Publications by authors named "Javier Martinez"

246 Publications

Lightweight Thermal Compensation Technique for MEMS Capacitive Accelerometer Oriented to Quasi-Static Measurements.

Sensors (Basel) 2021 Apr 30;21(9). Epub 2021 Apr 30.

Department of Electronic Engineering and Communications, Universidad de Zaragoza, C/ María deuna 1, 50018 Zaragoza, Spain.

The application of MEMS capacitive accelerometers isimited by its thermal dependence, and each accelerometer must be individually calibrated to improve its performance. In this work, aight calibration method based on theoretical studies is proposed to obtain two characteristic parameters of the sensor's operation: the temperature drift of bias and the temperature drift of scale factor. This method requiresess data to obtain the characteristic parameters, allowing a faster calibration. Furthermore, using an equation with fewer parameters reduces the computational cost of compensation. After studying six accelerometers, modelIS3DSH, their characteristic parameters are obtained in a temperature range between 15 °C and 55 °C. It is observed that the Temperature Drift of Bias (TDB) is the parameter with the greatest influence on thermal drift, reaching 1.3 mg/°C. The Temperature Drift of Scale Factor (TDSF) is always negative and ranges between 0 and -400 ppm/°C. With these parameters, the thermal drifts are compensated in tests with 20 °C of thermal variation. An average improvement of 47% was observed. In the axes where the thermal drift was greater than 1 mg/°C, the improvement was greater than 80%. Other sensor behaviors have also been analyzed, such as temporal drift (up to 1 mg/h for three hours) and self-heating (2-3 °C in the first hours with the corresponding drift). Thermal compensation has been found to reduce the effect of theatter in the first hours after power-up of the sensor by 43%.
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http://dx.doi.org/10.3390/s21093117DOI Listing
April 2021

The oxidoreductase PYROXD1 uses NAD(P) as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response.

Mol Cell 2021 Apr 23. Epub 2021 Apr 23.

Max Perutz Labs, Medical University of Vienna, Vienna BioCenter (VBC), Dr. Bohr-Gasse 9/2, 1030 Vienna, Austria. Electronic address:

The tRNA ligase complex (tRNA-LC) splices precursor tRNAs (pre-tRNA), and Xbp1-mRNA during the unfolded protein response (UPR). In aerobic conditions, a cysteine residue bound to two metal ions in its ancient, catalytic subunit RTCB could make the tRNA-LC susceptible to oxidative inactivation. Here, we confirm this hypothesis and reveal a co-evolutionary association between the tRNA-LC and PYROXD1, a conserved and essential oxidoreductase. We reveal that PYROXD1 preserves the activity of the mammalian tRNA-LC in pre-tRNA splicing and UPR. PYROXD1 binds the tRNA-LC in the presence of NAD(P)H and converts RTCB-bound NAD(P)H into NAD(P), a typical oxidative co-enzyme. However, NAD(P) here acts as an antioxidant and protects the tRNA-LC from oxidative inactivation, which is dependent on copper ions. Genetic variants of PYROXD1 that cause human myopathies only partially support tRNA-LC activity. Thus, we establish the tRNA-LC as an oxidation-sensitive metalloenzyme, safeguarded by the flavoprotein PYROXD1 through an unexpected redox mechanism.
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http://dx.doi.org/10.1016/j.molcel.2021.04.007DOI Listing
April 2021

Turner syndrome, unicuspid aortopathy, and pregnancy: Difficult decisions for complex scenarios.

Arch Cardiol Mex 2021 ;91(2):252-254

Department of Cardiac Surgery. Área de Gestión Clínica del Corazón del Hospital Universitario Central de Asturias, Oviedo, Asturias, España.

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http://dx.doi.org/10.24875/ACM.20000176DOI Listing
January 2021

Intracranial arachnoid cysts and epilepsy in children: Should this be treated surgically? Our 29-year experience and review of the literature.

Neurocirugia (Astur) 2021 Apr 16. Epub 2021 Apr 16.

Department of Pediatrics, Universitary Hospital Miguel Servet, Zaragoza, Spain.

Introduction And Objective: Arachnoid cysts (ACs) are relatively frequent lesions related to different neurological symptoms, being mostly incidentally diagnosed. This study aims to clarify whether AC surgery in epileptic patients is useful in their treatment.

Material And Methods: The patients registered in the database of the Neuropediatrics Section from May 1990 to August 2019 are analyzed retrospectively. Patients in whom the diagnosis of ACs and epilepsy coincide are studied. The location, size and number of ACs, neurological development, age at diagnosis, follow-up time, the performance of surgery on the cyst, evolution, anatomical relationship between brain electrical activity and location of AC, and type of epilepsy are analyzed.

Results: After analyzing the database, we found 1881 patients diagnosed with epilepsy, of which 25 had at least one intracranial AC. In 9 of the patients, cerebral or genetic pathologies were the cause of epilepsy. Of the other 16, only 2 patients showed that the type of epilepsy and the epileptogenic focus coincided with the location of the AC; one of them was surgically treated without success, and the other one remained asymptomatic without receiving medical or surgical treatment.

Conclusions: Although it is necessary to design a prospective study to establish causality, the results of our research and the available literature suggest that there is no causal relationship between the presence of ACs and epilepsy. The study and treatment of these patients should be carried out in a multidisciplinary epilepsy surgery unit, without initially assuming that the AC is the cause of epilepsy.
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http://dx.doi.org/10.1016/j.neucir.2021.03.003DOI Listing
April 2021

Global multi-site, prospective analysis of cataract surgery outcomes following ICHOM standards: the European CAT-Community.

