tbuckley/cabot-search huggingface dataset:
High Failure Rate After Valve-sparing Aortic Root Replacement Using the “Remodeling Technique” in Acute Type A Aortic Dissection
Authors: Rainer G. Leyh, Stefan Fischer, Klaus Kallenbach, Theo Kofidis, Klaus Pethig, Wolfgang Harringer, Axel Haverich
Journal: Circulation (2002)

Background Valve-sparing surgery including the replacement of the sinus of valsalvae were initially meant to be promising approaches in the treatment of acute type A aortic dissection. However, the long-term outcome after valve-sparing aortic root replacement in acute type A dissection is currently the subject of intense debate, and the evidence reported in the literature is sparse. Here we report on our experience on valve sparing aortic root replacement inpatients with acute type A dissection. Methods From August 1995 to November 2000, 30 patients with acute type A dissection received valve-sparing aortic root replacement. Two different techniques were performed: the “remodeling” technique, first described by Yacoub in 1983 (8 patients) and the “reimplantation” technique, initially described by David and Feindel, in 1992 (22 patients). Endpoints of the study were early and late mortality, as well as aortic valve-related complications and reoperations. Results The mean follow-up time was 22.6±15.4 months. The overall 30 day mortality was 17% (5/29) and the late mortality 4% (1/24). During the observation period, 4 patients had to be reoperated (n=3) for acute aortic valve regurgitation after aortic root remodeling and for acute aortic valve endocarditis (n=1) after aortic root reimplantation. In the 3 patients with acute aortic valve regurgitation, symptoms occurred 44, 24, and 17 months after the initial operation in these patients. Intraoperatively prolapsing aortic leaflets because of commissural detachment was found in all 3 cases. In all other patients the latest echocardiographic follow-up examination revealed freedom from aortic regugitation higher than grade 1. Conclusions The high failure rate of aortic root remodeling inpatients with acute type A aortic dissection is discouraging. Whether this technique should be applied in acute type A aortic dissection is questionable. In contrast, aortic root reimplantation lead to favorable midterm outcome. Thus, we recommend consideration of this technique for surgical treatment of patients with acute type A aortic dissection.
Toll-like receptors in rheumatoid arthritis joint destruction mediated by two distinct pathways
Authors: C Ospelt
Journal: Annals of the Rheumatic Diseases (2004)

ovel therapies, in particular biological agents, have resulted in major breakthroughs in the treatment of rheumatoid arthritis (RA). However, none of the new and promising biologicals has resulted in an American College of Rheumatology (ACR) 70 above 50%, and none of them has shown sustained benefit after termination of therapy. These results are based on the fact that all these agents target the inflammatory cells in the joint, including macrophages, T and B lymphocytes, or vascular endothelium but not the activated synovial fibroblasts. RA synovial fibroblasts (RA-SFs) have to be considered key cells in joint destruction since they differ in their morphology and their biological behaviour from normal synoviocytes and, most importantly, show invasive growth into adjacent tissue. We have shown that RA-SFs maintain their activated phenotype independently of inflammatory cells and cytokines, considering that they invade human cartilage in the severe combined immunodeficiency (SCID) mouse model even in the absence of cytokine producing macrophages and T and B cells. 1
Pharmacokinetics of Insulin Aspart in Pump-Treated Subjects With Type 1 Diabetes: Reproducibility and Effect of Age, Weight, and Duration of Diabetes
Authors: Ahmad Haidar, Daniela Elleri, Kavita Kumareswaran, Lalantha Leelarathna, Janet M. Allen, Karen Caldwell, Helen R. Murphy, Malgorzata E. Wilinska, Carlo L. Acerini, Mark L. Evans, David B. Dunger, Marianna Nodale, Roman Hovorka
Journal: Diabetes Care (2013)

Insulin aspart, lispro, or glulisine are recommended in pump-treated type 1 diabetes (T1D). Aspart pharmacokinetics has been studied (1), but little is known about its reproducibility and associations with anthropometric and clinical factors.

We analyzed retrospectively data collected in 70 pump-treated subjects with T1D, comprising 39 females, 46 young, with mean (SD) BMI 22.7 (4.2) kg/m2, A1C 8.1% (1.3) (65.3 [14.4] mmol/mol), and total daily insulin 0.8 (0.3) units/kg/day, who were undergoing investigations, with ethical approval, of closed-loop insulin delivery. Participants/guardians signed consent/assent as appropriate. Participants were admitted twice to the research facility, 1–6 weeks apart, for 15–37 h, and consumed 1–4 meals accompanied by prandial insulin aspart. Basal aspart was delivered using closed-loop insulin delivery or conventional pump therapy. Venous blood samples were collected every 30–60 min to measure plasma insulin (Invitron, Monmouth, U.K.).

