Herramientas normativas sobre la compleja realidad ambiental : sus generalidades

p.1-5El presente trabajo tiene como objetivo de sistematizar el proceso de las herramientas jurídicas básicas sobre el medio ambiente ya que, es de fundamental importancia el conocimiento normativo que va a regular las relaciones sociales para que, desde una perspectiva holística se puedan lograr resoluciones integrales. El derecho ambiental es la respuesta normativa a la creciente degradación que sugre el medio en que vivimos. Se integra con una serie de normas de diverso nivel de importancia (leyes, decretos, ordenazas, resoluciones, etc.) y diverso origen (demanadas del estado nacional, de los estados provinciales o de los municipios), que en algunos casos se superponen y en otros se contradicen. Con una visión interdisciplinaria y en la necesidad de tomar cnocimiento del derecho ambiental y poder identificar, cuál sería la normativa aplicable a una determinada organización/actividad, en una primera instancia y a modo de guía se han elaborado una serie de preguantas esenciales que pueden resultar de gran utilidad para que, la gestión ambiental de los profesionales en su hacer se ajuste a derecho

Coronary plaque composition influences biomechanical stress and predicts plaque rupture in a morpho-mechanic OCT analysis

Plaque rupture occurs if stress within coronary lesions exceeds the protection exerted by the fibrous cap overlying the necrotic lipid core. However, very little is known about the biomechanical stress exerting this disrupting force. Employing optical coherence tomography (OCT), we generated plaque models and performed finite-element analysis to simulate stress distributions within the vessel wall in 10 ruptured and 10 non-ruptured lesions. In ruptured lesions, maximal stress within fibrous cap (peak cap stress [PCS]: 174 ± 67 vs. 52 ± 42 kPa, p<0.001) and vessel wall (maximal plaque stress [MPS]: 399 ± 233 vs. 90 ± 95 kPa, p=0.001) were significantly higher compared to non-ruptured plaques. Ruptures arose in the immediate proximity of maximal stress concentrations (angular distances: 21.8 ± 30.3° for PCS vs. 20.7 ± 23.7° for MPS); stress concentrations excellently predicted plaque rupture (area under the curve: 0.940 for PCS, 0.950 for MPS). This prediction of plaque rupture was superior to established vulnerability features such as fibrous cap thickness or macrophage infiltration. In conclusion, OCT-based finite-element analysis effectively assesses plaque biomechanics, which in turn predicts plaque rupture in patients. This highlights the importance of morpho-mechanic analysis assessing the disrupting effects of plaque stress

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome:an international cross-sectional study

Background:Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. Methods:Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). Results:A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH &gt;7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs −0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate—standard deviation score &lt; −2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P &lt; .001), suggesting renal phosphate wasting. Conclusions:Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.</p

Autosomal recessive polycystic kidney disease (ARPKD)-lessons learned from the international ARPKD registry study ARegPKD

Autosomal recessive polycystic kidney disease (ARPKD) is rare but is one of the most important causes of kidney failure in childhood and adolescence. ARPKD is characterized by obligatory hepatorenal involvement and pronounced phenotypic variability. In most cases, it is caused by variants in the PKHD1 gene encoding the ciliary protein fibrocystin. The treatment of ARPKD is purely symptomatic. Targeted therapy has not yet been established. The prediction of clinical courses remains difficult in ARPKD. As ARPKD occurs significantly less frequently than autosomal dominant polycystic kidney disease (ADPKD), clinical or radiological risk markers for kidney disease progression could not be established for ARPKD in a similar manner. Genotype-phenotype correlations cannot fully explain the differences in the clinical courses. Clinical research in the field of ARPKD faces a number of challenges, such as rarity of the disease, complex disease courses, late, atypical or liver-predominant manifestations as well as incomplete understanding of the molecular pathogenesis. An exact longitudinal phenotypic characterization of large numbers of patients in international collaborations is helpful for the establishment of clinical, radiological and laboratory risk markers that are the basis for evaluation of first treatment options. In this setting, the European registry study ARegPKD was established. This article presents the evolution of the ARegPKD and extracts of lessons learned

Co-localization of plaque macrophages with calcification is associated with a more vulnerable plaque phenotype and a greater calcification burden in coronary target segments as determined by OCT