Graefes Arch Clin Exp Ophthalmol 2021 Apr 14. Epub 2021 Apr 14.

Department of Ophthalmology (Qvision), Vithas Virgen del Mar Hospital, Almería, Spain.

Purpose: To evaluate in a large sample of patients from 10 different European centers the results of cataract surgery, characterizing the relationship between patient-reported outcomes (PROMs) and clinician-reported outcome measures (CROMs).

Methods: Prospective non-interventional multicenter observational descriptive study analyzing the clinical outcomes of a total of 3799 cases undergoing cataract surgery (mean age: 72.7 years). In all cases, the cataract surgery standard developed by the International Consortium for Health Outcomes Measurements (ICHOM) was used to register the clinical data. Three-month postoperative visual acuity and refraction data were considered CROMs, whereas Rasch-calibrated item 2 (RCCQ2) and total Catquest-9SF score (CQ) were considered PROMs.

Results: Postoperative corrected distance visual acuity (CDVA) was 0.3 logMAR or better in 88.7% (2505/2823) of eyes. Mean differences between preoperative and postoperative RCCQ2 and CQ scores were -3.09 and -2.39, respectively. Visual function improvement with surgery was reported by 91.5% (2163/2364) of patients. Statistically significant, although weak, correlations of postoperative CDVA with postoperative refraction, PROMs, and complications were found (0.133 ≤ r ≤0.289, p < 0.001). A predictive model (R: 0.254) of postoperative CDVA considering 10 variables was obtained, including preoperative CDVA, different ocular comorbidities, age, gender and intraoperative complications. Likewise, another predictive model (R: 0.148) of postoperative CQ considering a total of 14 variables was obtained, including additionally preoperative CQ, target refraction and previous surgeries.

Conclusions: Cataract surgery provides an improved functional vision in most of patients although this improvement can be limited by ocular comorbidities and complications. The relationship between PROMs and CROMs is multifactorial and complex.
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http://dx.doi.org/10.1007/s00417-021-05181-5DOI Listing
April 2021

Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis.

J Hepatol 2021 Apr 9. Epub 2021 Apr 9.

Gastroenterology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain.

Background And Aims: Antibiotic prophylaxis reduces the risk of infection and mortality in cirrhotic patients with acute variceal bleeding (AVB). This study examines the incidence and risk factors of bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis.

Methods: Post-hoc analysis of the database of an international, multicenter, observational study designed to examine the role of preemptive TIPS in patients with cirrhosis and AVB. Data collected on patients with cirrhosis hospitalized for AVB (n=2138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization.

Results: 1656 patients out of 1770 (93.6%) received antibiotic prophylaxis, the most frequently used being third-generation cephalosporins (76.2%) and quinolones (19.0%). Of these, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (OR 3.1; 95%CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95%CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95%CI 1.8-3.8), nasogastric tube (OR 1.7; 95%CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95%CI 1.2-4.9).

Conclusion: Bacterial infections develop in almost one fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Lay Summary: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infection is the most frequent and occurs early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
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http://dx.doi.org/10.1016/j.jhep.2021.03.026DOI Listing
April 2021

Involvement of ethylene receptors in the salt tolerance response of Cucurbita pepo.

Hortic Res 2021 Apr 1;8(1):73. Epub 2021 Apr 1.

Department of Biology and Geology, Agri-food Campus of International Excellence (CeiA3) and Research Center CIAMBITAL, University of Almería, 04120, Almería, Spain.

Abiotic stresses have a negative effect on crop production, affecting both vegetative and reproductive development. Ethylene plays a relevant role in plant response to environmental stresses, but the specific contribution of ethylene biosynthesis and signalling components in the salt stress response differs between Arabidopsis and rice, the two most studied model plants. In this paper, we study the effect of three gain-of-function mutations affecting the ethylene receptors CpETR1B, CpETR1A, and CpETR2B of Cucurbita pepo on salt stress response during germination, seedling establishment, and subsequent vegetative growth of plants. The mutations all reduced ethylene sensitivity, but enhanced salt tolerance, during both germination and vegetative growth, demonstrating that the three ethylene receptors play a positive role in salt tolerance. Under salt stress, etr1b, etr1a, and etr2b germinate earlier than WT, and the root and shoot growth rates of both seedlings and plants were less affected in mutant than in WT. The enhanced salt tolerance response of the etr2b plants was associated with a reduced accumulation of Na in shoots and leaves, as well as with a higher accumulation of compatible solutes, including proline and total carbohydrates, and antioxidant compounds, such as anthocyanin. Many membrane monovalent cation transporters, including Na/H and K/H exchangers (NHXs), K efflux antiporters (KEAs), high-affinity K transporters (HKTs), and K uptake transporters (KUPs) were also highly upregulated by salt in etr2b in comparison with WT. In aggregate, these data indicate that the enhanced salt tolerance of the mutant is led by the induction of genes that exclude Na in photosynthetic organs, while maintaining K/Na homoeostasis and osmotic adjustment. If the salt response of etr mutants occurs via the ethylene signalling pathway, our data show that ethylene is a negative regulator of salt tolerance during germination and vegetative growth. Nevertheless, the higher upregulation of genes involved in Ca signalling (CpCRCK2A and CpCRCK2B) and ABA biosynthesis (CpNCED3A and CpNCED3B) in etr2b leaves under salt stress likely indicates that the function of ethylene receptors in salt stress response in C. pepo can be mediated by Ca and ABA signalling pathways.
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http://dx.doi.org/10.1038/s41438-021-00508-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012379PMC
April 2021

Efficient Synthesis of Cyclic Carbonates from Unsaturated Acids and Carbon Dioxide and their Application in the Synthesis of Biobased Polyurethanes.

