tbuckley/cabot-search huggingface dataset:
OCTA, a sensitive screening for asymptomatic retinopathy, raises alarm over systemic involvements in patients with SLE
Authors: Yumiko Mizuno, Masayuki Nishide, Taku Wakabayashi, Kohji Nishida, Atsushi Kumanogoh
Journal: Annals of the Rheumatic Diseases (2018)

We have read with great interest the letter by Conigliaro et al 1 regarding the usefulness of an optical coherence tomography angiography (OCTA) for evaluating retinal microvasculature in patients with systemic lupus erythematosus (SLE). The authors suggested that OCTA is a sensitive tool to detect preclinical ocular changes, and retinal vascular abnormalities are related to renal involvement in patients with SLE. In addition to this, we wish to emphasise that patients with abnormal eye findings should be closely followed, even if it is asymptomatic and in an early phase, keeping in mind the possibility of neuropsychiatric SLE.

Previous study showed that patients with SLE with eye involvement often have neuropsychiatric dysfunction as well,2 and we here report a case of asymptomatic retinal …
Bacterial Vaginosis and Desquamative Inflammatory Vaginitis
Authors: Jorma Paavonen, Robert C. Brunham
Journal: New England Journal of Medicine (2018)

Bacterial vaginal infections are in two main classes: bacterial vaginosis, associated with a fishy-smelling discharge and increased pH, and desquamative inflammatory vaginitis, also associated with an increased pH. Both conditions increase the risk of pelvic inflammatory disease.
Economic Evaluation of Talimogene Laherparepvec Plus Ipilimumab Combination Therapy vs Ipilimumab Monotherapy in Patients With Advanced Unresectable Melanoma
Authors: Abdulaali R. Almutairi, Nimer S. Alkhatib, Mok Oh, Clara Curiel-Lewandrowski, Hani M. Babiker, Lee D. Cranmer, Ali McBride, Ivo Abraham
Journal: JAMA Dermatology (2018)

A phase 2 trial comparing talimogene laherparepvec plus ipilimumab vs ipilimumab monotherapy in patients with advanced unresectable melanoma found no differential benefit in progression-free survival (PFS) but noted objective response rates (ORRs) of 38.8% (38 of 98 patients) vs 18.0% (18 of 100 patients), respectively.To perform an economic evaluation of talimogene laherparepvec plus ipilimumab combination therapy vs ipilimumab monotherapy.For PFS, cost-effectiveness and cost-utility analyses using a 2-state Markov model (PFS vs progression or death) was performed. For ORRs, cost-effectiveness analysis of the incremental cost of 1 additional patient achieving objective response was performed. In this setting based on a US payer perspective (2017 US dollars), participants were patients with advanced unresectable melanoma.The PFS life-years and PFS quality-adjusted life-years were determined, and the associated incremental cost-effectiveness ratios (ICERs) and incremental cost-utility ratios (ICURs) were estimated. Also estimated was the ICER per 1 additional patient (out of 100 treated patients) achieving objective response. Base-case analyses were validated by sensitivity analyses.In PFS analyses, the cost of talimogene laherparepvec plus ipilimumab ($494 983) exceeded the cost of ipilimumab monotherapy ($132 950) by $362 033. The ICER was $2 129 606 per PFS life-years, and the ICUR was $2 262 706 per PFS quality-adjusted life-year gained. Probabilistic sensitivity analyses yielded an ICER of $1 481 208 per PFS life-year gained and an ICUR of $1 683 191 per PFS quality-adjusted life-year gained. In 1-way sensitivity analyses, the PFS hazard ratio and the utility of response were the most influential parameters. Talimogene laherparepvec plus ipilimumab has a 50% likelihood of being cost-effective at a willingness-to-pay threshold of $1 683 191 per PFS quality-adjusted life-year gained. In ORR analyses, talimogene laherparepvec plus ipilimumab ($474 904) vs ipilimumab alone ($132 810), a $342 094 difference, yielded an ICER of $1 629 019 per additional patient achieving objective response. In subgroup analyses by disease stage and BRAFV600E mutation status, ICERs ranged from $1 069 044 to $17 104 700 per 1 additional patient achieving objective response.The cost to gain 1 additional progression-free quality-adjusted life-year, 1 additional progression-free life-year, or to have 1 additional patient attain objective response is about $1.6 million. This amount may be beyond what payers typically are willing to pay. Combination therapy of talimogene laherparepvec plus ipilimumab does not offer an economically beneficial treatment option relative to ipilimumab monotherapy at the population level. This should not preclude treatment for individual patients for whom this regimen may be indicated.
The e13a2 BCR-ABL1 Transcript Is Associated with Higher Rates of Molecular Recurrence after Treatment-Free Remission Attempts: Retrospective Analysis of the Adelaide Cohort
Authors: Naranie Shanmuganathan, Susan Branford, Agnes S. M. Yong, Devendra K Hiwase, David T Yeung, David M Ross, Timothy P. Hughes
Journal: Blood (2018)
Abstract 15370: Evaluation of Fibrous Cap Thickness by Optical Coherence Tomography for Positive Remodeling and Low Attenuation Plaques Assessed by Computed Tomography Angiography
Authors: Akira Sato, Tomoya Hoshi, Yuki Kakefuda, Eiji Ojima, Toru Adachi, Hiroaki Watabe, Kazutaka Aonuma
Journal: Circulation (2011)

