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An increased risk of venous thromboembolism (VTE) in hospitalized patients with COVID-19 has been reported. We aimed to describe the incidence rate of VTE on patients with non-hematological cancer who required hospitalization due to COVID-19 at our center. In this prospective study, non-hematological cancer patients hospitalized for confirmed COVID-19 at our institution from 1st March to 30th April 2020, were evaluated daily for VTE complications during their hospital stay, and after discharge until 30th June 2020. Furthermore, Doppler ultrasound of lower limbs was routinely performed in asymptomatic patients based on D-dimer levels and current active cancer therapy. The primary outcome of this study was the cumulative incidence of VTE. Secondary outcomes were the cumulative incidence of bleeding and mortality. A total of 58 hospitalized non-hematological cancer patients and confirmed COVID-19 were identified. Median follow-up since initial symptoms of COVID-19 was 91 days (IQR 19–104). Pulmonary embolism was diagnosed in three (5%) patients. Symptomatic catheter-related deep vein thrombosis (DVT) was observed in one patient. Doppler ultrasound of lower limbs was done in 11 asymptomatic patients, showing distal DVT in two of them (18%). The cumulative incidence of VTE on day 14 after admission was 10%, without new VTE events after hospital discharge and up to 90 days follow-up. No bleeding complication was observed. Seventeen patients (29%) died in the first 14 days after COVID-19 diagnosis. Four patients died after discharge due to malignancy progression. The cumulative incidence of VTE in non-hematological cancer patients under active treatment was 10% at day 14 after admission, with no further new events in the following 12 weeks. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02448-w.

Ministerio de Ciencia e Innovación de España, Instituto de Salud Carlos III (convocatoria de investigación COVID-19 COV20 / 00181) cofinanciado por el Fondo Regional Europeo de Desarrollo “Una forma de lograr Europa”. Ministerio de Asuntos Económicos y Transformación Digital de España y Fondos Feder (beca PI18 / 00139). 8.490 JCR (2021) Q1, 3/29 Medical Laboratory Technology 1.295 SJR (2021) Q1, 292/2489 Medicine (miscellaneous) No data IDR 2021 UEM

The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon-s (16.7%). As of April 4, the case-fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C-reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.

Background:There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high dependency unit (HDU). On the other hand, limited resources at times of high demand may lead to rationing. Nevertheless, these variables may be used as static proxies for disease severity, as outcome measures for trials, and to inform planning and logistics.Methods:We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay.Results:Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors.Conclusions:Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly evolving situation.Funding:This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Smoking can play a key role in SARS-CoV-2 infection and in the course of the disease. Previous studies have conflicting or inconclusive results on the prevalence of smoking and the severity of the coronavirus disease (COVID-19).Observational, multicenter, retrospective cohort study of 14,260 patients admitted for COVID-19 in Spanish hospitals between February and September 2020. Their clinical characteristics were recorded and the patients were classified into a smoking group (active or former smokers) or a non-smoking group (never smokers). The patients were followed up to one month after discharge. Differences between groups were analysed. A multivariate logistic regression and Kapplan Meier curves analysed the relationship between smoking and in-hospital mortality.The median age was 68.6 (55.8-79.1) years, with 57.7% of males. Smoking patients were older (69.9 (59.6-78.0 years)), more frequently male (80.3%) and with higher Charlson index (4 (2-6)) than non-smoking patients. Smoking patients presented a worse evolution, with a higher rate of admission to the intensive care unit (ICU) (10.4 vs. 8.1%), higher in-hospital mortality (22.5 vs. 16.4%) and readmission at one month (5.8 vs. 4.0%) than in non-smoking patients. After multivariate analysis, smoking remained associated with these events.Active or past smoking is an independent predictor of poor prognosis in patients with COVID-19. It is associated with higher ICU admissions and in-hospital mortality.El tabaquismo puede tener un papel importante en la infección por SARS-CoV-2 y en el curso de la enfermedad. Los estudios previos muestran resultados contradictorios o no concluyentes sobre la prevalencia de fumar y la severidad en la enfermedad por coronavirus (COVID-19).Estudio de cohortes observacional, multicéntrico y retrospectivo de 14.260 pacientes que ingresaron por COVID-19 en hospitales españoles desde febrero a septiembre de 2020. Se registraron sus características clínicas y se clasificaron en el grupo con tabaquismo si tabaquismo activo o previo o en el grupo sin tabaquismo si nunca habían fumado. Se realizó un seguimiento hasta un mes después del alta. Se analizaron las diferencias entre grupos. La relación entre tabaquismo y mortalidad intrahospitalaria se valoró mediante una regresión logística multivariante y curvas de Kapplan Meier.La mediana de edad fue 68,6 (55,8–79,1) años, con un 57,7% de varones. El grupo con tabaquismo presentó mayor edad (69,9 (59,6–78,0 años)), predominio masculino (80,3%) y mayor índice de Charlson (4 (2−6)). La evolución fue peor en estos pacientes, con una mayor tasa de ingreso en UCI (10,4 vs 8,1%), mayor mortalidad intrahospitalaria (22,5 vs 16,4%) y reingreso al mes (5,8 vs 4,0%) que el grupo sin tabaquismo. Tras el análisis multivariante, el tabaquismo permanecía asociado a estos eventos.El tabaquismo de forma activa o pasada es un factor predictor independiente de mal pronóstico en los pacientes con COVID-19, estando asociada a mayor probabilidad de ingreso en UCI y a mayor mortalidad intrahospitalaria.