Chempluschem 2021 Mar;86(3):460-468

Universidad de Castilla-La Mancha, Departamento de Química Inorgánica, Orgánica y Bioquímica-Centro de Innovación en Química Avanzada (ORFEO-CINQA), Facultad de Ciencias y Tecnologías Químicas, Avda. Camilo José Cela, 10, 13071, Ciudad Real, Spain.

Bio-derived furan- and diacid-derived cyclic carbonates have been synthesized in high yields from terminal epoxides and CO . Furthermore, four highly substituted terpene-derived cyclic carbonates were isolated in good yields with excellent diastereoselectivity in some cases. Eleven new cyclic carbonates derived from 10-undecenoic acid under mild reaction conditions were prepared, providing the corresponding carbonate products in excellent yields. The catalyst system also performed the conversion of an epoxidized fatty acid n-pentyl ester into a cyclic carbonate under relatively mild reaction conditions (80 °C, 20 bar, 24 h). This bis(cyclic carbonate) was obtained in high yields and with different cis/trans ratios depending on the co-catalyst used. An allyl alcohol by-product was only observed as a minor product when bis(triphenylphosphine)iminium chloride was used as co-catalyst. Finally, two cyclic carbonates were used as building blocks for the preparation of non-isocyanate poly(hydroxy)urethanes by reaction with 1,4-diaminobutane.
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http://dx.doi.org/10.1002/cplu.202100079DOI Listing
March 2021

Extended-Spectrum b-Lactamase-Producing Enterobacteriaceae Causing Community-Acquired Urinary Tract Infections in Children in Colombia.

Indian Pediatr 2021 Feb;58(2):144-148

Department of Medical Epidemiology, Fundación Universitaria de Ciencias de la Salud (FUCS) - Hospital de San José and Hospital Infantil Universitario de San José de Bogotá, Colombia.

Objective: To characterize the pediatric patients presenting at the two pediatric centers in Bogotá, with first isolate urine culture of community-acquired extended-spectrum b-lactamase (ESBL)-producing enterobacteriaceae.

Methods: Review of microbiological data of children between January, 2012 and December, 2018, obtained using the WHONET software.

Results: A total of 2657 Escherichia coli, Klebsiella spp and Proteus mirabilis - positive urine cultures were obtained within a 6-year period; data of 132 patients were finally selected. Frequency of ESBL-producing bacteria infections in community-acquired urinary tract infections (UTI) was 5%: 123 E. coli (93.2%), 7 K. pneumoniae (5.2%), 1 K. oxytoca (0.8%), and 1 P. mirabilis (0.8%).

Conclusion: A predominance of female sex, preschool children, and lower tract urinary infections were found, as well as a low frequency of comorbidities. Adequate sensitivity to amikacin and nitrofurantoin was found in this study.
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February 2021

BLOOD PARASITE INFECTIONS IN STRIGIFORMES AND PSITTACIFORMES SPECIES IN CAPTIVITY WITH A NEW RECORD OF POTENTIAL FATAL BLOOD PARASITE TRANSMISSION TO PARROTS.

J Zoo Wildl Med 2021 Jan;51(4):799-813

Department of Evolutionary Ecology, National Museum of Natural Sciences, Consejo Superior de Investigaciones Científicas, Madrid, Spain.

Although parrot species are infrequently infected by hemoparasites in the wild, some fatal infections have been reported in captive individuals. Conversely birds of prey are frequently infected by hemoparasites. In this study, 193 captive birds from Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) centers in Madrid, Spain, belonging to orders Psittaciformes, Accipitriformes, Strigiformes, and Falconiformes, were blood-sampled in search of parasite infections. Molecular and microscopic analyses were conducted to detect parasites of the following genera: , , , , and . Infections by microfilariae and Coccidia were also searched in blood samples. Surprisingly, infections by a common parasite from owls, were detected in the cadavers of two species of parrots, and . The same haplotype was also detected in the cadavers of two owl species, and . All these birds were housed and died in the same center. Infections by species of and were also found in different species of raptors. Nocturnal raptors (Strigiformes) show significantly higher prevalence of infection by blood parasites than diurnal raptors (Falconiformes and Accipitriformes). In conclusion, a potential fatal transmission of from Strigiformes to Psittaciformes species, is reported and several infections by different blood parasites were detected in birds of prey. These results emphasize the importance of increasing prevention measures to avoid or reduce the transmission of blood parasites among birds from different species housed in these types of centers.
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http://dx.doi.org/10.1638/2019-0187DOI Listing
January 2021

Hyperkalemia influences the outcome of patients with cirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF).

Dig Liver Dis 2021 Jan 11. Epub 2021 Jan 11.

Liver Unit, Hospital Clinic, Spain; Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), y Centro de Investigaciones en Red Hepaticas y Digestivas (CIBERehd), Barcelona, Catalonia, Spain; Faculty of Medicine and health sciences, University of Barcelona. Electronic address:

Introduction: The presence of hyperkalemia in different clinical scenarios has been described as a risk factor for mortality. Information about this electrolyte disorder in patients with cirrhosis is limited and there are no data in patients with acute-on-chronic liver failure (ACLF).

Aim: The aim of this study was to investigate whether hyperkalemia is a risk factor for mortality in patients with cirrhosis and acute decompensation (AD) with and without ACLF.

Methods: We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,314 consecutive patients admitted to 29 European centers with AD both with and without associated ACLF (294 and 1020 respectively). Hyperkalemia was defined as serum potassium ≥ 5.0 mEq/L. All patients had at least one valid measure of serum potassium from admission and/or through the whole hospitalization.