Positive vessel remodeling (PR) and low-attenuation plaques (LAP) by computed tomography angiography (CTA) might be associated with plaque vulnerability. The purpose of this study was assessed the relationship between coronary plaques with PR and LAP by CTA and fibrous cap thickness estimated by optical coherence tomography (OCT) in vivo. Methods: One hundred two coronary plaques in patients with coronary artery disease (unstable angina pectoris, n= 24; stable angina pectoris, n=78) were assessed by CTA and OCT. Plaque characteristics were divided into three groups; 2 feature-positive plaques (PR and LAP), 1 feature-positive plaques (PR or LAP), and 2 feature-negative plaques (Neither PR and LAP). PR was defined as a remodeling index > 1.05 and LAP was < 50 HU. Results: There were no significant differences in clinical characteristics among the three groups. There were significant differences among the groups classified by plaque characteristics with respect to the fibrous cap thickness estimated by OCT: ...
Neonatal gut colonization by<i>Staphylococcus aureus</i>strains with certain adhesins and superantigens is negatively associated with subsequent development of atopic eczema
Authors: F.L. Nowrouzian, A. Ljung, S. Nilsson, B. Hesselmar, I. Adlerberth, A.E. Wold
Journal: British Journal of Dermatology (2018)

Insufficient early immune stimulation may predispose to atopic disease. Staphylococcus aureus, a skin and gut colonizer, produces the B‐cell mitogen protein A and T‐cell‐activating superantigens. Early gut colonization by S. aureus strains that possess the superantigens encoded by the enterotoxin gene (egc) cluster and elastin‐binding protein is negatively associated with development of atopic eczema. To investigate (i) whether these findings could be replicated in a second birth cohort, FARMFLORA, and (ii) whether nasal colonization by S. aureus also relates to subsequent atopic eczema development. Faecal samples and nasal swabs from infants in the FARMFLORA birth cohort (n = 65) were cultured for S. aureus. Individual strains were distinguished by random amplified polymorphic DNA and assessed for adhesin and superantigen gene carriage by polymerase chain reaction. Atopic eczema at 18 months of age was related to nasal and gut S. aureus colonization patterns during the first 2 months of life (well before onset of eczema). Staphylococcus aureus colonization per se was unrelated to subsequent eczema development. However, gut S. aureus strains from the infants who subsequently developed atopic eczema less frequently carried the ebp gene, encoding elastin‐binding protein, and superantigen genes encoded by egc, compared with strains from children who remained healthy. Nasal colonization by S. aureus was less clearly related to subsequent eczema development. The results precisely replicate our previous observations and may suggest that mucosal colonization by certain S. aureus strains provides immune stimulation that strengthens the epithelial barrier and counteracts the development of atopic eczema.
Sixty seconds on . . . the 10 year plan
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

Not quite. We were hoping to bring you full details of the government’s grand plan to reboot the NHS for the next decade.

