tbuckley/cabot-search huggingface dataset:
Abstract 110: Histologic Assessment of a Case of Likely Kawasaki Disease in 1870 London
Authors: Standford T Shulman, Anne Rowley, Jan Orenstein
Journal: Circulation (2015)

William Shrosbree, a 7 yo boy, died in 1870 at St. Bartholomew’s Hospital in London, England, “in consequence of scarlatinal dropsy” after a 2 d hospitalization. His case was cryptically reported briefly by Dr. Samuel Gee in 1871, who found 3 epicardial coronary artery (CA) aneurysms at autopsy, each containing “small recent clots, quite loose.” Two aneurysms were “pea-sized” at the apex close to the tip of the right auricular appendage, while the 3 rd was the size of a “horse bean” and located in the sulcus at the posterior base of the ventricles. “Specks of atheroma” were described in the aorta “near the valves” and on the aortic cusp of the mitral valve. The heart was reported to be of normal size, and the valves were healthy. We have had the opportunity to study a limited number of CA photomicrographs of this specimen. Overall, the vasculopathy in this case is highly compatible with our recent description of pathognomonic histologic features in 41 fatal or transplanted KD cases with severe disease (PLoS One, 2012). Of the 3 characteristic linked pathologic processes we reported, the limited number of sections do not show acute self-limiting necrotizing arteritis, which is relatively rare. Areas of subacute/chronic (SA/C) vasculitis containing barely recognizable lymphocytes, variably damaged media and prominent fibrotic adventitial fibrosis are seen. Very little of the internal and external elastic lanima could be seen in EVG and methylene blue stained sections. The most characteristic of the 3 processes, luminal myofibroblastic proliferation (LMP), is variable in prominence. The medium power magnification, H+E and methylene blue stained sections show a relatively uniform circumferential luminal layer thicker than the normal media. A higher magnification H+E section shows up to 100% LMP narrowing of the lumen involving about half the vessel, containing relatively prominent pleomorphic cells that may be myofibroblasts. The lumen in another section shows total obliteration by LMP with similar myofibroblasts and half of the media replaced by LMP. The gross and histologic features of the CA of the child who died in 1870 in London are highly compatible with the changes noted in severe KD, suggesting that this illness was present as early as the 19 th Century.
General practice out-of-hours service in Ireland provides a new source of syndromic surveillance data on influenza
Authors: E D Brabazon, M W Carton, C Murray, L Hederman, D Bedford
Journal: Eurosurveillance (2010)

The use of routinely available electronic sources of healthcare data on the spread of influenza has the potential to enhance current surveillance activities. This study aimed to develop a method for identifying influenza-related records from general practitioner(GP) out-of-hours (OOH) services in Ireland. Data from one such service were interrogated for keywords relating to influenza-like illness (ILI) and a proxy measure of influenza activity in the community setting was developed. Comparison of this syndromic surveillance measure with national data on ILI consultation rates demonstrated a statistically significant temporal correlation.In five out of six influenza seasons investigated,peaks in the GP OOH influenza-related calls appeared at least one week ahead of peaks in the national ILI consultation rates. The method described in this paper has been extended to nine OOH services in Ireland (covering 70% of the Irish population) to provide weekly figures on self-reported illness for influenza in the community and its data have been incorporated into the national weekly influenza reports produced by the Health Protection Surveillance Centre. These data should provide early warnings of both seasonal and pandemic influenza in Ireland.
Abstract 10098: Predictors of Sleep Quality Improvement Among Overweight or Obese Individuals: A Randomized Controlled Trial
Authors: Soohyun Nam, Kerry J Stewart, Devon A Dobrosielski
Journal: Circulation (2012)

