tbuckley/cabot-search huggingface dataset:
Burden, treatment use, and outcome of secondary mitral regurgitation across the spectrum of heart failure: observational cohort study
Authors: Philipp E Bartko, Gregor Heitzinger, Noemi Pavo, Maria Heitzinger, Georg Spinka, Suriya Prausmüller, Henrike Arfsten, Martin Andreas, Cornelia Gabler, Guido Strunk, Julia Mascherbauer, Christian Hengstenberg, Martin Hülsmann, Georg Goliasch
Journal: BMJ (2021)

Abstract Objectives To define prevalence, long term outcome, and treatment standards of secondary mitral regurgitation (sMR) across the heart failure spectrum. Design Large scale cohort study. Setting Observational cohort study with data from the Viennese community healthcare provider network between 2010 and 2020, Austria. Participants 13 223 patients with sMR across all heart failure subtypes. Main outcome measures Association between sMR and mortality in patients assigned by guideline diagnostic criteria to one of three heart failure subtypes: reduced, mid-range, and preserved ejection fraction, was assessed. Results Severe sMR was diagnosed in 1317 patients (10%), correlated with increasing age (P&lt;0.001), occurred across the entire spectrum of heart failure, and was most common in 656 (25%) of 2619 patients with reduced ejection fraction. Mortality of patients with severe sMR was higher than expected for people of the same age and sex in the same community (hazard ratio 7.53; 95% confidence interval 6.83 to 8.30, P&lt;0.001). In comparison with patients with heart failure and no/mild sMR, mortality increased stepwise with a hazard ratio of 1.29 (95% confidence interval 1.20 to 1.38, P&lt;0.001) for moderate and 1.82 (1.64 to 2.02, P&lt;0.001) for severe sMR. The association between severe sMR and excess mortality was consistent after multivariate adjustment and across all heart failure subgroups (mid-range ejection fraction: hazard ratio 2.53 (95% confidence interval 2.00 to 3.19, P&lt;0.001), reduced ejection fraction: 1.70 (1.43 to 2.03, P&lt;0.001), and preserved ejection fraction: 1.52 (1.25 to 1.85, P&lt;0.001)). Despite available state-of-the-art healthcare, high volume heart failure, and valve disease programmes, severe sMR was rarely treated by surgical valve repair (7%) or replacement (5%); low risk transcatheter repair (4%) was similarly seldom used. Conclusion Secondary mitral regurgitation is common overall, increasing with age and associated with excess mortality. The association with adverse outcome is significant across the entire heart failure spectrum but most pronounced in those with mid-range and reduced ejection fractions. Despite these poor outcomes, surgical valve repair or replacement are rarely performed; similarly, low risk transcatheter repair, specifically in the heart failure subsets with the highest expected benefit from treatment, is seldom used. The current data suggest an increasing demand for treatment, particularly in view of an expected increase in heart failure in an ageing population.
Infographic. Sex differences and ACL injuries
Authors: Hana Marmura, Dianne M Bryant, Alan MJ Getgood
Journal: British Journal of Sports Medicine (2021)

Females are 2–10 times more likely to suffer an anterior cruciate ligament (ACL) injury than males when playing the same sports,1 a discrepancy which has garnered significant research effort and warrants further attention.

It is critical to understand the sex-related differences influencing ACL injuries to improve research and care. The Sex and Gender Equity in Research Guidelines provide instructions for incorporating sex and gender differences into health research and emphasise the need to explicitly discuss the associated implications for interpretation of study results and clinical application: https://wwweaseorguk/wp-content/uploads/2016/09/Sagerfor-webpdf.2

While traditionally presented as dichotomous, biological sex is a nuanced topic with variations across the population. However, we are currently unable to draw any evidence-based conclusions regarding biological sex variations and ACL injuries, with rigorous research required in this …
A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis
Authors: Angela Dispenzieri, Efstathios Kastritis, Ashutosh D. Wechalekar, Stefan O. Schönland, Kihyun Kim, Vaishali Sanchorawala, Heather J. Landau, Fiona Kwok, Kenshi Suzuki, Raymond L. Comenzo, Deborah Berg, Guohui Liu, Arun Kumar, Douglas V. Faller, Giampaolo Merlini
Journal: Leukemia (2021)

