tbuckley/cabot-search huggingface dataset:
A phase II study of weekly gemcitabine and docetaxel in first and second line metastatic breast cancer
Authors: C. Isaacs, A. Wang, R. Warren, M. Wilkinson, G. Grana, M. C. Liu, V. Stearns, Y. H. Park, A. Novielli
Journal: Journal of Clinical Oncology (2006)

10668 Background: Combination chemotherapy for metastatic breast cancer has generally been demonstrated to be associated with a higher response rate than single agent therapy, however such therapy is often accompanied by increased toxicity. Thus there is a need to develop well-tolerated combination chemotherapy regimens. Gemcitabine and docetaxel are both active agents in the treatment of this disease, and are effective and well tolerated when administered on a weekly basis. The purpose of this study was to evaluate the therapeutic efficacy and toxicity of weekly gemcitabine and docetaxel as first or second line treatment of metastatic breast cancer (MBC). Methods: Patients with measurable MBC who had received no more than 1 prior chemotherapy regimen in the metastatic setting were treated with gemcitabine 800 mg/m 2 and docetaxel 30 mg/m 2 on days 1 and 8 every 21 days without growth factor support. Results: Thirty-one patients were enrolled. Twenty-nine patients were evaluable for toxicity and 25 for efficacy. Median age was 55 (range 30 to 79). Visceral disease was the dominant site in 74% of patients. Doxorubicin and paclitaxel were previously administered in 74% and 48% of patients respectively. The overall response rate was 56% (complete response in 1 patient and partial responses in 13 patients). Stable disease was evident in 10 additional patients (38.4%). The progression free survival was 35 weeks (range 9 to 101 weeks) and the median overall survival was 17 months. Treatment was well tolerated with the majority of toxicities being grade 1 or 2 (85%). The only grade 3 (G3) or 4 (G4) toxicities observed were neutropenia in 14 participants (G3 41%; G4 7%), anemia in 4 (13%), G3 elevated transaminases in 3 (10%), G3 thrombocytopenia in 1 (3%), G3 flu-like symptoms in 2 (7%) and G3 edema in 1 (3%). Conclusions: The regimen of gemcitabine 800 mg/m 2 and docetaxel 30 mg/m 2 given two weeks out of three for MBC showed excellent overall response of 56% with very good tolerability. The findings from our trial compare well to the response rates of 36% to 79% seen in prior phase II trials utilizing higher doses of this combination chemotherapy. [Table: see text]
Natural history of t(11;14) multiple myeloma
Authors: A Lakshman, M Alhaj Moustafa, S V Rajkumar, A Dispenzieri, M A Gertz, F K Buadi, M Q Lacy, D Dingli, A L Fonder, S R Hayman, M A Hobbs, W I Gonsalves, Y L Hwa, P Kapoor, N Leung, R S Go, Y Lin, T V Kourelis, J A Lust, S J Russell, S R Zeldenrust, R A Kyle, S K Kumar
Journal: Leukemia (2017)
Pooled safety analysis of EGFR-TKI therapy in patients with <i>EGFR</i>-mutated non-small cell lung cancer.
Authors: Masayuki Takeda, Isamu Okamoto, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2014)

