tbuckley/cabot-search huggingface dataset:
TREM-1, the ideal predictive biomarker for endoscopic healing in anti-TNF-treated Crohn’s disease patients?
Authors: Bram Verstockt, Sare Verstockt, Helene Blevi, Isabelle Cleynen, Magali de Bruyn, Gert Van Assche, Séverine Vermeire, Marc Ferrante
Journal: Gut (2018)

We read with great interest the study by Gaujoux et al , who described a whole blood marker for anti-tumour necrosis factor (TNF) responsiveness in patients with Crohn’s disease (CD). The availability of anti-TNF agents dramatically changed therapeutic strategies for patients with CD. However, an overall non-response rate of 30% has been observed, and, together with the approval of new classes of biological agents with a different mode of action, clearly indicates the need for predictive biomarkers. Gaujoux et al identified triggering receptor expressed on myeloid cells 1 ( TREM1) expression in whole blood as a biomarker for anti-TNF (non)response (higher expression in responders).1 In inflamed colonic tissue, TREM1 expression is also decreased in future infliximab responders.1 2 TREM-1 is known to amplify inflammation, whereas TREM-1 inhibition in vivo attenuates colitis by modulating autophagy and endoplasmic reticulum (ER) stress.3 

We first measured serum TREM-1 (sTREM-1) (Human sTREM-1 ELISA (HK348), Hycult Biotech, Uden, the Netherlands) in 85 patients with CD with active disease prior to anti-TNF therapy (table 1). To reduce the risk of including treatment failures secondary to immunogenicity (and not drug mechanistic failure) or non-drug-related healers, all included patients had to have a good drug exposure, defined as a maintenance trough level >3.0 µg/mL for infliximab or >5.0 µg/mL for adalimumab. Interestingly, patients who achieved mucosal healing (complete absence of ulcerations and erosions4) after 6 months of anti-TNF therapy (adalimumab and infliximab) had significantly lower baseline sTREM-1 levels compared with non-responders (50.8 pg/mL …
Communicating, consulting, and caring differently
Authors: R M Pope, S M Ali, C D Muir, A A Schulte
Journal: BMJ (2018)

Richards exhorts us, with passion, to work differently, for poorly served patients and overburdened staff.1 We need new approaches to healthcare interactions.

We see such systems having several key components: digital healthcare records shared between providers (“communicate differently”) and video based consultations (“consult differently”). We have developed a digital platform for patients that includes and engages people with self management—not by turning them into “mini medics,” but by …
A phase I safety study of topical calcitriol (BPM 31543) for the prevention of chemotherapy-induced alopecia (CIA).
Authors: Mario E. Lacouture, Jason A. Konner, Viswanath Reddy Belum, Janice Stevens, Hedy Dion, Kathryn Ciccolini, Sarah Kitts, Ran Ye, Shobha Ravipaty, Viacheslav R Akmaev, Rangaprasad Sarangarajan, Joaquin Juan Jimenez, Niven R. Narain, Brian Berman, Shari Beth Goldfarb
Journal: Journal of Clinical Oncology (2017)

e14064 Background: Chemotherapy-induced alopecia (CIA) may lead to significant psychosocial and quality of life issues. Currently there are no FDA approved oral or topical agents available to prevent CIA. In murine studies, topical calcitriol reduced CIA, likely due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy. Methods: A prospective dose escalation study is being performed in up to 31 women with breast cancer, gynecologic cancer and sarcomas. Each patient is applying 1mL of BPM 31543 to her scalp BID, ≥ 5 days prior to initiation of taxane-based chemotherapy for at least 3 months or until the completion of chemotherapy. The study cohorts are: 5/10/20/40/60/80 μg/mL. All 6 cohorts have been completely enrolled. Each patient undergoes PK analysis, adverse event (AE) monitoring, patient self-assessment diaries (1-10 scale), and blinded photographic assessments. Results: Twenty-eight patients have been enrolled (evaluable, n = 21). PK data (n = 21; 5-80 μg/mL) showed inter-individual variability, with increases in serum vitamin D in the 10/20/40/60/80 μg/mL cohorts (range, &lt; 21.3-110 pg/mL). Treatment-related AEs (probably/possibly) were mild/moderate in nature and included scalp pain (n = 1; 5 μg/mL), elevated vitamin D levels in 3 patients (20/40/60 μg/mL) and passage of renal calculus in another (n = 1; 40 μg/mL). A clinical response was observed at each dose level. The study will be complete and final study data will be available and presented at ASCO. Conclusions: Data have shown that the twice daily application of BPM 31543 in patients receiving taxane-based chemotherapy was safe and well-tolerated. The Maximum Tolerated Dose (MTD) was not detected. No Dose Limiting Toxicities (DLTs) or severe treatment-related adverse events occurred in any of the dose cohort. A signal of efficacy was detected at each dose level. Clinical trial information: NCT01588522.
Elevations in Troponin I After Percutaneous Coronary Interventions Are Associated With Abnormal Tissue-Level Perfusion in High-Risk Patients With Non–ST-Segment–Elevation Acute Coronary Syndromes
Authors: LeonardoBolognese, KennethDucci, PaoloAngioli, GiovanniFalsini, FrancescoLiistro, SilviaBaldassarre, AntonioBurali
Journal: Circulation (2004)

