital importance for the treatment of breast cancer. The recent discovery of long noncoding RNAs (lncRNAs) has gained widespread attention. To identify critical lncRNAs that contributed to breast cancer metastasis, we profiled their expression in 5 pairs of primary tumors and lymph nodes metastasis loci by HTA2.0 microarray. LINC02273 is significantly upregulated in metastasis loci and its high expression is associated with poor diseases free survival in a validation set of 254 patients. LINC02273 was mainly located in the cell nucleus . RACE-PCR showed two isoforms and the longest one was the most abundant isoform in breast cancer. Through transwell assay, 3D spheroid invasion assay and mice xenograft metastasis model, we found that LINC02273 promoted breast cancer cell migration, invasion and metastasis. Via mass spectrometry, hnRNPL was found to interact with LINC02273 to enhance its stability, which was further confirmed by Actinomycin D inhibition assay and luciferase reporter assay. Furthermore, ChIRP-seq and ChIP-seq showed that LINC02273 stimulated oncogene AGR2 expression by directly binding to the AGR2 promoter region and increasing H3K27ac modification. Triplex formation assay was performed for verification. We demonstrated that the expression level and oncogenic ability of AGR2 were regulated by hnRNPL through LINC02273. Clinical data and mouse xenograft tumors also revealed the positive correlation of AGR2 and LINC02273. In conclusion, LINC02273, which is stabilized by hnRNPL can promote breast cancer metastasis through upregulation of AGR2 and may serve as a prognostic biomarker for breast cancer. Citation Format: Xiu B, Chi Y, Ji W, Zhang Q, Wu J. LINC02273 interacts with hnRNPL and promotes metastasis through directly activating AGR2 in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-08.
Hippo Signaling Controls NLR Family Pyrin Domain Containing 3 Activation and Governs Immunoregulation of Mesenchymal Stem Cells in Mouse Liver Injury
Authors: Changyong Li, Yuting Jin, Song Wei, Yishuang Sun, Longfeng Jiang, Qiang Zhu, Douglas G. Farmer, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski, Bibo Ke
Journal: Hepatology (2019)

The Hippo pathway, an evolutionarily conserved protein kinase cascade, tightly regulates cell growth and survival. Activation of yes‐associated protein (YAP), a downstream effector of the Hippo pathway, has been shown to modulate tissue inflammation. However, it remains unknown as to whether and how the Hippo‐YAP signaling may control NLR family pyrin domain containing 3 (NLRP3) activation in mesenchymal stem cell (MSC)‐mediated immune regulation during liver inflammation. In a mouse model of ischemia/reperfusion (IR)‐induced liver sterile inflammatory injury, we found that adoptive transfer of MSCs reduced hepatocellular damage, shifted macrophage polarization from M1 to M2 phenotype, and diminished inflammatory mediators. MSC treatment reduced mammalian Ste20‐like kinase 1/2 and large tumor suppressor 1 phosphorylation but augmented YAP and β‐catenin expression with increased prostaglandin E2 production in ischemic livers. However, disruption of myeloid YAP or β‐catenin in MSC‐transferred mice exacerbated IR‐triggered liver inflammation, enhanced NLRP3/caspase‐1 activity, and reduced M2 macrophage phenotype. Using MSC/macrophage coculture system, we found that MSCs increased macrophage YAP and β‐catenin nuclear translocation. Importantly, YAP and β‐catenin colocalize in the nucleus while YAP interacts with β‐catenin and regulates its target gene X‐box binding protein 1 (XBP1), leading to reduced NLRP3/caspase‐1 activity after coculture. Moreover, macrophage YAP or β‐catenin deficiency augmented XBP1/NLRP3 while XBP1 deletion diminished NLRP3/caspase‐1 activity. Increasing NLRP3 expression reduced M2 macrophage arginase1 but augmented M1 macrophage inducible nitric oxide synthase expression accompanied by increased interleukin‐1β release. Conclusion: MSCs promote macrophage Hippo pathway, which in turn controls NLRP3 activation through a direct interaction between YAP and β‐catenin and regulates XBP1‐mediated NLRP3 activation, leading to reprograming macrophage polarization toward an anti‐inflammatory M2 phenotype. Moreover, YAP functions as a transcriptional coactivator of β‐catenin in MSC‐mediated immune regulation. Our findings suggest a therapeutic target in MSC‐mediated immunotherapy of liver sterile inflammatory injury.
Don’t be like Jimmy: why quality improvement matters
Authors: Anne-Martine Storm van Leeuwen, Jo- Inge Myhre
Journal: BMJ (2010)

Friday afternoon, 4 pm. Jimmy turns around and starts discussing the coming weekend with some friends. Jimmy is in medical school, and he is attending a lecture on patient safety. The abstract material in the lecture and the lack of any practical experience causes Jimmy to be distracted. He doesn’t quite understand what the professor is talking about but catches the last part: “So after a root cause analysis of this near miss we can conclude …