tbuckley/cabot-search huggingface dataset:
S118 IMPACT OF PRE‐TRANSPLANT DONOR‐SPECIFIC ANTI‐HLA ANTIBODIES IN CORD BLOOD TRANSPLANTATION ON BEHALF OF THE TRANSPLANT COMPLICATIONS WORKING GROUP OF JSHCT
Authors: S. Fuji, K. Oshima, K. Ohashi, M. Sawa, K. Saito, T. Eto, M. Tanaka, M. Onizuka, H. Nakamae, S. Shiratori, Y. Ozawa, M. Hidaka, T. Nagamura‐Inoue, H. Tanaka, T. Fukuda, T. Ichinohe, Y. Atsuta, M. Ogata
Journal: HemaSphere (2019)

Background: Cord blood transplant (CBT) is an effective treatment for hematological diseases. Graft failure (GF) remains a major complication of CBT. Although presence of pre‐transplant donor‐specific anti‐HLA antibody (DSA) was reported to be associated with an increased risk of GF after CBT, data is still limited. Aims: In order to clarify the impact of pre‐transplant DSA, we conducted a retrospective analysis of recipients of CBT with pre‐transplant anti‐HLA antibody using the database of Japan Society for Hematopoietic Cell Transplantation (JSHCT). Methods: Data for recipients of CBT with pre‐transplant anti‐HLA antibody from 2010 to 2014 were obtained from the Transplant Registry Unified Management Program. Additional data such as detailed information about anti‐HLA antibody were collected. This study was approved by the institutional review boards of the JSHCT and Oita University. Results: In total, 343 patients who received CBT with detailed information about anti‐HLA antibody were included in the further analysis. Median age was 51 years (range, 0 to 71). Regarding DSA, 25 patients had mean fluorescence intensity (MFI) &gt;1000 (DSA‐positive group) and 318 patients had MFI&lt;1000 (DSA‐negative group). Cumulative incidence of neutrophil engraftment at 60 days after CBT was 75.7% (95% CI, 70.6–80.1) in the DSA‐negative group and 56.0% (95% CI, 34.1–73.1) in the DSA‐positive group (P = 0.03, Figure). Grouped according to the HLA class of DSA, cumulative incidence of neutrophil engraftment was 71.4% in patients with DSA against HLA class II antigen (n = 14), 44.4% in those with DSA against HLA class I antigen (n = 9), 0% in those with DSA against both HLA class I and class II antigens (n = 2). Stratified according to the achievement of neutrophil engraftment, the probabilities of overall survival at 1 year after CBT were 62.7% (95% CI, 56.2–68.5) in the engrafted patients and 19.5% (11.8–28.5) in the non‐engrafted patients (P &lt; 0.001). Summary/Conclusion: Our study is a largest cohort of CBT recipients with pre‐transplant anti‐HLA antibody. Pre‐transplant DSA was associated with an increased risk of GF. The importance of target HLA antigen should be clarified in the future study. image
Sorafenib (S) alone versus S combined with gemcitabine and oxaliplatin (GEMOX) in first-line treatment of advanced hepatocellular carcinoma (HCC): Final analysis of the randomized phase II GONEXT trial (UNICANCER/FFCD PRODIGE 10 trial).
