tbuckley/cabot-search huggingface dataset:
Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis
Authors: Jan Menne, Eva Dumann, Hermann Haller, Bernhard M. W. Schmidt
Journal: PLoS Medicine (2019)

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent a new class of oral hypoglycemic agents used in the treatment of type 2 diabetes mellitus. They have a positive effect on the progression of chronic kidney disease, but there is a concern that they might cause acute kidney injury (AKI). Methods and findings We conducted a systematic review and meta-analysis of the effect of SGLT2is on renal adverse events (AEs) in randomized controlled trials and controlled observational studies. PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov were searched without date restriction until 27 September 2019. Data extraction was performed using a standardized data form, and any discrepancies were resolved by consensus. One hundred and twelve randomized trials (n = 96,722) and 4 observational studies with 5 cohorts (n = 83,934) with a minimum follow-up of 12 weeks that provided information on at least 1 adverse renal outcome (AKI, combined renal AE, or hypovolemia-related events) were included. In 30 trials, 410 serious AEs due to AKI were reported. SGLT2is reduced the odds of suffering AKI by 36% (odds ratio [OR] 0.64 [95% confidence interval (CI) 0.53–0.78], p < 0.001). A total of 1,089 AKI events of any severity (AEs and serious AEs [SAEs]) were published in 41 trials (OR 0.75 [95% CI 0.66–0.84], p < 0.001). Empagliflozin, dapagliflozin, and canagliflozin had a comparable benefit on the SAE and AE rate. AEs related to hypovolemia were more commonly reported in SGLT2i-treated patients (OR 1.20 [95% CI 1.10–1.31], p < 0.001). In the observational studies, 777 AKI events were reported. The odds of suffering AKI were reduced in patients receiving SGLT2is (OR 0.40 [95% CI 0.33–0.48], p < 0.001). Limitations of this study are the reliance on nonadjudicated safety endpoints, discrepant inclusion criteria and baseline hypoglycemic therapy between studies, inconsistent definitions of renal AEs and hypovolemia, varying follow-up times in different studies, and a lack of information on the severity of AKI (stages I–III). Conclusions SGLT2is reduced the odds of suffering AKI with and without hospitalization in randomized trials and the real-world setting, despite the fact that more AEs related to hypovolemia are reported.
Proteomics in the Study of Qualitative Platelet Defects: Validation of the Approach in the Gray Platelet Syndrome and Quebec Platelet Disorder.
Authors: Raj S. Kasthuri, Lorraine B. Anderson, LeeAnn Higgins, Jorge Di Paola, Georges E. Rivard, Catherine P.M. Hayward, Nigel S. Key
Journal: Blood (2007)
Impact of patient navigation on breast cancer outcomes
Authors: N. A. Haideri, J. Moormeier
Journal: Journal of Clinical Oncology (2009)

6572 Background: Disparities between U.S. population groups in cancer incidence, treatment and outcome have been well documented. There is little information available about effective means of eliminating these differences utilizing patient navigator programs. Through the evaluation of the processes and outcomes of breast cancer care at a safety net hospital, this study attempts to better define, the impact of a patient navigation program. Methods: This was a retrospective case series analysis. Navigator program was established in January 2000. Eligible women with a diagnosis of breast cancer between January 1, 1997 and December 31, 1999, were included in the standard management (SM) group. Women with breast cancer diagnosed between January 1, 2000 and December 31, 2003, were included in the Patient Navigator (PN) group. The time interval from symptom presentation or abnormal mammogram to first access to treatment which includes surgery, chemotherapy or radiation was obtained. Statistical data was analyzed using SPSS software. Results: Three hundred and thirty five women were diagnosed between January 1, 1997 and December 31, 2003. Thirteen patients were ineligible leaving a final study population of 322 women; 103 women in the SM group, and 219 women in the PN group. The time interval from initial presentation to the date of definitive therapy was shorter during the period of time when PN was available with a median time to first treatment was 9 days shorter (42 days in SM group compared to 33 days in PN group). The stage of cancer at the time of presentation and treatment was not different between the two groups. One potential impact of PN program was dramatic increase in proportion of insured patients. Overall survival was not influenced by the PN program. Conclusions: The PN program at this safety net hospital did not influence the stage of presentation or the overall survival of women with breast cancer. There was a modest decrease in the time between initial presentation and definitive therapy. The utility of navigator programs is likely to vary with each institution and the program should be modified to respond to the unique needs of the patients being served. No significant financial relationships to disclose.
Red blood cell membrane-enveloped O<sub>2</sub> self-supplementing biomimetic nanoparticles for tumor imaging-guided enhanced sonodynamic therapy
Authors: Cheng Li, Xiao-Quan Yang, Jie An, Kai Cheng, Xiao-Lin Hou, Xiao-Shuai Zhang, Yong-Guo Hu, Bo Liu, Yuan-Di Zhao
Journal: Theranostics (2019)