Background— In the setting of non–ST-segment–elevation (NSTE) acute coronary syndromes (ACS), the pathophysiological mechanisms underlying post–percutaneous coronary intervention (PCI) cardiac troponin I (cTnI) elevation remain unclear. Methods and Results— We evaluated the relationship between troponin elevation and tissue-level perfusion using the TIMI flow grade, corrected TIMI frame count, TIMI myocardial perfusion grade (TMPG), and myocardial contrast enhancement by intracoronary myocardial contrast echocardiography (MCE) before and immediately after PCI performed within 24 to 48 hours of hospital admission in 42 high-risk (angina at rest, unequivocal ST-segment depression, and cTnI elevation) patients with NSTE-ACS. All patients were treated with glycoprotein IIb/IIIa inhibitors (27 with tirofiban and 15 with abciximab) and had successful PCI. Fourteen patients had a postprocedural cTnI elevation, whereas 28 did not. TMPG 0/1 after PCI was observed more frequently in patients with postprocedural cTn...
Is miR200b-5p a new predictor of lymphoma or associated with lymphocytes infiltrate within salivary glands?
Authors: Gaetane Nocturne, Raphaele Seror, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2018)

We read with great interest the paper by Kapsogeorgou et al published recently in The Annals of the Rheumatic Diseases focusing on the link between miR200-5bp and the risk of lymphoma in primary Sjogren syndrome (pSS).1 In this study, the authors assess the level of this miRNA within salivary gland biopsy in three groups of patients with pSS: group 1 is made of patients without lymphoma, group 2 is made of patients at high risk of lymphoma and who developed lymphoma in median 3.67 years after biopsy and the last group 3 is made of patients with lymphoma at the time of biopsy. Interestingly, the authors demonstrate that miR200b-5p is significantly decreased in patients with lymphoma and moreover in patients at high risk of lymphoma. This result strongly suggests that miR200b-5p could be considered as a new biomarker predictor of future occurrence of lymphoma in …
Simultaneous Bilateral Endoscopic Surgery (SBES) for Patients with Bilateral Upper Tract Urolithiasis: Technique and Outcomes
Authors: Guido Giusti, Silvia Proietti, Moises E. Rodríguez-Socarrás, Brian H. Eisner, Giuseppe Saitta, Guglielmo Mantica, Luca Villa, Andrea Salonia, Francesco Montorsi, Franco Gaboardi
Journal: European Urology (2018)
<i>MUC5B</i> Promoter Polymorphism and Development of Acute Respiratory Distress Syndrome
Authors: Angela J. Rogers, Joseph F. Solus, Gary M. Hunninghake, Rebecca M. Baron, Nuala J. Meyer, David R. Janz, David A. Schwartz, Addison K. May, William E. Lawson, Timothy S. Blackwell, Lorraine B. Ware
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Abstract 14941: Substitution of Dietary Saturated Fatty Acids With Omega-6 Polyunsaturated Fatty Acids Decreases LDL ApoB-100 Production Rate in Men With Dyslipidemia Associated With Insulin-Resistance
Authors: Jean-Philippe Drouin-Chartier, André J Tremblay, Marie-Claude Lépine, Valéry Lemelin, Benoît Lamarche, Patrick Couture
Journal: Circulation (2016)

Introduction: The consumption of omega (n)-6 polyunsaturated fatty acids (PUFA) in replacement of saturated fatty acids (SFA) is advocated to prevent cardiovascular disease (CVD) as it is recognize...
A randomised trial of voriconazole and prednisolone monotherapy in acute-stage allergic bronchopulmonary aspergillosis complicating asthma
Authors: Ritesh Agarwal, Sahajal Dhooria, Inderpaul S. Sehgal, Ashutosh N. Aggarwal, Mandeep Garg, Biman Saikia, Arunaloke Chakrabarti
Journal: European Respiratory Journal (2018)