BACKGROUND:  Sleep disturbances have adverse cardiovascular consequences and are linked to glucose intolerance and obesity. Weight loss and exercise are primary treatments for obese patients with glucose intolerance yet few lifestyle intervention trials have evaluated changes in sleep quality in relation to changes in body composition and fitness.   METHODS:  We randomized persons aged 35-65 years with type 2 diabetes or pre-diabetes to 6-months of weight loss diet (D); or D combined with supervised moderate-intensity exercise training (D+E). Sleep quality was determined with a 50 item self-report questionnaire that identifies symptoms of apnea, daytime fatigue, hypersomnolence, circadian rhythm sleep disorder, insomnia, restless sleep, parasomnia, and dream disorders. Sleep quality is a composite score of all these items. Other measurements included weight; body mass index (BMI); total, abdominal subcutaneous and visceral fat by magnetic resonance imaging; and aerobic fitness expressed as VO 2 peak during treadmill testing.   RESULTS:  Of 77 subjects randomized, 55 participants (54.8 ± 7.8 years; n=24 of 38 D, n=31 of 39 D+E) completed the study. At 6 months, both groups improved from baseline (p 2 ; D+E:-104.16 ± 72.37 cm 2 , p= 0.92), VO 2 peak (D: 2.26 ± 3.92 ml/kg/min ; D+E:3.71 ±2.65 ml/kg/min, p=0.11), and sleep quality (D: -3.53 ± 7.69; D+E:-0.37 ±7.23, p=0.16). In bivariate analysis, improvement in sleep quality was associated with a reduction in BMI (r=0.47, p   CONCLUSION:  The novel finding herein is that a reduction in abdominal subcutaneous fat, with either diet alone or diet plus exercise, was associated with improved sleep quality. These data suggest that interventions that target central obesity may prove to be an effective strategy for reducing the incidence and severity of sleep disorders.
Re: Nicholas J. Giacalone, William U. Shipley, Rebecca H. Clayman, et al. Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience. Eur Urol 2017;71:952–60
Authors: Saeid Safiri, Erfan Ayubi
Journal: European Urology (2017)
Nonreproducibility of Preclinical Research—Reply
Authors: John P. A. Ioannidis
Journal: JAMA (2017)

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Immune Reconstitution (IR) after Allogeneic Hematopoietic Cell Transplantation (alloHCT): Comparing Results in Recipients of Unrelated Umbilical Cord Blood (UCB) to Those with an HLA-Matched Sibling Donor Peripheral Blood (MSD PB)
Authors: Nelli Bejanyan, Claudio G Brunstein, Qing Cao, Rohtesh S. Mehta, Xianghua Luo, Julie Curtsinger, Sarah Cooley, Bruce R. Blazar, Jeffrey S. Miller, Daniel Weisdorf, John E. Wagner, Michael R. Verneris
Journal: Blood (2016)
Стеатометрія й еластометрія як методи неінвазивної діагностики стеатозу та фіброзу підшлункової залози у дітей
Authors: Yu.M. Stepanov, N.H. Gravirovska, O.Yu. Lukianenko
Journal: GASTROENTEROLOGY (2017)