Non-invasive sonodynamic therapy (SDT) was developed because of its advantages of high penetration depth and low side effects; however, tumor hypoxia greatly restricts its therapeutic effect. In this study, we aimed to develop ideal O2 self-supplementing nanoparticles for imaging-guided enhanced sonodynamic therapy of tumors with the adept coalescence of biology with nanotechnology. Methods: Based on the natural enzyme system of red blood cells (RBC), biomimetic nanoparticles (QD@P)Rs were fabricated by encapsulating Ag2S quantum dots (QD) in RBC vesicle membranes. The anti-tumor drug PEITC was employed to increase the intracellular H2O2 concentration in tumor cells. Results:In vitro and in vivo experiments demonstrated excellent biocompatibility and prolonged blood circulation of (QD@P)Rs. Following oral administration of PEITC in mice to improve the H2O2 concentration, the enzyme in the nanoprobe catalyzed endogenous H2O2 to increase O2 content and effectively alleviate tumor hypoxia. Triggered by ultrasound under the guidance of fluorescence imaging, (QD@P)Rs generated reactive oxygen species (ROS) to induce tumor cell death, and the increased content of O2 significantly enhanced the effect of SDT. Conclusion: Ag2S QDs were used, for the first time, as a sonosensitizer in the SDT field. In this study, we integrated the advantages of the natural enzyme system and SDT to develop a novel approach for effective non-invasive treatment of cancer.
Allosteric regulation of protein 14-3-3ζ scaffold by small-molecule editing modulates histone H3 post-translational modifications
Authors: Yan-Jun Wan, Li-Xi Liao, Yang Liu, Heng Yang, Xiao-Min Song, Li-Chao Wang, Xiao-Wen Zhang, Yi Qian, Dan Liu, Xiao-Meng Shi, Li-Wen Han, Qing Xia, Ke-Chun Liu, Zhi-Yong Du, Yong Jiang, Ming-Bo Zhao, Ke-Wu Zeng, Peng-Fei Tu
Journal: Theranostics (2019)

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair.Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs. Methods and Results:In this study, we discovered a previously unexplored regulation mechanism for histone PTMs by targeting transcription regulation factor 14-3-3ζ.Mechanistic studies revealed 14-3-3ζ dimerization as a key prerequisite, which could be dynamically induced via an allosteric effect.The selective inhibition of 14-3-3ζ dimer interaction with histone H3 modulated histone H3 PTMs by exposing specific modification sites including acetylation, trimethylation, and phosphorylation, and reprogrammed gene transcription profiles for autophagy-lysosome function and endoplasmic reticulum stress.Conclusion: Our findings demonstrate the feasibility of editing histone PTM patterns by targeting transcription regulation factor 14-3-3ζ, and provide a distinctive PTM editing strategy which differs from current histone modification approaches.
Sequential Treatment with 5-Azacytidine, Valproic Acid (VPA), and All-Trans Retinoic Acid (ATRA) in Patients with High-Risk Acute Myeloid Leukemia (AML).
Authors: Emmanuel Raffoux, Adrienne de Labarthe, Claude Gardin, Marie-Therese Daniel, Christine Chomienne, Pierre Fenaux, Laurent Degos, Herve Dombret
Journal: Blood (2005)
The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial
Authors: Sarah Ekeloef, Morten Homilius, Maiken Stilling, Peter Ekeloef, Seda Koyuncu, Anna-Marie Bloch Münster, Christian S Meyhoff, Ossian Gundel, Julie Holst-Knudsen, Ole Mathiesen, Ismail Gögenur
Journal: BMJ (2019)

