tbuckley/cabot-search huggingface dataset:
Quality-of-Life Outcomes in Surgical vs Nonsurgical Treatment of Breast Cancer–Related Lymphedema
Authors: Morgan L. Fish, Ritwik Grover, Graham S. Schwarz
Journal: JAMA Surgery (2020)

Secondary lymphedema is a debilitating complication of breast cancer therapy and affects more than 1 in 5 breast cancer survivors. Patient-reported outcomes may be more important in predicting long-term health-related quality of life (HRQoL) than clinician-measured outcomes.To summarize published evidence on HRQoL outcomes for vascularized lymph node transfer (VLNT) and complex decongestive therapy (CDT) used in the treatment of breast cancer-related lymphedema.A literature search of PubMed/MEDLINE and Embase was conducted to identify articles on HRQoL in patients undergoing lymphedema treatment with CDT or VLNT published from January 1980 through April 2019. Studies using validated measurement instruments to assess HRQoL in patients with breast cancer-related lymphedema relative to baseline were included. This review is reported according to the PRISMA guidelines.A total of 16 articles were included in this review. Evidence regarding VLNT was reviewed from 2 studies involving 65 patients, and HRQoL was evaluated using the Lymphoedema Quality of Life Study questionnaire. Data on VLNT indicated favorable HRQoL outcomes at 12-month postoperative follow-up. Evidence regarding CDT was reviewed from 14 studies involving 569 patients, and HRQoL was evaluated using the 36-Item Short Form Health Survey, Functional Assessment of Cancer Therapy-Breast, European Organization for Research and Treatment of Cancer, and Functional Living Index-Cancer measures. Data on CDT demonstrated variable association with HRQoL, and a majority of articles reported improvement in at least 1 subscale. The use of diverse patient-reported outcome measures and variability in CDT protocol limited interpretation of results in this population and between treatment modalities.According to this review, in deciding among breast cancer-related lymphedema treatment modalities, HRQoL outcomes are an important consideration that cannot be compared based on currently available data. Health-related quality-of-life outcomes obtained through coordinated use of preference-based health utility measures may be required to compare outcomes among patients undergoing surgical and nonsurgical treatments of breast cancer-related lymphedema. Additional studies are needed to better understand the best lymphedema treatment options and direct evidence-based care.
Migration in the Management of Philadelphia Positive ALL: Towards a Lower Risk of VTE
Authors: Hassan Sibai, Maria Zigas, Arjun Datt Law, Umberto Falcone, Solaf Sami Kanfar, Naoko Sakurai, Vikas Gupta, Andre Schuh, Karen W.L. Yee, Aaron Schimmer, Mark D. Minden, Dawn Maze, Steven M. Chan, Jack Seki
Journal: Blood (2017)
Covid-19: Keep essential malaria services going during pandemic, urges WHO
Authors: Jacqui Thornton
Journal: BMJ (2020)

Transcriptome analysis by RNA-seq has emerged as a high-throughput, cost-effective means to evaluate the expression pattern of genes in organisms. Unlike other methods, such as microarrays or quantitative PCR, RNA-seq is a target free method that permits analysis of essentially any RNA that can be amplified from a cell or tissue. At its most basic, RNA-seq can determine individual gene expression levels by counting the number of times a particular transcript was found in the sequence data. Transcript levels can be compared across multiple samples to identify differentially expressed genes and infer differences in biological states between the samples. We have used this approach to examine gene expression patterns in chicken and human cells, with particular interest in determining response to heat stress.
The frequency of CD4 + CD25 + FoxP3 + CD127 − cells in Bet v 1 contiguous overlapping peptide immunotherapy as a putative marker of efficacy
Authors: Paweł Gajdanowicz, Dries Van Elst, Sylwia Smolińska, Andrzej Eljaszewicz, Liam O'Mahony, Alexander Kettner, Marek Jutel
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis
Authors: Eric Simpson, Robert Bissonnette, Lawrence F. Eichenfield, Emma Guttman-Yassky, Brett King, Jonathan I. Silverberg, Lisa A. Beck, Thomas Bieber, Kristian Reich, Kenji Kabashima, Marieke Seyger, Elaine Siegfried, Georg Stingl, Steven R. Feldman, Alan Menter, Peter van de Kerkhof, Gil Yosipovitch, Carle Paul, Philippe Martel, Ariane Dubost-Brama, John Armstrong, Rajeev Chavda, Steve Frey, Yolandi Joubert, Marina Milutinovic, Anne Parneix, Henrique D. Teixeira, Chen-Yen Lin, Luna Sun, Paul Klekotka, Brian Nickoloff, Yves Dutronc, Lotus Mallbris, Jonathan M. Janes, Amy M. DeLozier, Fabio P. Nunes, Amy S. Paller
Journal: Journal of the American Academy of Dermatology (2020)
Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model
Authors: Xu Yang, Jing-Lin Guo, Jing Han, Rui-Juan Si, Pan-Pan Liu, Zi-Rui Zhang, Ai-Min Wang, Ju Zhang
Journal: Military Medical Research (2020)

