Use of Monoclonal Antibodies in Immunocompromised Patients Hospitalized with Severe COVID-19: A Retrospective Multicenter Cohort

This work was supported by the Research Institute Puerta de Hierro-Segovia de Aranda (IDIPHSA), funding number 0040200108 (2.400€).Objective: We aim to describe the safety and efficacy of sotrovimab in severe cases of COVID-19 in immunocompromised hosts. Methods: We used a retrospective multicenter cohort including immunocompromised hospitalized patients with severe COVID-19 treated with sotrovimab between October 2021 and December 2021. Results: We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) and hematological malignancy (37.5%). Seven patients (21.9%) had respiratory progression: 12.5% died and 9.4% required mechanical ventilation. Patients treated within the first 14 days of their symptoms had a lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed to sotrovimab. Conclusions: Sotrovimab was safe and may be effective in its use for immunocompromised patients with severe COVID-19. More studies are needed to confirm these preliminary data.Depto. de MedicinaFac. de MedicinaTRUEResearch Institute Puerta de Hierro-Segovia de Aranda (IDIPHSA)pu

Diurnal and seasonal active layer and permafrost dynamics from boreholes of the Latin American permafrost network

Permafrost is present in the high-altitude mountains of the Trans-Mexican Volcanic Belt as well as the Andes, even in the extreme dry Atacama highland. The permafrost and active layer termal state are characterized at Latin American Permafrost Network study sites. Ice rich or extremely dry permafrost was observed during drilling operations from Mexico (Pico de Orizaba, 5636m a.s.l. Iztaccíhuatl, 5230m a.s.l.), Colombia, Ecuador (Chimborazo, 6263m a.s.l.), Peru (Coropuna 5250 m a.s.l., Ampato 5850 m a.s.l., Chachani 5600 m a.s.l.) including the highest human habitation in the world: La Rinconada 5100 m a.s.l., Bolivia (Chacaltaya 5300 m a.s.l. where glacier disappeared in 2005), and the Chilean/Argentinian border (up to 6750 m a.s.l. including Parinacota, Aucanquilcha, Ojos del Salado, Llullaillaco, Tupungato and Tupungatito). The Lower Limit of Alpine Permafrost (LLAP) is redrawn from this study between latitude 19˚N and 40˚S where it is mainly in the tropical and arid Andes. This is not a rock glacier monitoring program that not mapping sporadic permafrost, but continuous permafrost terrains for long term temperature monitoring and understanding for local hydrological problems such as glacier/snow melt runoff or sublimation rate of higher elevations. The maximum active layer is typically influenced by the diurnal fluctuations which is between 12-30 cm deep however, maximum 2m depth of the seasonal active layer was observed at Ojos del Salado near the LLAP (5200 m a.s.l.). Daily severe frost shattering occurs near the ground surface, producing a dusty, fine-material horizon at an active layer near the LLAP, however a few freeze-thaw actions are higher than 6400 m. The snow-covered periods are important for providing protection from strong tropic solar radiation

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Leakage of nitrous oxide emissions within the Spanish agro-food system in 1961-2009

Abstract In this paper we examine the trends of nitrous oxide (N2O) emissions of the Spanish agricultural sector related to national production and consumption in the 1961?2009 period.The comparison between production- and consumption-based emissions at the national level provides a complete overview of the actual impact resulting from the dietary choices of a given country and allows the evaluation of potential emission leakages. On average, 1.5 % of the new reactive nitrogen that enters Spain every year is emitted as N2O. Production- and consumption-based emissions have both significantly increased in the period studied and nowadays consumption-based emissions are 45 % higher than production-based emissions. A large proportion of the net N2O emissions associated with imported agricultural godos comes from countries that are not committers for the United Nations Framework Convention on Climate Change Kyoto Protocol Annex I. An increase in feed consumption is the main driver of the changes observed, leading to a arkable emission leakage in the Spanish agricultural sector. The complementary approach used here is essential to achieve an effective mitigation of Spanish greenhouse gas emissions

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients.MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated.ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir &lt;100 cells/μL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles.DiscussionWhereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available

