tbuckley/cabot-search huggingface dataset:
Clinician-Family Communication About Patients’ Values and Preferences in Intensive Care Units
Authors: Leslie P. Scheunemann, Natalie C. Ernecoff, Praewpannarai Buddadhumaruk, Shannon S. Carson, Catherine L. Hough, J. Randall Curtis, Wendy G. Anderson, Jay Steingrub, Bernard Lo, Michael Matthay, Robert M. Arnold, Douglas B. White
Journal: JAMA Internal Medicine (2019)

Little is known about whether clinicians and surrogate decision makers follow recommended strategies for shared decision making by incorporating intensive care unit (ICU) patients' values and preferences into treatment decisions.To determine how often clinicians and surrogates exchange information about patients' previously expressed values and preferences and deliberate and plan treatment based on these factors during conferences about prognosis and goals of care for incapacitated ICU patients.A secondary analysis of a prospective, multicenter cohort study of audiorecorded clinician-family conferences between surrogates and clinicians of 249 incapacitated, critically ill adults was conducted. The study was performed between October 8, 2009, and October 23, 2012. Data analysis was performed between July 2, 2014, and April 20, 2015. Patient eligibility criteria included lack of decision-making capacity, a diagnosis of acute respiratory distress syndrome, and predicted in-hospital mortality of 50% or more. In addition to the patients, 451 surrogates and 144 clinicians at 13 ICUs at 6 US academic and community medical centers were included.Two coders analyzed transcripts of audiorecorded conversations for statements in which clinicians and surrogates exchanged information about patients' treatment preferences and health-related values and applied them in deliberation and treatment planning.Of the 249 patients, 134 (54.9%) were men; mean (SD) age was 58.2 (16.5) years. Among the 244 conferences that addressed a decision about goals of care, 63 (25.8%; 95% CI, 20.3%-31.3%) contained no information exchange or deliberation about patients' values and preferences. Clinicians and surrogates exchanged information about patients' values and preferences in 167 (68.4%) (95% CI, 62.6%-74.3%) of the conferences and specifically deliberated about how the patients' values applied to the decision in 108 (44.3%; 95% CI, 38.0%-50.5%). Important end-of-life considerations, such as physical, cognitive, and social functioning or spirituality were each discussed in 87 (35.7%) or less of the conferences; surrogates provided a substituted judgment in 33 (13.5%); and clinicians made treatment recommendations based on patients' values and preferences in 20 conferences (8.2%).Most clinician-family conferences about prognosis and goals of care for critically ill patients appear to lack important elements of communication about values and preferences, with robust deliberation being particularly deficient. Interventions may be needed to better prepare surrogates for these conversations and improve clinicians' communication skills for eliciting and incorporating patients' values and preferences into treatment decisions.
Abstract 38: Lactate Clearance Is Associated with Improved Survival and Neurological Outcome in Post--Cardiac Arrest
Authors: Michael W Donnino, Justin Salciccioli, David F Gaieski, Benjamin S Abella, Mary Ann Peberdy, Jon C Rittenberger, Clifton W Callaway, Joseph Ornato, John Clore, Tyler Giberson, Michael N Cocchi
Journal: Circulation (2012)

