tbuckley/cabot-search huggingface dataset:
Transfusion-associated circulatory overload and transfusion-related acute lung injury
Authors: John W. Semple, Johan Rebetz, Rick Kapur
Journal: Blood (2019)

Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are syndromes of acute respiratory distress that occur within 6 hours of blood transfusion. TACO and TRALI are the leading causes of transfusion-related fatalities, and specific therapies are unavailable. Diagnostically, it remains very challenging to distinguish TACO and TRALI from underlying causes of lung injury and/or fluid overload as well as from each other. TACO is characterized by pulmonary hydrostatic (cardiogenic) edema, whereas TRALI presents as pulmonary permeability edema (noncardiogenic). The pathophysiology of both syndromes is complex and incompletely understood. A 2-hit model is generally assumed to underlie TACO and TRALI disease pathology, where the first hit represents the clinical condition of the patient and the second hit is conveyed by the transfusion product. In TACO, cardiac or renal impairment and positive fluid balance appear first hits, whereas suboptimal fluid management or other components in the transfused product may enable the second hit. Remarkably, other factors beyond volume play a role in TACO. In TRALI, the first hit can, for example, be represented by inflammation, whereas the second hit is assumed to be caused by antileukocyte antibodies or biological response modifiers (eg, lipids). In this review, we provide an up-to-date overview of TACO and TRALI regarding clinical definitions, diagnostic strategies, pathophysiological mechanisms, and potential therapies. More research is required to better understand TACO and TRALI pathophysiology, and more biomarker studies are warranted. Collectively, this may result in improved diagnostics and development of therapeutic approaches for these life-threatening transfusion reactions.
Cutaneous presentations of omphalomesenteric duct remnant: A systematic review of the literature
Authors: Efrat Solomon-Cohen, Moshe Lapidoth, Igor Snast, Dan Ben-Amitai, Omri Zidan, Rivka Friedland, Michael Moshe, Daniel Mimouni, Yael Ann Leshem, Emmilia Hodak, Assi Levi
Journal: Journal of the American Academy of Dermatology (2019)
Oral CHOP-like Chemotherapy in Elderly Patients with High-Grade Non Hodgkin B Cell Lymphoma
Authors: Stephanie Guidez, Cecile Tomowiak, Isabelle Princet, Brigitte Dreyfus, Gaelle Olivier, Emmanuel Fleck, Anne Corby, Carine Motard, Antoine Machet, Celine Debiais, Xavier Leleu, Joelle Guilhot, Vincent Delwail
Journal: Blood (2018)
Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial
Authors: Daimin Wei, Jia-Yin Liu, Yun Sun, Yuhua Shi, Bo Zhang, Jian-Qiao Liu, Jichun Tan, Xiaoyan Liang, Yunxia Cao, Ze Wang, Yingying Qin, Han Zhao, Yi Zhou, Haiqin Ren, Guimin Hao, Xiufeng Ling, Junzhao Zhao, Yunshan Zhang, Xiujuan Qi, Lin Zhang, Xiaohui Deng, Xiaoli Chen, Yimin Zhu, Xiaohong Wang, Li-Feng Tian, Qun Lv, Xiang Ma, Heping Zhang, Richard S Legro, Zi-Jiang Chen
Journal: The Lancet (2019)
Abstract 1162: Investigating the NAD metabolome in Ewing Sarcoma
Authors: Cornelia N. Mutz, Raphaela Schwentner, Maximilian O. Kauer, Jozef Ban, Dave N. T. Aryee, Sophie Erhardt, Dietmar Fuchs, Andreas Heitger, Heinrich Kovar
Journal: Cancer Research (2015)