Alas, we’re not. The NHS’s much awaited 10 year strategy for fiscal sustainability and improved patient care was promised for September. Then the autumn. And then definitely in the first days of December. But the …
Azacitidine Response Prediction in MDS Patients with NGS Data Using a Computational Biology Modeling (CBM) Based Clinical Decision Support System
Authors: Lubomir Minarik, Leylah M. Drusbosky, Taher Abbasi, Karina Vargova, Vojtech Kulvait, Anna Jonasova, Neeraj Kumar Singh, Yashaswini S Ullal, Sirisha Narayanabhatia, Aktar Alam, Kunal Ghosh Roy, Ashish Choudhary, Shireen Vali, Christopher R. Cogle, Tomas Stopka
Journal: Blood (2018)
[Na+] Increases in Body Fluids Sensed by Central Nax Induce Sympathetically Mediated Blood Pressure Elevations via H+-Dependent Activation of ASIC1a
Authors: Kengo Nomura, Takeshi Y. Hiyama, Hiraki Sakuta, Takashi Matsuda, Chia-Hao Lin, Kenta Kobayashi, Kazuto Kobayashi, Tomoyuki Kuwaki, Kunihiko Takahashi, Shigeyuki Matsui, Masaharu Noda
Journal: Neuron (2018)

Increases in sodium concentrations ([Na+]) in body fluids elevate blood pressure (BP) by enhancing sympathetic nerve activity (SNA). However, the mechanisms by which information on increased [Na+] is translated to SNA have not yet been elucidated. We herein reveal that sympathetic activation leading to BP increases is not induced by mandatory high salt intakes or the intraperitoneal/intracerebroventricular infusions of hypertonic NaCl solutions in Nax-knockout mice in contrast to wild-type mice. We identify Nax channels expressed in specific glial cells in the organum vasculosum lamina terminalis (OVLT) as the sensors detecting increases in [Na+] in body fluids and show that OVLT neurons projecting to the paraventricular nucleus (PVN) are activated via acid-sensing ion channel 1a (ASIC1a) by H+ ions exported from Nax-positive glial cells. The present results provide an insight into the neurogenic mechanisms responsible for salt-induced BP elevations.
Utility of Bladder-Sparing Therapy vs Radical Cystectomy for Muscle-Invasive Bladder Cancer—Reply
Authors: Stephen B. Williams, Ashish M. Kamat, Hemalkumar B. Mehta
Journal: JAMA Surgery (2018)

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Abstract 13732: SAP-12 Peptide: A Novel and Potent Cytoprotective Factor in Ischemic Stroke
Authors: QIng Guo, Jun Xie
Journal: Circulation (2017)

Identification of novel neuroprotective factors that block inflammation and neuronal cell death in ischemic stroke is essential for developing new therapies. The goal of this study is to identify new small neuroprotective peptides that can be delivered to the brain parenchyma without affecting the integrity of the blood brain barrier. We have recently discovered an unconventional extrinsic neuroprotective pathway mediated by a 12-amino acid peptide (termed SAP-12) derived from AATF (apoptosis antagonizing transcription factor). As a transcription factor, AATF is normally found in intracellular compartments. However, we have unexpected noted that a significant amount of AATF was secreted extracellularly by cortical neurons following glucose deprivation and chemical hypoxia, suggesting that AATF can be secreted without a classical N-terminal signal peptide. We found that secreted AATF binds to cell surface TRL4 receptors in cortical neurons, and blocks TLR4-mediated expression of pro-inflammatory cytokines,...
Abstract 12738: Improvement in Renal Function After Left Ventricular Assist Device Placement is a Prognostic Marker for Survival
Authors: Burhan Mohamedali, Gardner Yost, Geetha Bhat
Journal: Circulation (2015)