Introduction: Previous investigations demonstrated an association between lactate clearance and in-hospital mortality in post-cardiac arrest patients. These findings have yet to be validated in a multicenter study. Objective: To determine the association between lactate clearance and outcomes in post-cardiac arrest Methods: Four center prospective observational study conducted from 6/11 to 3/12. Inclusion criteria consisted of adult out-of-hospital non-traumatic cardiac arrest patients who were comatose after ROSC. The primary outcome was difference in lactate clearance between survivors/non-survivors, and secondary outcome was the difference in lactate clearance between those with good/poor neurological outcome. We compared baseline lactate between survivors and non-survivors using the students t-test. We used multivariate adjustments (age and downtime) with linear mixed-models to assess the trend in lactate clearance over 24-hrs between survivors/non-survivors and good/bad neurological outcome. Results: 111 patients were analyzed. The median age was 63 years (IQR: 50 - 75) and 41% were female. 97% received TH and overall survival was 47%. Survivors had lower baseline lactate levels compared to non-survivors (5.1 +/- 3.4 versus 7.7 +/- 4.7; p = 0.004). Patients with good neurologic outcomes had lower baseline levels of lactic acid compare to patients with poor neurologic outcomes (4.6 +/- 2.6 versus 7.4 +/- 4.7; p = 0.009). After multivariate adjustments survivors had better lactate clearance than non-survivors (p &lt; 0.001; Figure) and patients with good neurologic status had better lactate clearance compared those with poor neurologic status (p = 0.01). Conclusion: Lower initial lactate as well as more efficient lactate clearance over the first 24-hours post-CA is associated with improved in-hospital survival and good neurologic outcome.
Abstract P110: Gene-Gene Interaction: <i>SERPINE1</i> Interacts with <i>ANRIL</i> in Association with Coronary Artery Disease and Coronary Artery Calcium in a Non-Hispanic Population
Authors: Katherine A Pratte, Sharon M Lutz, Tasha E Fingerlin, Russell P Bowler, Gregory L Kinney, Kendra A Young, Michael H Cho, Richard Casaburi, Edwin K Silverman, James D Crapo, Matthew J Budoff, John E Hokanson
Journal: Circulation (2017)

Introduction: Long non-coding RNAs (lncRNA) are important regulators of gene expression. ANRIL ( CDKN2B-AS1 ) is an anti-sense lncRNA coded for at the Chr9p21 locus. GWAS have reported SNPs in the Chr9p21 to be associated with clinical coronary artery disease (CAD) and coronary artery calcium (CAC). A knockdown study of two isoforms of ANRIL reported the potential of ANRIL’s regulation of SERPINE1 expression. SERPINE1 encodes plasminogen activator inhibitor-1 (PAI-1) and has been reported to be associated with CAD and CAC. The 3’UTR of SERPINE1 has been reported to bind miRNA and lncRNA suggesting ANRIL may modify SERPINE1’s association with CAD and CAC. Hypothesis: We hypothesized that rs7242 or rs1050955, covering the LD of the 3’ UTR of SERPINE1, will interact with SNPs within ANRIL to affect their association with self-reported CAD and CAC in non-Hispanic Whites (NHW, n=6103) and African Americans (AA, n=2549) in the COPDGene Study. Methods: Interaction of SNPs from Illumina HumanOmniExpress Beadchip for ANRIL , and rs7242 and rs1050955 were evaluated in an additive genetic model with a cross-product interaction term. Logistic regression was used to evaluate the association of CAD (Yes/No) and CAC (Yes/No) with the SNP-SNP interactions, while controlling for genetic ancestry, ascertainment, age, sex, BMI, diabetes, hypertension, high cholesterol and pack-years of smoking. Analyses were stratified by race. Results: A significant interaction between rs7242 ( SERPINE1 ) and rs7049105 ( ANRIL ) and CAD (p=0.0004) and CAC (p=0.0023) were found in NHW (Figure 1). The risk estimates for the rs7242 G allele in SERPINE1 were higher in those with the rs7049105 AA genotype in ANRIL but were lower in those with the rs7049105 GG genotype in ANRIL . We did not find any significant interactions in AA. Conclusion: In this study, the previously identified GWAS signal for CAD and CAC in Chr9p21 ( ANRIL ) interacts with a SNP in SERPINE1 . This may be due to ANRIL lncRNA influences on gene expression of SERPINE1 and increases the risk of both CAC and CAD.
Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin
Authors: Sean J. Miller, Thomas Philips, Namho Kim, Raha Dastgheyb, Zhuoxun Chen, Yi-Chun Hsieh, J. Gavin Daigle, Malika Datta, Jeannie Chew, Svetlana Vidensky, Jacqueline T. Pham, Ethan G. Hughes, Michael B. Robinson, Rita Sattler, Raju Tomer, Jung Soo Suk, Dwight E. Bergles, Norman Haughey, Mikhail Pletnikov, Justin Hanes, Jeffrey D. Rothstein
Journal: Nature Neuroscience (2019)
Doctors alleging sexist behaviour at top of BMA criticise its formal conduct procedures
Authors: Melanie Newman
Journal: BMJ (2019)

The doctors behind accusations of sexism and inappropriate behaviour among senior members of the BMA have reported their lack of faith in the organisation’s own conduct processes.