To investigate whether remote ischaemic preconditioning (RIPC) prevents myocardial injury in patients undergoing hip fracture surgery.Phase II, multicentre, randomised, observer blinded, clinical trial.Three Danish university hospitals, 2015-17.648 patients with cardiovascular risk factors undergoing hip fracture surgery. 286 patients were assigned to RIPC and 287 were assigned to standard practice (control group).The RIPC procedure was initiated before surgery with a tourniquet applied to the upper arm and consisted of four cycles of forearm ischaemia for five minutes followed by reperfusion for five minutes.The original primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more caused by ischaemia. The revised primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more or high sensitive troponin I greater than 24 ng/L (the primary outcome was changed owing to availability of testing). Secondary outcomes were peak plasma troponin I and total troponin I release during the first four days after surgery (cardiac and high sensitive troponin I), perioperative myocardial infarction, major adverse cardiovascular events, and all cause mortality within 30 days of surgery, length of postoperative stay, and length of stay in the intensive care unit. Several planned secondary outcomes will be reported elsewhere.573 of the 648 randomised patients were included in the intention-to-treat analysis (mean age 79 (SD 10) years; 399 (70%) women). The primary outcome occurred in 25 of 168 (15%) patients in the RIPC group and 45 of 158 (28%) in the control group (odds ratio 0.44, 95% confidence interval 0.25 to 0.76; P=0.003). The revised primary outcome occurred in 57 of 286 patients (20%) in the RIPC group and 90 of 287 (31%) in the control group (0.55, 0.37 to 0.80; P=0.002). Myocardial infarction occurred in 10 patients (3%) in the RIPC group and 21 patients (7%) in the control group (0.46, 0.21 to 0.99; P=0.04). Statistical power was insufficient to draw firm conclusions on differences between groups for the other clinical secondary outcomes (major adverse cardiovascular events, 30 day all cause mortality, length of postoperative stay, and length of stay in the intensive care unit).RIPC reduced the risk of myocardial injury and infarction after emergency hip fracture surgery. It cannot be concluded that RIPC overall prevents major adverse cardiovascular events after surgery. The findings support larger scale clinical trials to assess longer term clinical outcomes and mortality.ClinicalTrials.gov NCT02344797.
Experience with Low Dose Thalidomide in Transfusion Dependent Beta Thalassaemia in a Resource Limited Setting
Authors: Pallavi Mehta, Neha Yadav, Priyanka Soni, Shinto Francis Thekuddan, Reema Singh, Vishvdeep Khushoo, Sumeet Prakash Mirgh, Narendra Agrawal, Rayaz Ahmed, Jyotsna Kapoor, Dinesh Bhurani
Journal: Blood (2019)
Dysregulated Expression of MicroRNA-16 Contributes to Abnormal Erythropoiesis in Patients with Polycythemia Vera
Authors: Paola Guglielmelli, Lorenzo Tozzi, Costanza Bogani, Niccolo’ Bartalucci, Simona Salati, Rossella Manfredini, Alberto Bosi, Alessandro M. Vannucchi
Journal: Blood (2008)
Polymorphisms in FcγRIIIA Are Genetically Linked to FcγRIIA and May Account for the Primary Predictive Role Ascribed to Polymorphisms in FcγRIIIA-158 in Determining Rituximab Responses.
Authors: Evdoxia Hatjiharissi, Mark Hansen, Sigitas Verselis, Daniel Ditzel Santos, Lian Xu, Robert Manning, Zachary Hunter, Xavier Leleu, Allen W. Ho, Christopher J. Patterson, Edward Fox, Steven P. Treon
Journal: Blood (2005)
RANDOMIZED STUDY OF CONVENTIONAL STRATEGY VERSUS IMPLANTABLE DEFIBRILLATOR AS 1ST-CHOICE THERAPY IN POSTINFARCT SUDDEN-DEATH SURVIVORS
Authors: Efd Wever, Rnw Hauer, Hjgm Crijns, Fjl Vancapelle, Pfa Bakker, Eor Demedina
Journal: Circulation (1993)
Abstract 13558: The Additive Effect of RAAS Blockade in Marfan Syndrome Patients after Bentall Operation
Authors: Seung-jun Lee, Jaewon Oh, Young-Guk Ko, Chi-Young Shim, Sak Lee, Taek-Yeon Lee, Byung-Chul Chang, Young-Ran Kwak, Donghoon Choi
Journal: Circulation (2012)