Authors: Eric Assenat, Valerie Boige, Simon Thézenas, Georges-Philippe Pageaux, Jean-Marie Peron, Yves Becouarn, Laetitia Dahan, Philippe Merle, Jean-Frédéric Blanc, Olivier Bouche, Mohamed Ramdani, Thibault Mazard, Jean-Pierre Bleuse, Marc Ychou
Journal: Journal of Clinical Oncology (2013)

4028 Background: HCC is a vascular tumor with poor prognosis. Although S has been shown to improve survival, its ability to induce tumor shrinkage is very low. Given the activity of Gemcitabine and Oxaliplatin (GEMOX) in HCC, a phase II trial combining S with GEMOX was undertaken to define efficacy and safety profile. Methods: Patients with inoperable advanced and/or metastatic HCC (BCLCC B or C), with or without prior palliative chemoembolization, Child pugh score A, WHO performance status (PS) 0-1, were eligible for this two-stage, randomized phase II trial. Patients received S (400 mg BID) alone (arm A) or in combination with GEMOX every 2 weeks (gem. 1000 mg/m² [10 mg/m²/min] on D1; oxaliplatin, 100 mg/m² on D2) (arm B). Randomization was stratified according to CLIP score (0-1 vs. 2-3) and center. Primary endpoint was crude 4-mo Progression-Free Survival (PFS) rate (H0, &lt; 50%; H1, ≥ 70%; α = 10%; 1- β= 90%). Results: From Dec 2008 to Oct. 2011, 94 pts were enrolled: median age, 64 yrs; male, 88%; PS 0 (69%) 1(31%), CLIP 0-1 (48%) 2-3 (52%), cirrhosis (63%), portal vein thrombosis (29%), extra liver metastasis (69%). These characteristics were well balanced in both arms. Median duration and dose intensity of S were 4 mo (1-27) and 81% in both arms, respectively. Median number of GEMOX cycles was 7 (1-12) in arm B. Main severe (grade 3-4) toxicity (arm A/B) consisted of neutropenia (grade 3-4: 0%/7%), fatigue (18%/24%), thrombocytopenia (0%/9%), diarrhea (grade 2-4: 10%/21%), peripheral neuropathy (grade 2-3: 0%/10%), and hand foot syndrome (grade 2-3: 13%/7%). For evaluable pts (n = 83), ORR was 9% / 16% and DCR was 70%/77% in arms A/B, respectively. For all pts (median follow-up, 17.6 mo), 4-mo PFS rate was 54%/61%, median PFS was 4.6 (3.9-6.2)/6.2 (3.8-6.8) mo, and median OS was 13.0 (10.4-22.2) /13.5 (7.5-19.1) mo in arms A/B, respectively. Conclusions: S plus GEMOX was feasible in HCC. This trial met its primary endpoint (4-mo PFS ≥ 50%) and ORR, median PFS and OS were encouraging data. Exploratory analyses are underway to identify subgroups of patients likely to derive most benefit from this combination. Clinical trial information: NCT00941967.
Заболевания кишечника и почки
Authors: A.E. Dorofeiev, N.N. Rudenko, I.A. Derkach, Yu.V. Chechula
Journal: GASTROENTEROLOGY (2020)

В представленном обзоре современных публикаций проведен анализ частоты сочетаний заболеваний кишечника и почек. Основное внимание уделено проблеме взаимосвязи заболеваний кишечника и мочекаменной болезни. Рассматриваются возможные патогенетические механизмы таких поражений, как генетически детерминированные нарушения кишечного всасывания и секреции, изменение кишечной микробиоты, системный воспалительный ответ, водно-электролитные нарушения.
Abstract #3233: Targeted therapy of human colonic, lung, and pancreatic cancer xenografts, growing in nude mice, with potent antibody conjugates of SN-38
Authors: Serengulam Govindan, Thomas Cardillo, Sung-Ju Moon, David Goldenberg
Journal: Cancer Research (2009)

SN-38 is a potent topoisomerase I inhibitor and the active drug form of the clinically used cancer therapeutic, CPT-11. To increase bioavailability and reduce toxicity, antibody (MAb)-targeted SN-38 chemotherapy was evaluated in preclinical models of human colonic, lung, and pancreatic carcinomas. Two improved bifunctional SN-38 derivatives, \#8220;CL2-SN-38\#8221; (maleimido-[x]-Phe-Lys-PABOCO-20-O-SN-38, where PAB is p-aminobenzyl and \#8216;x\#8217; comprises a PEG group for solubility) and its ethyl carbonate variant, \#8220;CL2-SN-38(Et)\#8221;, were conjugated to mildly reduced humanized MAbs, hPAM4 (anti-MUC-1), hMN-14 (anti-CEACAM5), hRS7 (anti-EGP-1), and an isotype-matched control, hLL2 (anti-CD22). SN-38/MAb molar substitutions in the conjugates were in the range of 6-7, and the conjugates\#8217; cytotoxicities were similar to that of SN-38. Female athymic nude mice with human tumor xenografts were treated i.p.with specific or non-targeting MAb-SN38 conjugates or an equidose mixture of specific MAb and SN-38 as follows: 0.46 mg conjugated SN-38/kg, q4d×8 (protocol-1) or q4d×4 (protocol-2); or 0.23 mg conjugated SN-38/kg, q4d×8 (protocol-3). In some experiments, CPT-11 was also used as a control. A lung metastatic model of GW-39 human colonic carcinoma and s.c. models of LS174T human colonic, Calu-3 human lung, and human CaPan1 pancreatic carcinomas were treated. In the lung metastatic model of human colon carcinoma, therapy with hMN-14-CL2-SN-38 conjugate (protocol-3; n = 8-10) increased median survival 1.7-3-fold to 147 days vs. controls. In the s.c. LS174T colon cancer model (protocol-1, n = 8), survival due to treatment with hMN-14-CL2-SN-38(Et) was significantly better than that due to all controls including treatment with the maximum tolerated dose (MTD; 40 mg/kg, q2d×5) of CPT-11 (log rank test, P  600% on day 28. Therapy data for ongoing pilot experiments in 2 additional colon cancer xenograft models as well as expanded study in the CaPan1 model will also be reported. These results show selective and significant therapeutic efficacies due to treatments with MAb-SN-38 conjugates in preclinical models of solid human tumors.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3233.
