tbuckley/cabot-search huggingface dataset:
Sociodemographic and obstetric characteristics of stillbirths in China: a census of nearly 4 million health facility births between 2012 and 2014
Authors: Jun Zhu, Juan Liang, Yi Mu, Xiaohong Li, Sufang Guo, Robert Scherpbier, Yanping Wang, Li Dai, Zheng Liu, Mingrong Li, Chunhua He, Changfei Deng, Ling Yi, Kui Deng, Qi Li, Xia Ma, Chunmei Wen, Dezhi Mu, Carine Ronsmans
Journal: The Lancet Global Health (2016)

Very little is known about the burden and determinants of stillbirths in China. We used data from a national surveillance system for health facility births to compute a stillbirth rate representative of all facility births in China and to explore sociodemographic and obstetric factors associated with variation in the stillbirth rate.We used data from China's National Maternal Near Miss Surveillance System between Jan 1, 2012, and Dec 31, 2014, which covers 441 hospitals in 326 urban districts and rural counties. The surveillance aimed to enumerate all maternal deaths and near misses in health facilities, and collected data prospectively for all pregnant or post-partum women admitted to the obstetric department. We restricted the analysis to births of 28 or more completed weeks of gestation or 1000 g or heavier birthweight. We examined the strength of association between sociodemographic characteristics, gestational age, and obstetric complications and stillbirths using logistic regression, taking account of the sampling strategy and clustering of births within hospitals and in cases of more than one birth per woman.There were 3 956 836 births and 37 855 stillbirths, giving a stillbirth rate of 8·8 per 1000 births (95% CI 8·8-8·9). The stillbirth rate was particularly high for women younger than 15 years of age (59·9 stillbirths per 1000 births), those who had not sought antenatal care (38·3 per 1000), the unmarried (32·5 per 1000), those with no education (26·9 per 1000), or those who had had four or more births (23·2 per 1000). A high proportion (29 319 [78·2%] of 37 514) of stillbirths occurred at gestational ages of younger than 37 weeks, and about two thirds (24 787 [66·1%] of 37 514) were in women without any maternal complication at the time of birth. Of babies born at normal gestations (37-41 weeks), maternal complications substantially increased the risk of stillbirth (odds ratio comparing antepartum or intrapartum complications with no complication 3·96 [95% CI 3·66-4·29]), but only a small proportion (1638 [4·4%] of 37 514) of stillbirths fell into this group.Our analysis of nearly 4 million births in 441 health facilities in China suggests a stillbirth rate of 8·8 per 1000 births between 2012 and 2014. Stillbirths do not feature in the Chinese Government's 5 year plans and most information systems do not include stillbirths. The Government need to start paying attention to stillbirths and invest strategically in antenatal care, particularly for the most disadvantaged women, including the very young, unmarried, and illiterate, and those at high parity.National Health and Family Planning Commission of the People's Republic of China, National Natural Science Foundation of China, China Medical Board, WHO, and UNICEF.
Production of Serotonin by a Transplantable Strain of Histamine-Producing Primary Gastric Carcinoid of &lt;italic&gt;Mastomys natalensis&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Suyama, T Saito, K Hara, H Kito, S Hosoda
Journal: JNCI Journal of the National Cancer Institute (1984)

Two biochemically distinguishable transplantable tumor strains (A and B) were established from a primary gastric carcinoid of Mastomys secreting histamine alone. Strain A in the third generation acquired a new ability to produce serotonin [5-hydroxytryptamine (5-HT)] and retained endocrine activities to produce both histamine and 5-HT through the following subpassages, whereas strain B (like the primary tumor) continued to produce histamine alone. The findings were further supported by the immunohistochemical demonstration of 5-HT-containing tumor cells in strain A after generation 3 and the absence of such cells in strain B and also by the ultrastructural demonstration of tumor cells containing pleomorphic secretory granules in strain A after the third generation but not in strain B. Sixteen samples of Formalin-fixed, paraffin-embedded primary gastric carcinoids of Mastomys were stained by the same immunohistochemical method for 5-HT detection. The positively stained tumor cells were demonstrated in 4 tumor samples, though they were scantily distributed in tumor parenchyma except for 1 metastasizing tumor. 5-HT-producing tumor cells appeared through many proliferative cycles of the deranged histamine-producing cells. The endocrinologic similarity was noted between this transplantable tumor strain and a specific type of gastric carcinoid in humans, and the possible histogenesis of the latter tumor was discussed on the basis of data obtained from the present transplantation experiments.
Predictive value of EGFR gene copy number and K-ras mutation for pathological response to preoperative cetuximab, 5FU, and radiation therapy in locally advanced rectal cancer (LARC)
Authors: C. Bengala, S. Bettelli, F. Bertolini, S. Salvi, C. Sonaglio, L. Losi, G. Sartori, C. Dealis, B. Gatteschi, P. F. Conte
Journal: Journal of Clinical Oncology (2008)