Background In Marfan syndrome (MFS) patients, prophylactic aortic operation and β-blocker reduced mortality. Recent studies showed Renin-Angiotensin-Aldosterone System (RAAS) blockade reduces aorti...
The doctors standing for election as MPs in 2019
Authors: Nillanee Nehrujee, Tom Moberly
Journal: BMJ (2019)

More than 50 doctors are running for election as MPs in this year’s general election. <b>Nillanee Nehrujee</b> and <b>Tom Moberly</b> hear from this year’s candidates about their expectations and experiences of canvassing and hustings
Association of Tumor-Infiltrating Lymphocytes with Homologous Recombination Deficiency and <i>BRCA1/2</i> Status in Patients with Early Triple-Negative Breast Cancer: A Pooled Analysis
Authors: Melinda L. Telli, Charles Chu, Sunil S. Badve, Shaveta Vinayak, Daniel P. Silver, Steven J. Isakoff, Virginia Kaklamani, William Gradishar, Vered Stearns, Roisin M. Connolly, James M. Ford, Joshua J. Gruber, Sylvia Adams, Judy Garber, Nadine Tung, Chris Neff, Ryan Bernhisel, Kirsten M. Timms, Andrea L. Richardson
Journal: Clinical Cancer Research (2019)

Patients with triple-negative breast cancer (TNBC) with homologous recombination deficient tumors achieve significantly higher pathologic complete response (pCR) rates when treated with neoadjuvant platinum-based therapy. Tumor-infiltrating lymphocytes (TIL) are prognostic and predictive of chemotherapy benefit in early stage TNBC. The relationship between TILs, BRCA1/2 mutation status, and homologous recombination deficiency (HRD) status in TNBC remains unclear.We performed a pooled analysis of five phase II studies that included patients with TNBC treated with neoadjuvant platinum-based chemotherapy to evaluate the association of TILs with HRD status (Myriad Genetics) and tumor BRCA1/2 mutation status. Furthermore, the relationship between pathologic response assessed using the residual cancer burden (RCB) index and HRD status with adjustment for TILs was evaluated.Among 161 patients, stromal TIL (sTIL) density was not significantly associated with HRD status (P = 0.107) or tumor BRCA1/2 mutation status (P = 0.391). In multivariate analyses, sTIL density [OR, 1.23; 95% confidence interval (CI), 0.94-1.61; P = 0.139] was not associated with pCR, but was associated with RCB 0/I status (OR 1.62; 95% CI, 1.20-2.28; P = 0.001). HRD was significantly associated with both pCR (OR 12.09; 95% CI, 4.11-44.29; P = 7.82 × 10-7) and RCB 0/I (OR 10.22; 95% CI, 4.11-28.75; P = 1.09 × 10-7) in these models.In patients with TNBC treated with neoadjuvant platinum-based therapy, TIL density was not significantly associated with either tumor BRCA1/2 mutation status or HRD status. In this pooled analysis, HRD and sTIL density were independently associated with treatment response, with HRD status being the strongest predictor.
New 2019 SLE EULAR/ACR classification criteria are valid for identifying patients with SLE among patients admitted for pericardial effusion
Authors: Karim Sacre, Laure Delaval, Antoine Dossier, Jean-Francois Alexandra, Marie Berleur, Marie-Paule Chauveheid, Gregory Ducrocq, Tiphaine Goulenok, Damien van Gysel, Diane Rouzaud, Thomas Papo
Journal: Annals of the Rheumatic Diseases (2019)

