Background
Gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification ...provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki‐67 cutoff values in GEP‐NENs.
Subjects, Materials, and Methods
A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors well differentiated) or NECs (neuroendocrine carcinomas poorly differentiated), and by Ki‐67 index as G1 (Ki‐67 <2%), G2 (Ki‐67 3%–20%), or G3 (Ki‐67 >20%). Patients were stratified into five cohorts: NET‐G1, NET‐G2, NET‐G3, NEC‐G2, and NEC‐G3.
Results
Five‐year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5‐year survival: 81% Ki‐67 3%–5%, 72% Ki‐67 6%–10%, 52% Ki‐67 11%–20%) and G3 NENs (5‐year survival: 35% Ki‐67 21%–50%, 22% Ki‐67 51%–100%). Five‐year survival was significantly greater for NET‐G2 versus NEC‐G2 (75.5% vs. 58.2%) and NET‐G3 versus NEC‐G3 (43.7% vs. 25.4%).
Conclusion
Substantial clinical heterogeneity is observed within G2 and G3 GEP‐NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index.
Implications for Practice
Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real‐world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.
This article evaluates the prognostic impact of histological differentiation within the WHO 2010 grading classifications and explores additional Ki‐67 cut‐off values for gastroenteropancreatic neuroendocrine neoplasms.
The implementation of the Ecosystem Services (ES) framework (including supply and demand) should be based on accurate spatial assessments to make it useful for land planning or environmental ...management. Despite the inherent dependence of ES assessments on the spatial resolution at which they are conducted, the studies analyzing these effects on ES supply and their relationships are still scarce. To study the influence of the spatial level of analysis on ES patterns and on the relationships among different ES, we selected seven indicators representing ES supply and three variables that describe forest cover and biodiversity for Catalonia (NE Iberian Peninsula). These indicators were estimated at three different scales: local, municipality and county. Our results showed differences in the ES patterns among the levels of analysis. The higher levels (municipality/county) removed part of the local heterogeneity of the patterns observed at the local scale, particularly for ES indicators characterized by a finely grained, scattered distribution. The relationships between ES indicators were generally similar at the three levels. However, some negative relationships (potential trade-offs) that were detected at the local level changed to positive (and significant) relationships at municipality and county. Spatial autocorrelation showed similarities between patterns at local and municipality levels, but differences with county level. We conclude that the use of high-resolution spatial data is preferable whenever available, in particular when identifying hotspots or trade-offs/synergies is of primary interest. When the main objective is describing broad patterns of ES, intermediate levels (e.g., municipality) are also adequate, as they conserve many of the properties of assessments conducted at finer scales, allowing the integration of data sources and, usually, being more directly relevant for policy-making. In conclusion, our results warn against the uncritical use of coarse (aggregated) spatial ES data and indicators in strategies for land use planning and forest conservation.
Display omitted
•Scale is a relevant aspect in the analysis and of Ecosystem Services (ES).•The effects of the spatial level of analysis on 7 ES indicators were assessed.•ES Indicators were estimated at local (1 km2), municipality and county levels.•Averaging effects at higher spatial levels obscured local ES heterogeneity patterns.•Identification of hotspots and ES relationships depend on the level of analysis.
We have applied the analytic model of general triclinic transpression with oblique extrusion to an active shear zone in southeastern Spain. This study opens a new methodological approach in the study ...of active fault zones. We are able to constrain the triclinic transpression model with absolute measures of active deformation, such as GPS velocity gradients, and have exhaustively explored the predictions of the model and compared them to the orientation data of field kinematic markers (fault-slip data and reorientation of fold hinges during progressive deformation), GPS data and the kinematic study of the fault gouge that is developed at the Alhama de Murcia Fault. The combined analysis allows the values of the kinematic vorticity number, the orientation of the vorticity vector, the orientation of the local and regional convergence vectors, the angle of extrusion in the shear zone and the amount of extrusion to be constrained. The results point to a highly partitioned heterogeneous shear zone with domains deforming in response to the same boundary conditions but are displaying different kinematic responses that reflect both their intrinsic properties and geometric effects related to competency contrasts. We propose that the Alhama de Murcia Fault is an incompletely coupled fault zone with two different domains: a low competency domain comprising the fault gouge, ductilely deformed, with low vorticity values, which probably experienced a steady-state, aseismic slip that reflects regional convergence vectors (convergence Eurasia–Nubia); and a domain outside of the fault gouge with episodic brittle failure, with higher vorticity values and showing convergence vectors which are parallel to the local convergence vectors calculated from the GPS velocity field.