Whole genome sequencing in psychiatric disorders: the WGSPD consortium
Authors: Stephan J. Sanders, Benjamin M. Neale, Hailiang Huang, Donna M. Werling, Joon-Yong An, Shan Dong, Goncalo Abecasis, P. Alexander Arguello, John Blangero, Michael Boehnke, Mark J. Daly, Kevin Eggan, Daniel H. Geschwind, David C. Glahn, David B. Goldstein, Raquel E. Gur, Robert E. Handsaker, Steven A. McCarroll, Roel A. Ophoff, Aarno Palotie, Carlos N. Pato, Chiara Sabatti, Matthew W. State, A. Jeremy Willsey, Steven E. Hyman, Anjene M. Addington, Thomas Lehner, Nelson B. Freimer
Journal: Nature Neuroscience (2017)
Identification of respiratory microbiota markers in ventilator-associated pneumonia
Authors: Stéphane Emonet, Vladimir Lazarevic, Corinne Leemann Refondini, Nadia Gaïa, Stefano Leo, Myriam Girard, Valérie Nocquet Boyer, Hannah Wozniak, Lena Després, Gesuele Renzi, Khaled Mostaguir, Elise Dupuis Lozeron, Jacques Schrenzel, Jérôme Pugin
Journal: Intensive Care Medicine (2019)

To compare bacteria recovered by standard cultures and metataxonomics, particularly with regard to ventilator-associated pneumonia (VAP) pathogens, and to determine if the presence of particular bacteria or microbiota in tracheal and oropharyngeal secretions during the course of intubation was associated with the development of VAP. In this case–control study, oropharyngeal secretions and endotracheal aspirate were collected daily in mechanically ventilated patients. Culture and metataxonomics (16S rRNA gene-based taxonomic profiling of bacterial communities) were performed on serial upper respiratory samples from patients with late-onset definite VAP and their respective controls. Metataxonomic analyses showed that a low relative abundance of Bacilli at the time of intubation in the oropharyngeal secretions was strongly associated with the subsequent development of VAP. On the day of VAP, the quantity of human and bacterial DNA in both tracheal and oropharyngeal secretions was significantly higher in patients with VAP than in matched controls with similar ventilation times. Molecular techniques identified the pathogen(s) of VAP found by culture, but also many more bacteria, classically difficult to culture, such as Mycoplasma spp. and anaerobes. Molecular analyses of respiratory specimens identified markers associated with the development of VAP, as well as important differences in the taxa abundance between VAP and controls. Further prospective trials are needed to test the predictive value of these markers, as well as the relevance of uncultured bacteria in the pathogenesis of VAP.