ObjectivesThe COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives.DesignA list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance.ResultsThe outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors.ConclusionImplementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research.

Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.

To the EditorA recent report in the present journal drew attention to lymphopenia in influenza infection [1]. Besides the authors’ main observation that a high rate of complications occurred in neu...

The role of viral load in the outcome of patients requiring hospital admission due to influenza is not well established. We aim to assess if there is an association between the viral load and the outcome in hospitalized patients with a confirmed influenza virus infection. A retrospective observational study including all adult patients who were hospitalized in our center with a confirmed influenza virus infection from January to May 2016. Viral load was measured by real-time reverse-transcriptase–polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on upper respiratory tract samples. Its value was categorized into three groups (low Ct, ≤ 20; intermediate Ct, > 20–30; and high Ct, > 30). Two hundred thirty-nine patients were included. Influenza A/H1N1pdm09 was isolated in 207 cases (86.6%). The mean Ct value was 26.69 ± 5.81. The viral load was higher in the unvaccinated group when compared with the vaccinated patients (Ct 25.17 ± 5.55 vs. 27.58 ± 4.97, p = 0.004). Only 27 patients (11.29%) presented a high viral load. Patients with a high viral load more often showed abnormal findings on chest X-ray (p = 0.015) and lymphopenia (p = 0.097). By contrast, there were no differences between the three groups (according to viral load), in associated pneumonia, respiratory failure, need for mechanical ventilation, sepsis, or in-hospital mortality. Our findings suggest that in patients admitted to the hospital with confirmed influenza virus infection (mostly A/H1N1pdm09), a high viral load is associated with a higher presence of abnormal findings on chest X-ray but not with a significant worse prognosis. In these cases, standardized quantitative PCR could be useful.

Background and objective Tuberous sclerosis (TS) is a condition whose manifestations in childhood have been extensively described, but whose presentation in adults is less well known. This study describes the clinical and genetic characteristics, therapeutic management and quality of life of a cohort of adult patients with TS. A comparative study of the characteristics of patients diagnosed in childhood and adulthood is also carried out. Material and methods This observational, retrospective, cross-sectional study included a large cohort of adult patients (≥ 16 years old) followed for 5 years in a specific rare diseases unit. Results Fifty-seven patients with a diagnosis of tuberous sclerosis were included, more than 50% of whom were diagnosed as adults. The mean age of the patients was 42 years (20–86). The central nervous system was the main area affected (97%), followed by the skin (80.7%) and kidneys (73%). The most frequent genetic alteration was a mutation in the TSC2 gene (47.7%). Among patients diagnosed in adulthood, there was less neurological involvement, with less frequency of epileptic seizures (30.8% vs 60.79% of patients diagnosed in childhood) and astrocytomas (3.8% vs 53.6%), less intellectual disability (11.5% vs 71.4%) and less expressiveness of the condition. 42% of patients were treated with mTOR pathway inhibitors, and presence of an angiomyolipoma was the main indication. In a quality-of-life analysis, the means of the summary indices were below the scores of the average Spanish population: (47.42 (SD ± 9.82) on the physical health scale, 45.61 (SD ± 7.99) on the mental health scale) versus 50 (SD ± 10) for the general population. Conclusions Up to 50% of adult patients with TS were diagnosed in adulthood, and the condition is less severe with less frequent epileptic seizures and intellectual disability. 42% require treatment with mTOR inhibitors, in most cases due to the presence of AMLs. The quality of life of adult patients with TS is diminished compared to the general population.