In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1-2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician's choice (dexamethasone ± melphalan, cyclophosphamide, thalidomide, or lenalidomide; n = 83) in 28-day cycles until progression or toxicity. Primary endpoints were hematologic response rate and 2-year vital organ deterioration or mortality rate. Only the first primary endpoint was formally tested at this interim analysis. Best hematologic response rate was 53% with ixazomib-dexamethasone vs 51% with physician's choice (p = 0.76). Complete response rate was 26 vs 18% (p = 0.22). Median time to vital organ deterioration or mortality was 34.8 vs 26.1 months (hazard ratio 0.53; 95% CI, 0.32-0.87; p = 0.01). Median treatment duration was 11.7 vs 5.0 months. Adverse events of clinical importance included diarrhea (34 vs 30%), rash (33 vs 20%), cardiac arrhythmias (26 vs 15%), nausea (24 vs 14%). Despite not meeting the first primary endpoint, all time-to-event data favored ixazomib-dexamethasone. These results are clinically relevant to this relapsed/refractory patient population with no approved treatment options.
Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study (vol 56, 2000130, 2020)
Authors: J P Corcoran, I Psallidas, S Gerry, F Piccolo, C F Koegelenberg, T Saba, C Daneshvar, I Fairbairn, R Heinink, A West, A E Stanton, J Holme, J A Kastelik, H Steer, N J Downer, M Haris, E H Baker, C F Everett, J Pepperell, T Bewick, L Yarmus, F Maldonado, B Khan, A Hart-Thomas, G Hands, G Warwick, D De Fonseka, M Hassan, M Munavvar, A Guhan, M Shahidi, Z Pogson, L Dowson, N D Popowicz, J Saba, N R Ward, R J Hallifax, M Dobson, R Shaw, E L Hedley, A Sabia, B Robinson, G S Collins, H E Davies, Yu L-M., R F Miller, N A Maskell, N M Rahman
Journal: European Respiratory Journal (2020)
Abstract 376: Confounders of Early Processed EEG to Stratify Neurological Injury After Cardiac Arrest
Authors: David B Seder, Ameldina Bilkanovic, John Dziodzio, Lee Lucas, Zana Haxhija, Sadie Denico, Lyn Ackert-Smith, David Gagnon, Sergey V Ryzhov, Teresa MAY, Richard Riker
Journal: Circulation (2019)

Introduction: Electroencephalographic suppression ratio (SR) measured six hours after resuscitation from cardiac arrest (SR6) can stratify risk of neurological-etiology death (NED) after cardiac arrest. Confounders of this tool for risk stratification have not been described. Hypothesis: Misclassification of risk of NED by SR6 is explained by characteristics of the patient, arrest, or treatment. Methods: Comatose patients prospectively enrolled in an IRB-approved cardiac arrest database were treated by protocol. Patients with brain death or death after withdrawal of life support measures (WLST) due to poor neurological prognosis were considered NED; neuroprognostication follows European Resuscitation Council guidelines. We analyzed patients misclassified by the SR6; high SR that did not suffer NED, or low SR6 that had NED. We reviewed factors associated with misclassification in bivariate analysis, and performed chart review for potential confounders of SR6. Results: Among 364 patients resuscitated from cardiac arrest and with complete data, SR6 predicted NED with AUC 0.89, and an optimal cutoff value of 55.5%. Forty (11%) patients with high SR6 and 17 (5%) with low SR6 were misclassified. In bivariate analysis, factors associated with high SR misclassification were older age 62.6(±14.9) vs. 56.4 (±16) p=0.02, prior neuropathology [20% vs 9.1%, p=0.049], and longer no-flow time (7 [4-9] vs 5 [2-7] minutes, p=0.01). Those associated with low SR misclassification were heart failure [29.4% vs 11.4%, p=0.045] hypertension [82.4% vs 44.6%, P=0.003], obesity [29.4% vs 10.7%, p=0.04], seizures [47.1% vs 21.5%, p=0.03], and higher BMI 33.9 [26.5-36.1] vs 27.8 [23.7-31.3], p=0.04. In chart review, misclassification was associated with early WLST due to family preference, drug or alcohol overdose, seizures, death due to non-neurological cause, preexisting neurological disease, and “favorable” SR6 trajectory. Conclusion: Age, seizures, drug overdose, and non-neurological causes of death may confound accurate neurological risk stratification using processed EEG very early after cardiac arrest. In addition to these “fixed” confounders, a few patients have dynamic SR that improves after 6 hours, and deserve further study.
The Analysis of 12-Year Overall Survival in Non-Selected Patients with Chronic Myeloid Leukemia with Tyrosinekinase Inhibitors Therapy in Routine Practice
Authors: Lyudmila Vysotskaya, Tatiana Mitina, Elena Trifonova, Yulia Chernykh, Sergei Zakharov, Kirill Belousov, Elena Klinushkina, Elena Kataeva, Anna G Turkina, Anatoly Golenkov
Journal: Blood (2017)
The Antibiotic Efflux Protein TolC Is a Highly Evolvable Target under Colicin E1 or TLS Phage Selection
Authors: Yusuf Talha Tamer, Ilona Gaszek, Marinelle Rodrigues, Fatma Sevde Coskun, Michael Farid, Andrew Y Koh, William Russ, Erdal Toprak
Journal: Molecular Biology and Evolution (2021)