Glucocorticoids are the most widely used agents in the treatment of allergic bronchopulmonary aspergillosis (ABPA), a disorder characterised by immunologic reactions mounted against Aspergillus fumigatus colonising the airways of patients with asthma and cystic fibrosis [1, 2]. Unfortunately, the use of glucocorticoids is associated with several adverse reactions [3]. A novel treatment strategy in ABPA would be the use of antifungal triazoles as monotherapy. Recently, we have shown that itraconazole was effective as monotherapy in acute-stage ABPA [4]. Whether voriconazole monotherapy is also efficacious in acute-stage ABPA remains unknown. Voriconazole monotherapy is as effective, and safer, than glucocorticoids for the treatment of ABPA <http://ow.ly/jCix30l2Lb9>
High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia
Authors: Miriam Marquis, Cyrielle Beaubois, Vincent-Philippe Lavallée, Michal Abrahamowicz, Coraline Danieli, Sébastien Lemieux, Imran Ahmad, Andrew Wei, Stephen B. Ting, Shaun Fleming, Anthony Schwarer, David Grimwade, William Grey, Robert K. Hills, Paresh Vyas, Nigel Russell, Guy Sauvageau, Josée Hébert
Journal: Blood Cancer Journal (2018)

Abstract In acute myeloid leukemia (AML), risk stratification based on cytogenetics and mutation profiling is essential but remains insufficient to select the optimal therapy. Accurate biomarkers are needed to improve prognostic assessment. We analyzed RNA sequencing and survival data of 430 AML patients and identified HMGA2 as a novel prognostic marker. We validated a quantitative PCR test to study the association of HMGA2 expression with clinical outcomes in 358 AML samples. In this training cohort, HMGA2 was highly expressed in 22.3% of AML, mostly in patients with intermediate or adverse cytogenetics. High expression levels of HMGA2 ( H + ) were associated with a lower frequency of complete remission (58.8% vs 83.4%, P &lt; 0.001), worse 3-year overall survival (OS, 13.2% vs 43.5%, P &lt; 0.001) and relapse-free survival (RFS, 10.8% vs 44.2%, P &lt; 0.001). A positive HMGA2 test also identified a subgroup of patients unresponsive to standard treatments. Multivariable analyses showed that H + was independently associated with significantly worse OS and RFS, including in the intermediate cytogenetic risk category. These associations were confirmed in a validation cohort of 260 patient samples from the UK NCRI AML17 trial. The HMGA2 test could be implemented in clinical trials developing novel therapeutic strategies for high-risk AML.
Prevalence and Short-term Mortality of Acuteon-Chronic Liver Failure (ACLF) in the Veterans Affairs Hospitals (2004-2014): a National US Cohort.
Authors: Ruben Hernaez, Jennifer R. Kramer, Yan Liu, Aylin Tansel, Yamini Natarajan, Khozema B. Hussain, Pere Gines, Elsa Sola, Richard Moreau, Alexander L. Gerbes, Hashem B. El-Serag, Fasiha Kanwal
Journal: Hepatology (2017)
Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes
Authors: Yong Joon Kim, Sungsoo Kim, Yooju Jung, Eunji Jung, Ho Jeong Kwon, Joon Kim
Journal: Journal of Clinical Investigation (2018)

Ciliopathies are clinically overlapping genetic disorders involving structural and functional abnormalities of cilia. Currently, there are no small-molecule drugs available to treat ciliary defects in ciliopathies. Our phenotype-based screen identified the flavonoid eupatilin and its analogs as lead compounds for developing ciliopathy medication. CEP290, a gene mutated in several ciliopathies, encodes a protein that forms a complex with NPHP5 to support the function of the ciliary transition zone. Eupatilin relieved ciliogenesis and ciliary receptor delivery defects resulting from deletion of CEP290. In rd16 mice harboring a blinding Cep290 in-frame deletion, eupatilin treatment improved both opsin transport to the photoreceptor outer segment and electrophysiological responses of the retina to light stimulation. The rescue effect was due to eupatilin-mediated inhibition of calmodulin binding to NPHP5, which promoted NPHP5 recruitment to the ciliary base. Our results suggest that deficiency of a ciliopathy protein could be mitigated by small-molecule compounds that target other ciliary components that interact with the ciliopathy protein.
Melanoma risk after in vitro fertilization: A review of the literature
Authors: Juliana Berk-Krauss, Amy Kalowitz Bieber, Maressa C. Criscito, Jane M. Grant-Kels, Marcia S. Driscoll, Martin Keltz, Miriam Keltz Pomeranz, Kathryn J. Martires, Tracey N. Liebman, Jennifer A. Stein
Journal: Journal of the American Academy of Dermatology (2018)
Transepidermal water loss in healthy adults: a systematic review and meta-analysis update
Authors: M. Akdeniz, S. Gabriel, A. Lichterfeld-Kottner, U. Blume-Peytavi, J. Kottner
Journal: British Journal of Dermatology (2018)