Актуальність. Ожиріння асоційовано з ектопічним накопиченням жиру з відкладенням жиру у паренхіматозних органах, у тому числі у підшлунковій залозі (ПЗ) з формуванням її стеатозу. Тривалий перебіг стеатозу підшлункової залози здатний призводити до хронічного запалення та фіброзу органу. Обмеженість проведення інвазивних досліджень у дітей обумовлює потребу у розробці та впровадженні в практику охорони здоров’я новітніх неінвазивних методів обстеження підшлункової залози. Мета: вивчити можливість ультразвукової діагностики стеатозу та фіброзу підшлункової залози у дітей з використанням методу стеатометрії (оцінка швидкості згасання ультразвуку) та еластометрії. Матеріали та методи. Було обстежено 60 дітей, які знаходились на стаціонарному лікуванні у відділенні дитячої гастроентерології ДУ «Інститут гастроентерології НАМН України». Розподіл за групами відбувся на основі наявності ожиріння й надмірної маси тіла: 1-шу групу становили 44 пацієнти з ожирінням і надмірною масою тіла, 2-гу групу — 16 дітей з нормальною масою тіла. Сонологічне дослідження, еластометрія та стеатометрія проводились на апараті Ultima PA Expert («Радмір», Україна). Наявність та ступінь стеатозу підшлункової залози визначались при попарному порівнянні ехогенності ПЗ з ехогенністю нирок та заочеревинного жиру. Результати. Було виявлено, що серед пацієнтів 1-ї групи 25 дітей (56,8 %) мали сонологічні ознаки стеатозу підшлункової залози, третина хворих мала ехографічні ознаки неспецифічних запальних зміни паренхіми залози. Аналіз даних стеатометрії ПЗ виявив, що середня величина коефіцієнту затухання ультразвуку у представників 1-ї групи була вірогідно вище за відповідний показник 2-ї групи (р &lt; 0,05) і становила (2,45 ± 0,39) дБ/см у представників 1-ї групи та (1,80 ± 0,23) дБ/см у представників 2-ї групи. Середній показник жорсткості паренхіми ПЗ у дітей із нормальною масою тіла був вище за аналогічний показник пацієнтів з ожирінням і надмірною масою тіла, але вірогідність відмінностей не була достатньою. У представників 1-ї групи середнє значення жорсткості паренхіми ПЗ становило (3,69 ± 0,78) кПа та (3,78 ± 0,27) кПа — у 2-й групі. Висновки. Встановлено, що середній показник коефіцієнту затухання ультразвуку під час сонографії підшлункової залози у дітей з ожирінням і надмірною масою тіла є вірогідно вищим порівняно з пацієнтами, які мають нормальну масу тіла, що свідчить на користь наявності стеатозу підшлункової залози у дітей з ожирінням/надмірною масою тіла. Проведене дослідження свідчить про можливість використання стеатометрії та еластометрії як методів діагностики стеатозу й фіброзу підшлункової залози у дітей.
Breast cancer liver metastases in a UK tertiary centre: Outcomes following referral to tumour board meeting
Authors: Hiba Abbas, Simon Erridge, Mikael H. Sodergren, Michail Papoulas, Aamir Nawaz, Krishna Menon, Nigel D. Heaton, Andreas A. Prachalias, Parthi Srinivasan
Journal: International Journal of Surgery (2017)
N-acetylcysteine (NAC) downregulates type I insulin-like growth factor receptor (IGF-IR) and epidermal growth factor receptor (EGFR) on colorectal carcinoma cell lines – possible mechanism underlying NAC-mediated chemoprevention and chemotherapy
Authors: RG Kelly, K Nally, GC O'Sullivan, F Shanahan, J O'Connell
Journal: Endoscopy (2006)

Aims: To determine the molecular mechanisms underlying the chemopreventive and chemotherapeutic effects of the thiol-containing antioxidant N-acetylcysteine (NAC).
Combined versus sequential antracycline and taxane adjuvant regimens in triple negative breast cancer patients.
Authors: Arzu Oguz, Gul Sema Yildiran Keskin, Zafer Akcali, Dilsen Colak, Ozden Altundag, Mustafa Kadri Altundag
Journal: Journal of Clinical Oncology (2016)