LL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers. However, the low stability of this peptide within the wound environment limits its clinical use. Chitosan (CS) hydrogel is commonly used as a base material for wound dressing material. CS hydrogel (2.5% w/v) was encapsulated with LL-37. Cytotoxicity of the product was examined in cultured NIH3T3 fibroblasts. Effects on immune response was examined by measuring tumor necrosis factor-α (TNF-α) release from RAW 264.7 macrophages upon exposure to lipopolysaccharides. Antibacterial activity was assessed using Staphylococcus aureus. Potential effect on pressure ulcers was examined using a mouse model. Briefly, adult male C57BL/6 mice were subjected to skin pressure using magnets under a 12/12 h schedule for 21 days. Mice were randomized to receive naked LL-37 (20 μg), chitosan gel containing 20-μg LL-37 (LL-37/CS hydrogel) or hydrogel alone under the ulcer bed (n = 6). A group of mice receiving no intervention was also included as a control. LL-37/CS hydrogel did not affect NIH3T3 cell viability. At a concentration of 1-5 μg/ml, LL-37/CS inhibited TNF-α release from macrophage. At 5 μg/ml, LL-37/CS inhibited the growth of Staphylococcus aureus. The area of the pressure ulcers was significantly lower in mice receiving LL-37/CS hydrogel in comparison to all other 3 groups on days 11 (84.24% ± 0.25%), 13 (56.22% ± 3.91%) and 15 (48.12% ± 0.28%). Histological examination on days 15 and 21 showed increased epithelial thickness and density of newly-formed capillary with naked LL-37 and more so with LL-37/CS. The expression of key macromolecules in the process of angiogenesis (i.e., hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A)) in wound tissue was increased at both the mRNA and protein levels. Chitosan hydrogel encapsulated with LL-37 is biocompatible and could promote the healing of pressure ulcers.
Covid-19: New government study aims to track infection and immunity in population
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The UK government has launched a nationwide surveillance study to track the prevalence of infection with SARS-CoV-2 in the general population. 

The study will include swab testing and serology testing to look at both the current rates of infection and how many people are likely to have developed antibodies to the virus. The government is inviting UK households to take part in the study and expects 25 000 to take part in the first phase. It aims to extend this to 300 000 households over the next 12 months.

The results will help guide the government’s strategy on when to relax the current lockdown measures, with initial study findings …
A randomized phase II study of gemcitabine with vinorelbine (GV) vs. sequential gemcitabine and vinorelbine (G/V) in metastatic breast cancer (MBC): An interim analysis.
Authors: Keun Seok Lee, Hyeong-Seok Lim, Hye Soo Kwon, Byung-Ho Nam, Jungsil Ro
Journal: Cancer Research (2006)