Background: The aim of the study was to analyze the clinical manifestations and outcome of the oldest old (people aged ≥85 years) who were admitted to the hospital with a confirmed influenza A virus infection in comparison with younger patients and to assess the role of inflammation in the outcome of influenza infection in this population. Methods: This is an observational prospective study including all adult patients with influenza A virus infection hospitalized in a tertiary teaching hospital in Madrid, in 2 consecutive influenza seasons (2016–17 and 2017–18). Results: Five hundred nine hospitalized patients with influenza A infection were included, of whom 117 (23%) were older than 85 years (median age: 89.3 ± 3.2). We compared the clinical characteristics and outcome with those of the rest of the population (median age: 72.8 ± 15.7). Overall, mortality was higher in older patients (10% vs. 4%; p = 0.03) with no differences in clinical presentation. Patients older than 85 years who ultimately died (12 out of 117) showed increased systemic inflammation expressed by higher levels of C-reactive protein (CRP) and ferritin compared to survivors who were discharged (odds ratio [OR] of CRP >20 mg/dL: 5.16, 95% confidence interval [CI]: 1.29–20.57, and OR of ferritin >500 mg: 4.3, 95% CI: 1.04–17.35). Conclusions: Patients aged 85 and older with influenza A virus infection presented a higher in-hospital mortality than younger subjects. CRP and ferritin levels were higher in the oldest old who died, suggesting that inflammation could play a key role in the outcome of this subset of patients.

IntroductionMonoclonal antibodies (mAb) targeting plasma cells are malignant gammopathy designed and approved therapies. In recent years, these antibodies have also been increasingly introduced for non-malignant conditions such as autoimmune-mediated diseases. The Anti-Phospholipid Syndrome (APS) is an immune-mediated disorder in which autoantibodies against phospholipid associated proteins could elicit the activation of the coagulation cascade in specific situations. Therefore, the mainstream treatment for APS patients is the use of anticoagulant therapy. However, there are refractory patients who would benefit from targeting the antibodies rather than their effects. Rituximab, a B-cell depleting mAb, and intravenous immunoglobulins (IVIG) have been used in APS patients without showing a clear beneficial effect or a significant drop in anti-phospholipid antibody (aPL) levels.Clinical caseWe present our first APS case treated with daratumumab, an anti-CD38 mAb, in a 21-year-old patient with APS who presented with recurrent venous thromboembolic events despite adequate anticoagulant therapy. She tested positive for lupus anticoagulant, anti-cardiolipin IgG, anti-beta-2-glycoprotein-I IgG and anti-phosphatidylserine/prothrombin IgG and IgM. She was administered one dose weekly of daratumumab for 4 weeks. The treatment showed an adequate safety profile and was well tolerated. The patient was discharged after undergoing a clinically significant improvement. After the therapy, her levels of positive aPL declined significantly and most continued to decrease during the next three months. The patient experienced a new thrombotic episode two years after the therapy associated with poor adherence to antithrombotic therapy.ConclusionsThe treatment with daratumumab showed an adequate safety profile, was well tolerated and led to a significant clinical improvement. Levels of aPL lowered on therapy and the next three months and then rose again during follow-up. Further investigation is needed to better elucidate the role and optimal timing and doses of daratumumab in treatment of refractory APS.

BackgroundThe role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.MethodsWe conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone (“CS group”) or associated to intravenous tocilizumab (400-600 mg, one to three doses) (“CS-TCZ group”). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied.ResultsOverall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 – 0.68;P-value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 – 0.68;P-value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 – 0.72;P-value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 – 3.41;P-value ConclusionsThe combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.

The aim of our study was to elucidate if SARS-CoV-2 viral load on admission, measured by real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on nasopharyngeal samples, was a marker of disease severity. All hospitalized adult patients with a diagnosis of SARS-CoV-2 infection by rRT-PCR performed on a nasopharingeal sample from March 1 to March 18 in our institution were included. The study population was divided according to the Ct value obtained upon admission in patients with high viral load (Ct 30). Demographic, clinical and laboratory variables of the different groups were analyzed to assess the influence of viral load on the development of respiratory failure during admission. Overall, 455 sequential patients were included. The median Ct value was 28 (IQR: 24–32). One hundred and thirty patients (28.6%) had a high viral load, 175 (38.5%) an intermediate viral load and 150 (33%) a low viral load. Advanced age, male sex, presence of cardiovascular disease and laboratory markers such as lactate dehydrogenase, lymphocyte count and C-reactive protein, as well as a high viral load on admission, were predictive of respiratory failure. A Ct value

Background: Venous thrombotic events (VTE) are frequent in COVID-19, and elevated plasma D-dimer (pDd) and dyspnea are common in both entities. Objective: To determine the admission pDd cut-off value associated with in-hospital VTE in patients with COVID-19. Methods: Multicenter, retrospective study analyzing the at-admission pDd cut-off value to predict VTE and anticoagulation intensity along hospitalization due to COVID-19. Results: Among 9386 patients, 2.2% had VTE: 1.6% pulmonary embolism (PE), 0.4% deep vein thrombosis (DVT), and 0.2% both. Those with VTE had a higher prevalence of tachypnea (42.9% vs. 31.1%; p = 0.0005), basal O2 saturation 1.0 µg/ml treated with prophylactic dose (p < 0.0001), 28.8% for pDd for patients with pDd >2.0 µg/ml treated with intermediate dose (p = 0.0001), and 31.3% for those with pDd >3.0 µg/ml and full anticoagulation (p = 0.0183). Conclusions: In hospitalized patients with COVID-19, a pDd value greater than 3.0 µg/ml can be considered to screen VTE and to consider full-dose anticoagulation. © 2021, Society of General Internal Medicine.