4125 Background: Cetuximab improves activity of chemotherapy in metastatic colorectal cancer (mCRC). Gene copy number (GCN) of EGFR has been suggested to be a predictive factor of response to Cetuximab in patients (pts) with mCRC; moreover K-ras mutation has been associated with resistance to cetuximab in mCRC. Methods: We have designed a phase II study with Cetuximab as single agent weekly for 3 weeks followed by the combination with 5-FU and radiation therapy (50 Gy) as neoadjuvant treatment for LARC. The trial included the analysis of EGFR expression, EGFR GCN and K-ras mutation on diagnostic biopsy. EGFR was determined by immunohistochemistry, EGFR GCN by FISH, K-ras mutation (codons 12 and 13) by PCR-based sequencing. High GCN was defined as EGFR/nucleus ratio > 2.9 or a EGFR/CEP7 polysomy > 4 in at least 50 % of the cells. Tumor regression grade (TRG) was evaluated according to Dworak on surgical specimens. Results: Forty pts have been treated. Median age was 59 years (range 35- 74); median number of cetuximab administrations was 8 (range 1–8) with 70 % of the pts completing the planned doses. Two pts did not undergo to surgery: for refusal (1 pt), for progression of disease (1 pt). A TRG 3 and 4 was achieved in 9 (23.1%) and 3 pts (7.7%) respectively. IHC and FISH data are available on 39 pts. So far K-ras mutation status is available on 26 pts. Twenty-one pts (53.8%) had a high EGFR GCN; moreover 22 pts (56.4%) had a polisomy. The concordance between the two tests was 97 %. Eleven of the 21 pts with high GCN (52.4 %) had a TRG 3–4 compared to 1 out of 17 pts (5.6%) with low GCN (p: 0.0016). Moreover 12 of the 22 pts with high polysomy (54.6%) had a TRG 3–4 compared with no response in the 17 pts with a low polysomy: (p=0.0003). Three of the 14 EGFR (IHC) positive pts (21.4%) had a TRG 3–4 vs. 9 of the 25 (36%) negative pts (p: 0.34). K-ras mutation was found in 5 pts (19%). Pts with K-ras mutation had lower rate of high TRG: 20 % vs. 38.1% (p: 0.45). Conclusions: Our analysis confirms that EGFR amplification is predictive of high TRG to neoadjuvant cetuximab plus 5FU and radiotherapy in pts with LARC. Moreover K-ras mutation is associated with a lower rate of pathological tumor regression. No significant financial relationships to disclose.
Follicular lymphoma with t(8;14)(q24;q32): a distinct clinical and molecular subset of t(8;14)-bearing lymphomas
Authors: M Ladanyi, K Offit, NZ Parsa, MR Condon, N Chekka, JP Murphy, DA Filippa, SC Jhanwar, R Dalla-Favera, RS Chaganti
Journal: Blood (1992)
Abstract 19661: Integrin Imaging for the Detection of Diffuse Myocardial Fibrosis in Patients with Hypertrophic Cardiomyopathy: Direct Comparison Between Single-Photon Emission Computer Tomography and Cardiovascular Magnetic Resonance The SCAR Study
Authors: Myra S Cocker, Girish Dwivedi, Brian Marvin, Marlie Poirier, Carole Dennie, Glenn Wells, Kathy Ascah, Robert Roberts, Alexander Dick, Terry D Ruddy
Journal: Circulation (2012)