e19078 Background: Three epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)—afatinib, erlotinib, and gefitinib—are available for non-small cell lung cancer (NSCLC) patients with EGFR positive-mutations in daily clinical practice; however, no reported trials have directly compared one EGFR-TKI with another EGFR-TKI in terms of efficacy and safety. Thus, we performed a pooled analysis of occurrence of severe adverse events (AEs) according to the type of EGFR-TKI used and ethnicity. This was based on data extracted from prospective clinical trials that evaluated the clinical efficacy of gefitinib, erlotinib, or afatinib monotherapy in patients harboring EGFR mutations. Methods: We searched published reports that prospectively evaluated the clinical efficacy of gefitinib, erlotinib, or afatinib in patients harboring EGFR mutations. Results: A total of 20 trials between 2006 and 2013, consisting of 1,229 patients with EGFR-mutated NSCLC, were eligible for this study. Patients in 13 studies (n = 457) received gefitinib, in 5 studies (n = 513) received erlotinib, and in 2 studies (n = 259) received afatinib. Grade ≥ 3 rashes were significantly more frequent with afatinib therapy than erlotinib therapy, which in turn was significantly higher than gefitinib therapy. The frequency of grade ≥ 3 diarrhea was significantly higher with afatinib therapy than with erlotinib therapy, and there was no significant difference between erlotinib and gefitinib therapies. The estimated incidence of grade ≥ 3 ILD was low in all three EGFR-TKIs, with no significant difference among them. Patients treated with gefitinib had a significantly higher frequency of grade ≥ 3 hepatotoxicity than those treated with erlotinib. The frequency of grade ≥ 3 hepatotoxicity was higher with geftinib therapy than with erlotinib therapy among Asian patients; however, rates of hepatotoxicity between erlotinib and gefitinib were similar in non-Asian populations, thus suggesting that hepatotoxicity may not occur in a dose-dependent manner. Conclusions: Information on the frequency of severe AE according to the type of EGFR-TKI used in the present study may help in selecting the most appropriate EGFR-TKI in EGFR-mutated NSCLC.
Is Terminal Ileal Biopsy Worthwhile in Confirming Complete Colonoscopy?
Authors: S McMillan, E Grabham, P Sharma, R Ahmad, JS McCourtney
Journal: Endoscopy (2006)

Aims: Objective proof of completion at colonoscopy is best obtained by terminal ileal (TI) intubation and biopsy. We wished to assess whether this manoeuvre was valuable in confirming completion when performed by an experienced colonoscopist.
Illnesses and creativity: Byron's appetites, James Joyce's gut, and Melba's meals and mesalliances
Authors: J. Baron
Journal: BMJ (1997)

Even for amateurs the retrospective rediagnosis of the famous is one of the lowest forms of medical history, but I hope this three course dinner with its appetiser (Byron), main course (Joyce), and dessert (Melba) will prove worthy of Christmas 1997.

George Gordon Byron1 2 3 4 5 6 7 8 9 was born in 1788 and was unfortunate in his ancestors. On his father's side were psychopathic noblemen. His great uncle, the 5th “wicked” lord, killed his cousin in 1765 in a duel over the best way to hang game, and after his wife left him begat a bastard by one of his servants, “Lady Betty.” 5 Byron's admiral grandfather, “Foulweather Jack”, was an irresponsible rake, as was his father, “Mad Jack”, who degraded, impoverished and deserted Byron's mother, had an incestuous affair with his own sister Frances,7 and died in 1792. Catherine Gordon, Byron's mother, boasted descent from James I of Scotland, but her ancestors were brigands and melancholics, with her grandfather in 1760 and her father in 1779 both drowning, presumed to be suicidal.

Byron's widowed mother abused him for his father's vices. Byron claimed his nursemaid beat and seduced him.9 In 1798 the 5th lord died, and at the age of 10 Byron inherited the title and moved with his mother from Aberdeen to Newstead Abbey, given to the family by Henry VIII. He lived there on and off until he left England in 1816, never to return.

It would be presumptuous to extol the glories of Byron's poetry or his role as the exemplar of the Romantic hero. His general medical history is well known, especially his lameness, usually thought to be a club foot, for which he wore a brace and boot “which haunted him like a curse.”2 It was …
BROCA gene panel testing in African descendants from northeastern Brazil: Genetic susceptibility profile of an admixed population.
Authors: Gabriela Espirito Santo Felix, Yonglan Zheng, Rodrigo Santa Cruz Guindalini, Taisa Manuela Bonfim Machado-Lopes, Jing Zhang, Juliana Côrtes, Pollyanna Carozo Oliveira, Irlânia S Santos, Thais Bomfim, Bernardo Garicochea, Maria Betania Toralles, Kiyoko Abe-Sandes, Ivana Lucia Oliveira Nascimento, Mary-Claire King, Tom Walsh, Olufunmilayo I. Olopade
Journal: Journal of Clinical Oncology (2017)