Introduction: Chronic renal dysfunction is common in end stage heart failure. Left Ventricular Assist Devices (LVADs) are increasingly being used in such patients. In this study, we evaluated patients who had poor renal function prior to LVAD placement with subsequent improvement in renal function after LVAD implantation. Hypothesis: Patients with poor renal function after LVAD implant have a poor prognosis. Methods: In this study, 229 patients with LVADs were enrolled. Patients were divided into 3 groups. Group 1 had patients with pre- and post-implant GFR of &lt;60. Group II consisted of pre-implant Glomerular Filtration Rate (GFR) of &lt;60, but subsequent improvement to ≥60 post-LVAD, and Group III comprised of patients with pre- and post-LVAD GFR of ≥60. Chi square testing and Kaplan-Meier (KM) survival analysis was performed. Results: The three groups had a mean pre-implant and post-implant GFR: Group I (N=95), 43±13 vs. 45±10, Group 2 (N=56) 48±8 vs. 75±15 and Group III (N=78) 81±18 vs. 89±22 respectively. There was a significant difference in overall survival between the three groups (42% vs 63% vs 73%, p&lt;0.001). KM survival analysis also revealed significant differences in survival between the groups (Mean survival of 1037 days vs 1675 days vs 1745 days, p=0.015). When individual groups were analyzed, there was a significant difference between Group I vs II and Group I vs III, however; there was no difference in survival between Group II and III (Figure 1). Conclusions: Our findings suggest that patients with poor renal function pre-LVAD can be distinguished into two distinct phenotypes consisting of patients who improve their GFR to ≥60 after LVAD surgery and patients whose low GFR persists even after LVAD implantation. Survival of patients with improvement in GFR tended to normalize to their peers with pre-implant GFR of ≥60. Post-LVAD GFR can serve as an important prognostic marker for LVAD patients.
Hematopoietic Deficiency of the Long Noncoding RNA MALAT1 Promotes Atherosclerosis and Plaque Inflammation
Authors: Sebastian Cremer, Katharina M. Michalik, Ariane Fischer, Larissa Pfisterer, Nicolas Jaé, Carla Winter, Reinier A. Boon, Marion Muhly-Reinholz, David John, Shizuka Uchida, Christian Weber, Wolfgang Poller, Stefan Günther, Thomas Braun, Daniel Y. Li, Lars Maegdefessel, Ljubica Perisic Matic, Ulf Hedin, Oliver Soehnlein, Andreas Zeiher, Stefanie Dimmeler
Journal: Circulation (2019)

Background: The majority of the human genome comprises noncoding sequences, which are in part transcribed as long noncoding RNAs (lncRNAs). lncRNAs exhibit multiple functions, including the epigenetic control of gene expression. In this study, the effect of the lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) on atherosclerosis was examined. Methods: The effect of MALAT1 on atherosclerosis was determined in apolipoprotein E–deficient (Apoe − /− ) MALAT1-deficient (Malat1 −/− ) mice that were fed with a high-fat diet and by studying the regulation of MALAT1 in human plaques. Results: Apoe −/− Malat1 −/− mice that were fed a high-fat diet showed increased plaque size and infiltration of inflammatory CD45 + cells compared with Apoe −/− Malat1 +/+ control mice. Bone marrow transplantation of Apoe −/− Malat1 −/− bone marrow cells in Apoe −/− Malat1 +/+ mice enhanced atherosclerotic lesion formation, which suggests that hematopoietic cells mediate the proatherosclerotic phenotype. Indeed, bone marrow cells isolated from Malat1 −/− mice showed increased adhesion to endothelial cells and elevated levels of proinflammatory mediators. Moreover, myeloid cells of Malat1 −/− mice displayed enhanced adhesion to atherosclerotic arteries in vivo. The anti-inflammatory effects of MALAT1 were attributed in part to reduction of the microRNA miR-503. MALAT1 expression was further significantly decreased in human plaques compared with normal arteries and was lower in symptomatic versus asymptomatic patients. Lower levels of MALAT1 in human plaques were associated with a worse prognosis. Conclusions: Reduced levels of MALAT1 augment atherosclerotic lesion formation in mice and are associated with human atherosclerotic disease. The proatherosclerotic effects observed in Malat1 −/− mice were mainly caused by enhanced accumulation of hematopoietic cells.
Mechanism of prostate cancer progression in androgen-independent variants of LAPC4 cells with or without androgen receptor
Authors: Chen Sun, Ahmed Mohamed, Ying Hu, David McLeod, Shiv Srivastava
Journal: Cancer Research (2008)