Bacteriophages and bacterial toxins are promising antibacterial agents to treat infections caused by multidrug-resistant (MDR) bacteria. In fact, bacteriophages have recently been successfully used to treat life-threatening infections caused by MDR bacteria (Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, et al. 2017. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 61(10); Chan BK, Turner PE, Kim S, Mojibian HR, Elefteriades JA, Narayan D. 2018. Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Health. 2018(1):60-66; Petrovic Fabijan A, Lin RCY, Ho J, Maddocks S, Ben Zakour NL, Iredell JR, Westmead Bacteriophage Therapy Team. 2020. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat Microbiol. 5(3):465-472). One potential problem with using these antibacterial agents is the evolution of resistance against them in the long term. Here, we studied the fitness landscape of the Escherichia coli TolC protein, an outer membrane efflux protein that is exploited by a pore forming toxin called colicin E1 and by TLS phage (Pagie L, Hogeweg P. 1999. Colicin diversity: a result of eco-evolutionary dynamics. J Theor Biol. 196(2):251-261; Andersen C, Hughes C, Koronakis V. 2000. Chunnel vision. Export and efflux through bacterial channel-tunnels. EMBO Rep. 1(4):313-318; Koronakis V, Andersen C, Hughes C. 2001. Channel-tunnels. Curr Opin Struct Biol. 11(4):403-407; Czaran TL, Hoekstra RF, Pagie L. 2002. Chemical warfare between microbes promotes biodiversity. Proc Natl Acad Sci U S A. 99(2):786-790; Cascales E, Buchanan SK, Duché D, Kleanthous C, Lloubès R, Postle K, Riley M, Slatin S, Cavard D. 2007. Colicin biology. Microbiol Mol Biol Rev. 71(1):158-229). By systematically assessing the distribution of fitness effects of ∼9,000 single amino acid replacements in TolC using either positive (antibiotics and bile salts) or negative (colicin E1 and TLS phage) selection pressures, we quantified evolvability of the TolC. We demonstrated that the TolC is highly optimized for the efflux of antibiotics and bile salts. In contrast, under colicin E1 and TLS phage selection, TolC sequence is very sensitive to mutations. Finally, we have identified a large set of mutations in TolC that increase resistance of E. coli against colicin E1 or TLS phage without changing antibiotic susceptibility of bacterial cells. Our findings suggest that TolC is a highly evolvable target under negative selection which may limit the potential clinical use of bacteriophages and bacterial toxins if evolutionary aspects are not taken into account.
Allogeneic Hematopoietic Stem Cell Transplantation in Older Patients Aged 50 Years or Older with Severe Aplastic Anaemia: Results from the European Society for Blood and Marrow Transplant and the Center for International Blood and Marrow Transplant Research
Authors: Carmel Rice, Diderik-Jan Eikema, Judith Marsh, Cora Knol, Kyle Hebert, Eefke Petersen, H. Joachim Deeg, Constantijn J.M. Halkes, Joseph Pidala, Paolo Anderlini, Johanna Tischer, Nicolaus Kröger, Andrew McDonald, Joseph H. Antin, Nicolaas Schaap, Michael J. Hallek, Hermann Einsele, Vikram Mathews, Neena Kapoor, Jaap Jan Boelens, Ghulam Mufti, Victoria Potter, Regis Peffault De Latour, Mary Eapen, Carlo Dufour
Journal: Blood (2017)
Selective and caspase-independent cytotoxicity of bioactive glasses towards giant cell tumor of bone derived neoplastic stromal cells but not to bone marrow derived stromal cells
Authors: Fabian Westhauser, Marcela Arango-Ospina, Sarina Losch, Sebastian Wilkesmann, Burkhard Lehner, Muhammad S. Ali, Wolfgang Peukert, Aldo R. Boccaccini, Jörg Fellenberg
Journal: Biomaterials (2021)
A microbial signature following bariatric surgery is robustly consistent across multiple cohorts
Authors: Farnaz Fouladi, Ian M. Carroll, Thomas J. Sharpton, Emily Bulik-Sullivan, Leslie Heinberg, Kristine J. Steffen, Anthony A. Fodor
Journal: Gut Microbes (2021)

