The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain.

OBJECTIVES: ANCA-associated vasculitis (AAV) are chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. METHODS: Patients with AAV who started avacopan between June 2022-September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. RESULTS: 29 patients treated with avacopan were analyzed. Twelve patients (41.4%) were male, median age was 56 years. Most of patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean eGFR of 23.2 ml/minMedian follow-up was 456.8 ± 181.7 days with a remission rate of 86.2%. eGFR increased from 23.2 ± 11.2-38.38 ± 18.55 ml/min after 12 months of diagnosis.2 patients had Adverse Events related to avacopan as severe neutropenia and a gastrointestinal affectation , 13 infections were reported and 1 death.Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (p-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups. CONCLUSION: The combination of avacopan in clinical practice presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR, and removal of steroids.

Síndrome de tolosa hunt: presentación de caso clínico / Tolosa Hunt syndrome: case report

El síndrome de Tolosa-Hunt es una entidad poco frecuente cuya etiopatogenia y mecanismos fi- siopatológicos son controversiales, se caracteri- za por cefalea asociada a parálisis de uno o más nervios craneales, diplopía, estrabismo y ptosis palpebral, ocasionados por el compromiso del seno cavernoso o la fisura orbitaria superior. Su diagnóstico es un reto y se aborda dentro de los diagnósticos diferenciales de las oftalmoplejías dolorosas. Con el objetivo de describir y actua- lizar el conocimiento sobre esta enfermedad se presenta el caso de una paciente de 14 años que acudió a consulta por cefalea intensa, dolor ocu- lar y afección de nervios craneales. Los hallazgos clínicos y la resonancia magnética confirmaron el diagnóstico del síndrome de Tolosa Hunt...(AU)

Chemical composition of rainwater under two events of aerosol transport: A Saharan dust outbreak and wildfires.

A one-year campaign of joint sampling of aerosols and precipitation, carried out in León, Spain, allowed to study the impact of two special events that affected the air quality in the north of the country, on rainfall in the city: a period with wildfires and a Saharan dust intrusion. The wildfires that occurred in northern Portugal and northwestern Spain in August 2016 affected the chemistry of rainfall on 15 August 2016, causing an increase in concentrations of NH4+, Na+, Cl-, K+, Mg2+, Ca2+, SO42- and NO3- and in the concentrations of organic acids, which was reflected in the levels of soluble and insoluble organic carbon. This led to acidification of rainwater (pH = 4.8). The second precipitation event was registered between 11 and 14 February 2017, during which the rainwater was collected in four daily fractions (P1, P2, P3 and P4). The rain sample of 12 February (P2) coincided with a Saharan dust intrusion that reached northern Iberia that day. The chemical composition of P2 showed an increase in the Ca2+ (>800%), Mg2+ (71%), Cl- (62%), and SO42- (33%) concentrations, with respect to P1. The input of crustal elements to the atmosphere helped to neutralize the P2 rainwater, causing pH values higher than 6.5. Once the dust intrusion left the north of the Peninsula, the composition of rainwater P3 and P4 revealed a mixture of marine contribution with local anthropogenic emissions, as well as a decrease in ion concentrations and conductivity, and an increase in pH values.

Determinants of renal and patient outcomes in a Spanish cohort of patients with ANCA-associated vasculitis and renal involvement.

The classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. The main objective of this study was to define the respective values of ANCA serotype-based classification, clinicopathological classification, and histopathological classification in predicting patient and renal outcomes in a Spanish cohort of patients with ANCA with specificity for myeloperoxidase, MPO-ANCA, versus ANCA with specificity for proteinase 3, PR3-ANCA. Two hundred and forty-five patients with ANCA-AAV and biopsy-proven renal involvement diagnosed between 2000 and 2104 were recruited in 12 nephrology services. Clinical and histologic data, renal outcomes, and mortality were analyzed. We applied the Chapel Hill Consensus Conference definition with categories for granulomatosis with the polyangiitis (GPA) and microscopic polyangiitis (MPA), the classification based on ANCA specificity, and the histopathological classification proposed in 2010. Eighty-two percent were MPO-ANCA positive and 18.0% PR3-ANCA positive. Altogether, 82.9% had MPA and 17.1% GPA. The median follow-up was 43.2 months (0.1-169.3). Neither ANCA-based serological nor clinical classification was predictive of renal outcomes or patient survival on bivariate or multivariate Cox regression analysis. Histopathological classification was found to predict development of end-stage renal disease (p = 0.005) in Kaplan-Meier analysis. ANCA specificity was more predictive of relapse than clinicopathological classification in multivariate analysis (HR 2.086; 95% CI 1.046-4.158; p = 0.037). In our Spanish cohort, a majority of patients had an MPO-ANCA-AAV. A classification based on ANCA specificity has a higher predictive value for relapse occurrence and could be used for decision-making with respect to induction treatment and maintenance therapies.

Influence of design, physico-chemical and environmental parameters on pharmaceuticals and fragrances removal by constructed wetlands.

The ability of several mesocosm-scale and full-scale constructed wetlands (CWs) to remove pharmaceuticals and personal care products (PPCPs) from urban wastewater was assessed. The results of three previous works were considered as a whole to find common patterns in PPCP removal. The experiment took place outdoors under winter and summer conditions. The mesocosm-scale CWs differed in some design parameters, namely the presence of plants, the vegetal species chosen (Typha angustifolia versus Phragmites australis), the flow configuration (surface flow versus subsurface flow), the primary treatment (sedimentation tank versus HUSB), the feeding regime (batch flow versus continuous saturation) and the presence of gravel bed. The full-scale CWs consisted of a combination of various subsystems (ponds, surface flow CWs and subsurface flow CWs). The studied PPCPs were ketoprofen, naproxen, ibuprofen, diclofenac, salicylic acid, carbamazepine, caffeine, methyl dihydrojasmonate, galaxolide and tonalide. The performance of the evaluated treatment systems was compound dependent and varied as a function of the CW-configuration. In addition, PPCP removal efficiencies were lower during winter. The presence of plants favoured naproxen, ibuprofen, diclofenac, salicylic acid, caffeine, methyl dihydrojasmonate, galaxolide and tonalide removal. Significant positive correlations were observed between the removal of most PPCPs and temperature or redox potential. Accordingly, microbiological pathways appear to be the most likely degradation route for the target PPCPs in the CWs studied.

Digestion of cattle manure under mesophilic and thermophilic conditions: characterization of organic matter applying thermal analysis and 1H NMR.

Digestion of cattle manure collected from a livestock farm together with bedding material (straw) has been studied under mesophilic and thermophilic conditions in batch reactors. The digestion was carried out for a prolonged period with the aim of evaluating the changes undergone by the organic matter. The mesophilic digestion carried out revealed a greater capacity to produce gas and transform organic matter, while a higher conversion rate, but a lower gas yield, was obtained under thermophilic conditions. Degradation of the organic matter was evaluated by means of thermal analysis and (1)H NMR. Stabilisation through anaerobic digestion (either mesophilic or thermophilic) resulted in an increase in the quality of the organic matter, as characterised by an enrichment in thermostable compounds, and an accumulation of long chain aliphatic materials. The experiments performed demonstrated the transformation of organic matter into complex materials under anaerobic conditions with an accumulation of aliphatic components under both types of conditions tested. Degradation through mesophilic digestion, in comparison to the thermophilic process, resulted in a greater destruction of straw particles.

Cholecalciferol supplements improve vitamin D deficiency in renal transplant recipients.