5268   Background: It is not clear whether the activity of the GV combination regimen would translate into better progression-free or overall survival (OS) when compared with the sequential therapy of Gemcitabine (G) and Vinorelbine (V) especially during toward the late phases of management in MBC. This randomized phase II study was conducted to evaluate the overall response rate (RR) of GV  vs.  G/V. Secondary objectives included individual responses of G and V, time to progression (TTP), time to treatment failure (TTF), OS, and toxicities. Patients and Methods: Patients(pts) with histologic or cytologic diagnosis of stage IV or recurrent breast cancer who had ECOG PS ≤2 and measurable disease were randomized to receive GV(G 1,000 mg /m 2  and V 25 mg/m 2 , D1 and D8 q3wk until PD) or G/V(G 1,000 mg/m 2  D1, D8, D15 q4wks until PD then V 30 mg/ m 2  D1 and D8 q3wks until PD). Randomization was performed according to number of prior metastatic chemotherapy ≥3  vs   vs  the rest. Pts received anthracycline and taxane and/or capecitabine chemotherapy in adjuvant and/or metastatic setting. Of total 82 patients to be accrued, 60 patients have been enrolled from 4/2004 to 10/2005. TTP of G/V arm was calculated from the day of randomization to the day of progression on V. Results: Of 60 pts enrolled, 32 pts were randomized to GV arm and 28 to G/V arm. 27% of pts were stage IV and 73% recurrent disease. 43% of pts received ≥3 previous chemotherapies. To date 58 pts were qualified for safety, TTF, TTP, and OS analysis, and 50 for response analysis. Baseline values were balanced between GV and G/V arms. For overall RR, TTF, TTP, and OS analysis, refer to Table 1. Hemtologic and non-hematologic toxicities were mild, and similar in each arm except for more G4 neutropenia in the GV arm (27%) than G/V arm (7%) without statistical significance (p=0.081). Conclusion: TTP was longer in G/V arm than GV arm (p=0.0195). RR, toxicity profiles and OS between two arms were not significantly different. This suggests that pts with MBC in the late phases of management would get more benefit by sequential administration of single agents.
Abstract 267: Injuries Associated With Mechanical Chest Compressions in Patients With Out-Of-Hospital Cardiac Arrest: A Comparison of LUCAS 2 and LUCAS 2 Active Decompression
Authors: Polina Petrovich, Per-Olav Berve, Gitta Erika Turowski, Arne Stray-Pedersen, Jo Kramer-Johansen, Lars Wik
Journal: Circulation (2019)

Background: Skeletal injuries (rib or sternum fractures) are common complications after cardiopulmonary resuscitation (CPR). Visceral injuries are also reported. During manual chest compressions, incidence of rib fractures is reported to be 13-97% and sternal fractures 1-43%. Studies on active compression decompression (AD) devices report incidence on rib fractures ranging from 4-87% and sternal fractures 0-93%. The aim of the present study is to describe and compare injury patterns caused by two mechanical, piston-based chest compression devices; LUCAS 2 and LUCAS 2AD in patients with out-of-hospital cardiac arrest. Method: In the randomized clinical trial comparing standard LUCAS 2 with LUCAS 2AD, patients who died were eligible for medical or forensic autopsy. The pathologists described injury pattern in each patient focusing on CPR-related injuries, but was blinded for the device used. We used Pearson X 2 test with an alpha level of 0.05 to evaluate our findings. Results: Of the 221 patients included between April 2015 and April 2017, 204 patients died of whom 115 were autopsied, LUCAS 2 n=62 and LUCAS 2 AD n=53. Median age was 63 (range: 19-91) and men represented 70%. CPR related rib fractures occurred in 70%, and sternal fractures in 45% of all patients. When comparing LUCAS 2 to LUCAS 2AD we found no difference in incidence of rib fractures (69% vs. 70%; p-value: 0.9) or in sternal fractures (44% vs. 47%; p-value: 0.7). Most frequent non-skeletal complication was bleeding in pleura (25), pericardium (13), mediastinum (7), abdomen (5), and ventricle (3). Many patients had bleedings reported from more than one location, but the amount of blood was mostly small and considered to not contribute to the cause of death. A total of 10 patients had injuries on internal organs such as lungs (6), liver (2), spleen (1), and diaphragm (1). Conclusion: Comparing LUCAS 2 with LUCAS 2AD we found no difference in rib- or sternal fractures. CPR related injuries on internal organs were rare. We conclude that LUCAS 2AD do not cause more skeletal or non-skeletal injuries compared to LUCAS 2.
Decoy receptor 2 mediation of the senescent phenotype of tubular cells by interacting with peroxiredoxin 1 presents a novel mechanism of renal fibrosis in diabetic nephropathy
Authors: Chen Jia, Chen Ke-Hong, Xiao Fei, Dai Huan-Zi, Yang Jie, Wang Li-Ming, Wang Xiao-Yue, Zhang Jian-Guo, He Ya-Ni
Journal: Kidney International (2020)

