Synthesis of Vicinal anti-Amino Alcohols from N-tert-Butanesulfinyl Aldimines and Cyclopropanols.

The stereoselective synthesis of vicinal amino alcohols derivatives from 1-substituted cyclopropanols and chiral N-tert-butanesulfinyl imines is described. Cyclopropanols are easily prepared from carboxylic esters upon reaction with ethylmagnesium bromide in the presence of titanium tetraisopropoxide and undergo carbon-carbon bond cleavage by means of diethylzinc to produce, upon base deprotonation, enolized zinc homoenolates, which react with chiral sulfinyl imines in a highly regio- and stereoselective manner.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Adverse Event Profile During the Treatment of Helicobacter pylori: A Real-World Experience of 22,000 Patients From the European Registry on H. pylori Management (Hp-EuReg).

INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management." METHODS: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. DISCUSSION: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

Helicobacter pylori first-line and rescue treatments in patients allergic to penicillin: Experience from the European Registry on H pylori management (Hp-EuReg).

BACKGROUND: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. AIM: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). METHODS: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. RESULTS: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. CONCLUSION: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

Xanthogranulomatous pancreatitis: a lesion that mimics pancreatic cancer.

Xanthogranulomatous pancreatitis (XGP) is an extremely rare entity. In most cases, XGP is preoperatively misdiagnosed as a pancreatic neoplasm. The pathogenesis is not well established. To our knowledge, only 15 cases have been reported in the English language literature. Surgical resection was performed before the histologic diagnosis in all published cases. We report the first case of XGP described in Spain, diagnosed by CT-guided biopsy, without requiring surgical resection, in a patient initially diagnosed as having a pancreatic neoplasm.

Effect of acute hyperglycemia on moderately hypothermic GL261 mouse glioma monitored by T1-weighted DCE MRI.

OBJECTIVE: We sought to evaluate the effects of acute hyperglycemia induced by intraperitoneal injection of glucose (2.7 g/kg) on vascular delivery to GL261 mouse gliomas kept at moderate hypothermia (~30 °C). MATERIALS AND METHODS: Seven GL261 glioma-bearing mice were studied by T1-weighted DCE MRI before and after an injection of glucose (n = 4) or saline (n = 3). Maximum relative contrast enhancement (RCE) and initial area under the enhancement curve (IAUC) were determined in each pixel. RESULTS: The mean tumor parameter values showed no significant changes after injecting either saline (RCE -5.9 ± 5.0 %; IAUC -3.7 ± 3.6 %) or glucose (RCE -1.6 ± 9.0 %; IAUC +0.6 ± 6.4 %). Pixel-by-pixel analysis revealed small post-injection changes in RCE and IAUC between the glucose and saline groups, all within 13 % range of their baseline values. CONCLUSION: Perturbing the metabolism of GL261 tumors kept at moderate hypothermia with hyperglycemia did not induce significant changes in the permeability/perfusion of these tumors. This is relevant for future studies with this model since regional differences in glucose accumulation could thus reflect basal heterogeneities in vasculature and/or metabolism of GL261 tumors.

DCE@urLAB: a dynamic contrast-enhanced MRI pharmacokinetic analysis tool for preclinical data.

BACKGROUND: DCE@urLAB is a software application for analysis of dynamic contrast-enhanced magnetic resonance imaging data (DCE-MRI). The tool incorporates a friendly graphical user interface (GUI) to interactively select and analyze a region of interest (ROI) within the image set, taking into account the tissue concentration of the contrast agent (CA) and its effect on pixel intensity. RESULTS: Pixel-wise model-based quantitative parameters are estimated by fitting DCE-MRI data to several pharmacokinetic models using the Levenberg-Marquardt algorithm (LMA). DCE@urLAB also includes the semi-quantitative parametric and heuristic analysis approaches commonly used in practice. This software application has been programmed in the Interactive Data Language (IDL) and tested both with publicly available simulated data and preclinical studies from tumor-bearing mouse brains. CONCLUSIONS: A user-friendly solution for applying pharmacokinetic and non-quantitative analysis DCE-MRI in preclinical studies has been implemented and tested. The proposed tool has been specially designed for easy selection of multi-pixel ROIs. A public release of DCE@urLAB, together with the open source code and sample datasets, is available at http://www.die.upm.es/im/archives/DCEurLAB/.