1572 Background: The rising global burden of breast cancer (BC) in developing countries demands innovative interventions to accelerate progress in cancer control and prevention. Given the high rates of aggressive young onset breast cancer in Brazil, we sought to examine genetic susceptibility to the disease in the State of Bahia in the Northeast of Brazil, which has the largest population of African descendants. Methods: We screened cases, high-risk breast cancer patients with and without family history of breast cancer, and controls (cancer-free women) for twenty-eight breast cancer susceptibility genes using a validated targeted capture and multiplex sequencing approach – the BROCA panel. Each participant gave informed consent under IRB approved protocols and provided clinical-pathological and epidemiological data. Results: A total of 292 consecutive and unrelated individuals (173 cases and 119 controls) were included. Nearly 2/3rds of the cases (116/173) and about 90% of the controls (108/119) self-reported as African-descendant. Mutations considered pathogenic were identified in 37 (21.4%) cases and in one control (0.84%, RAD51C c.266insA), OR = 27.75 and p = 0.008. The mutated genes in cases were BRCA1 (in 12 patients), BRCA2 (10), ATM (3), PALB2 (3), BRIP1 (3), BRCA2/ BARD1 (1), FAM175A (1), FANCM (1), NBN (1), SLX4 (1) and TP53 (1). Three recurrent mutations accounted for 12.4% (9/37) of the total: 3 BRCA1 c.3331_3334delCAAG (known European mutation), 3 BRCA1 c.211A &gt; G (known Galician mutation), and 3 PALB2c.1671_1674delTATT (novel mutation). Conclusions: Mutations in BRCA1 and BRCA2 (64.85%) or another breast cancer gene (35.15%) occur in one in five high-risk breast cancer patients in the largest study of Northeastern Brazil to date, and a significant proportion were recurrent mutations of European origin, which can be explained by the admixture pattern of the Brazilian population. This result underscores the importance of using multigene panel in cancer genetic epidemiologic research of understudied populations where unexpected findings, such as the recurrent and novel variant in PALB2 c.1671_1674delTATT, can be detected.
Utility of PET/CT for surveillance of asymptomatic patients with resected stage III or IV melanoma.
Authors: Roberto Antonio Leon-Ferre, Lisa A. Kottschade, Val J. Lowe, Svetomir Markovic
Journal: Journal of Clinical Oncology (2015)

9051 Background: Evidence-based guidelines for the use of surveillance imaging in melanoma patients are lacking. Here, we present a retrospective review of the Mayo Clinic experience using PET/CT (PET) for surveillance of asymptomatic patients with resected stage III-IV melanoma. Methods: A search of our radiologic database identified 601 melanoma patients seen at Mayo Clinic who underwent PET between 1/1/2008 and 6/30/2009. 153 met the inclusion criteria of having a resected cutaneous or mucosal stage III-IV melanoma, and at least 2 PETs performed < 1 year apart for surveillance. Results: 95(62%) were male and 58(38%) were female. 120(78%) had resected stage III [IIIA: 49(32%), IIIB: 51(33%), IIIC: 20(13%)], while 33(22%) had resected stage IV. Primary was cutaneous in 128(84%), mucosal in 8(5%) and MUP in 17(11%). Mean age at diagnosis of stage III or IV was 54. Of all patients, 80(52%) developed a first recurrence. 39(49%) were asymptomatic, not apparent on exam and detected by PET, 7(9%) were asymptomatic and detected by other imaging techniques, while 27(33%) were symptomatic and 7(9%) were detected on exam. Treatment to no evidence of disease (NED) with resection, radiation or ablation was possible in 26(67%) recurrences detected by PET and in 25(74%) symptomatic or exam-detected recurrences (p = 0.64). Median survival was superior among patients whose first recurrence was successfully treated to NED compared to patients in whom treatment to NED was not possible (7.08 vs 2.92 years, p = 0.0002). However, median survival was similar regardless of method of detection of first recurrence (5.04 in the PET group vs 5.18 years in the symptomatic group, p = 0.87). Median time to detection of first recurrence was 12 months by PET vs 10.7 months by symptoms/exam (p = 0.93). Median number of PET per patient was 9. Conclusions: Survival was superior among patients with resected stage III or IV melanoma whose first recurrence was amenable treatment to NED. Use of PET, however, did not appear to increase the proportion of patients that benefited from treatment to NED of first recurrence. Survival did not appear to be different among asymptomatic recurrences detected by PET compared to recurrences that were symptomatic or detectable on exam.
Towards Stratification of Lymphomas with Involvement of the Central Nervous System Using miRNA-Seq from Small Volumes of Cerebrospinal Fluid
Authors: Sarah Grasedieck, Medhanie A. Mulaw, Christina Miller, Arefeh Rouhi, Jeanette K Doorduijn, Jacoline E. Bromberg, Florian Kuchenbauer, Daniel Mertens
Journal: Blood (2016)
Abstract 12190: Physiologic Dysregulation Experienced by Immigrants is Mitigated by Immigrating at a Younger Age and Family Reunification: The Africans in America Study
Authors: Brianna A Bingham, Michelle T Duong, Paola C Aldana, Madia Ricks, Lilian S Mabundo, Margaret Udahogora, David Berrigan, Anne E Sumner
Journal: Circulation (2016)