Most renal transplant recipients display vitamin D deficiency or insufficiency. The KDIGO guidelines suggest that this deficit should be treated as in the general population. Since there are few studies about the effects of cholecalciferol in de novo renal transplant recipients, we sought to assess these effects in long-term kidney graft recipients. Among 37 renal transplant recipients (19 males, 18 females) at a mean of 105±82 months posttransplantation, vitamin D insufficiency or deficiency was treated with cholecalciferol (400-800 IU/d) plus calcium supplements (600-1200 mg/d of elemental calcium). These subjects were compared with 37 untreated recipients for a period between 6 and 12 months. At baseline, there were no differences between the groups in age at transplantation, sex, length of follow-up after grafting, function measured by estimated glomerular filtration rate (44.4±16.8 treated vs 42.0±15.0 mL/min/1.73 m2 untreated; P=.527); iPTH (157±103 treated vs 176±118 pg/mL untreated; P=.461); 25OHD (14.7±4.7 treated vs 15.7±9.7 ng/mL untreated; P=.584); or 1.25OHD (34.1±26.0 treated vs 34.0±13.0 pg/mL untreated; P=.950). When compared with baseline values, iPTH (157±103 vs 144±89 pg/mL; P=.11) and 1.25OHD levels at 6 months (34.1±26.0 vs 35.9±26.3 pg/mL; P=.282) showed no change but 25OHD levels (14.7±4.7 vs 22.6±7.4 ng/mL; P=.000) and phosphate tubular reabsorption (64%±17% baseline vs 69%±14% at 6 months; P=.030) were increased in the treated patients. There were no differences in the parameters studied in untreated patients. Among the 27 recipients followed at 12 months, iPTH was decreased compared with baseline values (157±103 vs 124±62 pg/mL; P=.024) and 25OHD remained stable with respect to the values at 6 months (21.1±5.3 ng/mL). No adverse effects of cholecalciferol were observed such as those to increase urinary calcium excretion. Low doses of cholecalciferol improved vitamin D status and decreased iPTH levels at 12 months. Higher doses than those used in our study are needed to increase serum 25OHD concentrations above 30 ng/mL.

Management of chronic kidney disease after renal transplantation: is it different from nontransplant patients?

BACKGROUND: The Kidney Disease Quality Initiative (K/DOQI) of the National Kidney Foundation has published guidelines for the diagnosis and management of chronic kidney disease (CKD). Renal transplant recipients frequently have CKD and complications similar to native kidney disease patients. The purpose of the present study was to compare the management of CKD complications of transplant recipients and nontransplant patients. PATIENTS AND METHODS: Eighty three renal transplant recipients with CKD stages 4T and 5T were compared with 83 nontransplant CKD patients matched by CKD stage. RESULTS: There were no differences between the groups in serum hemoglobin, prevalence of anemia, and percentage of patients treated with erythropoiesis-stimulating agents, but serum ferritin levels were higher among recipients (186.3 +/- 161.3 vs 119.1 +/- 113.4 ng/mL; P = .003). Mean blood pressure (BP) was similar in both groups but a systolic BP > 130 mm Hg was more frequent among recipients (83.3% vs 72.6%). More recipients were treated with either angiotensin-converting enzyme (ACE)-inhibitors or angiotensin receptor antagonist (43.3% vs 8.4%; P < .001). Low-density lipoprotein cholesterol was lower in recipients (108.9 +/- 30.3 vs 120.8 +/- 39.5 mg/dL; P = .033) and a higher percentage was on statin treatment (44.6% vs 28.9%; P = .053). Serum calcium was higher in transplant recipients (9.5 +/- 0.8 vs 8.9 +/- 0.7 mg/dL; P < .005) and phosphate was lower (3.9 +/- 0.9 vs 4.2 +/- 1.1; P = .043); there were no differences in intact parathyroid hormone blood levels. CONCLUSIONS: The management of renal transplant recipients is no worse than that of nontransplant patients. However, in both populations, some parameters are far from the target recommended by the guidelines.

Trigeminothalamic barrelette neurons: natural structural side asymmetries and sensory input-dependent plasticity in adult rats.