Results: 1314 patients were admitted with AD and 294 of them had ACLF at admission. Prevalence of hyperkalemia was significantly higher in ACLF versus AD (22.4% and 8.6% respectively, p<0.001). Hyperkalemia was associated with an increased 90, 180 and 360-day mortality risk in ACLF compared to AD (HR 10 vs 2.3 at 90-day p<0.001, 8.9 vs 3.1 at 180-day, p<0.001 and 5.8 vs 3.8 at 360-day, p<0.001). In a multivariate analysis, the presence of hyperkalemia during admission was independently associated with 90-day mortality [HR 2.4 (1.7 - 3.4)]. Variability of potassium between two valid measures ≥ 0.9 mg/dl was always also associated with a higher mortality rate. Addition of hyperkalemia to MELD score (MELD-K model) improved the accuracy to predict 90-day mortality risk.

Conclusions: Hyperkalemia is an independent risk factor of mortality in patients with AD and ACLF. Addition of hyperkalemia to the MELD score improves diagnostic accuracy to predict 90-day mortality in patients with AD and ACLF.
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http://dx.doi.org/10.1016/j.dld.2020.12.009DOI Listing
January 2021

Nicotine pharmacokinetics of electronic cigarettes: A pooled data analysis from the literature.

Toxicol Rep 2021 19;8:84-95. Epub 2020 Dec 19.

Japan Tobacco International SA, 8 rue Kazem Radjavi, 1202, Geneva, Switzerland.

Several regulatory initiatives around the world restrict the amount of nicotine permitted in electronic cigarette liquids in an attempt to reproduce the nicotine delivery of combusted tobacco products, such as cigarettes, and or reduce the risk of consumers absorbing too much nicotine into their body at one time. Such an approach, however, assumes that (i) there is a strong correlation between the levels of nicotine in electronic cigarette liquids and nicotine intake into the body and (ii) that this correlation holds true across the various different types of electronic cigarette devices currently available on the market. In order to test these hypotheses, this study examines the available scientific literature on nicotine intake from electronic cigarettes, as measured by levels in the blood. Analysis of the published data reveals that nicotine absorption into the body is influenced by a combination of many factors, including electronic cigarette liquid composition, user behavior and device characteristics. Notably, it was observed that open-tank (refillable) electronic cigarettes, which often enable users to vary device power, can deliver high nicotine levels to consumers, sometimes at greater doses than a conventional tobacco cigarette, even at the lower nicotine liquid concentrations typically available. For electronic cigarettes to be viable alternative choices to smoking, they should provide consumers with an equally satisfying experience, including in terms of nicotine absorption into the body. Therefore, any regulation seeking to restrict the amount of nicotine in electronic cigarette liquids should take all the factors influencing nicotine intake into account.
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http://dx.doi.org/10.1016/j.toxrep.2020.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786013PMC
December 2020

Clinical Analysis of Central Islands after Small Incision Lenticule Extraction (SMILE).

Curr Eye Res 2021 Jan 4:1-5. Epub 2021 Jan 4.

Department of Ophthalmology (Qvision), Vithas Virgen del Mar Hospital, Almería, Spain.

: To evaluate the incidence of central islands after 6-month follow-up of Small Incision Lenticule Extraction (SMILE) and to assess their role in safety and accuracy.: Analysis of the preoperative and postoperative corneal tomography, best spectacle refraction and corrected distance visual acuity of 82 subjects that underwent SMILE. Incidence of central islands was assessed through total corneal spherical aberration (SA) over 4 mm of central diameter and the SA was compared between two groups with and without safety loss (CDVA difference ≥0.1 logMAR from preoperative). The cut-off value for detecting the risk of postoperative central island development was calculated. The influence in accuracy was calculated through magnitude of error of the spherical equivalent and astigmatism, both for spectacle refraction at corneal plane (SE-Rx and AST-Rx) and for total corneal refractive power at 3 mm (SE-TCRP3 and AST-TCRP3).: Five from 82 eyes resulted in a loss of safety, obtaining significant differences in SA, both preoperatively ( = .01) and postoperatively ( = .007) after stratification by safety loss. A preoperatively cut-off value ≤0.012 μm of SA predicted the appearance of central islands with sensitivity of 100% and specificity of 75%. Despite postoperative SA being related to the preoperative spherical equivalent, for both SE-Rx and SE-TCRP3, this tendency disappeared after readjusting results according to a nomogram.: Central islands in SMILE, despite being a rare adverse event, can affect the safety of the procedure and are related to preoperative central steepness, not corrected by the spherical lenticule, which is clearly visible postoperatively.
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http://dx.doi.org/10.1080/02713683.2020.1867188DOI Listing
January 2021

Toward a Neutral Single-Component Amidinate Iodide Aluminum Catalyst for the CO Fixation into Cyclic Carbonates.

Inorg Chem 2021 Jan 29;60(2):1172-1182. Epub 2020 Dec 29.

Laboratorio de Química Inorgánica, Facultad de Química y Farmacia, Pontificia Universidad Católica de Chile, Casilla 306, Santiago-22 6094411, Chile.