Premature senescence of renal tubular epithelial cell (RTEC), which is involved in kidney fibrosis, is a key event in the progression of diabetic nephropathy. However, the underlying mechanism remains unclear. Here we investigated the role and mechanism of decoy receptor 2 (DcR2) in kidney fibrosis and the senescent phenotype of RTEC. DcR2 was specifically expressed in senescent RTEC and associated with kidney fibrosis in patients with diabetic nephropathy and mice with streptozotocin-induced with diabetic nephropathy. Knockdown of DcR2 decreased the expression of α-smooth muscle actin, collagen I, fibronectin and serum creatinine levels in streptozotocin-induced mice. DcR2 knockdown also inhibited the expression of senescent markers p16, p21, senescence-associated beta-galactosidase and senescence-associated heterochromatic foci and promoted the secretion of a senescence-associated secretory phenotype including IL-6, TGF-β1, and matrix metalloproteinase 2 in vitro and in vivo. However, DcR2 overexpression showed the opposite effects. Quantitative proteomics and validation studies revealed that DcR2 interacted with peroxiredoxin 1 (PRDX1), which regulated the cell cycle and senescence. Knockdown of PRDX1 upregulated p16 and cyclin D1 while downregulating cyclin-dependent kinase 6 expression in vitro, resulting in RTEC senescence. Furthermore, PRDX1 knockdown promoted DcR2-induced p16, cyclin D1, IL-6, and TGF-β1 expression, whereas PRDX1 overexpression led to the opposite results. Subsequently, DcR2 regulated PRDX1 phosphorylation, which could be inhibited by the specific tyrosine kinase inhibitor genistein. Thus, DcR2 mediated the senescent phenotype of RTEC and kidney fibrosis by interacting with PRDX1. Hence, DcR2 may act as a potential therapeutic target for the amelioration of diabetic nephropathy progression.
Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2‐Bl/HLA‐G
Authors: Mayumi Ishikawa, Andrew J. Brooks, Manuel A. Fernández‐Rojo, Johan Medina, Yash Chhabra, Shiro Minami, Kathryn A. Tunny, Robert G. Parton, Julian P. Vivian, Jamie Rossjohn, Viral Chikani, Grant A. Ramm, Ken K.Y. Ho, Michael J. Waters
Journal: Hepatology (2020)

Background and Aims Growth hormone (GH) is important for liver regeneration after partial hepatectomy (PHx). We investigated this process in C57BL/6 mice that express different forms of the GH receptor (GHR) with deletions in key signaling domains. Approach and Results PHx was performed on C57BL/6 mice lacking GHR ( Ghr −/− ), disabled for all GH‐dependent Janus kinase 2 signaling ( Box1 −/− ), or lacking only GH‐dependent signal transducer and activator of transcription 5 (STAT5) signaling ( Ghr391 −/− ), and wild‐type littermates. C57BL/6 Ghr −/− mice showed striking mortality within 48 hours after PHx, whereas Box1 −/− or Ghr391 −/− mice survived with normal liver regeneration. Ghr −/− mortality was associated with increased apoptosis and elevated natural killer/natural killer T cell and macrophage cell markers. We identified H2‐Bl, a key immunotolerance protein, which is up‐regulated by PHx through a GH‐mediated, Janus kinase 2–independent, SRC family kinase–dependent pathway. GH treatment was confirmed to up‐regulate expression of the human homolog of H2‐Bl (human leukocyte antigen G [ HLA‐G ]) in primary human hepatocytes and in the serum of GH‐deficient patients. We find that injury‐associated innate immune attack by natural killer/natural killer T cell and macrophage cells are instrumental in the failure of liver regeneration, and this can be overcome in Ghr −/− mice by adenoviral delivery of H2‐Bl or by infusion of HLA‐G protein. Further, H2‐Bl knockdown in wild‐type C57BL/6 mice showed elevated markers of inflammation after PHx, whereas Ghr −/− backcrossed on a strain with high endogenous H2 ‐ Bl expression showed a high rate of survival following PHx. Conclusions GH induction of H2‐Bl expression is crucial for reducing innate immune‐mediated apoptosis and promoting survival after PHx in C57BL/6 mice. Treatment with HLA‐G may lead to improved clinical outcomes following liver surgery or transplantation.
Endpiece: Clamming up
Authors: Aarti Sarwal
Journal: BMJ (2004)

It's been troubling me. Now, why is it that most of us can talk openly about the illnesses of our bodies, but when it comes to our brain and illnesses of the mind we clam up and because we clam up, people with emotional disorders feel ashamed, stigmatised, and don't seek the help that can make the difference.