AB1271 DESCRIPTION OF A COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS AND ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA)
Authors: Sycille Jeria, Hyesang Park, Andrea García-Guillén, David Lobo, Ana Laiz, Berta Magallares, Patricia Moya, Ana Milena Millán Arciniegas, Cesar Díaz-Torné, Susana P. Fernandez-Sanchez, Hector Corominas, Ivan Castellví
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The presence of antineutrophil cytoplasmic antibodies (ANCA) in systemic sclerosis (SSc) has been described rarely. The series published in the literature are scarce<sup>1</sup> Its role in the evolution on the disease is unknown <h3>Objectives:</h3> To describe the epidemiological and clinical characteristics of ANCA positive patients from a cohort of patients with SSc <h3>Methods:</h3> Retrospective observational descriptive study in a cohort of 312 SSc. We analyzed those patients who were positive for ANCA, collecting variables: gender, race, age, age at diagnosis of SSc, at onset of symptoms, type and immunological profile, clinical manifestations of SSc, association with other systemic autoimmune diseases (SAD), capillaroscopic findings, and treatment. Regarding the ANCA profile, pattern, specificity and titration, as the time of evolution of SSc until the appearance of ANCA <h3>Results:</h3> Four of 312 patients with SSc had ANCA (prevalence = 1.28%). All were women and 2 had perinuclear pattern. The reason to request ANCA was kidney failure with proteinuria in 2 cases. One patient developed anti-myeloperoxidase (MPO) renal vasculitis and biopsy showed segmental glomerular necrosis and extracapillary proliferation. Other had proteinuria with hematuria without renal failure and biopsy with glomeruli in wafer. Regarding clinical manifestations all ANCA had some degree pulmonary disease 3 interstitial lung disease (ILD)1 pulmonary arterial hypertension (PAH) confirmed by right heart catheterization (KT). Three had SAD associated Characteristics of the sample in table 1 <h3>Conclusion:</h3> In our cohort the presence of positive ANCA was associated with renal vasculitis in one case. All patients with ANCA had vascular or interstitial pulmonary involvement, as well as other associated SADs. Further studies are needed to characterize the clinical associations of the presence of ANCA in SSc <h3>References</h3> [1] J Rheumatol21:864–870 [2] Rheumatol Int (2006) 26: 369–375 <h3>Disclosure of Interests:</h3> Sycille Jeria: None declared, HyeSang Park: None declared, Andrea García-Guillén: None declared, DAVID LOBO: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Berta Magallares: None declared, Patricia Moya: None declared, Ana Milena Millán Arciniegas: None declared, Cesar Díaz-Torné: None declared, Susana P. Fernandez-Sanchez: None declared, Hector Corominas: None declared, Ivan Castellví Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND
Prognostic Implications of PD-L1 Expression in Breast Cancer: Systematic Review and Meta-analysis of Immunohistochemistry and Pooled Analysis of Transcriptomic Data
Authors: Alexios Matikas, Ioannis Zerdes, John Lövrot, François Richard, Christos Sotiriou, Jonas Bergh, Antonios Valachis, Theodoros Foukakis
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer. Experimental Design: Medline, Embase, Cochrane Library, and Web of Science Core Collection were searched, and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells, or both, per subtype and per antibody used, and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed. Results: Of the initial 4,184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI, 15%–33%) in tumor cells and 33% (95% CI, 14%– 56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR, 1.63; 95% CI, 1.07–2.46; P = 0.02); there was significant heterogeneity (I2 = 80%, Pheterogeneity &amp;lt; 0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR, 0.82; 95% CI, 0.74–0.90; P &amp;lt; 0.001 for OS) and in basal-like tumors (HR, 0.64; 95% CI, 0.52–0.80; P &amp;lt; 0.001 for OS; Pinteraction 0.005). Conclusions: The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like breast cancer. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.
Abstract 13468: Endocardial Area Change Rate by Three-dimensional Speckle-tracking as an Accurate Predictor of Left Ventricular Relaxation
Authors: Kazuhiro Tatsumi, Hidekazu Tanaka, Kensuke Matsumoto, Yoshiki Yamadori, Takuma Sawa, Yoshiki Motoji, Junichi Imanishi, Tatsuya Miyoshi, Yasuhide Mochizuki, Yuko Fukuda, Toshiro Shinke, Ken-ichi Hirata
Journal: Circulation (2013)

Background: The early diastolic mitral inflow and annulus velocities ratio (E/e’) were considered as the parameter to estimate left ventricular (LV) filling pressure. According to the guidelines, t...