1226  Introduction: Prostate cancer (CaP) poses a significant clinical challenge both in terms of its prevalence and its complexity. Molecular mechanism involved in androgen refractory CaP is under active investigation. We have developed androgen independent variants of LAPC4 cells to evaluate the molecular mechanisms involved in CaP progression.  Methods: Androgen dependent LAPC4 cells were kindly provided by Dr. Charles L. Sawyers (UCLA, CA). LAPC4 cells were grown under cell culture condition mimicking androgen ablation. Androgen independent LAPC4 cells (LAPC4-AI) represent a cell culture model that continued to grow in the absence of androgen but expressed androgen receptor (AR). To further evaluate the role that AR plays in androgen independent cell growth, two LAPC4-AI sub-lines, LAPC4-AI-1 and LAPC4-AI-2 were established by using lentiviral AR-shRNA. In contrast to LAPC4-AI cells, LAPC4-AI-1 expresses AR protein at decreased levels, whereas AR expression is knocked down to non-detectable levels in LAPC4-AI-2 cells. Cell growth features as well as AR signaling was evaluated in LAPC4-AI variants.  Results: LAPC4-AI cellsexhibited androgen independent cell growth both in soft agar and in cell proliferation assay in comparison to LAPC4 cells whose growth was synthetic androgen (R1881) dependent. In contrast to parental LAPC4 cells, PSA expression was undetectable in LAPC-AI cells in the absence or presence of R1881. Bicalutamide antagonized AR transcriptional activity and cell growth in LAPC4 cells but failed to inhibit the growth of LAPC4-AI cells. Interestingly, cell growth of LAPC4-AI-1 and LAPC4-AI-2 cells was similar to LAPC4-AI cells both in the presence or absence of R1881. Further evaluation of the effect of AR knock down on CaP progression in LAPC4-AI cells in vitro and in vivo is in progress.  Conclusion: In contrast to parental LAPC4 cells,LAPC4-AI variants exhibit androgen independent cell growth which is disassociated from AR expression and activities. This study provides a new CaP cell model where AR is expressed but it is non-functional with respect to its effect on cell growth. These cell culture models may recapitulate some features of clinical progression of CaP leading to therapeutic resistance to androgen ablation.
激光治疗早期伤口愈合, 以改善疤痕 形成
Authors: K.E. Karmisholt, C.A. Banzhaf, M. Glud, K. Yeung, U. Paasch, A. Nast, M. Haedersdal
Journal: British Journal of Dermatology (2018)