In an article for GPOnline 1 on 1 April, Zoe Norris and Katie Bramall-Stainer from the BMA’s General Practitioners Committee (GPC) described a misogynistic and outdated culture at the top of the organisation, which they said had forced women out of medical politics. Norris has decided to step down from the GPC in protest.

Chaand Nagpaul, chair of BMA Council, said that the BMA was committed to an external investigation, independent of the association, to look into this matter.

But Norris and Bramall-Stainer told The BMJ that they had no confidence in any inquiry led by the BMA and that only a “wholly independent” investigation would do. To be truly independent the investigation would have to be run by someone with no ties to the organisation, they said.

Norris said, “My faith in the BMA and its leadership is so broken that unless the inquiry is conducted by someone with no association with it or its senior officers—historical or otherwise —I believe it will not be done properly. The investigation has to be wholly independent.”

On …
Publisher Correction: Fgf10 is essential for limb and lung formation
Authors: Keisuke Sekine, Hideyo Ohuchi, Masanori Fujiwara, Masahiro Yamasaki, Tatsuya Yoshizawa, Takashi Sato, Naoko Yagishita, Daisuke Matsui, Yoshihiko Koga, Nobuyuki Itoh, Shigeaki Kato
Journal: Nature Genetics (2019)
Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum
Authors: Adam Cuker, Allison Burnett, Darren Triller, Mark Crowther, Jack Ansell, Elizabeth M. Van Cott, Diane Wirth, Scott Kaatz
Journal: American Journal of Hematology (2019)

Abstract Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non‐specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.
Machine Learning in Medicine
Authors: Alvin Rajkomar, Jeffrey Dean, Isaac Kohane
Journal: New England Journal of Medicine (2019)

Interview with Dr. Isaac Kohane on machine learning in medicine. (16:31)Download In this view of the future of medicine, patient–provider interactions are informed and supported by massive amounts of data from interactions with similar patients. These data are collected and curated to provide the latest evidence-based assessment and recommendations.
Intra-articular delivery of synovium-resident mesenchymal stem cells via BMP-7-loaded fibrous PLGA scaffolds for cartilage repair
Authors: Hee Jung Kim, Min Ah. Han, Ji Young Shin, Jeong Hwa Jeon, Seung Jin Lee, Mi Yun Yoon, Han-Jun Kim, Eun-Ji Choi, Sun Hee Do, Victor C. Yang, Huining He, Young-Il Yang
Journal: Journal of Controlled Release (2019)
抗‐TIF‐1b 抗体与皮肌炎
Authors: I. Ueda‐Hayakawa, Y. Hamaguchi, N. Okiyama, S. Motegi, T. Yamaoka, S. Miyake, A. Higashi, H. Okamoto, K. Takehara, M. Fujimoto
Journal: British Journal of Dermatology (2019)