In the rodent trigeminal principal nucleus (Pr5) the barrelette thalamic-projecting neurons relay information from individual whiskers to corresponding contralateral thalamic barreloids. Here we investigated the presence of lateral asymmetries in the dendritic trees of these neurons, and the morphometric changes resulting from input-dependent plasticity in young adult rats. After retrograde labeling with dextran amines from the thalamus, neurons were digitally reconstructed with Neurolucida, and metrically and topologically analyzed with NeuroExplorer. The most unexpected and remarkable result was the observation of side-to-side asymmetries in the barrelette neurons of control rats. These asymmetries more significantly involved the number of low-grade trees and the total dendritic length, which were greater on the left side. Chronic global input loss resulting from infraorbital nerve (IoN) transection, or loss of active touch resulting from whisker clipping in the right neutralized, or even reversed, the observed lateral differences. While results after IoN transection have to be interpreted in the context of partial neuron death in this model, profound bilateral changes were found after haptic loss, which is achieved without inflicting any nerve damage. After whisker trimming, neurons on the left side closely resembled neurons on the right in controls, the natural dendritic length asymmetry being reversed mainly by a shortening of the left trees and a more moderate elongation of the right trees. These results demonstrate that dendritic morphometry is both side- and input-dependent, and that unilateral manipulation of the sensory periphery leads to bilateral morphometric changes in second order neurons of the whisker-barrel system. The presence of anatomical asymmetries in neural structures involved in early stages of somatosensory processing could help explain the expression of sensory input-dependent behavioral asymmetries.

Glomerulonefritis membranoproliferativa y gammapatía monoclonal de significado incierto / No disponible

No disponible

Perioperative cerebral ischaemia in cardiac surgery and BIS.

A 46-year-old woman was monitored by bispectral index monitoring (BIS) during redo aortic and mitral valve replacement. On release of the aortic cross clamp there was a sudden, severe, unexplained, and sustained fall in the BIS value. Postoperatively, a CT scan was consistent with multiple ischaemic lesions. The lesions were presumed to be due to air embolism. This case suggests that a sudden unexplained and persistent fall in BIS may indicate cerebral ischaemia.

Information coding by ensembles of resonant neurons.

In the present paper, we propose a novel neural procedure for signal processing and coding based on the subthreshold oscillations and resonance of the neural membrane potential that could be used by real neurons to perform frequency spectra analysis and information coding of incoming signals. Taking into account the biophysical properties of the neural membranes, we note that the subthreshold resonant behaviour they exhibit can be used to analyse incoming signals and represent them in the frequency domain. We study the reliability of the representation of signals depending on the biophysical parameters of the neurons, the fault-tolerance of this coding scheme and its robustness against noise and in the presence of spikes. The principal characteristics of our system are the use of the physical phenomenon of neural resonance (rarely considered in the literature for signal coding); it fits well with the biophysical parameters of most neurons that exhibit subthreshold oscillations; it is compatible with experimental data; and it can be easily integrated in a more general model of information processing and coding that includes communication between neurons based on spikes.

Influence of the application of sewage sludge on the degradation of pesticides in the soil.

A study was made of the influence of the application of sewage sludge on the degradation of pesticides in the soil. Two kinds of sludge were used, with different characteristics, one from an urban treatment plant and one from a food processing plant. Three organophosphorus insecticides, fenitrothion, diazinon and dimethoate, were studied. The relative importance was determined of the chemical and biological degradation processes, which involved experiments on soil and sterile soil samples. A comparative study was also made of the degradation of pesticide residues and the evolution of the microbial population. The application of sludge seems to have a complex effect on the degradation of pesticides, determined by the bioavailability and biodegradability of their active ingredient. The biodegradation of pesticide residues brings about alterations in the microorganism population of the soil.

High concentrations of N-BNP are related to non-infectious severe SIRS associated with cardiovascular dysfunction occurring after off-pump coronary artery surgery.