e12578 Background: Chemotherapy regimens that contain both antracyclines and taxanes have been shown to increase disease free and overall survivals in patients with operable breast cancer patients. For node-positive patient group, sequential antracycline+cyclophosphamide (AC) and taxane regimen improved disease free survival (DFS) when compared with concurrent doxorubisin, cyclophosphamide and docetaxel (TAC) combination. To our knowledge, there is no data regarding the difference in between these regimens for the molecular subtypes of breast cancer. In this study we aimed to compare the clinical outcomes of triple negative breast cancer (TNBC) patients who had received adjuvant TAC versus AC followed by paclitaxel chemotherapy regimens. Methods: The files of TNBC patients were reviewed retrospectively and the demographical and clinicopathological properties of the patients and tumors were noted. The patients who had taken AC followed by paclitaxel or TAC regimens in adjuvant setting were identified and overall survival (OS) and DFS values were compared between these 2 groups. Results: A total of 414 TNBC patients’ files were reviewed and of these 328 (79.2%) had taken adjuvan treatments. TAC was given to 46 patients and AC followed by paclitaxel was given to 78 patients in adjuvant setting. Median ages were 44 and 46 years and there was no difference in between two groups (p:0.737).T and N stages; presence of lymphovascular and perineural invasion and extracapsular extension were compared in between two groups and there was no significant difference in between (p > 0.05 for all). Median DFS was 94.3 months for sequential group but it was not reached in TAC group and the difference was statistically significant (p:0.033). Median OS values were not reached in both groups, but survival in TAC group was statistically longer than other group (p:0.011) Conclusions: In this retrospective study, TAC regimen seems to be more effective than sequential regimen in TNBC subgroup. But prospectively designed studies are needed to verify this finding whether molecular subtypes and genetic profiles make the difference.
Do BRCA 1 mutations affect selected molecular variables in women with breast and ovarian cancer carrying cerebral metastases?
Authors: Janina Markowska, Anna Markowska, Monika Szarszewska, Stefan Sajdak, Pawel Knapp, Anna Grybos, Anita Olejek, Wiesława Bednarek, Andrzej Marszalek, Ewa Markwitz, Robert Jach, Piotr Tomczak, Anita Monika Chudecka-Glaz, Rodryg Ramlau, Violetta Filas, Marian Grybos, Joanna Stanislawiak-Rudowicz, Karolina Jaszczyńska-Nowinka, Krystyna Adamska
Journal: Journal of Clinical Oncology (2017)

e13017 Background: Cerebral metastases develop in 10-30% of patients with breast cancer and in around 3.3 to 4% of patients with ovarian cancer. The present study evaluates the expression of ER alpha and beta receptors, PR, HER2 and markers associated with metastases: stromal cell-derived factor-1 (SDF1) and its receptor CXCR4, breast cancer metastasis suppressor (BRMS1), astrocyte elevated gene (AEG-1), depending on the status of BRCA1 protein in cancerous cells of the patients (somatic mutation). Methods: The material originated from 30 women with breast cancer and 22 patients with ovarian cancer in whom cerebral metastases were detected. The studies were conducted on paraffin block sections, the markers were detected using immunocytochemistry, employing specific antibodies. Results: In the breast cancer group, BRCA 1 protein expression was detected in 11 patients, absence of the protein in 19. No significant differences were disclosed in the grade of ER, PR, HER2, SDF1, CXCR4, BRMS1 or AG-1 expression which would be dependent on the status of BRCA1. Expression of the proteins failed to correlate with patients' age, clinical advancement at diagnosis, presence of metastases to lymph nodes. Patients with no PR expression significantly more frequently manifested high expression of CXCR4 (p = 0.0436). The ovarian cancer group included 7 patients with expression of BRCA1 protein, absence of such expression was recorded in 15 patients. No statistically significant differences were disclosed in the expression of the studied factors which would be related to the status of BRCA1 in cancer cells. Also, no differences were detected in the expression of the studied factors which would depend on the patient’s age, primary advancement of the disease or histological type of the cancer. Conclusions: Among numerous molecular factors examined in women with breast or ovarian cancer no statistically significant differences were detected which would depend on BRCA1 protein status in cancer cells. The absence of PR expression in women with breast cancer was associated with high expression of CXCR4, which might indicate that PR-negative women with breast cancer exhibit higher metastatic potential.
Response to ado-trastuzumab emtansine according to RANO criteria in central nervous system metastases of HER2 positive breast cancers.
Authors: Audrey Mailliez, Edwina Girard, Thomas Boulanger, Claire Giraud, Jacques Bonneterre, Emilie Le Rhun
Journal: Journal of Clinical Oncology (2016)