皮肌炎是一种皮肤和肌肉发炎的疾病。它有时候只影响肌肉,有时候只影响皮肤。大部分患者为肌肉和皮肤同时发炎。如果肌肉发炎,可以在血流中发现肌酸激酶 (CK) 增高,且肌电图等检查可能异常。皮肌炎是一种自身免疫性疾病,存在针对患者自身组织的抗体(自身抗体)。这些抗体的不同模式与该病的不同亚组相关。少数皮肌炎成人患者中还有潜在癌症。一组自身抗体特异性地与肌肉炎症相关。其中一个家族称为抗‐TIF(转录中介因子)抗体,包括抗‐TIF‐1α 和 ‐1γ 抗体。抗‐TIF‐1α 抗体总是与抗‐TIF‐1γ 一起出现。在这篇来自日本的论文中,作者们调查了当第三种自身抗体抗‐TIF‐1β 单独出现(无另外两种抗体任何一种)时会发生什么情况。在 3442 份来自结缔组织病患者的储存血清(血液)样本中,他们发现了 7 名此类患者。6 名患有皮肌炎,但在 2 名中,肌肉并未受累(一名患者)或虽然受累但未出现症状(一名患者);其余 4 名患者有经典皮肌炎,但肌肉受累轻,4 名中只有一名 CK 增高。但是,这 4 名患者中有 1 名存在潜在癌症。第 7 名患者有“未分化结缔组织病”。作者们得出结论称,抗‐TIF‐1β 抗体与无肌肉炎症或只有轻度肌肉炎症的皮肌炎相关。
Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers
Authors: Alex Calizzano, Pascale Perret, Marie-Dominique Desruet, Mitra Ahmadi, Ghislaine Reboulet, Loïc Djaileb, Gérald Vanzetto, Daniel Fagret, Gilles Barone-Rochette, Catherine Ghezzi
Journal: Clinical Nuclear Medicine (2019)

Insulin resistance is a key feature of the metabolic syndrome and type 2 diabetes, in which noninvasive assessment is not currently allowed by any methodology. We previously validated an iodinated tracer of glucose transport (6DIG) and a new methodology for the in vivo quantification of cardiac insulin resistance in rodents. The aim of this study was to investigate the safety, biodistribution, and radiation dosimetry of this method using I-6DIG in 5 healthy and 6 diabetic volunteers.The collection of adverse effects (AEs) and medical supervision of vital parameters and biological variables allowed the safety evaluation. Biodistribution was studied by sequentially acquiring whole-body images at 1, 2, 4, 8, and 24 hours postinjection. The total number of disintegrations in each organ normalized to the injected activity was calculated as the area under the time-activity curves. Dosimetry calculations were performed using OLINDA/EXM.No major adverse events were observed. The average dose corresponding to the 2 injections of I-6DIG used in the protocol was 182.1 ± 7.5 MBq. A fast blood clearance of I-6DIG was observed. The main route of elimination was urinary, with greater than 50% of urine activity over 24 hours. No blood or urine metabolite was detected. I-6DIG accumulation mostly occurred in elimination organs such as kidneys and liver. Mean radiation dosimetry calculations indicated an effective whole-body absorbed dose of 3.35 ± 0.57 mSv for the whole procedure.I-6DIG was well tolerated in human with a dosimetry profile comparable to that of other commonly used iodinated tracers, thereby allowing further clinical development of the tracer.
Abstract 19922: Phosphatidylserine Receptor Upregulation in Stroke for Targeted Carrier Delivery
Authors: Tao Peng, David D McPherson, Shao-Ling Huang
Journal: Circulation (2015)

Introduction: The phosphatidylserine receptor (PSR) plays an important role in apoptosis and inflammation. Whether this receptor is expressed in damaged brain cells in the early stages of stroke is unknown. Hypothesis: The purpose of this study was to determine if this receptor is expressed on ischemic neurovascular endothelial cells and if so, can it bind with PS-containing liposomes (PS-liposomes). The latter would allow for a neurovascular targeting strategy for therapeutic delivery to ischemic brain cells. Methods: Sprague Dawley rats (n=22) were randomly divided into sham, cerebral ischemia, and subarachnoid hemorrhage (SAH) injury groups. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 hours using an intraluminal suture method. SAH was induced by an endovascular perforation method. Brain tissue was harvested for immunofluorescence staining at day 2 after surgery. Cultured human umbilical vein endothelial cells (HUVEC) were pre-treated with tumor necrosis factor alpha (TNFα) to stimulated PSR. Fluorescence labeled PS-containing liposomes (FITC-PS-Liposomes) were used. The PSR expression and the adhesion of liposomes were observed using fluorescence microscopy. Results: Normal brain tissue did not demonstrate PSR expression (Fig.1A). After brain injury, PSR expression was observed in the injured area and colocalized with the endothelium both in the MCAO (Fig.1B) and SAH animals (Fig.1C). Normal HUVEC did not demonstrate fluorescence (Fig.1D). Weak fluorescence was observed in normal cells that incorporated the PS-liposomes (Fig.1E). Strong fluorescence was observed in the TNFα-activated HUVEC that incorporated the FITC-PS-Liposomes (Fig.1F). Conclusions: This is first report that PSR expression occurs in cerebral microvascular endothelial cells in the early stages of stroke and can be recognized by PS-liposomes. This may allow development of a targeted liposomal carrier for novel targeted stroke treatment.
Patterns in the relationship between life expectancy and gross domestic product in Russia in 2005–15: a cross-sectional analysis
Authors: Vladimir M Shkolnikov, Evgeny M Andreev, Rustam Tursun-zade, David A Leon
Journal: The Lancet Public Health (2019)