To determine the proportion of patients with COVID-19 who were readmitted to the hospital and the most common causes and the factors associated with readmission. Multicenter nationwide cohort study in Spain. Patients included in the study were admitted to 147 hospitals from March 1 to April 30, 2020. Readmission was defined as a new hospital admission during the 30 days after discharge. Emergency department visits after discharge were not considered readmission. During the study period 8392 patients were admitted to hospitals participating in the SEMI-COVID-19 network. 298 patients (4.2%) out of 7137 patients were readmitted after being discharged. 1541 (17.7%) died during the index admission and 35 died during hospital readmission (11.7%, p = 0.007). The median time from discharge to readmission was 7 days (IQR 3–15 days). The most frequent causes of hospital readmission were worsening of previous pneumonia (54%), bacterial infection (13%), venous thromboembolism (5%), and heart failure (5%). Age [odds ratio (OR): 1.02; 95% confident interval (95% CI): 1.01–1.03], age-adjusted Charlson comorbidity index score (OR: 1.13; 95% CI: 1.06–1.21), chronic obstructive pulmonary disease (OR: 1.84; 95% CI: 1.26–2.69), asthma (OR: 1.52; 95% CI: 1.04–2.22), hemoglobin level at admission (OR: 0.92; 95% CI: 0.86–0.99), ground-glass opacification at admission (OR: 0.86; 95% CI:0.76–0.98) and glucocorticoid treatment (OR: 1.29; 95% CI: 1.00–1.66) were independently associated with hospital readmission. The rate of readmission after hospital discharge for COVID-19 was low. Advanced age and comorbidity were associated with increased risk of readmission.

SummaryBackgroundMore contagious SARS-CoV-2 virus variants, breakthrough infections, waning immunity, and sub-optimal rates of COVID-19 vaccination account for a new surge of infections leading to record numbers of hospitalizations and deaths in several European countries. This is a particularly concerning scenario for resource-limited countries, which have a lower vaccination rate and fewer clinical tools to fight against the next pandemic waves. There is an urgent need for clinically valuable, generalizable, and parsimonious triage tools assisting the appropriate allocation of hospital resources. We aimed to develop and extensively validate CODOP, a machine learning-based tool for accurately predicting the clinical outcome of hospitalized COVID-19 patients.MethodsCODOP was built using modified stable iterative variable selection and linear regression with lasso regularisation. To avoid generalization problems, CODOP was trained and tested with three time-sliced and geographically distinct cohorts encompassing 40 511 blood-based analyses of COVID-19 patients from more than 110 hospitals in Spain and the USA during 2020-21. We assessed the discriminative ability of the model using the Area Under the Receiving Operative Curve (AUROC) as well as horizon and Kaplan-Meier risk stratification analyses. To reckon the fluctuating pressure levels in hospitals through the pandemic, we offer two online CODOP calculators suited for undertriage or overtriage scenarios. We challenged their generalizability and clinical utility throughout an evaluation on a cohort of patients hospitalized in five hospitals from three Latin American countries.FindingsCODOP uses 12 clinical parameters commonly measured at hospital admission and associated with the pathophysiology of COVID-19. CODOP reaches high discriminative ability up to nine days before clinical resolution (AUROC: 0·90-0·96, 95% CI 0·879-0·970), it is well calibrated, and it enables an effective dynamic risk stratification during hospitalization. The two CODOP online calculators demonstrate their potential for triage decisions when challenged with the distinctive Latin American evaluation cohorts (73-100% sensitivity and 84-100% specificity).InterpretationThe high predictive performance of CODOP in geographically disperse patient cohorts and the easiness-of-use, strongly suggest its clinical utility as a global triage tool, particularly in resource-limited countries.FundingThe Max Planck Society.Research in contextEvidence before this studyWe have searched PubMed for articles about the existence of in-hospital COVID-19 mortality predictive models, using the search terms “coronavirus”, “COVID-19”, “risk”, “death”, “mortality”, and “prediction”, focusing on studies published between March 1, 2020 and 31 August, 2021. The studies we identified generally used small-medium size cohorts of patients that are geographically restricted to small regions of the developed world (many times, to the same city). We haven’t found studies that challenged their models in extended cohorts of patients from very distinct health system populations, particularly from resource-limited countries. Further, most of the previous models are rigid by not acknowledging the fluctuating availability of hospital resources during the pandemic (e.g., beds, oxygen supply). These and other limitations have been pointed out by expert reviews indicating that published in-hospital COVID-19 mortality predictive models are subject to high risk of bias, report an over-optimistic performance, and have limited clinical value in assisting daily triage decisions. A parsimonious, accurate and extensively validated model is yet to be developed.Added value of this studyWe analysed clinical data from different cohorts totalling 21 607 COVID-19 patients treated in more than 110 hospitals in Spain and the USA during three different pandemic waves extending from February 2020 to April 2021. The new CODOP in-hospital mortality prediction model is based on 11 blood biochemistry parameters (representing main biological pathways involved in the pathogenesis of SARS-CoV-2) plus Age, all of them commonly measured upon hospitalization. CODOP accurately predicted mortality risk up to nine days before clinical resolution (AUROC: 0·90-0·96, 95% CI 0·879-0·970), it is well calibrated, and it enables an effective dynamic risk stratification during hospitalization. We offer two online CODOP calculator subtypes (https://gomezvarelalab.em.mpg.de/codop/) tailored to overtriage and undertriage scenarios. The online calculators were able to reach the desired prediction performance in five independent evaluation cohorts gathered in hospitals of three Latin American countries from March 7th 2020 to June 7th 2021.Implications of all the available evidenceWe present here a highly accurate, parsimonious and extensively validated COVID-19 in-hospital mortality prediction model, derived from working with the largest number and the most geographically extended representation of patients and health systems to date.The rigorous analytical methods, the generalizability of the model in distinct world regions, and its flexibility to reckon with the changing availability of hospital resources point to CODOP as a clinically useful tool potentially improving the outcome prediction and the management of COVID-19 hospitalized patients.