The new 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) have been recently published.1 Seritis is a prominent—often inaugural—feature of active SLE. Low titers of antinuclear antibodies (ANA) have been frequently reported in patients with idiopathic pericarditis.2 3 Of note, ANA positivity at a titer ≥1/80 is now mandatory as an entry criterion in the 2019 SLE EULAR/ACR classification criteria. Although classification criteria have theoretically no individual diagnostic purpose, we aimed at testing this new criteria set in unselected patients with pericardial effusion.

In a retrospective study performed in the Department of Internal Medicine, University Paris Diderot, a French competence centre for rare systemic autoimmune diseases (AIDs), all consecutive adult patients hospitalised from January 2009 to January 2019 for pericardial effusion were reviewed. Clinical and biological data …
Use of early tumor shrinkage as a response to VEGF inhibitors as a predictor of progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC).
Authors: Viktor Gruenwald, Christoph Seidel, Martin Fenner, Michael Woike, Daniel Kalanovic
Journal: Journal of Clinical Oncology (2012)

4631 Background: Several novel targeted agents significantly prolong overall survival (OS) in metastatic renal cell cancer (mRCC) patients (pts.). Translational research, however, has not identified any prospectively validated prognostic or predictive biomarkers. Recently, progression free survival (PFS), overall response rate (ORR) and early tumor shrinkage were proposed as putative predictors for clinical outcome. In this study we aim to explore the potential role of treatment induced tumor remission as a prognostic or predictive parameter in mRCC. Methods: In our analyses we investigated the putative prognostic role of best response according to RECIST 1.1 criteria (complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD)) in first line Tyrosine-kinase inhibitor (TKI) treatment in n=83 pts. Responders were defined by achieving CR, PR or SD at any time during the course of treatment. Furthermore, we tested whether tumor shrinkage of 10% or more within 12 weeks of treatment qualifies as a potential cut-off-parameter to predict PFS or OS. Uni- and multivariate analyses were performed using Log-rang test, Kaplan-Meier-, and Cox-regression analysis. Results: Univariate analyses revealed that first-line treatment non-responders had a significantly shorter OS than responders (p &lt;0.0001). Tumor shrinkage of &lt;10% or ≥10% also correlated with an OS of 14.5 vs. 29.1 mo. (p=0.001) and a PFS of 3.0 vs. 11.5 mo. (p &lt;0.001). In multivariate analyses tumor shrinkage of ≥10% was tested with other common variables such as ECOG, MSKCC-score, histology, and metastatic sites and proved to be a significant independent prognostic (HR 0.361; 95% CI 0.156-0.833) and predictive (HR 0.306; 95% CI 0.152-0.612) parameter. Conclusions: Our results outline that sensitivity to first line treatment of mRCC is an important prognostic factor in mRCC. Hereby tumor shrinkage of ≥10% within 12 weeks of treatment reveals a novel cut-off-parameter, which showed to be a promising prognostic and predictive marker in mRCC. Further investigations are needed to validate this parameter.
Abstract 2485: Prognostic Implications of A Normal Real Time Myocardial Perfusion Response in Patients With High Framingham Risk Scores
Authors: Saritha Dodla, Feng Xie, David Cloutier, Thomas R Porter
Journal: Circulation (2007)