Benzodiazepine receptor agonists and subsequent risk of psoriasis: A 5-year follow-up cohort study
Authors: I-Hsun Li, Wei-Ming Wang, Wu-Chien Chien, Hui-Han Kao, Jui-Hu Shih, Yih-Dih Cheng, Ke-Ting Pan, Li-Ting Kao
Journal: Journal of the American Academy of Dermatology (2019)
FRI0153 OPHTHALMOLOGICAL ADVERSE EVENTS UNDER JAK INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS: CASE ANALYSIS OF THE EUROPEAN PHARMACOVIGILANCE DATABASE
Authors: Sophie Hecquet, Marie Blanche Rabier, Marion Lepelley, Frank Verhoeven, Anne Sophie Gauthier, Clément Prati, Bernard Delbosc, Daniel Wendling
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Ophthalmological manifestations in rheumatoid arthritis (RA) include dry syndrome, scleritis, episcleritis, uveitis and peripheral ulcerative keratitis (PUK). Recently, a new class of synthetic molecules has been developed, called JAK inhibitors (JAKinhib). We observed one case of PUK occurring two months after the introduction of baricitinib treatment with corneal perforation with secondary improvement after discontinuation of JAKinhib. <h3>Objectives</h3> The aim of this study is to describe and characterize the ophthalmological side effects of JAK inhibitors (JAK inhib) in patients with rheumatoid arthritis (RA) from European pharmacovigilance (PV) data. <h3>Methods</h3> The ophthalmological manifestations that appeared under JAK inhib were extracted from the European PV database (May 2018), EUDRAVIGILANCE following a request addressed to the National Drug Safety Agency carried out according to the following MedDRA classification "SOC eye disorders and BARICITINIB" and "SOC eye disorders and TOFACITINIB". <h3>Results</h3> A total of 41 patients with ophthalmic adverse events (AEs) on JAK inhib were reported. Among patients, 12 were treated with BARICITINIB and 29 with TOFACITINIB. Of these AEs, 51% were reported by the medical profession, 39% by patients and 10% by paramedical teams. The database analysis revealed 4 scleritis, 3 uveitis, 1 PUK and 1 corneal ulceration. The average time to onset of AEs was 13.2 months. The infectious causes had been eliminated. <h3>Conclusion</h3> Ophthalmological manifestations under JAKinhib seem to be rare but not exceptional, the rheumatologist must be aware of them in order to discuss the imputability of the treatment. A discontinuation of it seems justified pending an ophthalmological opinion. <h3> Disclosure of Interests</h3> None declared
Follow-Up of Patients With Ulcerative Colitis and Histological Normalization
Authors: Amanda Israel, Britt Christensen, Katia El Jurdi, Victoria Rai, Jacob E. Ollech, Russell D. Cohen, Atsushi Sakuraba, Sushila R. Dalal, David T. Rubin
Journal: Clinical Gastroenterology and Hepatology (2019)
A homogenized approach to classify advanced gastric cancer patients with limited and adequate number of pathologically examined lymph nodes
Authors: Sharvesh Raj Seeruttun, Lipu Xu, Fangwei Wang, Xiaodong Yi, Cheng Fang, Zhimin Liu, Wei Wang, Zhiwei Zhou
Journal: Cancer Communications (2019)

Abstract Background The prognosis of gastric cancer patients with a limited number of pathologically examined lymph nodes (eLN, &lt; 16) is dismal compared to those with adequately eLN (≥ 16), yet they are still classified within the same subgroups using the American Joint Committee on Cancer (AJCC) staging system. We aimed at formulating an easy‐to‐adopt and clinically reliable stratification approach to homogenize the classification for these two categories of patients. Methods Patients staged according to the 8th AJCC pathological nodal (N) and tumor‐node‐metastasis (TNM) classification were stratified into a Limited and Adequate eLN cohort based on their number of pathologically examined LNs. The statistical differences between the 5‐year overall survival (OS) rates of both cohorts were determined and based on which, patients from the Limited eLN cohort were re‐classified to a proposed modified nodal (N′) and TNM (TN′M) classification, by matching their survival rates with those of the Adequate eLN cohort. The prognostic performance of the N′ and TN′M classification was then compared to a formulated lymph‐node‐ratio‐based nodal classification, in addition to the 8th AJCC N and TNM classification. Results Significant heterogeneous differences in 5‐year OS between patients from the Limited and Adequate eLN cohort of the same nodal subgroups were identified (all P &lt; 0.001). However, no significant differences in 5‐year OS were observed between the subgroups N0, N1, N2, and N3a of the Limited eLN cohort when compared with N1, N2, N3a, and N3b from the Adequate eLN cohort, respectively ( P = 0.853, 0.476, 0.114, and 0.230, respectively). A novel approach was formulated in which only patients from the Limited eLN cohort were re‐classified to one higher nodal subgroup, denoted as the N′ classification. This re‐classification demonstrated superior stratifying and prognostic ability as compared to the 8th AJCC N and lymph‐node‐ratio classification (Akaike information criterion values [AIC]: 12,276 vs. 12,358 vs. 12,283, respectively). The TN′M classification also demonstrated superior prognostic ability as compared to the 8th AJCC TNM classification (AIC value: 12,252 vs. 12,312). Conclusion The proposed lymph node classification approach provides a clinically practical and reliable technique to homogeneously classify cohorts of gastric cancer patients with limited and adequate number of pathologically examined lymph nodes.