El presente estudio retrospectivo observacional tiene como objetivo analizar la utilidad de las escalas SOFA (Sequential Organ Failure Assessment), qSOFA (Quick SOFA), NEWS (National Early Warning Score ) y Quick NEWS para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 atendidos fuera de la Unidad de Cuidados Intensivos (UCI). Se incluyeron 237 adultos con COVID-19 hospitalizados seguidos durante un mes o hasta su fallecimiento. El fallo respiratorio se definió como un cociente PaO2/FiO2 ≤ 200 mmHg o la necesidad de ventilación mecánica. Setenta y siete pacientes (32,5%) desarrollaron fallo ventilatorio; 29 (12%) precisaron ingreso en UCI, y 49 fallecieron (20,7%). La discriminación del fallo ventilatorio fue algo mayor con la puntuación NEWS, seguida de la SOFA. En cuanto a la mortalidad, la puntuación SOFA fue más exacta que las otras escalas. En conclusión, las escalas de sepsis son útiles para predecir el fallo respiratorio y la muerte en COVID-19. Una puntuación ≥ 4 en la escala NEWS sería el mejor punto de corte para predecir fallo respiratorio.

Background The impact of late-onset cytomegalovirus (CMV) infection (LOCI) on cardiac allograft vasculopathy (CAV) has yet to be established. Methods A retrospective study was performed for patients who had undergone heart transplantation (HT) between January 1995 and October 2017 to analyze epidemiology of LOCI (any positive level of CMV pp65 antigenemia or DNAemia after 100 days, without previous CMV replication) and its association with CAV. Our main hypothesis was that LOCI causes less direct and indirect effects compared to early onset infection (EOCI). Results Late-onset cytomegalovirus infection developed in 57 of 410 patients (13.9%) in a median time of 4.7 months post-transplant. CAV at 10 years was diagnosed in 31.6% of patients with LOCI, 34.6% with EOCI, and in 19.3% of CMV-uninfected patients. In the multivariate analysis, EOCI was an independent variable for developing CAV (HR 1.8, 95% CI 1.13-2.82, P = .01). Patients with LOCI showed a trend toward a higher risk of CAV, but the difference was not statistically significant (HR 1.7, 95% CI 0.95-3.08, P = .07). In the complementary log-log model, LOCI and EOCI had a similar CAV-free survival, and a higher probability of developing CAV than CMV-uninfected patients (P = .02). Conclusions Cytomegalovirus infection after HT may result in the same long-term events regardless of its onset, with a higher risk of developing CAV at 10 years than patients without CMV.

Coronavirus disease 2019 (COVID‐19) can lead to a massive cytokine release. The use of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6‐point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6‐point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon‐β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06‐0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06‐0.99; P = .048) were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C‐reactive protein levels dropped by day 2. There were no TCZ‐attributable adverse events. In this observational single‐center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID‐19 pneumonia., Highlights COVID‐19 can lead to a hyperinflammatory state that mirrors the cytokine release syndrome.The off‐labeluse of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab has been proposed to abrogate this deleterious inflammatory response, although the supporting evidence is scarce.In the present single‐centre study comprising 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous tocilizumab between March 16 and 27, 2020, the rates of clinical improvement (defined by discharge to home and/or a decrease of = 2 points on a six‐point ordinal scale) were 44.3% (39/88) and 73.9% (65/88) by days 7 and 14, respectively.The previous or concomitant use of interferon‐β and baseline serum lactate dehydrogenase levels >450 U/L were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8%, with no tocilizumab‐attributable adverse events.