Background. Clinical trials examining the negative predictive value of various stress tests often include patients who have low pre-test probability of coronary artery disease (CAD). Myocardial per...
From ARIA guidelines to the digital transformation of health in rhinitis and asthma multimorbidity
Authors: Jean Bousquet, Josep M. Anto, Claus Bachert, Sinthia Bosnic-Anticevich, Marina Erhola, Tari Haahtela, Peter W. Hellings, Piotr Kuna, Oliver Pfaar, Boleslaw Samolinski, Holger J. Schünemann, Aziz Sheikh, Dana Wallace
Journal: European Respiratory Journal (2019)

<b>ARIA has evolved, with strong political commitment, from the first multimorbidity guideline in respiratory diseases to an exemplar for the future digital transformation of health and care for the management of patients with long-term conditions</b>http://bit.ly/35fBlhN
RHAMM/CD168-R3 Peptide Vaccination of Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM) Elicits Immunological and Clinical Responses.
Authors: Michael Schmitt, Anita Schmitt, Krzysztof Giannopoulos, Li Li, Peter Liebisch, Jinfei Chen, Mark Ringhoffer, Phillipe Guillaume, Gerd Ritter, Markus Rojewski, Sascha Gnjatic, Hartmut Dohner, Jochen Jochen
Journal: Blood (2006)
Peter Robert Bradley Pedlow
Authors: Roger Armour, Beryl Whitehead
Journal: BMJ (2019)

Peter Robert Bradley Pedlow was born in Lurgan, Northern Ireland, into a medical family. He attended Campbell College before studying medicine.

Peter married Nessa in 1957, and they had two daughters, Linda and Deirdre. He did a three year working tour, taking in a year each in Jamaica, Nigeria, and London, from …
Loss of IL-10 signaling in macrophages limits bacterial killing driven by prostaglandin E2
Authors: Subhankar Mukhopadhyay, Eva Heinz, Immacolata Porreca, Kaur Alasoo, Amy Yeung, Huei-Ting Yang, Tobias Schwerd, Jessica L. Forbester, Christine Hale, Chukwuma A. Agu, Yoon Ha Choi, Julia Rodrigues, Melania Capitani, Luke Jostins-Dean, David C. Thomas, Simon Travis, Daniel Gaffney, William C. Skarnes, Nicholas Thomson, Holm H. Uhlig, Gordon Dougan, Fiona Powrie
Journal: The Journal of Experimental Medicine (2019)

Loss of IL-10 signaling in macrophages (Mφs) leads to inflammatory bowel disease (IBD). Induced pluripotent stem cells (iPSCs) were generated from an infantile-onset IBD patient lacking a functional IL10RB gene. Mφs differentiated from IL-10RB−/− iPSCs lacked IL-10RB mRNA expression, were unable to phosphorylate STAT3, and failed to reduce LPS induced inflammatory cytokines in the presence of exogenous IL-10. IL-10RB−/− Mφs exhibited a striking defect in their ability to kill Salmonella enterica serovar Typhimurium, which was rescuable after experimentally introducing functional copies of the IL10RB gene. Genes involved in synthesis and receptor pathways for eicosanoid prostaglandin E2 (PGE2) were more highly induced in IL-10RB−/− Mφs, and these Mφs produced higher amounts of PGE2 after LPS stimulation compared with controls. Furthermore, pharmacological inhibition of PGE2 synthesis and PGE2 receptor blockade enhanced bacterial killing in Mφs. These results identify a regulatory interaction between IL-10 and PGE2, dysregulation of which may drive aberrant Mφ activation and impaired host defense contributing to IBD pathogenesis.