BACKGROUND:The presence of plaque macrophages and microcalcifications are acknowledged features of plaque vulnerability. Experimental data suggest that microcalcifications promote inflammation and macrophages foster microcalcifications. However, co-localization of plaque macrophages and calcification (ColocCaMa) in coronary segments and its impact on plaque phenotype and lesion vulnerability is unexplored. METHODS:Plaque morphology including ColocCaMa of calcified coronary target segments in patients with stable coronary artery disease (n = 116) was analyzed using optical coherence tomography (OCT) prior to coronary intervention. Therefore we considered macrophages co-localized with calcification if their distance in an OCT frame was <100μm and OCT-defined microcalcifications with a calcium arc <22.5°. RESULTS:ColocCaMa was present in 29/116(25.0%) coronary segments. Calcium burden was greater (calcium volume index:1731±1421°*mm vs. 963±984°*mm, p = 0.002) and calcifications were more superficial (minimal thickness of the fibrous cap overlying the calcification 35±37μm vs. 64±72μm, p = 0.005) in the presence of ColocCaMa. Segments with ColocCaMa demonstrated a higher incidence of newly suggested features of plaque vulnerability, with a 3.5-fold higher number of OCT-defined microcalcifications (0.7±1.0 vs. 0.2±0.6, p = 0.022) and a 6.7-fold higher incidence of plaque inflammation (macrophage volume index:148.7±248.3°*mm vs. 22.2±57.4°*mm, p<0.001). Clinically, intima-media thickness (IMT) in carotid arteries was increased in patients with ColocCaMa (1.02±0.30mm vs. 0.85±0.18, p = 0.021). In a multivariate model, IMT (OR1.76 for 100μm, 95%CI 1.16-2.65, p = 0.007), HDL-cholesterol (OR0.36 for 10mg/dl, 95%CI 0.16-0.84, p = 0.017), calcium volume index (OR1.07 for 100°*mm, 95%CI 1.00-1.14, p = 0.049), macrophage volume index (OR5.77 for 100°*mm, 95%CI 2.04-16.3, p = 0.001) and minimal luminal area (OR3.41, 95%CI 1.49-7.78, p = 0.004) were independent predictors of ColocCaMa. CONCLUSION:Plaque macrophages co-localize with calcifications in coronary target segments and this is associated with high-risk morphological features including microcalcifications and macrophage infiltration as well as with greater calcification burden. Our data may add to the understanding of the relationship between plaque macrophages, vascular calcification and their clinical impact

Quantitative Flow Ratio Is Related to Intraluminal Coronary Stenosis Parameters as Assessed with Optical Coherence Tomography

Background: Quantitative flow ratio (QFR) is a novel method for assessing hemodynamic relevance of a coronary lesion based on angiographic projections without the need of a pressure wire. Various studies demonstrated that QFR consistently related to fractional flow reserve (FFR); however, it is still unclear to what extent QFR reflects intraluminal stenosis parameters. Given that optical coherence tomography (OCT) is currently the gold standard to assess intraluminal stenosis parameters, we investigated the relationship between OCT-derived lesion geometry and QFR. Methods: We determined QFR in 97 lesions from 87 patients who underwent coronary angiography and OCT due to stable angina. QFR was measured with proprietary software and compared with OCT-based assessment of intraluminal stenosis parameters as well as lesion morphology. Results: Mean QFR was 0.79 +/- 0.10. QFR demonstrated a consistent association with FFR (r = 0.834, p < 0.001). Interestingly, QFR was associated with OCT-derived parameters such as minimal lumen area (MLA, r = 0.390, p = 0.015), percent area stenosis (r = 0.412, p < 0.001), minimal lumen diameter (MLD, r = 0.395, p < 0.001), and percent diameter stenosis (r = 0.400, p < 0.001). Both minimal luminal area (ROC = 0.734, optimal cut-off 1.75 mm(2)) and minimal luminal diameter (ROC = 0.714, optimal cut-off 1.59 mm) presented a good diagnostic accuracy in diagnosing hemodynamic relevance (QFR <= 0.80). There was no significant association between QFR and anatomic features of plaque vulnerability. Conclusion: OCT-derived intraluminal stenosis parameters are related to QFR values and predict hemodynamic lesion relevance. The data supports the validity of QFR as 3D-vessel reconstruction method to assess coronary physiology without the need of a pressure wire

Coronary plaque composition influences biomechanical stress and predicts plaque rupture in a morpho-mechanic OCT analysis