Bariatric surgery induces significant shifts in the gut microbiota which could potentially contribute to weight loss and metabolic benefits. The aim of this study was to characterize a microbial signature following Roux-en-Y Gastric bypass (RYGB) surgery using novel and existing gut microbiota sequence data. We generated 16S rRNA gene and metagenomic sequences from fecal samples from patients undergoing RYGB surgery (n = 61 for 16S rRNA gene and n = 135 for metagenomics) at pre-surgical baseline and one, six, and twelve-month post-surgery. We compared these data with three smaller publicly available 16S rRNA gene and one metagenomic datasets from patients who also underwent RYGB surgery. Linear mixed models and machine learning approaches were used to examine the presence of a common microbial signature across studies. Comparison of our new sequences with previous longitudinal studies revealed strikingly similar profiles in both fecal microbiota composition (r = 0.41 ± 0.10; p < .05) and metabolic pathways (r = 0.70 ± 0.05; p < .001) early after surgery across multiple datasets. Notably, Veillonella, Streptococcus, Gemella, Fusobacterium, Escherichia/Shigella, and Akkermansia increased after surgery, while Blautia decreased. Machine learning approaches revealed that the replicable gut microbiota signature associated with RYGB surgery could be used to discriminate pre- and post-surgical samples. Opportunistic pathogen abundance also increased post-surgery in a consistent manner across cohorts. Our study reveals a robust microbial signature involving many commensal and pathogenic taxa and metabolic pathways early after RYGB surgery across different studies and sites. Characterization of the effects of this robust microbial signature on outcomes of bariatric surgery could provide insights into the development of microbiome-based interventions for predicting or improving outcomes following surgery.
Management of children and young people with idiopathic pituitary stalk thickening, central diabetes insipidus, or both: a national clinical practice consensus guideline
Authors: Manuela Cerbone, Johannes Visser, Chloe Bulwer, Ashraf Ederies, Kirtana Vallabhaneni, Stephen Ball, Ian Kamaly-Asl, Ashley Grossman, Helena Gleeson, Márta Korbonits, Vasanta Nanduri, Vaya Tziaferi, Tom Jacques, Helen A Spoudeas
Journal: The Lancet Child & Adolescent Health (2021)
Abstract 220: Epigenetic Reprogramming Rescues Diabetic Endothelial Progenitor Cell Dysfunctions and Enhances Their Reparative Activities in Ischemic Tissue Repair
Authors: Jibin Zhou, Venkata N Garikipati, Cheng Zhongjian, Cindy Benedict, Emily Nickoloff, Erhe Gao, Suresh Verma, Mohsin Khan, Raj Kishore
Journal: Circulation Research (2016)