BackgroundSince 2005, Russia has made substantial progress, experiencing an almost doubling of per-capita gross domestic product by purchasing power parity (GDP [PPP]) to US$24 800 and witnessing a 6-year increase in life expectancy, reaching 71·4 years by 2015. Even greater gains in GDP (PPP) were seen for Moscow, the Russian capital, reaching $43 000 in 2015 and with a life expectancy of 75·5 years. We aimed to investigate whether mortality levels now seen in Russia are consistent with what would be expected given this new level of per-capita wealth.MethodsWe used per-capita GDP (PPP) and life expectancy from 61 countries in 2014–15, plus those of Russia as a whole and its capital Moscow, to construct a Preston curve expressing the relationship between mortality and national wealth and to examine the positions of Russia and other populations relative to this curve. We adjusted life expectancy values for Moscow for underestimation of mortality at older ages. For comparison, we constructed another Preston curve based on the same set of countries for the year 2005. We used the stepwise replacement algorithm to decompose mortality differences between Russia or Moscow and comparator countries with similar incomes into age and cause-of-death components.FindingsLife expectancy in 2015 for both Russia and Moscow lay below the Preston-curve-based expectations by 6·5 years and 4·9 years, respectively. In 2015, Russia had a lower per-capita income than 36 of the comparator countries but lower life expectancy than 60 comparator countries. However, the gaps between the observed and the Preston-expected life expectancy values for Russia have diminished by about 25% since 2005, when the life expectancy gap was 8·9 years for Russia and 6·6 years for Moscow. When compared with countries with similar level of income, the largest part of the life expectancy deficit was produced by working-age mortality from external causes for Russia and cardiovascular disease at older ages for Moscow.InterpretationGiven the economic wealth of Russia, its life expectancy could be substantially higher. Sustaining the progress seen over the past decade depends on the ability of the Russian Government and society to devote adequate resources to people's health.FundingThis work was partly funded through the International Project on Cardiovascular Disease in Russia supported by a Wellcome Trust Strategic Award (100217) and was supported by the Russian Academic Excellence Project 5-100.
Dietary nicotine: Won't mislead on passive smoking. . .: New insight into myocardial protection
Authors: J L Repace, M J Jarvis
Journal: BMJ (1994)

Tuberculous pericarditis ED1TOR,-The case of tuberculous pericarditis presented by C P Clifford and G J Davies' contained a misleading characterisation of the findings on admission as classic tamponade.Kuss- maul's sign and an abnormal third heart sound are inconsistent with the physiology of classic tamponade.'Indeed, it is the virtual elimination of the rapid filling period necessary to produce a third heart sound that is a classic feature of tamponade.It is far more likely that this patient already had, under the tamponading fluid, an epicardial con- striction with its typically mixed picture; a pulsus paradoxus with a 20 mm Hg fall in blood pressure is unusual while a third heart sound and Kussmaul's sign are the rule in constriction.2Although acute tuberculous pericarditis can progress rapidly to acute or subacute constriction, this was not such a case.34Finally, I wish to argue against the term "peri- cardial knock."The abnormal early diastolic sound of constrictive pericarditis does not usually present an auscultatory knocking quality.More importantly, this description clouds concepts even if this form of the third heart sound did always "knock."The early diastolic sound of constrictive pericarditis is an especially early and often loud third heart sound with all necessary abnormal dynamics-accelerated early ventricular filling, with abrupt deceleration, into ventricles made abnormally stiffby pericardial scarring.'
The Role of Dietary Phytoestrogens and the Nuclear Receptor PPARγ in Adipogenesis: An <i>in Vitro</i> Study
Authors: Julie M. Hall, Heather R. Powell, Lara Rajic, Kenneth S. Korach
Journal: Environmental Health Perspectives (2019)