Background Hypertrophic cardiomyopathy (HCM) promotes diffuse myocardial collagen synthesis, disarray and hypertrophy. Cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) can detect focal fibrosis in HCM, although the injury process in HCM may be global and diffuse. αvβ3 is a vitronectin integrin receptor associated with fibroblasts and collagen synthesis. A 99 Technetium compound ( 99m Tc- NC100692 ) that binds with high affinity to αvβ3 has been developed. Thus, we hypothesize that 99m Tc- NC100692 could be used to detect focal and diffuse myocardial fibrosis in patients with HCM. Methods 5 patients (62±11 years, 4 male) with a diagnosis of HCM from echocardiography were prospectively recruited. Patients underwent SPECT 99m Tc- NC100692 and CMR LGE imaging. Using a 17-segment model, 99m Tc- NC100692 images were visually assessed for myocardial uptake using a 3-point scale. LGE images were assessed for the presence or absence of enhancement per segment. Results For the 5 patients, 85 segments were evaluated and all had some degree of 99m Tc- NC100692 uptake. Three patients had evidence for focal LGE in 9 segments. Of these 9 segments, 5 had matched high-grade 99m Tc- NC100692 uptake. One patient had strong apical 99m Tc- NC100692 uptake without any evidence of hypertrophy nor LGE. The remaining 79 segments had low-grade 99m Tc- NC100692 uptake with lack of evidence for LGE. Conclusion Diffuse low-grade myocardial uptake of 99m Tc- NC100692 in patients with HCM may be suggestive of diffuse fibrosis. 99m Tc-NC10069 may serve as a marker of myocellular disarray although further studies are required to determine the specificity of 99m Tc-NC100692.
Who needs health care?
Authors: Brian Neeson
Journal: BMJ (2005)

Modified Mediterranean diet and survival Evidence for diet linked longevity is substantialEditor-The EPIC-elderly cohort study was designed to investigate the association between a modified Mediterranean diet and longer life expectancy among an elderly subpopulation (older than 60) that is part of the larger EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. 1 2 Focusing the attention on a sample with a more restricted age range seems to reinforce previous findings on diet linked longevity, but important risk factors were not taken into account in collecting the data.Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and blood pressure are well known determinants of cardiovascular disease.The study's outcomes are expressed in term of mortality, and cardiovascular disease remains the most important of all causes of death.The benefits of a healthy eating pattern with respect to these variables have been shown. 3he same might not be sustained if the total EPIC cohort were considered (aged 20-85). 2 Have the authors considered any possible statistical gain from including these risk factors in the analysis when considering the younger subgroup?We believe that the conclusions for participants older than 60 are stronger if the risk of cardiovascular disease in men and women after the menopause is considered.In a world in which people eat mainly processed foods that are rich in saturated fats, the analysis is a warning to adopt a healthier dietary pattern and, broadly, lifestyle changes.
Role of <i>KRAS</i> mutation in predicting response, progression-free survival, and overall survival in irinotecan-refractory patients treated with cetuximab plus irinotecan for a metastatic colorectal cancer: Analysis of 281 individual data from published series
Authors: F. Di Fiore, E. Van Cutsem, P. Laurent-Puig, S. Siena, M. Frattini, W. De Roock, A. Lièvre, A. Sartore-Bianchi, A. Bardelli, S. Tejpar
Journal: Journal of Clinical Oncology (2008)

4035 Background: Cetuximab, a monoclonal antibody (mAb) directed against the epidermal growth factor receptor (EGFR), is approved in combination with irinotecan (Iri) for the treatment of Iri-refractory metastatic colorectal cancer (MCRC) expressing EGFR. Recent studies have shown that KRAS mutation (mut) confers resistance to anti-EGFR mAbs. We extracted data of 281 patients (pts) from 7 series (Lievre 2006 and 2008, Moroni 2005, Di Fiore 2007, De Roock 2007, Benvenuti 2007, Frattini 2007) to determine the role of KRAS mut in Iri-refractory MCRC patients treated with cetuximab plus Iri based-chemotherapy (CT). Methods: The following data were collected: sex, age, previous CT lines, anti-EGFR regimen, response rate based on RECIST criteria, progression-free survival (PFS), overall survival (OS) and KRAS mutational status. Response rate was evaluated using the Fischer exact test. PFS and OS were calculated using the Kaplan-Meier method and compared with log-rank test. Predictive factors of response and survival were determined by logistic regression and Cox-regression model, respectively. Results: A total of 281 pts were included, 174 men and 107 women with a mean age of 59.8 yrs. Pts received a mean of 2.4 prior CT lines. 77 pts (27.4%) responded (3 complete response (CR) and 74 partial response (PR)), 107 (38.1%) had stable disease (SD) and 97 (34.5%) had disease progression (PD). A KRAS mut was detected in 98 pts including 40/107 (37.4%) pts with SD and 58/97 (59.8%) with PD. All responders were KRAS wild-type. KRAS mut was significantly associated with PD (p< 0.0001). Median PFS and OS were significantly lower in mutated KRAS pts, 12 weeks (wks) vs 24 wks (p<0.0001) and 36 wks vs 44 wks (p<0.0001), respectively. The absence of KRAS mut was identified as predictive factor of disease control (CR+PR+SD) (p<0.0001,OR:0.17;95IC:0.10–0.30) and OS (p<0.0001,OR:0.51;95IC:0.37–0.70), respectively. Conclusions: KRAS mutational status plays a key role in response rate, PFS and OS in Iri-refractory MCRC pts treated with cetuximab and Iri. Our results demonstrate the potentially major impact of KRAS mutation in pts selection. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Merck Merck Amgen
Panitumumab (pmab) regimen evaluation in colorectal cancer to estimate primary response to treatment (PRECEPT): Effect of <i>KRAS</i> mutation status on second-line treatment (tx) with pmab and FOLFIRI
Authors: A. L. Cohn, D. A. Smith, M. A. Neubauer, G. Houston, P. Khandelwal, R. G. Wiggans, S. Suzuki, M. Yassine, R. Deeter, R. Sikorski
Journal: Journal of Clinical Oncology (2008)