Background Which are the consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) infection in liver transplant (LT) recipients? Methods We attempted to address this question by reviewing our single‐center experience during the first two months of the pandemics at a high incidence area. Results Nineteen adult patients (5 females) were diagnosed by May 5th, 2020. Median age was 58 (range 55‐72), and median follow‐up since transplantation was 83 (range 20‐183) months. Cough (84.2%), fever (57.9%) and dyspnea (47.4%) were the most common symptoms. Thirteen patients (68.4%) had pneumonia in X‐ray/CT scan. Hydroxychloroquine was administered in 11 patients, associated with lopinavir/ritonavir and interferon β in 2 cases each. Immunomodulatory therapy with tocilizumab was used in 2 patients. Immunosuppression (IS) was halted in one patient, and modified in only other two due to potential drug interactions. Five (26.3%) patients were managed as outpatient. Two patients (10.5%) died, 10 (52.6%) were discharged home, and 2 (10.5%) were still hospitalized after a median follow‐up of 41 days from the onset of symptoms. Baseline IS regimen remained unchanged in all surviving recipients, with good liver function. Conclusions Our preliminary experience shows a broad spectrum of disease severity in LT patients with COVID‐19, with a favorable outcome in most of them without needing to modify baseline IS.

Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is to analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Prospective design study with concurrent data retrieval from automated medical records of all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64.6 ± 18.2 years. One hundred eighty-one (34.7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR 6–11). In-hospital mortality was 23.8% (124/521). The modeling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0.85 (0.82–0.88). The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02748-2.

AIM Previous studies have suggested a more frequent and severe course of novel coronavirus Sars-coV-2 infection in cancer patients undergoing active oncologic treatment. Our aim was to describe the characteristics of the disease in this population and to determine predictive factors for poor outcome in terms of severe respiratory distress (ARDS) or death. PATIENTS AND METHODS Patients consecutively admitted for SARS-CoV-2 infection were prospectively collected and retrospective statistical analysis was performed. Univariate and multivariate analyses were performed to assess potential factors for poor outcomes defined as ARDS or death. RESULTS 63 patients were analyzed, 34 of them developed respiratory failure (70% as ARDS). Lymphocytes/mm3 (412 vs. 686; p=0.001), serum albumin (2.84 vs. 3.1); LDH (670vs. 359; p, Highlights • Cancer patients are supposed to be specially vulnerable for Sars-CoV-2 infection. • Active cancer treatment could be deleterious in case of simultaneous SARS-CoV-2 infection. • Outcomes of patients under treatment and admitted for SARS-CoV-2 infection are described. • Hospitalized SARS-CoV-2 cancer patients show similar death rate to non-cancer patients.

Background Information regarding the incidence and characteristics of COVID-19 pneumonia amongst pregnant women is scarce. Methods Single-centre experience with 32 pregnant women diagnosed with COVID-19 between March 5 to April 5, 2020 at Madrid, Spain. Findings COVID-19 pneumonia was diagnosed in 61·5% (32/52) women. Only 18·7% (6/32) had some underlying condition (mostly asthma). Supplemental oxygen therapy was required in 18 patients (56·3%), with high-flow requirements in six (18·7%). Eight patients (25·0%) fulfilled the criteria for acute distress respiratory syndrome. Invasive mechanical ventilation was required in two patients (6·2%). Tocilizumab was administered in five patients (15·6%). Delivery was precipitated due to COVID-19 in three women (9·4%). All the newborns had a favourable outcome, with no cases of neonatal SARS-CoV-2 transmission. Severe cases of pneumonia requiring supplemental oxygen were more likely to exhibit bilateral alveolar or interstitial infiltrates on chest X-ray (55·6% vs. 0·0%; P-value = 0·003) and serum C-reactive protein (CRP) levels >10 mg/dL (33·0% vs. 0·0%; P-value = 0·05) at admission than those with no oxygen requirements. Interpretation Pregnant women with COVID-19 have a high risk of developing pneumonia, with a severe course in more than half of cases. The presence of bilateral kung infiltrates and elevated serum CRP at admission may identify women at-risk of severe COVID-19 pneumonia. Funding Instituto de Salud Carlos III (COV20/00,181), Spanish Ministry of Science and Innovation.

