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101.
102.
Histopathological evaluation including subtyping and grading is the current cornerstone for endometrial cancer (EC) classification. This provides clinicians with prognostic information and input for further treatment recommendations. Nonetheless, patients with histologically similar ECs may have very different outcomes, notably in patients with high-grade endometrial carcinomas. For endometrial cancer, four molecular subgroups have undergone extensive studies in recent years: POLE ultramutated (POLEmut), mismatch repair-deficient (MMRd), p53 mutant (p53abn) and those EC lacking any of these alterations, referred to as NSMP (non-specific molecular profile). Several large studies confirm the prognostic relevance of these molecular subgroups. However, this ‘histomolecular’ approach has so far not been implemented in clinical routine. The ongoing PORTEC4a trial is the first clinical setting in which the added value of integrating molecular parameters in adjuvant treatment decisions will be determined. For diagnostics, the incorporation of the molecular parameters in EC classification will add a level of objectivity which will yield biologically more homogeneous subclasses. Here we illustrate how the management of individual EC patients may be impacted when applying the molecular EC classification. We describe our current approach to the integrated diagnoses of EC with a focus on scenarios with conflicting morphological and molecular findings. We also address several pitfalls accompanying the diagnostic implementation of molecular EC classification and give practical suggestions for diagnostic scenarios. 相似文献
103.
Sonia D'Souza Hironobu Murata Moncy V. Jose Sholpan Askarova Yuliya Yantsen Jill D. Andersen Collin D.J. Edington William P. Clafshenkel Richard R. Koepsel Alan J. Russell 《Biomaterials》2014
The field of polymer-based membrane engineering has expanded since we first demonstrated the reaction of N-hydroxysuccinimide ester-terminated polymers with cells and tissues almost two decades ago. One remaining obstacle, especially for conjugation of polymers to cells, has been that exquisite control over polymer structure and functionality has not been used to influence the behavior of cells. Herein, we describe a multifunctional atom transfer radical polymerization initiator and its use to synthesize water-soluble polymers that are modified with bisphosphonate side chains and then covalently bound to the surface of live cells. The polymers contained between 1.7 and 3.1 bisphosphonates per chain and were shown to bind to hydroxyapatite crystals with kinetics similar to free bisphosphonate binding. We engineered the membranes of both HL-60 cells and mesenchymal stem cells in order to impart polymer-guided bone adhesion properties on the cells. Covalent coupling of the polymer to the non-adherent HL-60 cell line or mesenchymal stem cells was non-toxic by proliferation assays and enhanced the binding of these cells to bone. 相似文献
104.
Collin Jacobs Christian Walter Thomas Ziebart Sarah Grimm Dan Meila Elena Krieger Heinrich Wehrbein 《Clinical oral investigations》2014,18(3):901-908
Objectives
Mechanical loading is a potential activator of inflammation and able to stimulate factors for periodontal and alveolar bone destruction. Aim of this study was to investigate the inflammatory response and synthesis of proteinases by human periodontal ligament fibroblast (HPdLF) dependent on different strengths of static tensile strain (STS).Materials and methods
HPdLFs were loaded with different STS strengths (1, 5, and 10 %) in vitro. Gene expressions of cyclooxygenase (COX)-2 and interleukin (IL)-6 were analyzed by quantitative real-time polymerase chain reaction. Production of IL-6, prostaglandin E2 (PGE2), matrix metalloproteinase (MMP)-8, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were measured by enzyme-linked immunosorbent assay. Receptor activator of nuclear factor-kappa ligand (RANKL) synthesis was detected by immunocytochemical staining.Results
Ten percent STS led to an increased gene expression of IL-6 and COX-2 (34.4-fold) in HPdLF, and 1 and 5 % STS slightly reduced the gene expression of IL-6. Synthesis of IL-6 was significantly reduced by 1 % STS and stimulated by 10 % STS. Ten percent STS significantly induced PGE2 production. RANKL was not detectable at any strength of STS. MMP-8 synthesis showed significantly higher values only at 10 % STS, but TIMP-1 was stimulated by 5 and 10 % STS, resulting into highest TIMP-1/MMP-8 ratio at 5 % STS.Conclusions
High-strength STS is a potent inducer of periodontal inflammation and MMP-8, whereas low-strength STS shows an anti-inflammatory effect. Moderate-strength STS causes the highest TIMP-1/MMP-8 ratio, leading to appropriate conditions for reformation of the extracellular matrix.Clinical relevance
Furthermore, this study points out that the strength of force plays a pivotal role to achieve orthodontic tooth movement without inducing periodontal inflammation and to activate extracellular matrix regeneration. 相似文献105.