Introduction: Immigration from Africa to the United States is stressful. Stress causes cardiovascular (CV), metabolic and immune dysregulation. Allostatic load score (ALS) quantifies the effect of dysregulation in these 3 systems. Objective: Our goal was to determine the influence of age of immigration, reason for immigration and unhealthy assimilation behavior on ALS in 238 African immigrants (AI) (age 40±10, mean±SD, range 21-64y). Methods: ALS was calculated using 10 variables, 6 were CV (SBP, DBP, triglyceride, cholesterol, homocysteine), 4 were metabolic (BMI, A1C, albumin, eGFR) and 1 was immune (CRP). Each variable was divided into sex-specific quartiles. High risk was defined by the highest quartile for each variable except albumin and eGFR which were defined by the lowest quartile. Each biomarker was assigned 1 point if in the high risk quartile and 0 if not. Unhealthy assimilation behavior was defined by increases in smoking, alcohol intake and sedentary activity after living in the US for ≥10y. Results: At enrollment all AI were adults (≥18y). Overall, 16% of AI were childhood immigrants (arrived in US &lt;18y); 84% were adulthood immigrants (arrived in US≥18y). Compared to adulthood AI, childhood AI were younger (30±7 vs. 42±9, P &lt;.01) and lived in the US longer (20±8 vs. 12±9y, P &lt;.01). Age-adjusted ALS were similar in childhood and adult AI (2.78±1.83 vs. 2.73±1.69, P =.87). In multiple regression analysis (adjR 2 =0.24), older age at immigration and more years in the US were associated with higher ALS. Whereas current age, education and income had no effect on ALS. Reasons for immigration were: family reunification, work, study, marriage, lottery and asylum. Compared to all other reasons combined, immigration for family reunification was associated with the lowest ALS (1.94±1.51 vs. 3.03±1.86, P =.03). Smoking, alcohol intake and physical activity did not differ in adulthood AI living in the US for &lt;10y vs. ≥10y (all P ≥.2) suggesting AI do not develop unhealthy assimilation behaviors. Conclusions: As measured by ALS, the physiologic dysregulation, experienced by AI is mitigated by younger age of immigration and family reunification. To decrease ALS in AI, family reunification may be more valuable than lifestyle intervention or medical therapy.
Nonmaleficence, Nondisclosure, and Nocebo: Response to Open Peer Commentaries
Authors: John T. Fortunato, Jason Adam Wasserman, Daniel Londyn Menkes
Journal: The American Journal of Bioethics (2017)

"Nonmaleficence, Nondisclosure, and Nocebo: Response to Open Peer Commentaries." The American Journal of Bioethics, 17(7), pp. W4–W5
Treatment outcome and prognostic factors in male patients with stage IV breast cancer: A population-based study.
Authors: Ying Huang, Wei Chen, Sean Szeja, Sandra S. Hatch, Andrew M Farach, Darlene Miltenburg, E. Brian Butler, Bin S. Teh
Journal: Journal of Clinical Oncology (2016)

572 Background: Stage IV male breast cancer (MBC) is a rare disease, previously described in small, single institutional studies. The purpose of this study is to investigate treatment outcome and prognostic factors in stage IV MBC. Methods: Patients with stage IV MBC diagnosed between 1988 and 2012 who did not receive radiation therapy as part of the first course of treatment were selected from the SEER database. Treatment outcome and prognostic factors for disease-specific survival (DSS) and overall survival (OS) were evaluated. Results: We identified 8292 MBC cases and included 394 patients with stage IV disease, who had the required treatment information. Median overall survival was 21 months. The 5-year DSS and OS for stage IV MBC patients were 38.3% and 21.1%, respectively. Of those with known progesterone receptor (PR) status, 68.6% were PR-positive (PR+), which was associated with better DSS (P = 0.003) and OS (P < 0.001). Of the 394 patients, 197 (50%) received surgery for the primary tumor and 197 (50%) did not. Those undergoing primary tumor surgery had longer median DSS than those who did not (36 months VS 21months; p < 0.001). Additional factors that correlated with prolonged DSS and OS were smaller tumor size (P = 0.005, P = 0.009) and younger age (P = 0.021, P = 0.001). Significant associations with race, year of diagnosis, ER status, HER2 status, use of radiation therapy to the primary tumor were not observed. In multivariate analysis, smaller tumor size (OR, 1.93; 95% CI, 1.2-3.104), PR+ positivity (OR, 1.665; 95%CI, 1.201-2.309), younger age (OR, 1.456; 95%CI, 1.053-2.014) and surgery for primary tumor (OR, 0.506; 95%CI, 0.368-0.695) were associated with longer DSS. Conclusions: Although stage IV MBC has poor DSS and OS, patients with PR-negative (PR-) disease, older age ( > 65 years), tumor size > 2cm or those did not undergo initial surgery for primary tumor had the worst prognosis. This is the largest study of stage IV MBC to date and these findings will help address some of the inconsistencies regarding this rare type of breast cancer.
Decreased risk of sudden death in heart failure questions need for ICDs
Authors: Susan Mayor
Journal: BMJ (2017)

The risk of sudden death in patients with symptomatic heart failure has halved over the past 20 years, a large study has reported.1 The authors suggest that the decrease is paralleled by greater use of evidence based drugs, such as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers, and they question the benefit of implantable cardioverter defibrillators (ICDs) in most patients.

The study analysed data from …
Is a Positive Family History an Important Determinant of Survival Following Colorectal Cancer?
Authors: G Doherty, D Fennelly, D Keegan, A White, B Nolan, J Hyland, K Sheahan, D O'Donoghue, H Mulcahy
Journal: Endoscopy (2006)

Introduction: Normal subjects with a family history of colorectal cancer are frequently overly negative about their possible risk of developing this disease and their potential for survival if diagnosed. Furthermore, newly identified colorectal cancer patients with a family history also tend to be pessimistic regarding their possible outcome.
Sexually transmitted infections: challenges ahead
Authors: Magnus Unemo, Catriona S Bradshaw, Jane S Hocking, Henry J C de Vries, Suzanna C Francis, David Mabey, Jeanne M Marrazzo, Gerard J B Sonder, Jane R Schwebke, Elske Hoornenborg, Rosanna W Peeling, Susan S Philip, Nicola Low, Christopher K Fairley
Journal: The Lancet Infectious Diseases (2017)
Green environment and incident depression in South Africa: a geospatial analysis and mental health implications in a resource-limited setting
Authors: Andrew Tomita, Alain M Vandormael, Diego Cuadros, Enrico Di Minin, Vuokko Heikinheimo, Frank Tanser, Rob Slotow, Jonathan K Burns
Journal: The Lancet Planetary Health (2017)