BackgroundSpain has been one of the countries most affected by the COVID-19 pandemic.ObjectiveTo create a registry of patients with COVID-19 hospitalized in Spain in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease.MethodsA multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records.ResultsUp to April 30th 2020, 6,424 patients from 109 hospitals were included. Their median age was 69.1 years (range: 18-102 years) and 56.9% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.2%, 39.7%, and 18.7%, respectively. The most frequent symptoms were fever (86.2%) and cough (76.5%). High values of ferritin (72.4%), lactate dehydrogenase (70.2%), and D-dimer (61.5%), as well as lymphopenia (52.6%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.7%) and lopinavir/ritonavir (62.4%). 31.5% developed respiratory distress. Overall mortality rate was 21.1%, with a marked increase with age (50-59 years: 4.2%, 60-69 years: 9.1%, 70-79 years: 21.4%, 80-89 years: 42.5%, ≥ 90 years: 51.1%).ConclusionsThe SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

Background: Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Methods: We retrospectively recruited all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). Findings: We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64·6 ± 18·2 years, with 317 patients (60.8%) over 60 years. One hundred eighty-one (34·7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR: 6-11) and the in-hospital mortality was 23·8% (124/521). The modelling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0·85 (0·82-0·88). Interpretation: The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients. Funding: This study was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COVID-19 research call COV20/00181) — co‐ financed by the European Development Regional Fund “A way to achieve Europe”. Mikel Mancheno-Losa was supported by a Research Contract “Rio Hortega” from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (CM19/00226). Mario Fernandez-Ruiz holds a research contract “Miguel Servet” from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (CP 18/00073). Declaration of Interests: The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript. Ethics Approval Statement: The protocol was approved by the Hospital 12 de Octubre Clinical Research Ethics Committee (reference 20/117) and granted a waiver of informed consent due to its retrospective observational design.

We report our experience with pregnant women with COVID-19 pneumonia diagnosed between March 5 to April 5, 2020 at a tertiary-care center at Madrid, Spain COVI

Small grid-tied wind turbines based on permanent magnet generators often use a cost-effective power converter topology consisting of a passive rectifier, a boost converter, and an H-bridge inverter. Speed or position sensors are rarely used due to cost issues. Model-based estimators relying on electrical magnitudes are used instead. However, such estimators are parameter sensitive, which limit their accuracy. Further concerns arise if these parameters change with the operating condition of the machine, mainly due to temperature. Speed sensorless control using the rectifier voltage ripple is analyzed in this paper. This technique provides good dynamic response and does not depend on machine parameters. Simulations are provided for speed and power tracking comparison with an accurate model-based speed estimation method operating at non-rated parameters. They show the speed accuracy and power tracking capability of the proposed method are similar to that provided by a speed sensor. This is translated into a 0.9% power increase when the model-based speed estimator shows 9% of error. Experimental results are carried out to test the effect of current and temperature in the estimation, showing temperature insensitivity and some distortion due to fast current transients. A speed estimation accuracy of zero mean error and 1.7% standard error is experimentally obtained in the regular operation of the wind turbine.

Resumen Las mordeduras producidas por animales y por seres humanos suponen un motivo de consulta no infrecuente. Tienen un mayor riesgo de infeccion las producidas por gatos y seres humanos, las heridas extensas o profundas, las que afectan a la cara y a las manos o que estan proximas a las articulaciones, y aquellas con retraso en la atencion medica o infringidas a pacientes inmunodeprimidos. Los microorganismos responsables son los habituales de la flora bacteriana bucal de los animales. El tratamiento inicial implica una evaluacion cuidadosa de los danos y del riesgo de infeccion, el lavado de la herida y la elevacion del miembro. En los casos con riesgo de infeccion debe considerarse un curso corto de antibioticos profilacticos. Es importante, asimismo, la reevaluacion de la herida a corto plazo. En los casos de infeccion asociada, debe incidirse en la limpieza de la herida, la escision de tejido necrotico y cuerpos extranos y un curso mas prolongado de antibioticos.

Soft-stall control of small wind turbines is a method to protect the generation system or the load from high wind speeds while keeping the system generating. Soft-stall activation must be due to an excess of power or torque/current. This paper proposes a method to improve the existing soft-stall methods for over torque/current protection by the development of a turbine torque estimator. Due to the inconvenience of the continuously changing weather conditions, wind turbine emulators are broadly used by researchers instead of actual wind turbines. This paper also proposes two methods to emulate the wind turbine inertia without communications between the load drive (wind turbine emulator) and the generation system controller.