•Test of the analytic model of triclinic transpression with oblique extrusion with absolute data of active deformation.•Fault gouge, slickensides and fold hinges helped to constrain vorticity values and extrusion direction in an active shear.•The Alhama de Murcia Fault is a transpressional deformation zone with different deformation domains.•The fault gouge flow is dominated by the coaxial component consistent with Eurasia-Nubia convergence vector.•The folds and slickensides data indicates higher vorticity number consistent with local convergence vector.
Almost all the information about the effect of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnoea (OSA) comes from clinical trials involving only middle-aged ...patients. The objective of this study was to assess the effect of CPAP treatment in elderly patients with severe OSA on clinical, quality-of-life and neurocognitive spheres. We performed an open-label, randomised, multicentre clinical trial in a consecutive clinical cohort of 224 elderly (≥70 years old) patients with confirmed severe OSA (apnoea-hypopnea index ≥30) randomised to receive CPAP (n=115) or no CPAP (n=109) for 3 months. A sleep study was performed by either full polysomnography or respiratory polygraphy. CPAP titration was performed by an autoCPAP device. The primary endpoint was quality of life (Quebec Sleep Questionnaire) and secondary endpoints included sleep-related symptoms, presence of anxiety/depression, office-based blood pressure and some neurocognitive tests. The mean±sd age was 75.5±3.9 years. The CPAP group achieved a greater improvement in all quality-of-life domains (p<0.001; effect size: 0.41-0.98), sleep-related symptoms (p<0.001; effect size 0.31-0.91) as well as anxiety (p=0.016; effect size 0.51) and depression (p<0.001; effect size: 0.28) indexes and some neurocognitive tests (digit symbol test (p=0.047; effect size: 0.20) and Trail Making Test A (p=0.029; effect size: 0.44)) in an intention-to-treat analysis. In conclusion, CPAP treatment resulted in an improvement in quality of life, sleep-related symptoms, anxiety and depression indexes and some neurocognitive aspects in elderly people with severe OSA.
Abstract Oral sensory perception may play an important role in food preferences, driving food intake and energy balance. Fat perceived in oral cavity has been associated with satiety and homeostatic ...signals. The purpose of this study was to test the hypothesis that fat oral-intensity perception may be associated with BMI, food preferences and consumption of fat-rich foods. The ability to perceive linoleic acid at different concentrations by intensity scaling was measured in young adults (n = 121), characterized by anthropometric measurements such as body mass index (BMI), waist circumference (WC) and total body fat (TBF) percentage. Additionally, dietary habits were recorded online during 35 days using a questionnaire designed according to the 24-hour recall and the food diary methods. Finally, food preferences were evaluated online using a nine-point hedonic scale. Taste sensitivity (intensity scaling with suprathreshold concentrations) was estimated with different linoleic acid concentrations using a linear scale of 150 mm labeled at the ends. Four groups were established after the ratings for oral-intensity perception of linoleic acid: quartile high ratings (QH ), quartile medium-high ratings (QMH ), quartile medium-low ratings (QML ) and quartile low ratings (QL ). Participants with high-intensity ratings for linoleic acid (QH ) had lower BMI (p = 0.04) and waist circumference (WC) (p = 0.03) values than participants in the QL group. High-fat foods (foods with more than 20% of energy from lipids such as fast foods and Mexican street foods) were less preferred by participants with high-intensity ratings for linoleic acid (QH ) than by participants with medium- (QMH , QML ) and low-(QL ) intensity ratings (p < 0.01). Also, participants with high-intensity ratings for linoleic acid (QH ) presented lower consumption of high-fat foods like fast foods (p = 0.04) and Mexican street foods (p = 0.03) than subjects with medium- (QMH , QML ) and low-(QL ) intensity ratings. Overall, these data suggest that the participant's intensity ratings for oral perception of linoleic acid were inversely correlated with BMI, WC, preference and consumption of high-fat foods such as fast foods and Mexican street foods, and it may serve as a predisposing factor for fat consumption in humans.
High degree cardiac conduction disturbances (HDCD) remain a major complication after transcatheter aortic valve replacement (TAVR), especially with self-expandable valves (SEV). Our aim was to ...investigate peri-procedural and in-hospital modification of atrioventricular and intracardiac conduction associated to new generation SEV implantation, and the development of new HDCD resulting in permanent pacemaker implantation (PPM) in patients undergoing TAVR.