Type 2 Diabetes mellitus (DM) is the leading cause of death in the United States with concomitant complications from circulatory disorders including endothelial cell (EC)/endothelial progenitor cell (EPC) dysfunction in a variety of organs including heart. Although clinical trials of bone marrow progenitors/EPCs have shown some promise, however, diabetic dysfunction of EPC limits the functional benefits of stem/EPC-based cellular therapies. Emerging evidence suggests that epigenetic silencing of functional genes leads to dysfunctional EPCs in diabetes. In the present study, we show that epigenetic modulation of diabetic EPCs using small molecules epigenetic modifiers rescue diabetes-induced EPC dysfunction. EPCs from diabetic (db/db) mice were treated with valproic acid (VPA, histone deacetylase inhibitor) and 5’-azacytidine (5’-Aza; DNA methyltransferase, DNMT, inhibitor), and their function was determined both in vitro and in vivo. In contrast to untreated EPCs, treatment with VPA/5’-Aza, enhanced their angiogenic activities including tube formation, survival and proliferation. Expression of multiple pro-angiogenic genes including eNOS, and VEGF/VEGFR2 was upregulated in reprogrammed EPCs and chromatin immunoprecipitation experiments confirmed enhanced histone3-lysine9 acetylation (H3K9ac) of these gene promoters. Reprogrammed EPCs displayed reduced protein expression of DNMT3a and DNMT3b; whereas expression of histone H3K9ac and H3K14ac (gene activating epigenetic mark) was up-regulated. In db/db mouse hind limb ischemia model, transplantation of reprogrammed EPCs restored blood flow, enhanced capillary density and muscle architecture and resulted in significant limb salvage. In a myocardial ischemia model in db/db mice, transplantation of reprogrammed EPCs enhanced left ventricular functions, reduced infarct size and increased capillary density in the border zone. Taken together our data suggests that the reprogramming of db/db-derived EPCs might result in pattern shift of epigenetic modifications, leading to up-regulation of functional genes repressed by hyperglycemia and may rescue dysfunctional EC/EPC phenotype leading to improved functional repair capacity of diabetic stem cells/EPCs.
Acquisition of Non-Driver Mutations during Follow-up in Patients with Polycythemia Vera and Essential Thrombocythemia
Authors: Alicia Senín, Concepción Fernández Rodríguez, Beatriz Bellosillo, Laura Camacho, Lierni Fernández, Raquel Longarón, Anna Angona, Carlos Besses Raebel, Alberto Alvarez Larran
Journal: Blood (2017)
Art in Endoscopy: “This colon has a heart! Does it have feelings too?”
Authors: Manoop S. Bhutani
Journal: Endoscopy (2021)

After this perfectly “heart-shaped” colonic polyp was removed by endoscopic mucosal resection, pathology revealed a sessile serrated adenoma (or “sessile serrated lesion,” to use the term recommended by the World Health Organization in 2019 in preference to sessile serrated adenoma or polyp). Ironically, this procedure was done around the time of Valentine’s Day in February, when an abundance of heart-shaped chocolates, candies, and other products are given and received as gifts.
進行性乳癌に対するESO-ESMO国際コンセンサスガイドライン第5版(ABC 5)
Authors: F Cardoso, S Paluch-Shimon, E Senkus, G Curigliano, M S Aapro, F Andre, C H Barrios, J Bergh, G S Bhattacharyya, L Biganzoli, F Boyle, Cardoso M.-J., L A Carey, J Cortes, N S El Saghir, M Elzayat, A Eniu, L Fallowfield, P A Francis, K Gelmon, J Gligorov, R Haidinger, N Harbeck, X Hu, B Kaufman, R Kaur, B E Kiely, Kim S.-B., N U Lin, S A Mertz, S Neciosup, B V Offersen, S Ohno, O Pagani, A Prat, F Penault-Llorca, H S Rugo, G W Sledge, C Thomssen, D A Vorobiof, T Wiseman, B Xu, L Norton, A Costa, E P Winer
Journal: Annals of Oncology (2020)
Need for Contraceptive Services Among Women of Reproductive Age — 45 Jurisdictions, United States, 2017–2019
Authors: Lauren B. Zapata, Karen Pazol, Kathryn M. Curtis, Debra J. Kane, Tara C. Jatlaoui, Suzanne G. Folger, Ekwutosi M. Okoroh, Shanna Cox, Maura K. Whiteman
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

TABLE 2. Estimated numbers and percentages of women aged 18-49 years who
Labour calls for transparency in appointment of new head of NHS England
Authors: Abi Rimmer
Journal: BMJ (2021)

Labour has called for the appointment process of the new chief executive of NHS England to be transparent, based on merit, and without undue political influence.

In a letter sent to cabinet secretary Simon Case on 19 June, Labour’s shadow health minister Jonathan Ashworth also called for the process to be “free from the cronyism that has existed over the past year.”

“This is a matter of the utmost importance for both patients and NHS …
A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving
Authors: Xiaojuan Zhang, Chuanchuan He, Yun Sun, Xiaoguang Liu, Yan Chen, Chen Chen, Ruicong Yan, Ting Fan, Tan Yang, Yao Lu, Jun Luo, Xiang Ma, Guangya Xiang
Journal: Acta Pharmaceutica Sinica B (2021)

Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.