Regional left ventricular endocardial strains estimated from low-dose 4DCT: Comparison with cardiac magnetic resonance feature tracking.

BACKGROUND: Estimates of regional left ventricular (LV) strains provide additional information to global function parameters such as ejection fraction (EF) and global longitudinal strain (GLS) and are more sensitive in detecting abnormal regional cardiac function. The accurate and reproducible assessment of regional cardiac function has implications in the management of various cardiac diseases such as heart failure, myocardial ischemia, and dyssynchrony. PURPOSE: To develop a method that yields highly reproducible, high-resolution estimates of regional endocardial strains from 4DCT images. METHODS: A method for estimating regional LV endocardial circumferential ( ε c c ) $( {{\epsilon }_{cc}} )$ and longitudinal ( ε l l ${\epsilon }_{ll}$ ) strains from 4DCT was developed. Point clouds representing the LV endocardial surface were extracted for each time frame of the cardiac cycle from 4DCT images. 3D deformation fields across the cardiac cycle were obtained by registering the end diastolic point cloud to each subsequent point cloud in time across the cardiac cycle using a 3D point-set registration technique. From these deformation fields, ε c c and ε l l ${\epsilon }_{cc}\ {\rm{and\ }}{\epsilon }_{ll}$ were estimated over the entire LV endocardial surface by fitting an affine transformation with maximum likelihood estimation. The 4DCT-derived strains were compared with strains estimated in the same subjects by cardiac magnetic resonance (CMR); twenty-four subjects had CMR scans followed by 4DCT scans acquired within a few hours. Regional LV circumferential and longitudinal strains were estimated from the CMR images using a commercially available feature tracking software (cvi42). Global circumferential strain (GCS) and global longitudinal strain (GLS) were calculated as the mean of the regional strains across the entire LV for both modalities. Pearson correlation coefficients and Bland-Altman analyses were used for comparisons. Intraclass correlation coefficients (ICC) were used to assess the inter- and intraobserver reproducibility of the 4DCT-derived strains. RESULTS: The 4DCT-derived regional strains correlated well with the CMR-derived regional strains ( ε c c ${\epsilon }_{cc}$ : r = 0.76, p < 0.001; ε l l ${\epsilon }_{ll}$ : r = 0.64, p < 0.001). A very strong correlation was found between 4DCT-derived GCS and 4DCT-derived EF (r = -0.96; p < 0.001). The 4DCT-derived strains were also highly reproducible, with very low inter- and intraobserver variability (intraclass correlation coefficients in the range of [0.92, 0.99]). CONCLUSIONS: We have developed a novel method to estimate high-resolution regional LV endocardial circumferential and longitudinal strains from 4DCT images. Except for the definition of the mitral valve and LV outflow tract planes, the method is completely user independent, thus yielding highly reproducible estimates of endocardial strain. The 4DCT-derived strains correlated well with those estimated using a commercial CMR feature tracking software. The promising results reported in this study highlight the potential utility of 4DCT in the precise assessment of regional cardiac function for the management of cardiac disease.

Effectiveness and Safety of High-Dose Dual Therapy: Results of the European Registry on the Management of Helicobacterpylori Infection (Hp-EuReg).