Plaque rupture occurs if stress within coronary lesions exceeds the protection exerted by the fibrous cap overlying the necrotic lipid core. However, very little is known about the biomechanical stress exerting this disrupting force. Employing optical coherence tomography (OCT), we generated plaque models and performed finite-element analysis to simulate stress distributions within the vessel wall in 10 ruptured and 10 non-ruptured lesions. In ruptured lesions, maximal stress within fibrous cap (peak cap stress [PCS]: 174 +/- 67 vs. 52 +/- 42 kPa, p<0.001) and vessel wall (maximal plaque stress [MPS]: 399 +/- 233 vs. 90 +/- 95 kPa, p=0.001) were significantly higher compared to non-ruptured plaques. Ruptures arose in the immediate proximity of maximal stress concentrations (angular distances: 21.8 +/- 30.3 degrees for PCS vs. 20.7 +/- 23.7 degrees for MPS); stress concentrations excellently predicted plaque rupture (area under the curve: 0.940 for PCS, 0.950 for MPS). This prediction of plaque rupture was superior to established vulnerability features such as fibrous cap thickness or macrophage infiltration. In conclusion, OCT-based finite-element analysis effectively assesses plaque biomechanics, which in turn predicts plaque rupture in patients. This highlights the importance of morpho-mechanic analysis assessing the disrupting effects of plaque stress

Quantitative Flow Ratio Is Related to Anatomic Left Main Stem Lesion Parameters as Assessed by Intravascular Imaging

Introduction: Previously, an association between anatomic left main stem (LMS) lesion parameters, as described by intravascular ultrasound (IVUS) and fractional flow reserve (FFR), was shown. Quantitative flow ratio (QFR) is a novel, promising technique which can assess functional stenosis relevance based only on angiography. However, as little is known about the relationship between anatomic LMS parameters and QFR, it was thus investigated in this study. Methods: In 53 patients with LMS disease, we tested the association between anatomic assessment using OCT (n = 28) or IVUS (n = 25) on the one hand and functional assessment as determined by QFR on the other hand. LMS-QFR was measured using a dedicated approach, averaging QFR over left anterior descending (LAD) and circumflex (LCX) and manually limiting segment of interest to LMS. Results: The minimal luminal area of the LMS (LMS-MLA) as measured by intravascular imaging showed a consistent correlation with QFR (R = 0.61, p &lt; 0.001). QFR could predict a LMS-MLA &lt; 6 mm2 with very good diagnostic accuracy (AUC 0.919) and a LMS-MLA &lt; 4.5 mm2 with good accuracy (AUC 0.798). Similar results were obtained for other stenosis parameters. Conclusions: QFR might be a valuable tool to assess LMS disease. Further studies focusing on patient outcomes are needed to further validate the effectiveness of this approach

High cardiovascular risk of patients with type 2 diabetes is only partially attributed to angiographic burden of atherosclerosis

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events and present more severe coronary artery disease (CAD). The Gensini and COURAGE scores are established angiographic instruments to assess CAD severity, which may also predict future cardiovascular risk. However, it is unclear if these scores are able to depict the increased risk of patients with T2DM and stable CAD (T2DM-SAP). Methods: We performed quantitative coronary angiography and assessed the Gensini and COURAGE scores in 124 patients with T2DM-SAP. Angiographic data were compared to patients with stable angina without T2DM (Non-DM-SAP, n = 74), and to patients with acute coronary syndrome and T2DM (T2DM-ACS, n = 53). Results: T2DM-SAP patients had similar Gensini and COURAGE-scores compared to Non-DM-SAP-patients (Gensini: 14.44 +/- 27.34 vs 11.49 +/- 26.99, p = 0.465; COURAGE: 3.48 +/- 4.49 vs 3.60 +/- 4.72, p = 0.854). In contrast, T2DM-SAP patients had significantly lower Gensini (14.44 +/- 27.34 vs 30.94 +/- 48.74, p = 0.003) and lower COURAGE (3.48 +/- 4.49 vs 5.30 +/- 4.63, p = 0.016) scores compared to T2DM-ACS-patients. Conclusion: Both the Gensini and the COURAGE score fail to predict the high cardiovascular risk of patients with T2DM-SAP. Therefore, these scores should be used with caution in the assessment of future risk of patients with T2DM. However, among T2DM-ACS patients, both scores are increased, reflecting the high cardiovascular risk in this patient population