Mountain permafrost in the Tropical Andes of Peru: the 0°C isotherm as a potential indicator

In the tropical Andes of Peru very little is known about the occurrence and extent of mountain permafrost. Only recently systematic studies have been carried out on the high elevation sites of the mountain ranges (cordilleras). In the framework of the first pioneering studies, and with the objective to improve the understanding of characteristics of mountain permafrost and rock glaciers, we analyze how mountain permafrost in the Peruvian Andes is correlated with the altitude of the 0°C isotherm (ZIA). Climate change has generated an increase in air temperature and in the ZIA in the past decades. These temperature changes could lead to impact the state of the mountain permafrost. In this research, we focus on two mountain regions: The Cordillera Central (CC) and the Cordillera Volcánica (CV), the first located in the central zone and the second in the south zone of Peru. The study used air temperature data from 20 weather stations (2002–2016) to calculate the mean annual air temperature (MAAT), interpolated using a multiple linear regression model (MLRM) and digital elevation model (MERIT DEM). Occurrence and extent of 46 intact rock glaciers (IRG) and the global model of permafrost (Permafrost Zonation Index) were used to validate the results. The MAAT of CC has a minimum value around -4.1°C (R2 = 0.8) and a ZIA average of ~5152 m a.s.l. None of the IRGs are located above the ZIA. The MAAT of CV has a minimum value around of -5.5°C (R2 = 0.8), a ZIA average of ~4861 m a.s.l., and 60% of the IRGs are located above of the ZIA. The results show a greater variation of the position of the ZIA in CC in comparison to CV, which could indicate a possible degradation of mountain permafrost in these mountain ranges

Ocular Syphilis with Retinal and Disc Neovascularization Treated with Bevacizumab: A Case Report

We report the findings observed in a young woman with ocular syphilis complicated with retinal and disc neovascularization successfully treated with intravitreal bevacizumab. Fluorescein angiography revealed in both eyes intense hyperfluorescence at the level of the disc, multifocal venous wall staining, multifocal paravenous leakage, multiple peripheral saccular venular dilations, diffuse retinal and macular edema, and retinal and disc neovascularization. There was no evidence of retinal ischemia in both eyes. After antibiotic and corticosteroid treatment, the neovascularization persisted in both eyes. Three consecutive doses of intravitreal bevacizumab were administered, with total regression of the retinal and disc neovascularization. Disc and retinal neovascularization along with nonocclusive retinal vasculitis may be a form of presentation of ocular syphilis. Combination of specific treatment, oral corticosteroids, and intravitreal bevacizumab may be useful for treating this clinical manifestation

Trypanosoma cruzi arginine kinase characterization and cloning. A novel energetic pathway in protozoan parasites

This work contains the first description of a guanidino kinase in a flagellar unicellular parasite. The enzyme phosphorylates L-arginine and was characterized in preparations from Trypanosoma cruzi, the ethiological agent of Chagas' disease. The activity requires ATP and a divalent cation. Under Standard assay conditions (1 mM L-arginine), the presence of 5-fold higher concentrations of canavanine or histidine produced a greater than 50% enzyme inhibition. The base sequence of this enzyme revealed an open reading frame of 357 amino acids and a molecular weight of 40,201. The amino acid sequence shows all of the characteristic consensus blocks of the ATP:guanidino phosphotransferase family and a putative 'actinin-type' actin-binding domain. The highest amino acid identities of the T. cruzi sequence, about 70%, were with arginine kinases from Arthropoda. Southern and chromosome blots revealed that the kinase is encoded by a single-copy gene. Moreover, Northern blot analysis showed an mRNA subpopulation of about 2.0 kilobases, and Western blotting of T. cruzi-soluble polypeptides revealed a 40-kDa band. The finding in the parasite of a phosphagen and its biosynthetic pathway, which are totally different from those in mammalian host tissues, points out this arginine kinase as a possible chemotherapy target for Chagas' disease.Fil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Alonso, Guillermo Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Paveto, Maria Cristina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Iribarren, Adolfo Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Cabanas, María Laura. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Torres, Hector Norberto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Flawia, Mirtha Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin