tbuckley/cabot-search huggingface dataset:
Reply to X. Armoiry et al
Authors: Chrissy H.Y. van Beurden-Tan, Margreet G. Franken, Hedwig M. Blommestein, Carin A. Uyl-de Groot, Hedwig M. Blommestein, Carin A. Uyl-de Groot, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2017)

We would like to thank Armoiry et al1 for investing the time and effort to further advance our research.We carefully considered their solution to our assumption regarding the equal relative effectiveness of bortezomib (Bor) versus dexamethasone (Dex) and bortezomib plus dexamethasone (BorDex) versus Dex. [...]
Aesthetic outcome and complications of simple interrupted versus running subcuticular sutures in facial surgery: A randomized controlled trial
Authors: Xiaomeng Liu, Patty J. Nelemans, Lisa D.S. Frenk, Helma Sengers, Stephania M.H. Tuinder, Peter M. Steijlen, Klara Mosterd, Nicole W.J. Kelleners-Smeets
Journal: Journal of the American Academy of Dermatology (2017)
DNA repair efficiency as a model for personalized therapy with Trabectedin
Authors: Rafael Rosell, Federica Grosso, Patrick Schoffski, Paolo Casali, Robert Maki, Miquel Taron, Pedro Mendez, Imane Chaib, Antonio Nieto, Juan Carlos Tercero, Robin Jones, Ian Judson, Jean-Yves Blay, Axel Lecesne, Jose Jimeno
Journal: Clinical Cancer Research (2007)

A57  Trabectedin is a DNA binding and transcription interacting agent under advanced clinical development with activity in advanced pre-treated sarcoma, ovarian, breast and prostate cancer. Objective responses and tumour control have been noted in patients resistant to conventional therapy. Moreover, the emergence of acquired resistance to Trabectedin in sensitive patients is generally delayed. Such findings suggest a specific genotype in cancer cells correlated with sensitivity to Trabectedin. Experimental data have proposed a unique model of in vitro sensitivity to Trabectedin based on a DNA signature. In contrast with the pattern applicable to platinum salts and to anthracyclines, efficient nucleotide excision repair (NER) machinery clusters with sensitivity to Trabectedin, whereas functional homologous recombinant (HRR) DNA repair correlates with resistance to Trabectedin.  Recent data generated in a retrospective study conducted in paraffin embedded tumor samples from sarcoma and ovarian cancer patients treated with Trabectedin demonstrate an association between low levels of mRNA expression of BRCA1 and both progression free survival (PFS), a median of 4.2 months (mo) for low and 1.8 mo for high levels (p= 0.004) and median overall survival, of 15.4 vs 6.8 mo respectively (p 6mo) 68% vs 0% (p=0.006), (3) PFS rate 69% vs 0% (p=0.005), (4) median PFS 7.1 vs 1.4 mo (p=0.004) and (5) median survival 20.4 vs 5.8 mo (p=0.026), when comparing the sensitive vs the resistant patient subpopulations.  In conclusion, the data generated in this pharmacogenomic study demonstrate a unique molecular signature which constitutes a potential tool for personalized therapy with Trabectedin.
THU0065 Cytokines and lipocalin-2 in pregnant women with rheumatoid arthritis and systemic lupus erythematosus
Authors: TT Pedersen, MH Fenstad, TS Moksnes, M Wallenius, TH Flo, M Haug
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA), and especially seronegative RA, is often ameliorated by pregnancy, while systemic lupus erythematosus (SLE) is prone to flare and associated with pregnancy complications. Cytokines and chemokines are of great importance for immune processes during pregnancy. The inflammatory marker Lipocalin-2 (LCN2) has become increasingly relevant as a potential clinical biomarker of rheumatic diseases (1). LCN2 is produced in the maternal-fetal interface during normal pregnancies and correlates with the presence and severity of preeclampsia (2). <h3>Objectives</h3> To obtain a better understanding of immune regulation and the disparate immune responses in pregnant women with RA and SLE. In this pilot study, we analyzed levels of multiple cytokines, chemokines and LCN2 in women with seropositive RA, seronegative RA, SLE and healthy controls during pregnancy and postpartum. <h3>Methods</h3> The Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases collect serum samples in a biobank from women with inflammatory rheumatic diseases before pregnancy, during pregnancy week 10–12, week 23–25, week 30–32 and 6 weeks, 6 months and 12 months postpartum. Control serum samples were collected from healthy pregnant women at matching time-points. We analyzed serum cytokine and chemokine levels using a multiplex assay. A sandwich ELISA was used to measure LCN2. In this pilot study we included pregnant women with SLE (n=4), seropositive RA (n=4), seronegative RA (n=2) and healthy pregnant controls (n=4). The total cohort consists so far of 18 pregnant women with SLE and 23 pregnant women with RA. <h3>Results</h3> We observed lower LCN2 levels during pregnancy in SLE patients, compared to controls and RA patients. LCN2 levels in seropositive RA patients and controls were found to be comparable during pregnancy, whereas pregnant women with seronegative RA showed higher LCN2 levels. Levels of IFNγ, IL-6 and IP-10 were higher in SLE than in RA patients during the course of pregnancy. IL-17 was slightly higher only in seropositive RA patients compared to controls. TNFα was slightly higher in both SLE and RA patients compared to controls, levels of anti-inflammatory IL-10 were very low or undetectable in all groups. <h3>Conclusions</h3> We found interesting differences in cytokine, chemokine and LCN2 levels during pregnancy in women with SLE, seropositive RA and seronegative RA. The results need confirmation in the total cohort and will be further explored for a better understanding of the disparate immune modulation of RA and SLE during pregnancy. <h3>References</h3> Abella V et al. Biomarkers. 2015;20(8):565–71. Kim SM et al. Reproductive sciences. 2013;20(9):1083–9. <h3>Acknowledgements</h3> This study is supported by grants from St. Olavs Hospital and Norsk Revmatikerforbund. <h3>Disclosure of Interest</h3> None declared
Factors Associated With Underestimation of Invasive Cancer in Patients With Ductal Carcinoma In Situ
Authors: Carlos Chavez de Paz Villanueva, Valentina Bonev, Maheswari Senthil, Naveenraj Solomon, Mark E. Reeves, Carlos A. Garberoglio, Jukes P. Namm, Sharon S. Lum
Journal: JAMA Surgery (2017)

<h3>Importance</h3> Recent recognition of the overdiagnosis and overtreatment of ductal carcinoma in situ (DCIS) detected by mammography has led to the development of clinical trials randomizing women with non–high-grade DCIS to active surveillance, defined as imaging surveillance with or without endocrine therapy, vs standard surgical care. <h3>Objective</h3> To determine the factors associated with underestimation of invasive cancer in patients with a clinical diagnosis of non–high-grade DCIS that would preclude active surveillance. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted using records from the National Cancer Database from January 1, 1998, to December 31, 2012, of female patients 40 to 99 years of age with a clinical diagnosis of non–high-grade DCIS who underwent definitive surgical treatment. Data analysis was conducted from November 1, 2015, to February 4, 2017. <h3>Exposures</h3> Patients with an upgraded diagnosis of invasive carcinoma vs those with a diagnosis of DCIS based on final surgical pathologic findings. <h3>Main Outcomes and Measures</h3> The proportions of cases with an upgraded diagnosis of invasive carcinoma from final surgical pathologic findings were compared by tumor, host, and system characteristics. <h3>Results</h3> Of 37 544 women (mean [SD] age, 59.3 [12.4] years) presenting with a clinical diagnosis of non–high-grade DCIS, 8320 (22.2%) had invasive carcinoma based on final pathologic findings. Invasive carcinomas were more likely to be smaller (&gt;0.5 to ≤1.0 cm vs ≤0.5 cm: odds ratio [OR], 0.73; 95% CI, 0.67-0.79; &gt;1.0 to ≤2.0 cm vs ≤0.5 cm: OR, 0.42; 95% CI, 0.39-0.46; &gt;2.0 to ≤5.0 cm vs ≤0.5 cm: OR, 0.19; 95% CI, 0.17-0.22; and &gt;5.0 cm vs ≤0.5 cm: OR, 0.11; 95% CI, 0.08-0.15) and lower grade (intermediate vs low: OR, 0.75; 95% CI, 0.69-0.80). Multivariate logistic regression analysis demonstrated that younger age (60-79 vs 40-49 years: OR, 0.84; 95% CI, 0.77-0.92; and ≥80 vs 40 to 49 years: OR, 0.76; 95% CI, 0.64-0.91), negative estrogen receptor status (positive vs negative: OR, 0.39; 95% CI, 0.34-0.43), treatment at an academic facility (academic vs community: OR, 2.08; 95% CI, 1.82-2.38), and higher annual income (&gt;$63 000 vs &lt;$38 000: OR, 1.14; 95% CI, 1.02-1.28) were significantly associated with an upgraded diagnosis of invasive carcinoma based on final pathologic findings. <h3>Conclusions and Relevance</h3> When selecting patients for active surveillance of DCIS, factors other than tumor biology associated with invasive carcinoma based on final pathologic findings may need to be considered. At the time of randomization to active surveillance, a significant proportion of patients with non–high-grade DCIS will harbor invasive carcinoma.
Risk factors for positive or equivocal margins after wide local excision of 1345 cutaneous melanomas
Authors: Christopher J. Miller, Thuzar M. Shin, Joseph F. Sobanko, John M. Sharkey, John W. Grunyk, Rosalie Elenitsas, Emily Y. Chu, Brian C. Capell, Michael E. Ming, Jeremy R. Etzkorn
Journal: Journal of the American Academy of Dermatology (2017)
Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis
Authors: Roberto Carnevale, Valeria Raparelli, Cristina Nocella, Simona Bartimoccia, Marta Novo, Anna Severino, Elena De Falco, Vittoria Cammisotto, Chiara Pasquale, Clara Crescioli, Antonio Sili Scavalli, Oliviero Riggio, Stefania Basili, Francesco Violi
Journal: Journal of Hepatology (2017)
Geometrical Model of the Microvasculature of Rabbit Omentum from in Vivo Measurements
Authors: M. INTAGLIETTA, B. W. ZWEIFACH
Journal: Circulation Research (1971)

The diameter and length relationships of the anastomosing microvessels of the rabbit omentum were determined from serial photographs taken in vivo.Complete maps from input to output vessels in these microvascular beds were used to construct a hemodynamic model.The principal features are uniform distribution of surface area and volume from 20JU, arterioles to 25fi venules and uniform hydraulic hindrance up to the venules, where it drops to 5% of the total value.
Levels and Determinants of DDT and DDE Exposure in the VHEMBE Cohort
Authors: Fraser W. Gaspar, Jonathan Chevrier, Lesliam Quirós-Alcalá, Jonah M. Lipsitt, Dana Boyd Barr, Nina Holland, Riana Bornman, Brenda Eskenazi
Journal: Environmental Health Perspectives (2017)

Although indoor residual spraying (IRS) is an effective tool for malaria control, its use contributes to high insecticide exposure in sprayed communities and raises concerns about possible unintended health effects.The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort study initiated in 2012 to characterize prenatal exposure to IRS insecticides and exposures' impacts on child health and development in rural South Africa.In this report, we describe the VHEMBE cohort and dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) serum concentrations measured in VHEMBE mothers when they presented for delivery. In addition, we applied a causal inference framework to estimate the potential reduction in population-level p,p'-DDT and p,p'-DDE serum concentrations under five hypothetical interventions. A total of 751 mothers were enrolled.Serum concentrations of p,p' isomers of DDT and DDE were above the limit of detection (LOD) in ≥98% of the samples, whereas the o,p' isomers were above the LOD in at least 80% of the samples. Median (interquartile range) p,p'-DDT and p,p'-DDE serum concentrations for VHEMBE cohort participants were 55.3 (19.0-259.3) and 242.2 (91.8-878.7) ng/g-lipid, respectively. Mothers reporting to have lived in a home sprayed with DDT for malaria control had ~5-7 times higher p,p'-DDT and p,p'-DDE serum concentrations than those who never lived in a home sprayed with DDT. Of the five potential interventions tested, we found increasing access to water significantly reduced p,p'-DDT exposure and increasing the frequency of household wet mopping significantly reduced p,p'-DDT and p,p'-DDE exposure.Our findings suggest that several intervention approaches may reduce DDT/DDE exposure in pregnant women living in IRS communities. https://doi.org/10.1289/EHP353.
Discordance of histo-pathological diagnosis of patients with soft tissue sarcoma referred to tertiary care center.
Authors: Sameer Rastogi, Aditi Aggarwal, Kamal Raj Soti, Ilavarasi Vanidassane, Mehar C Sharma, Ajay Yadav, Aparna Sharma, Babita Kataria, S. V. S. Deo
Journal: Journal of Clinical Oncology (2017)