Karelis AD St-Pierre DH Conus F Rabasa-Lhoret R Poehlman ET 《The Journal of clinical endocrinology and metabolism》2004,89(6):2569-2575
Obesity is thought to be a heterogeneous disorder with several possible etiologies; therefore, by examining subtypes of obesity we attempt to understand obesity's heterogeneous nature. The purpose of this review was to investigate the roles of metabolic, body composition, and cardiovascular disease risk in subtypes of obesity. We briefly consider two subtypes of obesity that have been identified in the literature. One subset of individuals, termed the metabolically healthy, but obese (MHO), despite having large amounts of fat mass compared with at risk obese individuals shows a normal metabolic profile, but remarkably normal to high levels of insulin sensitivity. Preliminary evidence suggests that this could be due at least in part to lower visceral fat levels and earlier onset of obesity. A second subset, termed the metabolically obese, but normal weight (MONW), present with normal body mass index, but have significant risk factors for diabetes, metabolic syndrome, and cardiovascular disease, which could be due to higher fat mass and plasma triglycerides as well as higher visceral fat and liver content. We also briefly consider the potential role of adipose and gastrointestinal hormonal profiles in MHO and MONW individuals, which could lead to a better understanding of potential factors that may regulate their body composition. This information will eventually be invaluable in helping us understand factors that predispose to or protect obese individuals from metabolic and cardiovascular disease. Collectively, a greater understanding of the MHO and MONW individual has important implications for therapeutic decision making, the characterization of subjects in research protocols, and medical education. 相似文献
106.
Simon M Collin Rebecca F Baggaley Rudiger Pittrof Veronique Filippi 《BMC pregnancy and childbirth》2007,7(1):1-9
Background
For women who have a caesarean section in their preceding pregnancy, two care policies for birth are considered standard: planned vaginal birth and planned elective repeat caesarean. Currently available information about the benefits and harms of both forms of care are derived from retrospective and prospective cohort studies. There have been no randomised trials, and recognising the deficiencies in the literature, there have been calls for methodologically rigorous studies to assess maternal and infant health outcomes associated with both care policies. The aims of our study are to assess in women with a previous caesarean birth, who are eligible in the subsequent pregnancy for a vaginal birth, whether a policy of planned vaginal birth after caesarean compared with a policy of planned repeat caesarean affects the risk of serious complications for the woman and her infant.Methods/Design
Design: Multicentred patient preference study and a randomised clinical trial. Inclusion Criteria: Women with a single prior caesarean presenting in their next pregnancy with a single, live fetus in cephalic presentation, who have reached 37 weeks gestation, and who do not have a contraindication to a planned VBAC. Trial Entry & Randomisation: Eligible women will be given an information sheet during pregnancy, and will be recruited to the study from 37 weeks gestation after an obstetrician has confirmed eligibility for a planned vaginal birth. Written informed consent will be obtained. Women who consent to the patient preference study will be allocated their preference for either planned VBAC or planned, elective repeat caesarean. Women who consent to the randomised trial will be randomly allocated to either the planned vaginal birth after caesarean or planned elective repeat caesarean group. Treatment Groups: Women in the planned vaginal birth group will await spontaneous onset of labour whilst appropriate. Women in the elective repeat caesarean group will have this scheduled for between 38 and 40 weeks. Primary Study Outcome: Serious adverse infant outcome (death or serious morbidity). Sample Size: 2314 women in the patient preference study to show a difference in adverse neonatal outcome from 1.6% to 3.6% (p = 0.05, 80% power).Clinical Trial Registration
ISCTRN5397431 相似文献107.