BACKGROUND: Procalcitonin (PCT) blood concentrations are known to be an appropriate marker of severe systemic inflammatory response syndrome (SIRS) induced by coronary artery surgery with and without cardiopulmonary bypass. Pro-brain natriuretic peptide (N-BNP) is a newly described cardiac hormone considered to be an effective marker of severity and prognosis of acute coronary syndromes and congestive heart failure. We evaluated the perioperative time courses of PCT and N-BNP and investigated their role as early markers of severe SIRS (SIRS with cardiovascular dysfunction) induced by off-pump coronary artery bypass (OPCAB). METHODS: Sixty-three patients were prospectively included. The American College of Chest Physicians Classification was used to diagnose SIRS and organ system failure to define severe SIRS. Serum concentrations of PCT and N-BNP were determined before, during and after surgery. Receiver operating characteristic curves and cut-off values were used to assess the ability of these markers to predict postoperative severe SIRS. RESULTS: SIRS occurred in 25 (39%) patients. Nine of them (14%) showed severe SIRS. Significantly higher serum concentrations of N-BNP and PCT were found in patients with severe SIRS with peak concentrations respectively at 8887 pg ml(-1) (range 2940-29372 pg ml(-1)) for N-BNP and 9.50 ng ml(-1) (range 1-65 ng ml(-1)) for PCT. The area under the curve using N-BNP to detect postoperative severe SIRS was 0.799 before surgery (0.408 for PCT; P<0.01) and 0.824 at the end of surgery (0.762 for PCT; P<0.05). CONCLUSIONS: N-BNP may be an appropriate marker indicating the early development of non-infectious postoperative severe SIRS after OPCAB.

[Perioperative management of ventricular assist devices]. / Prise en charge périopératoire des assistances ventriculaires.

OBJECTIVE: To review the perioperative anaesthetic management of ventricular assist devices. DATA SOURCES: Extraction from Pubmed database of french and english articles on the perioperative anaesthetic management of ventricular assist devices for 15 years. DATA SELECTION: The collected articles were reviewed and selected according to their quality and originality. The more recent data were selected. DATA SYNTHESIS: Cardiac transplantation is an effective treatment for patients in end stage cardiac failure, but the average waiting time of 17 months, associated with the lack of organs (357 out of 832 candidates were transplanted in 1996) results in a high number of deaths in patients awaiting transplantation. The appearance in the 1980's, of the first ventricular assist device (VAD) provided a new possibility for the management of patients with end-stage cardiac failure awaiting transplantation ("bridge to transplant"). The perioperative anaesthetic management of these patients is complex. End stage cardiac failure, poorly responsive to pharmacological interventions, results rapidly in secondary organ dysfunctions. VADs produce a rapid improvement in haemodynamic, renal, hepatic and neuro-endocrine functions over a 2 months period, allowing transplantation to take place under optimal conditions. However VADs are not without complications (1 year mortality of 20%), of which the major are: infections (40%), perioperative haemorrhage (30%) and thrombo-embolic sequelae (30%). A best knowledge of pathophysiology of these complications is necessary to an optimal management of patients with ventricular assist devices.

Dye adsorption by sewage sludge-based activated carbons in batch and fixed-bed systems.

The present research work deals with the production of activated carbons by chemical activation and pyrolysis of sewage sludges. The adsorbent properties of these sewage sludges based activated carbons were studied by liquid-phase adsorption tests. Dyes removal from colored wastewater being a possible application for sludge based adsorbents, methylene blue and saphranine removing from solution was studied. Pure and binary adsorption assays were performed in batch and fixed bed systems. In all cases studied, the adsorbents produced from sewage sludges were able to adsorb both the compounds considered here. Nevertheless, time required for reaching equilibrium, adsorptive capacity and fixed bed characteristic parameters were different for these two compounds. Methylene blue adsorption occurred faster than that of saphranine, and it was preferably adsorbed when treating binary solutions. It could be concluded that the sewage sludge-based activated carbons may be promising for dyes removal from aqueous streams.

[Fusarium pleural effusion after a ventricular assist device]. / Pleurésie à Fusarium compliquant une implantation de ventricule artificiel.

We report the case of a 36-year-old man with a pleural effusion that complicates the postoperative period after the implantation of a ventricular assist device (VAD). The epidemiological, etiologic and therapeutic features of Fusarium infections were reviewed. Complete recovery of the infection was obtained after a treatment by liposomal amphotericine B (AmBisome) and 5 fluorocytosine.