From 5,804 plasma insulin measurements, we estimated, using a two-compartment model, the time-to-peak plasma insulin concentration ( t max [min]), the metabolic clearance rate of insulin (MCR in mL/kg/min), and the background residual plasma insulin concentration (mU/L). Results are …
Role of beta‐blockers in patients admitted for worsening heart failure in a real world setting: data from the Italian Survey on Acute Heart Failure†
Authors: Francesco Orso, Samuele Baldasseroni, Gianna Fabbri, Lucio Gonzini, Donata Lucci, Ciro D'Ambrosi, Milva Gobbi, Gabriella Lecchi, Silvia Randazzo, Giulio Masotti, Luigi Tavazzi, Aldo Pietro Maggioni
Journal: European Journal of Heart Failure (2009)
Morphology of Exertion-Triggered Plaque Rupture in Patients With Acute Coronary Syndrome
Authors: Atsushi Tanaka, Toshio Imanishi, Hironori Kitabata, Takashi Kubo, Shigeho Takarada, Takashi Tanimoto, Akio Kuroi, Hiroto Tsujioka, Hideyuki Ikejima, Satoshi Ueno, Hideaki Kataiwa, Keishi Okouchi, Manabu Kashiwaghi, Hiroki Matsumoto, Kazushi Takemoto, Nobuo Nakamura, Kumiko Hirata, Masato Mizukoshi, Takashi Akasaka
Journal: Circulation (2008)

Background— Plaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). One pathological study suggested that the morphologies of plaque rupture differed between rest-onset and exertion-triggered rupture in men who experienced sudden death. The aim of the present study was to use optical coherence tomography to investigate the relationship in patients with ACS between the morphology of a ruptured plaque and the patient’s activity at the onset of ACS. Methods and Results— The study population was drawn from 43 consecutive ACS patients (with or without ST-segment elevation) who underwent optical coherence tomography and presented with a ruptured plaque at the culprit site. Patients were divided into a rest group and an exertion group on the basis of their activities at the onset of ACS. The thickness of the broken fibrous cap correlated positively with activity at the onset of ACS. The culprit plaque ruptured at the shoulder more frequently in the exertion group than in the rest group (rest 57% versus exertion 93%, P =0.014). The thickness of the broken fibrous cap in the exertion group was significantly higher than in the rest-onset group (rest onset: 50 μm [interquartile median 15 μm]; exertion: 90 μm [interquartile median 65 μm], P &lt;0.01). Conclusions— The morphologies of exertion-triggered and rest-onset ruptured plaques differ in ACS patients. Our data suggest that a thin-cap fibroatheroma is a lesion predisposed to rupture both at rest and during the patient’s day-to day activity, and some plaque rupture may occur in thick fibrous caps depending on exertion levels.
Cancer-Selective Targeting of the NF-κB Survival Pathway with GADD45β/MKK7 Inhibitors
Authors: Laura Tornatore, Annamaria Sandomenico, Domenico Raimondo, Caroline Low, Alberto Rocci, Cathy Tralau-Stewart, Daria Capece, Daniel D’Andrea, Marco Bua, Eileen Boyle, Mark van Duin, Pietro Zoppoli, Albert Jaxa-Chamiec, Anil K. Thotakura, Julian Dyson, Brian A. Walker, Antonio Leonardi, Angela Chambery, Christoph Driessen, Pieter Sonneveld, Gareth Morgan, Antonio Palumbo, Anna Tramontano, Amin Rahemtulla, Menotti Ruvo, Guido Franzoso
Journal: Cancer Cell (2014)

Constitutive NF-κB signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-κB-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45β/MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates myeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-κB pathway is possible and, at least for myeloma patients, promises a profound benefit.
De Novo Assembly of the Manila Clam Ruditapes philippinarum Transcriptome Provides New Insights into Expression Bias, Mitochondrial Doubly Uniparental Inheritance and Sex Determination
Authors: F. Ghiselli, L. Milani, P. L. Chang, D. Hedgecock, J. P. Davis, S. V. Nuzhdin, M. Passamonti
Journal: Molecular Biology and Evolution (2011)