605 Background: Central nervous system (CNS) metastases are frequent in Her2 positive breast cancers (BC). Local treatment remains the standard of care, however systemic treatments may also represent a therapeutic option. Ado-trastuzumab Emtansine (TDM1) significantly improves outcomes of Her2 positive BC patients (pts), but only a few data have been published on its impact on CNS metastases. This multicentric retrospective cohort aims to evaluate the efficacy/safety of TDM1 in this setting in the common practice. Methods: Data from 14 pts treated with TDM1 for CNS metastases of Her2 positive breast cancers since February 2013 were retrospectively collected in two sites. RANO criteria were used for the CNS evaluation and RECIST criteria for systemic evaluation, both performed every 9 weeks. Safety was evaluated according to the NCI-CTC criteria. Results: Median age was 48.6 years (34.4-63.5). Median follow up was 12 months (mos) (5.4-35.9). Tumours were CCI (13/14) or CLI (1/14) and 10 (71%) expressed hormone receptors. Pts had brain metastases in 10 cases, leptomeningeal metastases in 1 and both in 3. Median number of previous chemotherapy regimens was 2 (0-7). Pts had received a prior treatment with trastuzumab in 13 cases, lapatinib in 11, pertuzumab in 1. TDM1 was administered as first treatment of CNS metastases in 1 case, and for progressive CNS metastases in 13. The median number of TDM1 cycles was 4 (1-13). CNS responses were achieved in 4/14 cases (28%), CNS stabilization in 3/14 cases (21%) and the median CNS progression free survival was 2.43 mos (2-9.4). Systemic responses were observed in 3/11 (27%) while systemic stabilizations were noted in 5 (45%) pts. First sites of progression were systemic: 2 cases (15%), CNS: 7 (53%) or both 2 (15%). TDM1 was discontinued in 2 pts for toxicity. TDM1 is still ongoing for one pt. The median OS was 9.07 mos (3.65-24.8). Ten pts are still alive. Treatment was well tolerated with only 2 grade 3/4 adverse events (1 pancreatitis and 1 skin toxicity). Conclusions: TDM1 shows significant efficacy in this non-selected population according to RANO criteria. This study is still ongoing prospectively and results will be updated for the meeting.
Identifying likely metastatic sites for triple negative breast cancers using immunohistochemical biomarkers.
Authors: Sergey Klimov, Andrew R. Green, Mohammed Aleskandarany, Emad Rakha, Ian O. Ellis, Michelle D. Reid, Padmashree C.G. Rida, Ritu Aneja
Journal: Journal of Clinical Oncology (2016)

1092 Background: Unique organ microenvironment may preferentially support growth of specific tumor clones because of which different breast cancer subtypes show distinct tropisms for sites of metastasis. While a few gene expressionbased signatures are known to predict sitespecific metastasis of breast cancer, little work has focused on identification of clinically facile immunohistochemical predictors of metastasis to specific sites, especially for triple negative breast cancers (TNBCs). Methods: Primary tumor samples from 322 TNBC patients were stained for 133 biomarkers and assessed by immunohistochemistry. Differences in average levels of these biomarkers were compared between patients with or without metastasis to specific sites (brain, bone, lungs, liver, lymph nodes). Significantly different biomarkers were then analyzed within a Cox regression model to evaluate their prognostic value when patients with metastasis to the site of interest were compared to patients with no metastasis. Ideal thresholds, based on maximizing model fit, stratified cohorts that show high and low expression of each biomarker. Results: Our analysis uncovered several biomarkers whose expression levels in primary tumors can predict the site of future metastasis in TNBCs. The variables which provided the largest significant (p < 0.01) change in hazard for a specific site included a low Adjacent CD8 for bone (HR = 3.642), high Poly (ADPribose) polymerase1 (PARP1) % (HR = 4.35) for brain, retinoidrelated orphan receptorγ cytoplasmic Hscore (HR = 5.292) for lung, high trefoil protein TFF1 % (HR = 2.194) for liver, and a low Vitamin D Receptor Nuclear Hscore (HR = 8.767) for lymph node. When tested using the whole dataset, (a) biomarkers that predicted metastasis to liver and brain showed sensitivity > 0.75, and (b) biomarkers that predicted metastasis to liver and lung, showed specificity > 0.75, respectively. Conclusions: Relatively simple and inexpensive immunohistochemical analyses of biomarkers in primary tumors of TNBCs may allow prediction of the site of future metastasis. Highrisk patients may benefit from increased surveillance of such sites.