几十年来,激光一直被用来治疗皮肤上的疤痕。近年来,医生们开始在伤口的实际愈合过程中使用激光,而不是在疤痕形成之后,以尽量减少疤痕的形成。然而,目前还没有一套方法来确切地说明如何最好地做到这一点。在这项来自德国和丹麦的研究中, 30 名做过皮肤手术的患者在手术前、拆线时和手术后 6 周都用一种叫做 1540 nm NAFL 的激光来治疗他们一半的伤口。另外一半的伤口没有接受任何激光治疗。三个月后,专家和患者使用不同的量表对疤痕进行评估。与未处理的一半相比,经过 NAFL 处理过的一半有更少红色,并且更柔软光滑。作者得出结论,在早期伤口愈合中提供的三种 NAFL 疗法可以改善疤痕形成,但经过 NAFL 治疗的伤口在愈合后不可能没有任何疤痕。可能有必要在手术后留出超过三个月的时间来正确评估疤痕形成和治疗效果。
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
Authors: Cristina García-Cáceres, Eglantine Balland, Vincent Prevot, Serge Luquet, Stephen C. Woods, Marco Koch, Tamas L. Horvath, Chun-Xia Yi, Julia A. Chowen, Alexei Verkhratsky, Alfonso Araque, Ingo Bechmann, Matthias H. Tschöp
Journal: Nature Neuroscience (2018)
Abstract 15345: Cost-Effectiveness Comparative Study for Clinical, Surgical or Percutaneous Treatment in Patients With Stable Multivessel Coronary Artery Disease: 10 Year Follow-Up
Authors: Cibelle D Magalhaes, Whady Hueb, Thiago Scudeler, Desidério Favarato, Eduardo Lima, Ricardo D Vieira, Edimar Bocchi
Journal: Circulation (2017)

Introduction: The MASS II Study (The Second Medicine, Angioplasty or Surgery Study) included 611 patients with Multivessel Coronary Artery Disease (CAD) and preserved systolic function; these patie...
CACHEXIO: Evaluation of body composition changes and immunotherapy in patients with metastatic cancer.
Authors: Eric Roeland, Areej El-Jawahri, Nora Horick, Sandahl H Nelson, Andrea Gallivan, Ryan David Nipp, Yael Cohen-Arazi, Sarah Friedman, Chris Sera, Joseph Ma, Vickie E Baracos, Sandip Pravin Patel, Hardeep Phull
Journal: Journal of Clinical Oncology (2018)

209 Background: Given body composition predicts toxicity for patients receiving cytotoxic chemotherapy, we explored changes in body composition and biomarkers as predictors of immune-related adverse events (irAEs) and health care utilization. Methods: We conducted a longitudinal study of patients with metastatic solid tumor receiving immunotherapy (07/2014-10/2017). Eligible patients had a computed tomography (CT) scan prior to first-line immunotherapy with at least two additional CT scans at three, six or nine months after immunotherapy initiation. We analyzed body composition using cross-sectional CT scans at the third lumbar vertebra. We utilized mixed effect linear regression models to assess longitudinal changes in body composition (weight, skeletal muscle, total adipose). We examined associations of baseline body composition and biomarkers (albumin, neutrophil-lymphocyte ratio (NLR)) with the incidence of irAEs and healthcare utilization (hospitalizations/ED visits) using logistic regression. Results: Of 140 patients treated with immunotherapy, 61 met inclusion criteria. The majority (80%) received prior chemotherapy and the most common malignancies included lung (26%), head and neck (20%), and melanoma (20%). We found that one-third (n=19) experienced an irAE and colitis (53%) was the most common irAE. Patients experienced substantial weight loss over time (B= -1.88, p&lt;0.001) with a decrease both in skeletal muscle (B= -3.08, p=0.001) and total adipose tissue (B =-50.44, p&lt;0.001). We found greater skeletal muscle at baseline was associated with lower risk of health care utilization (OR 0.98, 95% CI: 0.965-0.998, p=0.03). We observed no association with biomarkers and/or body composition variables with irAEs or health care utilization. Conclusions: Patients with metastatic cancer receiving immunotherapy lose weight including skeletal muscle and adipose tissue. Aside from higher baseline skeletal muscle predicting less health care utilization, we did not observe any other associations between body composition changes and irAEs or health care utilization.