Transepidermal water loss (TEWL) is one of the most important skin barrier characteristics. Higher TEWL is usually associated with skin barrier impairments, and lower TEWL with healthy skin. To update an existing systematic review and meta‐analysis to provide TEWL reference values for healthy skin in adults. The databases MEDLINE and Embase and other sources were searched. This update includes studies identified by two combined searches that cover the period from 1947 to 13 April 2017. Primary empirical observational and interventional studies in healthy adults providing quantitative estimates of TEWL measurements including measures of spread, such as SDs, with clear reporting of skin areas and age were included. Data were extracted per skin area and statistically pooled. After full‐text assessment, the results of 45 studies were included additionally to the existing meta‐analysis. TEWL estimates were identified for 86 skin areas in 212 studies. The lowest TEWL of 2·3 g m−2 h−1 (95% confidence interval 1·9–2·7) was reported for breast skin and the highest TEWL of 44·0 g m−2 h−1 (95% confidence interval 39·8–48·2) for the axilla. Sample sizes ranged from four (forehead middle left middle) to 4013 (mid volar right forearm). The clinical relevance of the difference between TEWL estimates for different measurement devices seems to be minimal. TEWL in elderly patients was either similar to or lower than values in the younger group. Reference estimates are useful for clinical study planning and interpretation of results. TEWL is highly dependent on skin area, and our results further support the symmetry between right and left measuring sites. TEWL in elderly people seems to be generally similar or decreased compared with younger individuals, but available evidence is limited. Reporting of TEWL should be improved: mean and spread parameters should always be reported in future studies.
Maxillofacial Spindle Cell Sarcoma With Lung Metastases on FDG PET/CT Imaging
Authors: Xiaodong Wu, Chunye Zhang, Yan Huang, Huoqiang Wang, Lei Jiang
Journal: Clinical Nuclear Medicine (2018)

Abstract A 45-year-old man presented with episodes of cough and chest discomfort. CT examination showed multiple nodules of bilateral lungs. The pathology of CT-guided biopsy was consistent with spindle cell sarcoma. FDG PET/CT scan was performed to detect the primary lesion, which showed that in addition to multiple hypermetabolic pulmonary nodules, a mass in the right maxillofacial region with high FDG uptake was also found. A biopsy confirmed spindle cell sarcoma.
Optic nerve sheath diameter measured sonographically as non-invasive estimator of intracranial pressure: a systematic review and meta-analysis
Authors: Chiara Robba, Gregorio Santori, Marek Czosnyka, Francesco Corradi, Nicola Bragazzi, Llewellyn Padayachy, Fabio Silvio Taccone, Giuseppe Citerio
Journal: Intensive Care Medicine (2018)
Copper-CX-5461: A novel liposomal formulation for a small molecule rRNA synthesis inhibitor
Authors: Ada W.Y. Leung, Malathi Anantha, Wieslawa H. Dragowska, Mohamed Wehbe, Marcel B. Bally
Journal: Journal of Controlled Release (2018)

CX-5461 is currently in Phase I/II clinical trials for advanced hematologic malignancies and triple negative or BRCA-deficient breast cancer. The compound is currently administered to patients intravenously (i.v.) at low pH (3.5) due to solubility challenges. Reliance of low pH to enhance solubility of CX-5461 can adversely impact pharmacokinetics, biodistribution and therapeutic potential. We have addressed this solubility issue through a formulation method that relies on the interactions between CX-5461 and copper. Copper binds CX-5461 through the nitrogens of the pyrazine ring. Here, we describe synthesizing this copper-complexed CX-5461 (Cu(CX-5461)) within liposomes. CX-5461 was added to copper-containing liposomes and incubated at 60 °C for 30 min. The pharmacokinetics of CX-5461 was assessed in mice following a single i.v. injection at 30 mg/kg. Efficacy studies were completed in multiple subcutaneous mouse xenografts as well as in a bone marrow engraftment model of acute myeloid leukemia (AML). The novel Cu(CX-5461) formulation was stable at pH 7.4 and exhibited increased plasma circulation longevity, increasing the total exposure to CX5461 by an order of magnitude. Cu(CX-5461) was more active than CX-5461 in AML models in vivo. In HCT116-B46 and Capan-1 solid tumour models that are BRCA-deficient, the Cu(CX-5461) formulation engendered activity that was comparable to that of the low pH CX-5461 formulation. We have generated the first Cu(CX-5461) formulation suitable for i.v. administration that is more efficacious than the existing low-pH formulation in pre-clinical models of AML. The Cu(CX-5461) formulation may serve as an alternative formulation for CX-5461 in BRCA-deficient cancers.
Long Noncoding RNAs and MicroRNAs in Cardiovascular Pathophysiology
Authors: ThomasThum, GianluigiCondorelli
Journal: Circulation Research (2015)