Abstract Ewing Sarcoma (ES) is the second most common bone cancer in children and adolescents with a high metastatic potential. Tumor development is driven by the specific t(11;22)(q24;q12) chromosomal translocation resulting in generation of the chimeric transcription factor EWS-FLI1. Recently, ES has been reported to be exquisitely sensitive to inhibitors of poly(ADP-ribose) polymerase 1 (PARP1). This enzyme uses NAD as substrate and was demonstrated to regulate EWS-FLI1 in a feed-back mechanism. NAD is a key metabolite essential for sustaining cellular energy metabolism. It plays a central role in cellular redox reactions, DNA repair, and in the maintenance of genomic stability serving as a donor of ADP-ribose. The other major mammalian NAD consumer is the deacetylase SIRT1 which we observed to be specifically highly expressed in ES metastases. PARP1 and SIRT1 are crucial for coupling cellular metabolism to transcriptional gene regulation as well as to stress response. Usually, NAD is regenerated from nicotinamide in the NAMPT-dependent salvage pathway or from the reduction of pyruvate via LDHA (Warburg effect), but can also be synthesized de novo from tryptophan. Interestingly, the knockdown of EWS-FLI1 in ES cells comes along with alterations in the expression of multiple enzymes involved in NAD biosynthesis and regeneration, including TDO2, KMO, NMNAT1, NAPRT, NAMPT, and LDHA. We are interrogating the role of EWS-FLI1 mediated modulation of these enzymes and of specific small molecule inhibitors on cellular tryptophan consumption, kynurenine production and intracellular NAD levels of Ewing sarcoma cells. Additionally, we are investigating the functional consequences thereof on constitutive and stress-induced protein poly(ADP)-ribosylation and acetylation. Preliminary results suggest that NAMPT inhibition diminishes PARP1 activity due to low NAD, implying a pivotal role for the regenerative salvage pathway in ES cells. TDO2-dependent tryptophan consumption increases in the absence of the oncogene. These studies aim at a better understanding of factors influencing Ewing sarcoma sensitivity to therapies targeting PARP1 and the NAD metabolome. Citation Format: Cornelia N. Mutz, Raphaela Schwentner, Maximilian O. Kauer, Jozef Ban, Dave N. T. Aryee, Sophie Erhardt, Dietmar Fuchs, Andreas Heitger, Heinrich Kovar. Investigating the NAD metabolome in Ewing Sarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1162. doi:10.1158/1538-7445.AM2015-1162
Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial
Authors: Tone S Løvvik, Sven M Carlsen, Øyvind Salvesen, Berglind Steffensen, Marie Bixo, Francisco Gómez-Real, Marianne Lønnebotn, Kristin V Hestvold, Renata Zabielska, Angelica L Hirschberg, Anastasia Trouva, Solveig Thorarinsdottir, Sissel Hjelle, Ann Hilde Berg, Frida Andræ, Inger S Poromaa, Johanna Mohlin, Maria Underdal, Eszter Vanky
Journal: The Lancet Diabetes & Endocrinology (2019)
Initiatives for improving the provision of assistance at mealtimes for older adults on hospital wards: a mixed methods systematic review [Poster presentation]
Authors: Deborah Jayne Edwards, Jane B. Hopkinson
Journal: BMJ (2014)

Background: In the UK, a third of older hospital patients are malnourished. Malnutrition is associated with staying in hospital longer, increased morbidity and mortality, especially for those with chronic conditions. Mealtime assistance may be important to improve nutritional intake, clinical outcomes and patient experience. Two previous quantitative systematic reviews have been undertaken. One explored the use of volunteers and the other feeding assistance in hospitals and care-homes. 

Aims: We are conducting the first mixed method systematic review about the provision of assistance at mealtimes for older adults on hospital wards to 

▸ i) determine the effectiveness of interventions 

▸ ii) explore the experiences of older adults and those involved with their care 

Aims:

Methods: The design is informed by methods developed by the Evidence for Policy and Practice Information Centre. This ‘mixed-methods’ triangulation approach combines data from i) effectiveness studies, ii) studies which obtain the views of participants and iii) current guidelines and policy. We have conducted a search of electronic databases (CINAHL, MEDLINE, BNI, Cochrane Library, EMBASE, PsychINFO, Open-Grey). Limits were English language; 1996 to present; adults. Abstracts have been assessed against inclusion/exclusion criteria by two researchers to select full-text for quality assessment and data extraction. The key elements of best practice will be extracted from current guidelines and policy documents. This will be used to derive a framework to guide analysis and interpretation of the evidence. 

Results: The findings will be presented as a conceptual map of initiatives for improving the provision of assistance at mealtimes for older adults on hospital wards. We will also present propositions of what might be most effective in assisting oral mealtime nutritional intake and the implications. 