A new iodide aluminum complex ({AlI(κ-naphbam)}, ) supported by a tetradentate amidinate ligand derived from a naphthalene-1,8-bisamidine precursor (naphbamH, ) was obtained in quantitative yield via reaction of the corresponding methyl aluminum complex ({AlMe(κ-naphbam)}, ) with 1 equiv of I in CHCl at room temperature. Complexes and were tested and found to be active as catalysts for the cyclic carbonate formation from epoxides at 80 °C and 1 bar of CO pressure. A first series of experiments were carried out with 1.5 mol % of the alkyl complex and 1.5 mol % of tetrabutylammonium iodide (TBAI) as a cocatalyst; subsequently, the reactions were carried out with 1.5 mol % of iodide complex as a single-component catalyst. Compound is one of the first examples of a nonzwitterionic halide single-component aluminum catalyst producing cyclic carbonates. The full catalytic cycle with characterization of all minima and transition states was characterized by quantum chemistry calculations (QCCs) using density functional theory. QCCs on the reaction mechanism support a reaction pathway based on the exchange of the iodine contained in the catalyst by 1 equiv of epoxide, with subsequent attack of I to the epoxide moiety producing the ring opening of the epoxide. QCCs triggered new insights for the design of more active halide catalysts in future explorations of the field.
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http://dx.doi.org/10.1021/acs.inorgchem.0c03290DOI Listing
January 2021

Efficacy and safety of once-monthly Risperidone ISM in schizophrenic patients with an acute exacerbation.

NPJ Schizophr 2020 Nov 25;6(1):37. Epub 2020 Nov 25.

Medical Department, Laboratorios Farmacéuticos ROVI, S.A, Madrid, Spain.

To evaluate the efficacy and safety of Risperidone ISM against placebo in patients with acute exacerbation of schizophrenia. A multicenter, randomized, double-blind, placebo-controlled study was conducted between June 2017 and December 2018 (NCT03160521). Eligible patients received once-monthly intramuscular injections of Risperidone ISM (75 or 100 mg) or placebo for 12 weeks. The primary efficacy outcome was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 12. The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Altogether, 438 patients were randomized (1:1:1) and 390 included in the modified ITT efficacy set. The PANSS total score (mean difference, 95% CI) improved significantly from baseline to day 85 with Risperidone ISM 75 and 100 mg, with placebo-adjusted differences of -13.0 (95% CI, -17.3 to -8.8); (p < 0.0001), and -13.3 (-17.6 to -8.9); (p < 0.0001), respectively. Significantly improved mean changes were also obtained for CGI-S score from baseline to day 85 for both doses of Risperidone ISM compared with placebo -0.7 (-1.0 to -0.5); p < 0.0001, for both doses. The statistically significant improvement for both efficacy outcomes were observed as early as 8 days after first injection. The most frequently reported treatment-emergent adverse events were increased blood prolactin (7.8%), headache (7.3%), hyperprolactinemia (5%), and weight increase (4.8%). Neither new nor unexpected relevant safety information was recorded. Risperidone ISM provided rapid and progressive reduction of symptoms in patients with acutely exacerbated schizophrenia without need of oral risperidone supplementation or loading doses. Both doses were safe and well tolerated.
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http://dx.doi.org/10.1038/s41537-020-00127-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688968PMC
November 2020

Pupil Diameter in Patients With Multifocal Intraocular Lenses.

J Refract Surg 2020 Nov;36(11):750-756

Purpose: To evaluate the distribution of pupil size in patients implanted with multifocal intraocular lenses (IOLs) and to assess the variations according to age.

Methods: A total of 168 eyes that had implantation of several multifocal IOLs and were measured at the 3-month follow-up visit were included in the analysis. The Keratograph 5M (Oculus Optikgeräte) was used to measure the photopic and mesopic pupil size, as well as the average between both (average pupil size). Eyes were stratified in four groups by age: 50 years or younger, 51 to 60 years, 61 to 70 years, and older than 70 years.

Results: Considering the total sample, 84.5% and 95.8% of eyes had a photopic pupil size of 3 and 3.5 mm or less, respectively. The mesopic pupil size was greater than 4.5 mm in 39.3% and greater than 5 mm in 16.7% of eyes. The average pupil size was 3.5 and 4 mm or less in 54.2% and 85.1% of eyes, respectively. Mesopic pupil size resulted in a steeper decrease with age than photopic pupil size: 0.028 versus 0.015 mm/year, respectively. Statistically significant differences were found among the four age groups (P < .0005). No significant mean differences were found between multifocal IOL models for photopic pupil size, mesopic pupil size, or average pupil size (P > .05).

Conclusions: Eyes implanted with multifocal IOLs had a photopic pupil size of 3.5 mm or less and mesopic pupil size of 5 mm or less. Mesopic and photopic pupil size decreased 0.28 and 0.15 mm per decade, respectively. This information can help surgeons to understand the general functioning of multifocal IOLs whose performance varies with pupil size. [J Refract Surg. 2020;36(11):750-756.].
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http://dx.doi.org/10.3928/1081597X-20200813-01DOI Listing
November 2020

Agreement between subjective and predicted high and low contrast visual acuities with a double-pass system.

Graefes Arch Clin Exp Ophthalmol 2020 Oct 31. Epub 2020 Oct 31.

Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.

Purpose: To evaluate the agreement between subjective high and low contrast visual acuity (VA) and predicted values from double-pass system measurements in healthy candidates to laser refractive surgery.

Methods: Ninety-two eyes measured during the preoperative screening to laser refractive surgery were included in this retrospective analysis. High contrast subjective visual acuity (HCVA) and low contrasts at 20% (LCVA20) and 9% (LCVA9) were compared with the predicted VA obtained with a commercial double-pass system (OQAS) at the same levels of contrast, 100% (OV100), 20% (OV20), and 9% (OV9). The agreement was evaluated with Bland-Altman analysis computing the limits of agreement (LoAs) and the correlations with the spearman rho.