4127^ Background: Pmab, a fully human antibody to the epidermal growth factor receptor (EGFr), has demonstrated efficacy as monotherapy in patients (pts) with metastatic colorectal cancer (mCRC) after disease progression (PD) on standard chemotherapy (CT). The mutation status of the KRAS gene in tumors has been shown to be a predictive biomarker of response to anti-EGFr antibody monotherapy in mCRC. This study was designed to prospectively estimate the efficacy of FOLFIRI+pmab tx according to tumor KRAS status in patients undergoing second-line tx for mCRC. Methods: 110 pts (as planned) with mCRC with PD after first-line tx with oxaliplatin- based CT+bevacizumab were enrolled in this phase 2, open-label, single-arm trial. Pts had unresectable, measurable disease (per RECIST), ECOG status 0 or 1, and tumor tissue available for KRAS testing. Pts received pmab (6 mg/kg) and FOLFIRI Q2W until PD or intolerability. Tumor assessments were performed at weeks 8, 16, 24, 32, and every 12 weeks thereafter. KRAS mutation status was assessed in extracted DNA from fixed tumor sections using real-time PCR. Safety endpoints included incidence and severity of adverse events (AEs). Efficacy endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS) by KRAS status. Results: At the time of interim data cutoff, 51 pts completed week-16 tumor assessments. Pts received a mean of 6 pmab doses. Pmab-related AEs were seen in 90% of pts. 43 pts (84%) had > grade 3 AEs (related and unrelated to tx). 19 pts (37%) had serious AEs. 7 (14%) pts had partial response (2 confirmed). Conclusions: Pmab/FOLFIRI tx was generally well tolerated and had activity within the expected range in the unselected population. Updated response, PFS, and OS data by KRAS status will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen Inc. Amgen Inc., Bristol-Myers Squibb, Genentech
What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC)
Authors: A. Drilon, G. Li, S. Dogan, M. Gounder, R. Shen, M. Arcila, L. Wang, D.M. Hyman, J. Hechtman, G. Wei, N.R. Cam, J. Christiansen, D. Luo, E.C. Maneval, T. Bauer, M. Patel, S.V. Liu, S.H.I. Ou, A. Farago, A. Shaw, R.F. Shoemaker, J. Lim, Z. Hornby, P. Multani, M. Ladanyi, M. Berger, N. Katabi, R. Ghossein, A.L. Ho
Journal: Annals of Oncology (2016)

BackgroundMammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion.Patients and methodsThis alteration was targeted with the pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against cell lines containing various NTRK1/2/3 fusions.ResultsA dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Structural modeling predicts that this alteration sterically interferes with drug binding, correlating to decreased sensitivity to drug inhibition observed in cell-based assays.ConclusionsThis first report of clinical activity with TrkC inhibition and the development of acquired resistance in an NTRK3-rearranged cancer emphasize the utility of comprehensive molecular profiling and targeted therapy for rare malignancies (NCT02097810).
Combination of oxaliplatin (OXA) and 5-fluorouracil, leucovorin (5-FU/LV), as first line therapy, in elderly patients &gt;70years, with metastatic colorectal cancer
Authors: H. G. Botto
Journal: Journal of Clinical Oncology (2004)