BACKGROUND: Randomized clinical trials and meta-analyses, primarily from Asian countries, have reported good effectiveness with high-dose dual therapy (HDDT) including a proton pump inhibitor (PPI) and amoxicillin when prescribed as H. pylori first-line or rescue treatment. However, combining amoxicillin with PPIs in the 1990s in several European countries yielded suboptimal results. METHODS: An international, multicenter, prospective non-interventional Registry (Hp-EuReg) aimed to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult cases treated with HDDT were registered at e-CRF AEG-REDCap platform until June 2021. Sixty patients were prescribed with HDDT (98% compliance), 19 of them received a first-line therapy and 41 a rescue treatment (second- to sixth-line). RESULTS: Overall HDDT effectiveness was 52% (per-protocol) and 51% (modified intention-to-treat). First-line and rescue treatment lines were equally effective, but the effectiveness was worse when patients had previously received metronidazole, tetracycline, or rifabutin. Adding bismuth to HDDT in rescue treatment did not yield better results. The incidence of adverse events was 30%, diarrhea being the most common (20% of patients); no serious adverse events were reported. CONCLUSION: Although HDDT is safe and has good compliance, it is not a good option in European first-line or rescue H. pylori treatment, even when adding bismuth.

Influence of metabolic syndrome on post-stroke outcome, angiogenesis and vascular function in old rats determined by dynamic contrast enhanced MRI.

Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes.

The Role of Statins on Helicobacter pylori Eradication: Results from the European Registry on the Management of H. pylori (Hp-EuReg).

Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effectiveness in the empirical group (OR = 1.3; 95%CI = 1.1-1.5), but no association was found with first-line treatment effectiveness (N = 7738); as an exception, statin use was specifically associated with lower effectiveness of standard triple therapy (OR = 0.76; 95%CI = 0.59-0.99). In the rescue therapy empirical group (N = 2228), statins were associated with higher overall effectiveness (OR = 1.9; 95%CI = 1.4-2.6). However, sub-analyses by treatment schemes only confirmed this association for the single-capsule bismuth quadruple therapy (OR = 2.8; 95%CI = 1.3-5.7). No consistent association was found between statin use and H. pylori therapy effectiveness. Therefore, the addition of statins to the usual H. pylori treatment cannot be currently recommended to improve cure rates.

Geometrical and Monte Carlo projectors in 3D PET reconstruction.

PURPOSE: In the present work, the authors compare geometrical and Monte Carlo projectors in detail. The geometrical projectors considered were the conventional geometrical Siddon ray-tracer (S-RT) and the orthogonal distance-based ray-tracer (OD-RT), based on computing the orthogonal distance from the center of image voxel to the line-of-response. A comparison of these geometrical projectors was performed using different point spread function (PSF) models. The Monte Carlo-based method under consideration involves an extensive model of the system response matrix based on Monte Carlo simulations and is computed off-line and stored on disk. METHODS: Comparisons were performed using simulated and experimental data of the commercial small animal PET scanner rPET. RESULTS: The results demonstrate that the orthogonal distance-based ray-tracer and Siddon ray-tracer using PSF image-space convolutions yield better images in terms of contrast and spatial resolution than those obtained after using the conventional method and the multiray-based S-RT. Furthermore, the Monte Carlo-based method yields slight improvements in terms of contrast and spatial resolution with respect to these geometrical projectors. CONCLUSIONS: The orthogonal distance-based ray-tracer and Siddon ray-tracer using PSF image-space convolutions represent satisfactory alternatives to factorizing the system matrix or to the conventional on-the-fly ray-tracing methods for list-mode reconstruction, where an extensive modeling based on Monte Carlo simulations is unfeasible.

Automatic estimation of aortic and mitral valve displacements in dynamic CTA with 4D graph-cuts.