Kirk Douglas
Deepening responses associated with improved progression-free survival with ixazomib versus placebo as posttransplant maintenance in multiple myeloma
Authors: Hartmut Goldschmidt, Meletios A. Dimopoulos, S. Vincent Rajkumar, Katja C. Weisel, Philippe Moreau, Wee-Joo Chng, Gábor Mikala, Michele Cavo, Karthik Ramasamy, Kaveri Suryanarayan, Zhaoyang Teng, Richard Labotka, Maria Victoria Mateos
Journal: Leukemia (2020)

Abstract In the TOURMALINE-MM3 study, post-autologous stem cell transplantation maintenance therapy with the oral proteasome inhibitor ixazomib versus placebo significantly improved progression-free survival (PFS), with a favorable safety profile. With ixazomib versus placebo maintenance, deepening responses occurred in 139/302 (46%) versus 60/187 (32%) patients with very good partial response or partial response (VGPR/PR) at study entry (relative risk 1.41, P = 0.004), and median time to best confirmed deepened response was 19.9 versus 30.8 months (24-month rate: 54.2 versus 41.4%; hazard ratio (HR): 1.384; P = 0.0342). Median PFS in patients with VGPR/PR at study entry was 26.2 versus 18.5 months (HR: 0.636, P &lt; 0.001) with ixazomib versus placebo; in a pooled analysis across arms, in patients with versus without deepening responses, the median PFS was not reached versus 15.9 months (HR: 0.245, P &lt; 0.001). In patients with deepening responses, 24-month PFS rate was 77.4 versus 68.3% with ixazomib versus placebo (HR: 0.831; P = 0.466); in patients without deepening responses, median PFS was 17.9 versus 14.1 months (HR: 0.741; P = 0.028). These analyses demonstrate the significantly higher rate of deepening responses with ixazomib versus placebo maintenance and the association between deepening response and prolonged PFS.
“Quadruple Rule-Out” With Computed Tomography in a COVID-19 Patient With Equivocal Acute Coronary Syndrome Presentation
Authors: Gianluca Pontone, Andrea Baggiano, Edoardo Conte, Giovanni Teruzzi, Nicola Cosentino, Jeness Campodonico, Mark G. Rabbat, Emilio Assanelli, Anna Palmisano, Antonio Esposito, Daniela Trabattoni
Journal: JACC. Cardiovascular imaging (2020)
Assessment of Completeness of Hospital Readmission Rates Reported in Medicare Advantage Contracts’ Healthcare Effectiveness Data and Information Set
Authors: Daeho Kim, Rajesh Makineni, Orestis A. Panagiotou, Amal N. Trivedi
Journal: JAMA Network Open (2020)

This cross-sectional study evaluates the agreement between readmission rates reported by Medicare Advantage contracts and readmission rates calculated from their encounter data in the Healthcare Effectiveness Data and Information Set (HEDIS).
<i>De Novo</i> Lipogenesis Alters the Phospholipidome of Esophageal Adenocarcinoma
Authors: Nima Abbassi-Ghadi, Stefan S. Antonowicz, James S. McKenzie, Sacheen Kumar, Juzheng Huang, Emrys A. Jones, Nicole Strittmatter, Gemma Petts, Hiromi Kudo, Stephen Court, Jonathan M. Hoare, Kirill Veselkov, Robert Goldin, Zoltán Takáts, George B. Hanna
Journal: Cancer Research (2020)

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging (MSI) can support objective diagnosis in minutes using a routine frozen tissue section. However, whether MSI can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here, we used desorption electrospray ionization-MSI (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariate models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (AUC = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in premalignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch
Denosumab and cinacalcet for primary hyperparathyroidism (DENOCINA): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Julius Simoni Leere, Jesper Karmisholt, Maciej Robaczyk, Simon Lykkeboe, Aase Handberg, Emilie Steinkohl, Jens Brøndum Frøkjær, Peter Vestergaard
Journal: The Lancet Diabetes & Endocrinology (2020)
Clinical Implications of 18F-FDG PET/CT in Malignant Glomus Tumors of the Esophagus
Authors: Romain-David Seban, Laurence Bozec, Laurence Champion
Journal: Clinical Nuclear Medicine (2020)

Abstract The majority of glomus tumors are localized to cutaneous sites and are benign. However, extracutaneous malignant glomus tumors have been reported and are aggressive. Here, we report a case of a 45-year-old man who presented severe dysphagia, diagnosed with malignant glomus tumor of the esophagus. 18 F-FDG PET/CT played a decisive role in several phases of the patient management offering previously unknown accuracy. It was first performed in the initial staging of local tumor extent before surgery. A year and a half after, 18 F-FDG PET/CT helped to detect recurrence and, finally, was performed for response evaluation of several systemic therapies.