Conclusion: We are conducting a systematic evaluation of literature to provide recommendations for the supportive nutritional care of older malnourished chronically ill people in hospital.
Abstract OT2-04-02: Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The Intergroup-Sentinel-Mamma (INSEMA)-trial
Authors: T Reimer, G von Minckwitz, S Loibl, G Hildebrandt, V Nekljudova, C Schneider-Schranz, B Gerber
Journal: Cancer Research (2017)

Abstract Background: Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary. Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement. Trial design: The goal of INSEMA is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding invasive disease-free survival (IDFS) outcome. Patients with planned breast-conserving surgery (BCS) will be first randomized (1:4 ratio) to either no axillary surgery or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized (1:1 ratio) to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than three involved nodes (one or two macrometastases). Primary objective: -IDFS after BCS (non-inferiority question) Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy) -Age at least 35 years -Preoperative imaging techniques with estimated tumor size of maximal 5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status) -Clinically and sonographically tumor-free axilla prior to core biopsy -In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration biopsy of the suspected lymph node is required -No clinical evidence for distant metastasis (M0) -Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Statistics: The calculated total case number for per-protocol analyses is 6,740 (5,940 German and 800 Austrian patients), the expected total number of randomized patients is 7,095. Time lines: -First patient in: September 2015 -Last patient in: August 2019 -Final analysis: End of 2024 Present accrural: In June 2016, more than 1.000 patients were recruited in Germany and Austria. Citation Format: Reimer T, von Minckwitz G, Loibl S, Hildebrandt G, Nekljudova V, Schneider-Schranz C, Gerber B. Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The Intergroup-Sentinel-Mamma (INSEMA)-trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-04-02.
Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity
Authors: Gabriel M. Pagnotti, Maya Styner, Gunes Uzer, Vihitaben S. Patel, Laura E. Wright, Kirsten K. Ness, Theresa A. Guise, Janet Rubin, Clinton T. Rubin
Journal: Nature Reviews Endocrinology (2019)
The GPI-Linked Protein LY6A Drives AAV-PHP.B Transport across the Blood-Brain Barrier
Authors: Juliette Hordeaux, Yuan Yuan, Peter M. Clark, Qiang Wang, R. Alexander Martino, Joshua J. Sims, Peter Bell, Angela Raymond, William L. Stanford, James M. Wilson
Journal: Molecular Therapy (2019)

Efficient delivery of gene therapy vectors across the blood-brain barrier (BBB) is the holy grail of neurological disease therapies. A variant of the neurotropic vector adeno-associated virus (AAV) serotype 9, called AAV-PHP.B, was shown to very efficiently deliver transgenes across the BBB in C57BL/6J mice. Based on our recent observation that this phenotype is mouse strain dependent, we used whole-exome sequencing-based genetics to map this phenotype to a specific haplotype of lymphocyte antigen 6 complex, locus A (Ly6a) (stem cell antigen-1 [Sca-1]), which encodes a glycosylphosphatidylinositol (GPI)-anchored protein whose function had been thought to be limited to the biology of hematopoiesis. Additional biochemical and genetic studies definitively linked high BBB transport to the binding of AAV-PHP.B with LY6A (SCA-1). These studies identify, for the first time, a ligand for this GPI-anchored protein and suggest a role for it in BBB transport that could be hijacked by viruses in natural infections or by gene therapy vectors to treat neurological diseases.
Treatment for Adult HIV Infection
Authors: Patrick G Yeni, Scott M Hammer, Martin S Hirsch, Michael S Saag, Mauro Schechter, Charles C J Carpenter, Margaret A Fischl, Jose M Gatell, Brian G Gazzard, Donna M Jacobsen, David A Katzenstein, Julio S G Montaner, Douglas D Richman, Robert T Schooley, Melanie A Thompson, Stefano Vella, Paul A Volberding
Journal: JAMA (2004)

Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection.To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails.Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management.Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004.Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached.Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel).Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.
Characteristics of metastatic renal cell carcinoma (mRCC) patients treated with delayed targeted therapy: Results from the International mRCC Consortium (IMDC).
Authors: Haoran Li, Toni K. Choueiri, Connor Wells, Neeraj Agarwal, Frede Donskov, Jae-Lyun Lee, Reuben James Broom, Takeshi Yuasa, Brian I. Rini, Sumanta Kumar Pal, Lori Wood, D. Scott Ernst, Christian K. Kollmannsberger, Ulka N. Vaishampayan, Sun Young Rha, Georg A. Bjarnason, Jennifer J. Knox, Sadia Saleem, Benoit Beuselinck, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2015)