BackgroundUnprecedented levels of habitat transformation and rapid urbanisation are changing the way individuals interrelate with the natural environment in developing countries with high economic disparities. Although the potential benefit of green environments for mental health has been recognised, population-level evidence to this effect is scarce. We investigated the effect of green living environment in potentially countering incident depression in a nationally representative survey in South Africa.MethodsWe used panel data from the South African National Income Dynamics Study (SA-NIDS). Our study used SA-NIDS data from three waves: wave 1 (2008), wave 2 (2010), and wave 3 (2012). Households were sampled on the basis of a stratified two-stage cluster design. In the first stage, 400 primary sampling units were selected for inclusion. In the second stage, two clusters of 12 dwelling units each were drawn from within each primary sampling unit (or 24 dwelling units per unit). Household and individual adult questionnaires were administered to participants. The main outcome, incident depression (ie, incident cohort of 11 156 study participants without significant depression symptoms at their first entry into SA-NIDS), was assessed in the adult survey via a ten item version of the Center for Epidemiologic Studies Depression Scale; a total score of ten or higher was used as a cutoff to indicate significant depressive symptoms. Each participant was assigned a value for green living space via a satellite-derived normalised difference vegetation index (NDVI) based on the GPS coordinates of their household location.FindingsOverall, we found uneven benefit of NDVI on incident depression among our study participants. Although the green living environment showed limited benefit across the study population as a whole, our final analysis based on logistic regression models showed that higher NDVI was a predictor of lower incident depression among middle-income compared with low-income participants (adjusted odds ratio [aOR] 0·98, 0·97–0·99, p<0·0001), although when this analysis was broken down by race, its positive effect was particularly evident amongst African individuals. Living in rural areas was linked to lower odds of incident depression (aOR 0·71, 0·55–0·92, p=0·011) compared with study participants residing in urban informal areas that often lack formal planning.InterpretationOur results imply the importance of green environments for mental wellbeing in sub-Saharan African settings experiencing rapid urbanisation, economic and epidemiological transition, reaffirming the need to incorporate environmental services and benefits for sustainable socioeconomic development.FundingSouth African Medical Research Council, National Institutes of Health, and Academy of Finland.
Epithelial Cadherin-Alpha-Catenin Cell Adhesion Dysfunction in Intestinal Type Gastric Cancer Preinvasive Lesions
Authors: JT Garvin, M Joyce, I Tobbia, L O'Grady, R Waldron, MJ Kerin, J Lee, L O'Donnell
Journal: Endoscopy (2006)

Introduction: Epithelial cadherin (E-cadherin) is the predominant cell-adhesion molecule in epithelial tissues. E-cadherin is complexed with catenin proteins to form a functional unit. Expression of this functional unit is reduced in early gastric cancer as well as in preinvasive gastric lesions. Smoking and helicobacter pylori (H. pylori) infection are both linked to the development of gastric cancer.
Quantitative Prediction of Paravalvular Leak in Transcatheter Aortic Valve Replacement Based on Tissue-Mimicking 3D Printing
Authors: Zhen Qian, Kan Wang, Shizhen Liu, Xiao Zhou, Vivek Rajagopal, Christopher Meduri, James R Kauten, Yung-Hang Chang, Changsheng Wu, Chuck Zhang, Ben Wang, Mani A Vannan
Journal: JACC. Cardiovascular imaging (2017)
La résection endoscopique des lésions superficielles étendues du duodénum et de la papille (LSL-D/P) est médicalement et économiquement avantageuse par rapport à la chirurgie
Journal: Endoscopy (2017)

Il est acquis que la résection des petits adénomes duodénaux doit être endoscopique. Il n’en est pas de même pour les larges adénomes, notamment ceux étendus à la papille, où la chirurgie est plus souvent proposée en dépit de sa morbi/mortalité.