11064 Background: Reaching to the correct histo-pathological diagnosis of soft tissue sarcomas (STS) is a great challenge and is cornerstone for treatment planning. Need of expertise for diagnosis is limited by lack of expert pathologists and dedicated sarcoma oncologists in India. Through this study we highlight the pattern of pathological diagnosis and accuracy outside specialist centre. Methods: We did retrospective analysis of all patients referred to us with diagnosis of STS in the last 12 months (January 2016 to 2017). According to protocol, all patients had pathology review from our institute. If blocks were available then they were reviewed and if necessary, fresh biopsy was performed. Besides, pathological diagnosis was reviewed in joint clinic, giving clinico-radiological inputs to sarcoma pathologists. For patients diagnosed outside and had discordant report, we divided them into major discrepancy (including change of diagnosis of sarcoma to benign or other histological entity that could potentially change the treatment plan) or minor discrepancy (like mild change in grade or histopathological diagnosis not affecting the treatment plan). Results: There were 149 patients registered with median age of 36 years (14-77 years) and 93 patients (62.4%) were males. 85(57%) patients had localized disease. Most common subtypes were synovial sarcoma 16%, liposarcoma 9%, soft tissue ewings sarcoma 9%, MPNST 9%, leiomyosarcoma 8%, pleomorphic undifferentiated sarcoma 8% etc. Of 149 patients, 42 had not been worked up outside and thus comparison was not possible while 4 patients couldn’t retrieve blocks and repeat biopsy could not be performed. Of 97 patients (biopsy = 84, FNAC = 13) who had diagnosis from outside, 37% had major discrepancy and 24% had minor discrepancy compared with our biopsy review. Major discrepancy was more in non extremity than extremity STS (p = 0.003). Conclusions: Pathological diagnosis of more than half of patients referred from outside was discordant with respect to diagnosis of our centre with major implications on 37%. We believe this is due to lack of sarcoma pathology experts and virtually non-existent multidisciplinary clinics in set up outside tertiary care centres.
Extending the Social Justice Call to Treatment Outcomes—Reply
Authors: Andrew D. Racine
Journal: JAMA Pediatrics (2017)

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Characteristics of very long responder to maintenance cetuximab after a platinum-cetuximab based chemotherapy for recurrent and/or metastatic head and neck squamous cell carcinomas (RM HNSCC).
Authors: Magalie Pascale Tardy, Celine Lescure, Jerome Doyen, Amaury Daste, Martin Lange, Mathilde Saint-Ghislain, Gautier Lefebvre, Victor Sarradin, Alexandre Bozec, Esma Saada-Bouzid, Frederic Peyrade
Journal: Journal of Clinical Oncology (2017)

e17524 Background: Standard treatment for first line RM HNSCC is the association of platinum-5FU and cetuximab. For non-progressive patients (pts), cetuximab is given weekly as maintenance until progression or unacceptable toxicity. In the EXTREME protocol (Vermorken et al, NEJM 2008), this strategy showed an OS of 10.1 months with a mean duration of maintenance of 3 months. This study aimed at describing pts who have benefited from a cetuximab maintenance for a longer period (i.e. &gt; 6 months). Methods: We did a retrospective study in 7 centers in France. Inclusion criteria were: pts &gt; 18 years with a RM HNSCC treated between November 2009 and January 2017, with platinum based chemotherapy and cetuximab followed by weekly cetuximab maintenance of more than 6 months. Results: 53 pts (45 male), with a median age of 57 [38-76] were recorded. Median follow-up was 63.7 months [14.8-237.6]. 72% [37/53] had an oral cavity or oropharynx tumor location with a well or moderately differentiated carcinoma (74%). 45/53 (85%) were smokers and 4/21 (19%) p16 positive. 46/53 (87%) had a Performans Status of 0-1. Mean BMI and albumin level were respectively 22.5 [SD: 4.19] and 40g/l [SD: 4.9]. EXTREME regimen was used for 44 pts, 2 pts had platinum and cetuximab and 7 received platinum, docetaxel and cetuximab. Mean number of chemotherapy cycles was 5 [3-7]. After chemotherapy, the number of pts with complete response (CR), partial response (PR) or stabilization was respectively 5 (9%), 23 (43%) and 25 (47%). 2 pts in PR finally achieved CR during maintenance. One of them stopped cetuximab and was still in CR 5 months later. Mean duration time of maintenance by cetuximab was 11 months [6-24]. Toxicities were mainly cutaneous: 47/53 pts had toxicities, of which 6 had grade 3. Presence of cutaneous toxicities seemed to be correlated with a longer response (p = 0.01). PFS and OS were respectively 15.5 and 27.4 months. Conclusions: Our study allowed us to identify a cohort of long responder pts to maintenance cetuximab including 2 pts who obtained a complete response. More analysis should be done to identify biomarkers able to predict long responder.
Ganoderma triterpenes retard renal cyst development by downregulating Ras/MAPK signaling and promoting cell differentiation
Authors: Limin Su, Liying Liu, Yingli Jia, Lei Lei, Jiangfeng Liu, Shuai Zhu, Hong Zhou, Ruoyun Chen, Hua Ann Jenny Lu, Baoxue Yang
Journal: Kidney International (2017)
Molecular surveillance of measles and rubella in the WHO European Region: new challenges in the elimination phase
Authors: S. Santibanez, J.M. Hübschen, M.C. Ben Mamou, M. Muscat, K.E. Brown, R. Myers, O. Donoso Mantke, H. Zeichhardt, D. Brockmann, S.V. Shulga, C.P. Muller, P.M. O'Connor, M.N. Mulders, A. Mankertz
Journal: Clinical Microbiology and Infection (2017)
Outcomes in BRCA1/2 breast cancer patients treated with everolimus followed by chemotherapy+/- PARP inhibitors.
Authors: Hatem Hussein Soliman, Matthew Anderson, Hyo S. Han
Journal: Journal of Clinical Oncology (2017)