RNAs not encoding proteins have gained prominence over the last couple of decades as fundamental regulators of cellular function. Not surprisingly, their dysregulation is increasingly being linked to pathology. Here, we review recent reports investigating the pathophysiological relevance of this species of RNA for the cardiovascular system, concentrating mainly on recent findings on long noncoding RNAs and microRNAs in cardiac hypertrophy and failure.
Trial of Viagra for fetal growth restriction is halted after baby deaths
Authors: Nigel Hawkes
Journal: BMJ (2018)

A Dutch trial using sildenafil (Viagra) to try to correct fetal growth restriction has been halted after 11 babies subsequently died.

An interim review by an independent committee of the STRIDER trial, which had randomly assigned 183 pregnant women to take sildenafil or placebo, showed that lung complications were more common in the babies born to women given the drug. Of these women, 17 had babies with lung problems: 11 of those babies have since died, compared with three in the placebo group, none of whom died.

A statement from …
Isolation of CD4<sup>+</sup> T cells specific for neoantigens created by recurrent driver mutations in non-small cell lung cancer (NSCLC) and melanoma.
Authors: Joshua Veatch, Brenda Jesernig, Sylvia Mina Lee, Matthew Fitzgibbon, A. McGarry Houghton, Stanley R. Riddell
Journal: Journal of Clinical Oncology (2018)

12054 Background: T cells specific for neoantigens encoded by mutated genes are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, almost all neoantigens result from random mutations that are patient-specific. Here, we describe CD4+ T cell responses one melanoma patient and two NSCLC patients that are specific for recurrent driver mutations in their cancers. Methods: Neoantigen-reactive T cells were expanded and cloned by peptide stimulation of the peripheral blood from cancer patients. Results: The melanoma patient had a CD4+ T cell response to the peptide encoded by the BRAF V600E mutation found in 40% of melanoma, and obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL). The BRAF V600E specific cells showed a Th1 memory phenotype, were preferentially localized to the tumor at the time of resection, and expanded and persisted in blood greater than 2 years after TIL therapy. Gene transfer of the BRAF V600E-specific T cell receptor (TCR) conferred recognition of class II MHC positive cells expressing the BRAF mutation. A CD4+ T cell response specific for KRAS G12V that is present in 5% of NSCLC and 10% of colon cancer was detected in one NSCLC patient. A second NSCLC patient had a CD4+ T cell response specific for the Her2 internal tandem duplication (ITD) found in 4% of NSCLC, and deep sequencing of TCR genes showed the mutation-specific T cell clone was enriched in a tumor resection sample, relative to the non-adjacent lung. The CD4+ T cells specific for the BRAF V600E, KRAS G12V, and Her2 ITD epitopes only recognized the mutant and not the wild-type peptide and were restricted by common class II HLA alleles found in 10-25% of the population. The neoantigen reactive Her2 and KRAS reactive TCRs are currently being cloned. Conclusions: This study greatly expands the number of driver mutations with known T cell responses, and suggests that adoptive transfer or vaccination strategies targeting recurrent driver mutations could help interrogate the role of CD4+ T cells in human anti-tumor immunity, and could have clinical activity across multiple patients.
Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women
Authors: MarianneCanonico, EmmanuelOger, GenevièvePlu-Bureau, JacquelineConard, GuyMeyer, HervéLévesque, NathalieTrillot, Marie-ThérèseBarrellier, DenisWahl, JosephEmmerich, Pierre-YvesScarabin
Journal: Circulation (2007)

Background— Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal estrogen may be safer. However, currently available data have limited the ability to investigate the wide variety of types of progestogen. Methods and Results— We performed a multicenter case–control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France. We recruited 271 consecutive cases with a first documented episode of idiopathic VTE (208 hospital cases, 63 outpatient cases) and 610 controls (426 hospital controls, 184 community controls) matched for center, age, and admission date. After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; ...