The location of the mitral and aortic valves in dynamic cardiac imaging is useful for extracting functional derived parameters such as ejection fraction, valve excursions, and global longitudinal strain, and when performing anatomical structures tracking using slice following or valve intervention's planning. Completely automatic segmentation methods are still challenging tasks because of their fast movements and the different positions that prevent good visibility of the leaflets along the full cardiac cycle. In this article, we propose a processing pipeline to track the displacement of the aortic and mitral valve annuli from high-resolution cardiac four-dimensional computed tomographic angiography (4D-CTA). The proposed method is based on the dynamic separation of left ventricle, left atrium and aorta using statistical shape modeling and an energy minimization algorithm based on graph-cuts and has been evaluated on a set of 15 electrocardiography-gated 4D-CTAs. We report a mean agreement distance between manual annotations and our proposed method of 2.52±1.06 mm for the mitral annulus and 2.00±0.69 mm for the aortic valve annulus based on valve locations detected from manual anatomical landmarks. In addition, we show the effect of detecting the valvular planes on derived functional parameters (ejection fraction, global longitudinal strain, and excursions of the mitral and aortic valves).

European Registry on Helicobacter pylori Management: Effectiveness of First and Second-Line Treatment in Spain.

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain.

[Medium-term management of protein-losing enteropathy of cardiac origin unresponsive to medical therapy in a patient awaiting heart transplantation]. / Manejo a medio plazo de la enteropatía pierde-proteínas de causa cardíaca, en un paciente que no responde al tratamiento médico, en espera de trasplante cardíaco.

Protein-losing enteropathy is characterized by excessive leaking of serum proteins into the gastrointestinal tract, as a result of disease progression in several diseases. We report the case of a 17-year-old-woman with hypoproteinemia, generalized edema and serosal effusions diagnosed as protein-losing enteropathy due to right ventricular failure secondary to previous surgical damage. All previously described therapies were ineffective in curing or relieving the disease or its symptoms, and the patient was listed for heart transplantation. During the 7-month period on the waiting list, the patient was managed as an outpatient, with fortnightly albumin infusions and intravenous furosemide administration, which allowed her a better quality of life during that period, avoiding further admissions.

Comparative study of six different sludges by sequential speciation of heavy metals.

The presence of heavy metals in the sludges produced in wastewater treatment plants restricts their use for agricultural purposes. This study looks at different types of sludge (aerobic, anaerobic, unstabilised, sludge from a waste stabilisation pond, sludge from an extended aeration plant and heat treated sludge) and compares the distribution of heavy metals with the treatment that they have undergone. In addition, the total quantity of metals (Cd, Cr, Cu, Ca, K, Fe, Mg, Ni, Na, Pb and Zn) and some agronomic parameters necessary for characterising a sludge as suitable for use as amendment were determined. The BCR method for heavy metal speciation was followed. Principal component analysis (PCA) was applied in order to obtain more information about metal speciation in the sewage sludges. It was confirmed that the concentration of heavy metals did not exceed the limits set out by European legislation and that the stabilisation treatment undergone by the sludges strongly influenced the heavy metal distribution and the phases to which they were associated. The waste stabilisation pond sludge, which has undergone a higher degree of mineralisation than the others, shows a lower metal bioavailability index since practically all the heavy metals in it are associated to the oxidisable and residual fraction. On the other hand the unstabilised sludge, which, along with that exposed to extended aeration, contains the highest accumulations of heavy metals in the most easily assimilable fractions.

Ecotoxicity, phytotoxicity and extractability of heavy metals from different stabilised sewage sludges.

The presence of heavy metals in the sludges produced in wastewater treatment plants restricts their use for agricultural purposes. This study compares different types of sludges (aerobic, anaerobic, unstabilised and sludge from a waste stabilisation pond) in order to assess the extractability of heavy metals using simple extraction, water and DTPA. The stabilisation treatment undergone by the sludges influenced the heavy metals extractability. The least mineralised sludges (unstabilised and aerobic) showed higher metal extractability. The sewage sludges were subjected to chemical characterisation and toxicity testing (ecotoxicity and phytotoxicity assays) in absence of substrate, to provide a preliminary assessment of their suitability for land application. The ecotoxicity assays confirmed that no sludge constituted a hazardous waste. The sludge extracts had significant adverse effect on the germination index (GI) of barley (Hordeum vulgare L.) and cress (Lepidium sativum L.), a fact which indicates that some characteristics affected root growth.