Background: Phytoestrogens, naturally occurring plant chemicals, have long been thought to confer beneficial effects on human cardiovascular and metabolic health. However, recent epidemiological studies, have yielded conflicting outcomes, in which phytoestrogen consumption was both positively and negatively correlated with adiposity. Interestingly, several dietary phytoestrogens are known to stimulate or inhibit the activity of the peroxisome proliferator-activated receptor gamma (PPARγ), a key physiological regulator of adipogenesis. Objective: The objective of this study was to test the hypothesis that the pro- or anti-adipogenic activity of phytoestrogen chemicals is related to the ability to activate PPARγ in adipocytes. Methods: The effects of resveratrol and the soy isoflavones genistein and daidzein on adipogenesis were examined in cell-based assays using the 3T3-L1 cell model. In parallel, ligand-mediated alterations in PPARγ target gene expression were measured by quantitative polymerase chain reaction. The agonist/antagonist activities of phytoestrogens on PPARγ were further assessed by quantifying their ability to affect recruitment of transcriptional cofactors to the receptor. Results: Resveratrol displayed significant anti-adipogenic activities as exhibited by the ability to antagonize PPARγ-dependent adipocyte differentiation, down-regulate genes involved in lipid metabolism, block cofactor recruitment to PPARγ, and antagonize the effects of the PPARγ agonist rosiglitazone. In contrast, genistein and daidzein functioned as PPARγ agonists while also displaying pro-adipogenic activities. Conclusions: These data provide biological evidence that the pro- or anti-obesity effects of phytoestrogens are related to their relative agonist/antagonist activity on PPARγ. Thus, PPARγ-activation assays may enable the screening of dietary components and identification of agents with adipogenic activities. https://doi.org/10.1289/EHP3444
Schnitzler 综合征与 CCL2
Authors: K. Krause, R. Sabat, E. Witte‐Händel, A. Schulze, V. Puhl, M. Maurer, K. Wolk
Journal: British Journal of Dermatology (2019)

Schnitzler 综合征是一种非常罕见的慢性病,通常在后半生发生。它表现为皮疹、肌肉/骨骼疼痛和发热。此病的触发因素和分子过程尚不清楚。但是,发现抑制名为白介素‐1ß 炎症分子的药物可缓解此病。这项德国研究的作者想知道是否还有其他分子与 Schnitzler 综合征有关。为此,在患者血液中定量分析了一系列有炎症性质的分子,作为比较,还在健康人和其他炎症疾病患者中进行了此定量分析。发现 Schnitzler 综合征患者的 CCL2 水平明显增高,CCL2 是一种已知会把炎症细胞吸引到受影响组织附近并在骨变化中发挥特殊作用的分子。在被严重影响的患者中(尤其是在有剧烈骨痛的患者中),CCL2 的水平尤其高。在骨骼中,已知 CCL2 由某些骨骼修饰细胞生成。实验室试验显示,免疫细胞和结缔组织细胞(纤维母细胞)也大量生成 CCL2。白介素‐1ß 以及炎症分子 TNF‐α 触发这些细胞生成 CCL2。当用白介素‐1ß‐阻滞药物治疗这些患者时,健康状况得到改善,同时 CCL2 水平下降。作者们得出结论称,在 Schnitzler 综合征中,CCL2 是骨骼和其他身体部位炎症过程中的重要一员,可在临床中作为一个疾病严重程度指标。