Males and females share the same genome, thus, phenotypic divergence requires differential gene expression and sex-specific regulation. Accordingly, the analysis of expression patterns is pivotal to the understanding of sex determination mechanisms. Many bivalves are stable gonochoric species, but the mechanism of gonad sexualization and the genes involved are still unknown. Moreover, during the period of sexual rest, a gonad is not present and sex cannot be determined. A mechanism associated with germ line differentiation in some bivalves, including the Manila clam Ruditapes philippinarum, is the doubly uniparental inheritance (DUI) of mitochondria, a variation of strict maternal inheritance. Two mitochondrial lineages are present, one transmitted through eggs and the other through sperm, as well as a mother-dependent sex bias of the progeny. We produced a de novo annotation of 17,186 transcripts from R. philippinarum and compared the transcriptomes of males and females and identified 1,575 genes with strong sex-specific expression and 166 sex-specific single nucleotide polymorphisms, obtaining preliminary information about genes that could be involved in sex determination. Then we compared the transcriptomes between a family producing predominantly females and a family producing predominantly males to identify candidate genes involved in regulation of sex-specific aspects of DUI system, finding a relationship between sex bias and differential expression of several ubiquitination genes. In mammalian embryos, sperm mitochondria are degraded by ubiquitination. A modification of this mechanism is hypothesized to be responsible for the retention of sperm mitochondria in male embryos of DUI species. Ubiquitination can additionally regulate gene expression, playing a role in sex determination of several animals. These data enable us to develop a model that incorporates both the DUI literature and our new findings.
Improving the care of elderly people.
Authors: M. J. Bendall
Journal: BMJ (1992)

maintaining a national network of perhaps half a dozen large milk banks.In 1949 Findlay Ford, a Glasgow paediatrician, wrote, "When breast milk can be obtained from the milk bank it is expensive in money and when the bank is part of a hospital activity it is expensive in nurses' time.It is therefore essential to find out if this is really so advantageous as to justify the financial outlay and the use of valuable nursing hours in collecting and processing it."'7More than 40 years on we still don't have the final answer.
Multimodal treatment with primary single-agent epirubicin in operable breast cancer: 5-year experience of the Michelangelo Cooperative Group
Authors: G. Bonadonna, M. Zambetti, C. Bumma, M. Donadio, A. Bolognesi, G. Robustelli della Cuna, G. Ambrosini, G. Lelli, M. Mansutti, P. Verderio, P. Valagussa
Journal: Annals of Oncology (2002)
Association Between Skilled Nursing Facility Quality Indicators and Hospital Readmissions
Authors: Mark D. Neuman, Christopher Wirtalla, Rachel M. Werner
Journal: JAMA (2014)

Hospital readmissions are common, costly, and potentially preventable. Little is known about the association between available skilled nursing facility (SNF) performance measures and the risk of hospital readmission.To measure the association between SNF performance measures and hospital readmissions among Medicare beneficiaries receiving postacute care at SNFs in the United States.Using national Medicare data on fee-for-service Medicare beneficiaries discharged to a SNF after an acute care hospitalization between September 1, 2009, and August 31, 2010, we examined the association between SNF performance on publicly available metrics (SNF staffing intensity, health deficiencies identified through site inspections, and the percentages of SNF patients with delirium, moderate to severe pain, and new or worsening pressure ulcers) and the risk of readmission or death 30 days after discharge to a SNF. Adjusted analyses controlled for patient case mix, SNF facility factors, and the discharging hospital.Readmission to an acute care hospital or death within 30 days of the index hospital discharge.Of 1,530,824 patients discharged, 357,752 (23.3%; 99% CI, 23.3%-23.5%) were readmitted or died within 30 days; 72,472 died within 30 days (4.7%; 99% CI, 4.7%-4.8%), and 321,709 were readmitted (21.0%; 99% CI, 20.9%-21.1%). The unadjusted risk of readmission or death was lower at SNFs with better staffing ratings. SNFs ranked lowest (19.2% of all SNFs) had a 30-day risk of readmission or death of 25.5% (99% CI, 25.3%-25.8%) vs 19.8% (99% CI, 19.5%-20.1%) among those ranked highest. SNFs with better facility inspection ratings also had a lower risk of readmission or death. SNFs ranked lowest (20.1% of all SNFs) had a risk of 24.9% (99% CI, 24.7%-25.1%) vs 21.5% (99% CI, 21.2%-21.7%) among those ranked highest . Adjustment for patient factors, SNF facility factors, and the discharging hospital attenuated these associations; we observed small differences in the adjusted risk of readmission or death according to SNF facility inspection ratings (lowest vs highest rating: 23.7%; 99% CI: 23.7%, 23.7%; vs 23.0%; 99% CI: 23.0%, 23.1%). Other measures did not predict clinically meaningful differences in the adjusted risk of readmission or death.Among fee-for-service Medicare beneficiaries discharged to a SNF after an acute care hospitalization, available performance measures were not consistently associated with differences in the adjusted risk of readmission or death.
Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells
Authors: Dorothee Viemann, Anke Strey, Annette Janning, Kerstin Jurk, Kerstin Klimmek, Thomas Vogl, Keiichi Hirono, Fukiko Ichida, Dirk Foell, Beate Kehrel, Volker Gerke, Clemens Sorg, Johannes Roth
Journal: Blood (2004)
Scar classification in cutaneous lupus erythematosus: morphological description
Authors: K. Al-Refu, M. Goodfield
Journal: British Journal of Dermatology (2009)