3717 Background: In a previous trial the efficacy of OXA-5-FU/LV combination was reported in Metastatic Colo-Rectal Cáncer (MCRC) patientes (pts), refractory to 5-FU/LV, (H.G.Botto ASCO, 2000, 1050). The purpose of this study was to evaluate the tolerance and effectiveness, of the combination of OXA-5-FU/LV given every two weeks, as first line therapy, to elderly pts ≥70 years (y) with MCRC. Methods: Fourteen elderly pts. ≥ 70 y previously untreated with MCRC, and with good hematological, cardiac and renal functions, compose the sample to this trial; median age was 73 years ( range 70–83 y), M/F 8/6; PS, 0=6, 1=5, 2=3; sites of disease: liver 8, locoregional 4, lung 2. Treatments: OXA 70 mg/m2 IV, 5 FU 500 mg/m2/LV 20 mg/m2, IV, every two weeks, until disease progression or toxicity; response was proved every 8 weeks, the median n° of cycles was 6 (range 4–12 cycles), the total n° of cycles was 86. In all pts the response to treatment, toxicity and survival have been evaluated. Results: PR 5/14 (35,71%), SD 5/14 (35,71%), PD 4/14 ( 28,58% ); OR, 5/14 (35,71%), all pts with hepatic metastasis; and SD 2/14 (14,28%) pts with hepatic metastasis, 2/14( 14,28%) pts with locoregional disease, and 1/14 (7.14%) pt with lung metastasis. Toxicity Gr 2/3: diarrea 6/14 (42,85%), neutropenia 7/14 (50%), thrombocitopenia 4/14 (28,58%), paresthesia 4/14 (28,58% ). Time to disease progression, median 7 months (4–12 m). Overall survival, median 16 months (10–36 m). One pt underwent tumoral hepatic resection after PR with Oxa-5FU/LV. Conclusions: The every two weeks combination of OXA-5-FU/LV, showed in elderly pts ≥ 70 y with metastatic colo-rectal cancer, positive antitumoral response, acceptable toxicity and good survival time. The most important antitumoral activity was detected in the hepatic metastasis. No significant financial relationships to disclose.
Induction of Tumors in Mice Given a Minute Single Dose of Dibenz[&lt;italic&gt;a,h&lt;/italic&gt;]anthracene or 3-Methylcholanthrene as Newborns. A Dose-Response Study
Authors: Roger W. O'Gara, Margaret G. Kelly, Jewel Brown, Nathan Mantel
Journal: JNCI Journal of the National Cancer Institute (1965)

Newborn, noninbred albino mice were given a single subcutaneous injection of either dibenz[a,h]anthracene (DBA) or 3-methyl-cholanthrene (MCA) in olive oil. The males were killed at 54 to 55 weeks of age, the females at 78 to 79 weeks. Eight logarithmically spaced dose levels of each carcinogen were used, ranging downward from 6.7 to 0.0031 μg of DBA and from 11.1 to 0.0051 μg of MCA. Control mice were given olive oil only. One hundred thirty litters were randomly distributed among the treatment and control groups. Subcutaneous fibrosarcomas at the site of the injection were induced at all dose levels of DBA, except one of the intermediate doses. In the animals given MCA, fibrosarcomas were induced at the 4 highest dose levels (11.1–0.4 μg) but not at the 4 lowest dose levels (0.137–0.0051 μg). Nearly all the subcutaneous fibrosarcomas appeared within the first 48 weeks after administration of carcinogen, and only one animal developed a fibrosarcoma after 56 weeks. At the highest DBA level (6.7 μg) and the two highest MCA levels (11.1 and 3.7 μg), the number of pulmonary tumors increased in animals autopsied during the first 55 weeks over those in control animals. Lung tumors were seen as early as 16 weeks after injection of the carcinogen. In female mice autopsied after 55 weeks, there was an increase in pulmonary tumors over controls at the 4 highest dose levels of both carcinogens, that is, from 0.2 μg upward for DBA and from 0.4 μg upward for MCA. A variety of other neoplasms, including leukemias, lymphomas, hepatomas, hemangiomas, and uterine tumors, were found in 10 to 13 percent of female mice 56 to 79 weeks old at death and in 0.8 to 4.5 percent of male mice 54 to 55 weeks old at death. These neoplasms did not appear to be related to the dose of carcinogen and were observed in controls as well as in mice given carcinogen.