Three-hundred forty-four consecutive patients with severe aortic stenosis who underwent TAVR with a new generation SEV Evolut-R/Pro (n = 130), Acurate-neo (n = 79), Portico (n = 75) and Allegra (n = 60) were included. An analysis of baseline, post-TAVR and pre-discharge ECG and procedural aspects were centrally performed. A significant increase in baseline PR interval (169.6 ± 28.2 ms) and QRS complex width (101.7 ± 25.9 ms) was noted immediately post-TAVR (188.04 ± 34.49; 129.55 ± 30.02 ms), with a partial in-hospital reversal (179.4 ± 30.1; 123.06 ± 30.94 ms), resulting in a net increase at hospital discharge of 12.6 ± 38.8 ms and 21.4 ± 31.6 ms (p < 0.001), respectively. The global incidence of new onset persistent HDCD at hospital discharge was 46.3%, with 17.7% of patients requiring PPM. Independent predictors of new onset HCDC at hospital discharge were valve recapture (OR: 2.8; 95% IC: 1.1–7.2, p = 0.033) and implantation depth ≥ 6 mm (OR: 1.9 05% IC 1.1–3.3, p = 0.015), while higher implantation (<3 mm (OR: 0.3, 95% IC 0.1–0.7, p = 0.014) and use of Acurate-Neo valve (OR: 0.4; 95% IC 0.2–0.8, p = 0.009) were protective factor.
New generation self-expanding aortic valves were associated with a significant increase in PR and QRS interval at hospital discharge leading to a very high rate of HDCD. While valve recapture and implantation depth were independent predictors for the occurrence of HDCD, use of Accurate-Neo valve was a protective factor.
•Conduction disturbances after TAVR are common with SEV. However electrocardiographic changes with new generation SEV have not been described.•New generation SEV is associated with significant PR interval prolongation and QRS widening immediately post-TAVR and at discharge.•While implantation depth and valve recapture were independent predictors of HDCD at discharge, Acurate-neo valve was associated with lower rates of HDCD.•Baseline RBBB, valve recapture, low implantation depth and significant increase in PR interval and QRS widening post-TAVR, predicted a higher in-hospital PPM rate with a modest discriminatory ability.
Different kinematic models have been proposed for the triple junction between the North American, Cocos and Caribbean plates. The two most commonly accepted hypotheses on its driving mechanism are ...(a) the North American drag of the forearc and (b) the Cocos Ridge subduction push. We present an updated GPS velocity field which is analyzed together with earthquake focal mechanisms and regional relief. The two hypotheses have been used to make kinematic predictions that are tested against the available data. An obliquity analysis is also presented to discuss the potential role of slip partitioning as driving mechanism. The North American drag model presents a better fit to the observations, although the Cocos Ridge push model explains the data in Costa Rica and Southern Nicaragua. Both mechanisms must be active, being the driving of the Central American forearc towards the NW analogous to a push-pull train. The forearc sliver moves towards the west-northwest at a rate of 12-14 mm/yr, being pinned to the North American plate in Chiapas and western Guatemala, where the strike-slip motion on the volcanic arc must be very small.
This study sought to investigate the clinical impact of the use of intravascular ultrasound (IVUS) during revascularization of patients with left main coronary artery (LM) disease with drug-eluting ...stents (DES).
Whether the use of IVUS during the procedure adds a clinical benefit remains unclear. There is only 1 previous observational study, with relevant limitations, supporting the value of this strategy.
We performed a patient-level pooled analysis of 4 registries of patients with LM disease treated with DES in Spain. A propensity score-matching method was used to obtain matched pairs of patients with and without IVUS guidance.
A total of 1,670 patients were included, and 505 patients (30.2%) underwent DES implantation under IVUS guidance (IVUS group). By means of the matching method, 505 patients without the use of IVUS during revascularization were selected (no-IVUS group). Survival free of cardiac death, myocardial infarction, and target lesion revascularization at 3 years was 88.7% in the IVUS group and 83.6% in the no-IVUS group (p = 0.04) for the overall population, and 90% and 80.7%, respectively (p = 0.03), for the subgroups with distal LM lesions. The incidence of definite and probable thrombosis was significantly lower in the IVUS group (0.6% vs. 2.2%; p = 0.04). Finally, IVUS-guided revascularization was identified as an independent predictor for major adverse events in the overall population (hazard ratio: 0.70, 95% confidence interval: 0.52 to 0.99; p = 0.04) and in the subgroup with distal lesions (hazard ratio: 0.54, 95% confidence interval: 0.34 to 0.90; p = 0.02).
The results of this pooled analysis show an association of IVUS guidance during percutaneous coronary intervention with better outcomes in patients with LM disease undergoing revascularization with DES.
Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum.
The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 ...m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed.
3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance NGT); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 1.33-1.92) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 1.28-2.83) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 1.00-2.09) and AGR persistence (OR: 2.57 1.05-6.31). Pregestational BMI ≥ 25 kg/m
(OR: 0.59 0.41-0.85), postdelivery weight gain (OR: 0.53 0.29-0.94), and waist circumference > 89.5 cm (OR: 0.54 0.36-0.79) reduced the likelihood of NGT persisting at 3 y.
3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.
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