Scarring represents the single most debilitating aspect of discoid lupus erythematosus (DLE) in patients with cutaneous lesions alone. Despite this, there have been no studies which have attempted to classify the types of scars seen in this chronic disease.The aim was to classify the types of scars based on morphological description.Forty-five patients with histologically confirmed DLE were included in the study. In the assessment of the types of scars, the scars were scored initially according to their anatomical localization. Each anatomical area was assessed for the types of scars which occurred in these areas.Scars in patients with DLE were initially classified morphologically into six types according to the site of the scar and then each type was classified into subtypes according to the morphology of the scar. Scars were seen in the majority of the patients and scarring affected mostly areas including the scalp, other hairy areas such as the eyebrows, nonhairy areas, mucosa, fatty layers of the skin and the nails. This study demonstrated that scars may not only produce textural changes but may also produce pigmentary changes. It is possible that other types of scars may yet occur in DLE but have not so far been detected.Early classification and identification of the types of scars in these patients may change management towards more aggressive therapy in those with continued disease activity, and it is possible that different types of scarring require different therapies.
Constrained by cadherins
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Natural killer (NK) cells get turned off by cadherins, according to a study on page 289. Ito and colleagues identify E-cadherin as a binding partner for the once-orphan inhibitory NK cell receptor KLRG1.






Figure 1

NK cell inhibitory receptor KLRG1 (blue) binds to cadherins (purple) on target cells.




NK cells must integrate both positive and negative signals—delivered by a variety of activating and inhibitory receptors on their cell surface—to determine whether a target cell should be attacked. Many NK cell inhibitory receptors, including Ly49 receptors (mice) and killer cell immunoglobulin-like receptors (humans), bind to MHC class I molecules on target cells. This allows NK cells to distinguish between normal cells, which express class I molecules, and abnormal cells, which often lack these proteins due to transformation or viral infection. The binding partners for other inhibitory receptors, including KLRG1, had not been identified.

Ito and colleagues now show that KLRG1 pairs up with cadherins (E-, N- and R-cadherin)—adhesion molecules that help form junctions between epithelial and endothelial cells. When the pairing of NK cells and target cells occurs via cadherins, they show, NK cell-mediated killing is inhibited.

Why would NK cells express receptors for adhesion proteins that are normally concealed in cell–cell junctions? One possibility is to promote surveillance of improperly detached cells. These cells, including many tumor cells, have reduced E-cadherin expression, allowing them to sever ties with adjacent cells. But without E-cadherin, tumor cells can no longer send inhibitory signals through KLRG1, possibly making them more prone to NK cell attack.
Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life
Authors: I J Hickman
Journal: Gut (2004)

<b>Background and aim:</b> Obesity is a risk factor for progression of fibrosis in chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C. The aim of this study was to investigate the longer term effect of weight loss on liver biochemistry, serum insulin levels, and quality of life in overweight patients with liver disease and the effect of subsequent weight maintenance or regain. <b>Patients:</b> Thirty one patients completed a 15 month diet and exercise intervention. <b>Results:</b> On completion of the intervention, 21 patients (68%) had achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body weight. Improvements in serum alanine aminotransferase (ALT) levels were correlated with the amount of weight loss (<i>r</i> = 0.35, p = 0.04). In patients who maintained weight loss, mean ALT levels at 15 months remained significantly lower than values at enrolment (p = 0.004), while in regainers (n = 10), mean ALT levels at 15 months were no different to values at enrolment (p = 0.79). Improvements in fasting serum insulin levels were also correlated with weight loss (<i>r</i> = 0.46, p = 0.04), and subsequent weight maintenance sustained this improvement. Quality of life was significantly improved after weight loss. Weight maintainers sustained recommended levels of physical activity and had higher fasting insulin levels (p = 0.03) at enrolment than weight regainers. <b>Conclusion:</b> In summary, these findings demonstrate that maintenance of weight loss and exercise in overweight patients with liver disease results in a sustained improvement in liver enzymes, serum insulin levels, and quality of life. Treatment of overweight patients should form an important component of the management of those with chronic liver disease.
Chromosomal Instability in Microsatellite-Unstable and Stable Colon Cancer
Authors: Karolin Trautmann, Jonathan P. Terdiman, Amy J. French, Ritu Roydasgupta, Nancy Sein, Sanjay Kakar, Jane Fridlyand, Antoine M. Snijders, Donna G. Albertson, Stephen N. Thibodeau, Frederic M. Waldman
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors. Experimental Design: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones. Results: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P = 0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization. Conclusion: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.