Results: An underestimation of VA was obtained with the double-pass system for the highest contrast. Differences between predictive and subjective measurements were statistically significant for 100% contrast (- 0.08 logMAR, p < 0.0005), but not for 20% (- 0.03 logMAR, p = 0.07) and 9% (- 0.02 logMAR, p = 0.9) of contrasts. The LoAs increased with the decrease of contrast from 0.29 with 100% to 0.39 logMAR with 9% of contrast. A weak correlation was obtained between subjective and predicted VA (rho ≤ 0.33) that was only significant for 100% (p = 0.001) and 20% (p = 0.004) contrasts.

Conclusion: Mean differences between methods were reasonably small so mean results obtained for predicted VA in OQAS studies can be considered as reliable, at least in healthy subjects and for low contrast. However, limits of agreement were considerably poor which means that OQAS cannot replace individual subjective measurements of VA in clinical practice.
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http://dx.doi.org/10.1007/s00417-020-04987-zDOI Listing
October 2020

Cancer and implantable cardiac defibrillator. Causality, confusion or chance?

Med Clin (Barc) 2020 Oct 14. Epub 2020 Oct 14.

Cardiología, Área Clínica del Corazón, Complejo Hospitalario de Navarra, Pamplona, España; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Navarra, España.

Introduction And Objectives: implantable cardiac defibrillator (ICD) has been established as a therapy for malignant ventricular arrhythmias in patients at high risk of suffering them. Some studies suggest a possible relationship between the development of cancer and some prosthetic materials. Likewise, some investigations describe a higher incidence of cancer in patients with an ICD that suggest a potential relationship.

Methods: Retrospective cohort study of patients that underwent implantation of an ICD in the Complejo Hospitalario de Navarra between 2000 and 2016. The follow-up finished in June 2018. Sociodemographic, comorbidities and oncological data was analysed. Cancer incidence rates were estimated and compared with the general population data and with data of a cohort of patients with reduced LVEF heart failure. Risk of cancer models were adjusted by competitive risk models.

Results: 497 patients were included, mostly male (89.1%), with a mean age of 59.98 (14.98) years and a proportion of smokers of 67.6% and of ischaemic heart disease of 51.6%. The cancer incidence rate in the sample was 1230.9 per 100.000 person-year. In our study, features associated with cancer were older age, higher tobacco use and ischaemic cardiopathy.

Conclusions: In our sample of ICD carriers the incidence of cancer is high. This finding mainly seems to be related to tobacco usage and higher age.
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http://dx.doi.org/10.1016/j.medcli.2020.07.027DOI Listing
October 2020

Sports-related lower limb muscle injuries: pattern recognition approach and MRI review.

Insights Imaging 2020 Oct 7;11(1):108. Epub 2020 Oct 7.

Medical Services, Fútbol Club Barcelona, Barcelona, Spain.

Muscle injuries of the lower limbs are currently the most common sport-related injuries, the impact of which is particularly significant in elite athletes. MRI is the imaging modality of choice in assessing acute muscle injuries and radiologists play a key role in the current scenario of multidisciplinary health care teams involved in the care of elite athletes with muscle injuries. Despite the frequency and clinical relevance of muscle injuries, there is still a lack of uniformity in the description, diagnosis, and classification of lesions. The characteristics of the connective tissues (distribution and thickness) differ among muscles, being of high variability in the lower limb. This variability is of great clinical importance in determining the prognosis of muscle injuries. Recently, three classification systems, the Munich consensus statement, the British Athletics Muscle Injury classification, and the FC Barcelona-Aspetar-Duke classification, have been proposed to assess the severity of muscle injuries. A protocolized approach to the evaluation of MRI findings is essential to accurately assess the severity of acute lesions and to evaluate the progression of reparative changes. Certain MRI findings which are seen during recovery may suggest muscle overload or adaptative changes and appear to be clinically useful for sport physicians and physiotherapists.
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http://dx.doi.org/10.1186/s13244-020-00912-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539263PMC
October 2020

Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide.

Sci Rep 2020 09 2;10(1):14430. Epub 2020 Sep 2.

Unit of Synthesis and Biomedical Applications of Peptides, IQAC-CSIC, Jordi Girona, 18-26, 08034, Barcelona, Spain.

Based on the structure of an HIV-1 entry inhibitor peptide two stapled- and a retro-enantio peptides have been designed to provide novel prevention interventions against HIV transmission. The three peptides show greater inhibitory potencies in cellular and mucosal tissue pre-clinical models than the parent sequence and the retro-enantio shows a strengthened proteolytic stability. Since HIV-1 fusion inhibitor peptides need to be embedded in the membrane to properly interact with their viral target, the structural features were determined by NMR spectroscopy in micelles and solved by using restrained molecular dynamics calculations. Both parent and retro-enantio peptides demonstrate a topology compatible with a shared helix-turn-helix conformation and assemble similarly in the membrane maintaining the active conformation needed for its interaction with the viral target site. This study represents a straightforward approach to design new targeted peptides as HIV-1 fusion inhibitors and lead us to define a retro-enantio peptide as a good candidate for pre-exposure prophylaxis against HIV-1.
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http://dx.doi.org/10.1038/s41598-020-71404-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468280PMC
September 2020

ANGEL2 is a member of the CCR4 family of deadenylases with 2',3'-cyclic phosphatase activity.

Science 2020 07;369(6503):524-530

Max Perutz Labs, Medical University of Vienna, Vienna BioCenter, 1030 Vienna, Austria.