Han S. Lim Mélèze Hocini Remi Dubois Arnaud Denis Nicolas Derval Stephan Zellerhoff Seigo Yamashita Benjamin Berte Saagar Mahida Yuki Komatsu Matthew Daly Laurence Jesel Carole Pomier Valentin Meillet Sana Amraoui Ashok J. Shah Hubert Cochet Frédéric Sacher Michel Haïssaguerre 《Journal of the American College of Cardiology》2017,69(10):1257-1269
Background
The underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood.Objectives
This study sought to investigate the complexity and distribution of AF drivers in PsAF of varying durations.Methods
Of 135 consecutive patients with PsAF, 105 patients referred for de novo ablation of PsAF were prospectively recruited. Patients were divided into 3 groups according to AF duration: PsAF presenting in sinus rhythm (AF induced), PsAF <12 months, and PsAF >12 months. Patients wore a 252-electrode vest for body surface mapping. Localized drivers (re-entrant or focal) were identified using phase-mapping algorithms.Results
In this patient cohort, the most prominent re-entrant driver regions included the pulmonary vein (PV) regions and inferoposterior left atrial wall. Focal drivers were observed in 1 or both PV regions in 75% of patients. Comparing between the 3 groups, with longer AF duration AF complexity increased, reflected by increased number of re-entrant rotations (p < 0.05), number of re-entrant rotations and focal events (p < 0.05), and number of regions harboring re-entrant (p < 0.01) and focal (p < 0.05) drivers. With increased AF duration, a higher proportion of patients had multiple extra-PV driver regions, specifically in the inferoposterior left atrium (p < 0.01), superior right atrium (p < 0.05), and inferior right atrium (p < 0.05). Procedural AF termination was achieved in 70% of patients, but decreased with longer AF duration.Conclusions
The complexity of AF drivers increases with prolonged AF duration. Re-entrant and focal drivers are predominantly located in the PV antral and adjacent regions. However, with longer AF duration, multiple drivers are distributed at extra-PV sites. AF termination rate declines as patients progress to longstanding PsAF, underscoring the importance of early intervention. 相似文献108.
Coronary computed tomography angiography (CTA) is a highly accurate noninvasive test that is increasingly used in symptomatic patients primarily for the diagnosis of coronary artery disease (CAD). Beyond its proven accuracy, data have now clearly demonstrated the incremental prognostic information available from coronary CTA related to the presence, extent, and severity of obstructive and nonobstructive CAD across a variety of clinical settings and patient populations. Current evidence supports the use of coronary CTA not only for the diagnosis of CAD in appropriately selected symptomatic patients but also to further refine their cardiovascular risk assessment following testing. 相似文献
109.
Tatsuhiko Urakami Kei Yoshida Remi Kuwabara Yusuke Mine Masako Aoki Junichi Suzuki Ichiro Morioka 《Journal of diabetes investigation.》2022,13(1):185
Aims/IntroductionWe examined the impact of scanning frequency with flash glucose monitoring on glycemic control in children and adolescents with type 1 diabetes.Materials and MethodsThe study included 85 patients, aged 14.0 ± 0.5 years, with type 1 diabetes. The median time in the target glucose range (TIR) and glycosylated hemoglobin (HbA1c) values were 50.0 ± 1.4% and 7.5 ± 0.1%, respectively.ResultsThe median scanning frequency using flash glucose monitoring was 12.0 ± 0.4 times/day. Scanning frequency showed a significant positive correlation with TIR and an inverse correlation with HbA1c. Scanning frequency was identified to be the determinant of TIR and HbA1c by using multivariate analysis. The participants whose scanning frequency was <12 times/day were categorized as the low‐frequency group (n = 40), and those who carried out the scanning >12 times/day were categorized as the high‐frequency group (n = 45). Patients in the high‐frequency group were more likely to be treated with insulin pumps compared with those in the low‐frequency group; however, this difference was not significant (21.3 vs 5.3%, P = 0.073). The high‐frequency group showed significantly greater TIR than the low‐frequency group (57 ± 1.6 vs 42 ± 1.7%, P = 0.002). Furthermore, the high‐frequency group showed significantly lower HbA1c levels than the low‐frequency group (6.8 ± 0.1 vs 8.0 ± 0.1%, P < 0.001).ConclusionsThese findings showed that patients with a higher scanning frequency had better glycemic control, with greater TIRs and lower HbA1c levels, compared with those with a lower scanning frequency. Scanning frequency of >12 times/day might contribute to better glycemic outcomes in real‐world practice in children with type 1 diabetes. 相似文献
110.