4558 Background: A small proportion of patients with mRCC may not require immediate targeted therapy (TT). Their clinicopathological features and prognoses are not well characterized. Methods: A retrospective analysis was conducted in mRCC patients who did not start TT until at least 1 year after diagnosis of metastatic disease (delayed TT). Patients treated with traditional immunotherapy were excluded. For comparison, patients that received immediate TT within 1 month of metastatic diagnosis were used (immediate TT). Results: 467/3202 (14.6%) mRCC patients had delayed TT. The majority of patients (96.6%) in delayed group had prior nephrectomy. Compared to patients who received immediate TT (n = 800), patients with delayed TT were more likely to have clear cell histology (87.8% vs. 82.7%, p = 0.02), lower grade primary lesions (low/int grade: 38.3% vs. 31.2%, p= 0.03), less likely to have sarcomatoid features (7.1% vs. 13.1%, p = 0.002), greater percentage of normal LDH (74.8% vs. 67.1%, p = 0.02) and less hyponatremia (11.9% vs. 19.3%, p < 0.01). However, slightly more brain and bone metastases at baseline were seen in the delayed TT vs immediate TT groups (8.7% vs. 5.7%, p = 0.046 and 38.3% vs. 31.4%, p = 0.02, respectively) and it is unknown if these patients were delayed due to metastatectomy or radiotherapy. IMDC risk factors were more favorable in delayed TT group, with less anemia (43.2% vs. 65.0%, p < 0.001), hypercalcemia (6.9% vs. 11.7%, p < 0.01), neutrophilia (11.3% vs. 22.0%, p < 0.001), thrombophilia (8.6% vs. 18.4%, p < 0.001), KPS < 80 (20.9% vs. 26.6%, p = 0.03). The response rate of TT was similar between two groups (27.0% vs. 27.0%, p = 1.0). The median PFS was 9.3 months in delayed TT patients vs 5.6 months in immediate group (p < 0.001), and the median OS was 26.6 months in delayed group vs 17.2 months in immediate group (p< 0.001). The differences in survival are due to patient selection. Conclusions: Patients with fewer adverse IMDC criteria were more likely to receive delayed systemic treatment. 14.6% of patients who start targeted therapy do so over a year from diagnosis of mRCC. Further studies are warranted to determine who can benefit most from delayed TT.
Long Term Efficacy, Safety and PK/PD Profile of the Anti-C1s Antibody (BIVV009) in Primary Cold Agglutinin Disease Patients
Authors: Ulrich Jaeger, Shirley D'Sa, Christian Schoergenhofer, Johann Bartko, Christian Sillaber, Petra Jilma-Stohlawetz, Michael Fillitz, Thomas Schenk, Gary Patou, Sandip Panicker, Graham C Parry, James C Gilbert, Bernd Jilma
Journal: Blood (2017)
Grass Pollen Hyposensitization versus Placebo Therapy.
Authors: A. Weyer, C. Doinel, M. Debbia, C. L'Heritier, L. Rivat, J. Le Mao, C. Hirth, B. David
Journal: Allergy (1981)

This study presents the pre‐ and post‐treatment levels of specific IgE and IgG and of total IgE in the sera of two groups of grass pollen‐sensitive patients, one receiving placebo injection (16 patients), the other being treated by repeated doses of a four‐grass pollen extract (17 patients). Total and specific IgE were evaluated by the radioimmunological methods based on the IgE‐anti‐IgE interaction. IgG specific to the pollen extract was determined by a radioimmunoassay measuring protein‐A bound pollen‐specific antibodies (IgG). The whole immunoglobulin content specific to the allergen was quantified by a haemagglutination technique. During the treatment period, the relative variations of total IgE, and specific IgE and IgG levels are significantly different in placebo‐ and pollen‐treated groups: 1) for total and specific IgE, were observed a relative decrease in the placebo group, and stable levels in the treated group; 2) for IgG, the level was stable in the placebo group and a relative increase was seen in the treated group. For most of the patients the specific serum IgE and IgG levels were determined also after the pollen season consecutive to the treatment. During the pollen season, the placebo group is characterized by an increase in specific IgE concentrations and stable IgG levels. The hyposensitized patients showed stable levels of specific IgE and a decrease in specific IgG during the same period. There is a significant correlation between the levels of specific haemagglutination litres and the IgG levels. After the treatment period the haemagglutination litre is significantly lower in the placebo‐treated patients than in the pollen‐treated ones. A significant positive correlation exists between the levels of specific IgE and IgG before and after treaiment, for the 33 patients. Moreover, during hyposensitization, the relative variations of specific IgE and IgG are highly correlated in the treated group only. No significant correlation at the P &lt; 0.05 level is observed between the clinical scores and the levels of the different biological parameters.