RNA molecules are frequently modified with a terminal 2',3'-cyclic phosphate group as a result of endonuclease cleavage, exonuclease trimming, or de novo synthesis. During pre-transfer RNA (tRNA) and unconventional messenger RNA (mRNA) splicing, 2',3'-cyclic phosphates are substrates of the tRNA ligase complex, and their removal is critical for recycling of tRNAs upon ribosome stalling. We identified the predicted deadenylase angel homolog 2 (ANGEL2) as a human phosphatase that converts 2',3'-cyclic phosphates into 2',3'-OH nucleotides. We analyzed ANGEL2's substrate preference, structure, and reaction mechanism. Perturbing ANGEL2 expression affected the efficiency of pre-tRNA processing, X-box-binding protein 1 () mRNA splicing during the unfolded protein response, and tRNA nucleotidyltransferase 1 (TRNT1)-mediated CCA addition onto tRNAs. Our results indicate that ANGEL2 is involved in RNA pathways that rely on the ligation or hydrolysis of 2',3'-cyclic phosphates.
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http://dx.doi.org/10.1126/science.aba9763DOI Listing
July 2020

Chest wall tuberculosis: a rare extrapulmonary localization.

Med Clin (Barc) 2020 Jul 18. Epub 2020 Jul 18.

Servicio de Medicina Interna. Hospital Universitario Virgen de las Nieves, Granada, España.

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http://dx.doi.org/10.1016/j.medcli.2020.04.045DOI Listing
July 2020

Pupil dependence assessment with multifocal intraocular lenses through visual acuity and contrast sensitivity defocus curves.

Eur J Ophthalmol 2020 Jul 3:1120672120940202. Epub 2020 Jul 3.

Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.

Purpose: To identify the most sensitive visual performance metric for evaluating the pupil-dependency of a multifocal intraocular lens (MIOL) and to determine the pupil measurement method most correlated with such metric.

Methods: Twenty-seven right eyes implanted with a MIOL were included in the analysis. Three pupil size measurements were obtained preoperatively and at 1 month after surgery with the Keratograph 5M system: photopic (PP), mesopic (MP), and the average from both (AP). Pupil was also measured with a rule (RP) under the same light conditions of postoperative visual performance measurements that included, corrected visual acuities (VA) at three distances (far, 67 cm and 40 cm), visual acuity (VADC) and contrast sensitivity defocus curves for optotype sizes of 0.3 logMAR (CSDC3) and 0.7 logMAR (CSDC7). Differences in visual performance were also analyzed for eyes with RP > 3 mm (Group A) and RP ⩽ 3 mm (Group B).

Results: PP diameter decreased after surgery by 16% ( = 0.001), whereas MP ( = 0.013) and AP ( = 0.008) decreased by 10%. The best agreement with RP was obtained for AP. Group B showed a trend to better performance than Group A for all the included metrics ( > 0.05). From the three types of defocus curves, CSDC3 obtained generally highest statistical power for testing differences between groups. The strongest statistically significant correlations between pupil size and CSDC3 were obtained for RP and AP.

Conclusion: The CSDC3 was the most sensitive metric to detect MIOL pupil-dependency. PR and AP were more correlated with CSDC3 than PP and MP.
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http://dx.doi.org/10.1177/1120672120940202DOI Listing
July 2020

Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature.

F1000Res 2019 4;8:1586. Epub 2019 Sep 4.

Scientific and Regulatory Affairs, Japan Tobacco International, Genève, Genève, 1202, Switzerland.

The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed. The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models and in transgenic rodent lines but have not been demonstrated in cases of human cancer. Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.
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http://dx.doi.org/10.12688/f1000research.20062.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308884PMC
October 2020

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients.

Liver Int 2020 09 7;40(9):2215-2227. Epub 2020 Jul 7.

Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

Background & Aims: Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child-Turcotte-Pugh (CTP) score and hepatic decompensation in HIV/HCV-coinfected and HCV-monoinfected patients with advanced cirrhosis.

Methods: A cross-sectional study was carried out in 62 HIV/HCV-coinfected and 28 HCV-monoinfected patients. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS-DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score).

Results: The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy-related metabolites and bacterial fermentation-related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched-chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV- and HCV-infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7).

Conclusion: Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV-coinfected and HCV-monoinfected patients.
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http://dx.doi.org/10.1111/liv.14580DOI Listing
September 2020

Clinical outcome and hemodynamic changes following HCV eradication with oral antiviral therapy in patients with clinically significant portal hypertension.

J Hepatol 2020 12 12;73(6):1415-1424. Epub 2020 Jun 12.

Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD).

Background & Aims: Clinically significant portal hypertension (CSPH), defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, persists 24 weeks after sustained virological response (SVR) in up to 78% of patients with HCV-related cirrhosis treated with direct-acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population.

Methods: We conducted a prospective multicenter study in 226 patients with HCV-related cirrhosis and CSPH who achieved SVR after antiviral therapy. Patients with CSPH 24 weeks after end of treatment (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96).

Results: All patients were clinically evaluated. Out of 176 patients with CSPH at SVR24, 117 (66%) underwent an HVPG measurement at SVR96. At SVR96, 55/117 (47%) patients had HVPG <10 mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥16 mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13 kPa) but did not correlate with HVPG changes (30% of patients with liver stiffness measurement <13.6 kPa still had CSPH). Seventeen (7%) patients presented with de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥16 mmHg and history of ascites.

Conclusions: Patients achieving SVR experienced a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53-65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation.

Lay Summary: As a major complication of cirrhosis, clinically significant portal hypertension (CSPH) is associated with adverse clinical outcomes. Herein, we show that CSPH persists at 96 weeks in just over half of patients with HCV-related cirrhosis, despite HCV elimination by direct-acting antivirals. Despite viral cure, patients with CSPH at the start of antiviral treatment remain at long-term risk of hepatic complications and should be managed accordingly.
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http://dx.doi.org/10.1016/j.jhep.2020.05.050DOI Listing
December 2020

Bimetallic Zinc Catalysts for Ring-Opening Copolymerization Processes.