e12569 Background: Research demonstrates blocking mTOR signaling can suppress homologous DNA repair pathways. Use of drugs like everolimus can sensitize cancer cells to DNA damaging agents, particularly if they already harbor defects in DNA repair, such as mutations in BRCA1/2 genes. We sought to analyze our Total Cancer Care (TCC) dataset including BRCA1/2 germline mutation carrier patients who were enrolled on a completed randomized phase 2 trial (NCT01506609) of carboplatin/taxol (CT) or temozolimide (TEM) +/- veliparib (PARPi) at Moffitt Cancer Center (MCC). Time on study treatment (TOT) for patients who received everolimus (EVE+) prior to study enrollment was compared to those who did not (EVE-). Methods: We identified MCC patients treated on trial who were TCC consented to provide clinicopathologic and treatment data. Information on prior treatments, EVE exposure, Estrogen receptor (ER) status, unblinded trial treatment if known, and TOT were collected. Summary statistics and comparison of median TOT in EVE+ vs. EVE- pts using a two tail Mann-Whitney test (significance p &lt; .05), and Wilcoxon Signed Rank Test of TOT EVE+ vs. reported PFS of CT+PARPi arm were performed. Results: Fourteen pts (6 EVE+, 8 EVE-) were identified with clinical data described in Table 1. Median TOT for EVE+ = 25.1 mos (95% CI 19.5-29.8), EVE- = 7.4 mos (95% CI 3.9-15.4) with p = .002. EVE+ TOT was significantly higher than median PFS of 14.1 mos for CT+PARPi arm (p = .03). Median TOT on EVE was 4.3 mos (95% CI 2.7-16.3). In EVE+ 5 pts discontinued for progression, 1 for toxicity. In EVE- 5 pts discontinued for progression, 3 for other causes. Conclusions: Significantly better TOT on DNA damaging therapy was observed in a small group of ER+ BRCA1/2 mutated breast cancer pts previously exposed to EVE compared to EVE- pts. This observation requires further study in the entire study population and confirmation in prospective trials with sequenced EVE-CT+/-PARPi for ER+ BRCA1/2 pts. [Table: see text]
Pure erythroid leukemia: The need gather data on this condition as defined in the World Health Organization classification
Authors: Barbara J. Bain
Journal: American Journal of Hematology (2017)

Wang and colleagues, in their review of pure erythroid leukemia (PEL),1 state that “PEL often evolves from prior MDS, but can also develop de novo”. It should be noted that, in the WHO classification, cases evolving from MDS are classified as ‘acute myeloid leukemia with myelodysplasia-related changes’. It would be useful if authors presenting data on PEL could specify if cases met the WHO criteria so that knowledge of this rare subtype of acute myeloid leukemia is increased. Wang et al. report that 10/10 cases studied by them had a TP53 mutation. This raises the question of how many of those patients had de novo disease and thus met the WHO criteria.