Inorg Chem 2020 Jun 26;59(12):8412-8423. Epub 2020 May 26.

Departamento de Quı́mica Inorgánica, Orgánica y Bioquı́mica-Centro de Innovación en Quı́mica Avanzada (ORFEO-CINQA), Facultad de Ciencias y Tecnologı́as Quı́micas, Universidad de Castilla-La Mancha, 13071-Ciudad Real, Spain.

Novel bimetallic zinc acetate complexes supported by heteroscorpionate ligands have been developed for the ring-opening copolymerization of cyclohexene oxide and CO and the terpolymerization of cyclohexene oxide, phthalic anhydride, and CO. Heteroscorpionate ligands precursors - were reacted with two equivalents of zinc acetate to afford the dinuclear zinc complexes [{Zn(κ-bpzappe)}(μ-OCCH)-{Zn(HOCCH)}] (), [{Zn(κ-bpzbdmape)}(μ-OCCH)-{Zn(HOCCH)}] (), and [{Zn(κ-bpzbdeape)}(μ-OCCH){Zn(HOCCH)}] () in excellent yields. The molecular structure of these compounds was determined spectroscopically and confirmed by X-ray diffraction analysis. Zinc acetate complexes - were screened as catalysts for the copolymerization of cyclohexene oxide and CO to produce poly(cyclohexene)carbonate, and complex was found to be the most active catalyst for this process in the absence of a cocatalyst. Furthermore, the terpolymerization of cyclohexene oxide, phthalic anhydride, and CO was studied using the combination of complex and 4-dimethylaminopyridine as catalyst system yielding the corresponding polyester-polycarbonate materials.
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http://dx.doi.org/10.1021/acs.inorgchem.0c00835DOI Listing
June 2020

Non-selective beta-blockers impair global circulatory homeostasis and renal function in cirrhotic patients with refractory ascites.

J Hepatol 2020 12 21;73(6):1404-1414. Epub 2020 May 21.

Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), CIBEREHD, Universidad de Alcalá, Madrid, Spain. Electronic address:

Background & Aims: The safety of non-selective β-blockers (NSBBs) has been questioned in refractory ascites (RA). We studied the effects of NSBBs on cardiac systolic function, systemic hemodynamics, and renal perfusion pressure (RPP) and function in patients with diuretic-responsive ascites (DRA) and RA.

Methods: We performed a prospective pre-post repeated-measures study in cirrhotic patients, 18 with DRA and 20 with RA on NSBBs for variceal bleeding prophylaxis. Systolic function (by ejection intraventricular pressure difference [EIVPD]), hepatic venous pressure gradient (HVPG), cardiopulmonary pressures, RPP, and sympathetic activation were measured at baseline and after 4 weeks of propranolol.

Results: EIVPD was elevated at baseline (RA 4.5 [2.8-5.7] and DRA 4.2 [3.1-5.7] mmHg; normal 2.4-3.6 mmHg) and directly related to the severity of vasodilation and sympathetic activation. NSBBs led to similar reductions in heart rate and HVPG in both groups. NSBBs reduced EIPVD in RA but not in DRA (-20% vs. -2%, p <0.01). In RA, the NSBB-induced reduction in EIPVD correlated with the severity of vasodilation and with higher plasma nitric oxide, norepinephrine and IL-6 (r >0.40, all p <0.05). NSBBs reduced RPP in both groups, but impaired renal function only in patients with RA. Reduced EIPVD correlated with decreases in RPP and estimated glomerular filtration rate (r >0.40, all p <0.01). After NSBB treatment, RPP dropped below the threshold of renal flow autoregulation in 11 of the 20 (55%) patients with RA, including the 4 fulfilling the criteria for HRS-AKI.

Conclusion: Renal perfusion and function depend critically on systolic function and sympathetic hyperactivation in RA. NSBBs blunt the sympathetic overdrive, hamper cardiac output, lower RPP below the critical threshold and impair renal function. β-blockade should be used cautiously or even avoided in patients with RA.

Lay Summary: We have identified the mechanisms by which non-selective beta-blockers could impair survival in patients with refractory ascites. We show that peripheral vasodilation and sympathetic activation lead to increased left ventricle systolic function in patients with cirrhosis and ascites, which acts as an adaptive mechanism to maintain renal perfusion. When ascites becomes refractory, this compensatory cardiac response to vasodilation is critically dependent on sympathetic hyperactivation and is hardly able to maintain renal perfusion. In this setting, β-blockade blunts the sympathetic overdrive of cardiac function, hampers cardiac output, lowers renal perfusion pressure below the critical threshold and impairs renal function.
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http://dx.doi.org/10.1016/j.jhep.2020.05.011DOI Listing
December 2020

Persistence of Clinically Significant Portal Hypertension After Eradication of Hepatitis C Virus in Patients With Advanced Cirrhosis.

Clin Infect Dis 2020 12;71(10):2726-2729

Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.

This prospective study of 34 patients with HCV cirrhosis (17 HIV positive) with baseline clinically significant portal hypertension (CSPH; HVPG ≥10 mmHg) and SVR after DAA therapy showed that disappearance of CSPH (primary endpoint) is a rare event (6/18 patients; 18%), indicating a persistent risk of clinical progression or death.
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http://dx.doi.org/10.1093/cid/ciaa502DOI Listing
December 2020

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

J Hepatol 2020 11 24;73(5):1082-1091. Epub 2020 Apr 24.

Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.

Background & Aims: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date.

Methods: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality.

Results: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not.

Conclusions: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB.

Lay Summary: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.
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http://dx.doi.org/10.1016/j.jhep.2020.04.024DOI Listing
November 2020