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets 225 U/l (OR:4.45; CI:1–19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Background Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report safety of RDV in patients with moderate COVID-19. Methods We conducted an open-label, phase 3 trial (NCT04252664) in hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned to receive RDV (5 or 10 days) or standard of care (SOC). RDV was dosed intravenously at 200 mg on day 1, 100 mg daily thereafter. Adverse events (AEs) and laboratory abnormalities were evaluated through the day 11 data cut; safety data through day 28 will be presented at the meeting. Results 584 patients were randomized and treated (5d RDV: n=191; 10d RDV, n=193; SOC: n=200). Baseline characteristics were balanced among groups; median (range) age was 57y (12-95y), 39% were female and 19% Black, 39% had arterial hypertension, 15% hyperlipidemia, 11% asthma. Briefly, across both the 5d and 10d arms, RDV was well tolerated with a similar rate of Grade 3 or 4 AEs and fewer SAEs compared to SOC (Table). AEs more common with RDV vs SOC included nausea, headache, and hypokalemia. Overall, across the 3 arms, incidence of AEs leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. In addition, median changes in renal and liver function tests from baseline were not statistically significant between the RDV 5d and RDV 10d groups compared to the SOC only group at d14 (Table 1). Table 1. Conclusion RDV given for 5d or 10d was well tolerated in patients with moderate COVID-19. No clinically significant safety signals were observed with RDV vs SOC. Disclosures Gerard J. Criner, MD, Gilead Sciences Inc. (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator) Gerard J. Criner, MD, NO DISCLOSURE DATA Mi Young Ahn, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Gregory Huhn, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator)Janssen (Grant/Research Support)Proteus (Grant/Research Support)US National Institutes of Health (Grant/Research Support)Viiv Healthcare (Grant/Research Support) Aruna Subramanian, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Carlos Lumbreras, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Stefan Schmiedel, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Robert H. Hyland, MD, Gilead Sciences Inc. (Employee, Shareholder) Vithika Suri, PhD, Gilead Sciences Inc. (Employee, Shareholder) Huyen Cao, MD, Gilead Sciences Inc. (Employee, Shareholder) Hongyuan Wang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Devi SenGupta, MD, Gilead Sciences Inc. (Employee, Shareholder) Anand Chokkalingam, PhD, Gilead Sciences (Employee) Anu Osinusi, MD, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Yao-Shen Chen, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Yao-Shen Chen, MD, NO DISCLOSURE DATA Huldrych Günthard, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) D Jose Sanz-Moreno, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Judith A. Aberg, MD, Theratechnology (Consultant) Emanuele Nicastri, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Owen Tak-Yin Tsang, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Owen Tak-Yin Tsang, MD, NO DISCLOSURE DATA

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence. This work was supported by GESITRA/SEIMC, ONT and‘Plan Nacional de I+D+I’ and Instituto de Salud Carlos III(Fondo de Investigaciones Sanitarias 12/02269 and ProyectoIntegrado de Excelencia 13/00045), Subdirección General de Redesy Centros de Investigacion Cooperativa, Spanish Ministry of Econ-omy and Competitiveness, Spanish Network for Research inInfectious Diseases (REIPI RD16/0016), co-financed by the Euro-pean Development Regional Fund A way to achieve Europe.

There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin ≥500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection.We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016-17 and 2017-18). Poor outcome was defined as the presence of at least one of the following: respiratory failure, admission to the intensive care unit, or in-hospital mortality.Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p 0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231-967 versus 217 ng/mL, range 140-394, p 0.0001). In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65-0.8, p 0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4-82.7%).Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome.

Introduction: liver laboratory tests improve in hepatitis C virus (HCV)-monoinfected and cirrhotic patients who achieve HCV cure after interferon-free treatment. Objective and methods: this study evaluates the changes in those tests in human immunodeficiency virus (HIV)-positive subjects with an eradicated HCV-coinfection using direct-acting antivirals and with a pre-therapy liver stiffness ≥ 14.6 kPa or clinical data of cirrhosis. Serum albumin, bilirubin, creatinine, platelet count and international normalized ratio (INR) values were collected at baseline, week 4, at the end of treatment and 24 weeks after the end-of-treatment. Fibrosis-4 score (FIB4) and Model for End-stage Liver Disease (MELD) score values were calculated and liver stiffness was estimated by transient elastography at baseline and 24 weeks after the end-of-treatment. The means were compared with the Student’s t test or the repeated measures ANOVA test. Results: direct-acting antivirals were prescribed to 131 HIV/HCV-coinfected cirrhotic patients. A sustained virological response was confirmed in 120 cases. Albumin, bilirubin and platelet count values improved in the entire population 24 weeks after the end-of-treatment. INR and MELD score values decreased when patients with atazanavir and/or acenocoumarol were excluded and liver fibrosis tests significantly diminished. Nine patients developed liver decompensation and there were three deaths. Conclusion: in conclusion, HCV eradication was associated with a short-term improvement in biochemical liver function and fibrosis tests in HIV-coinfected patients with cirrhosis, although clinical events still occur. Sin financiación 1.591 JCR (2019) Q4, 81/88 Gastroenterology & Hepatology 0.383 SJR (2019) Q3, 92/145 Gastroenterology, 1505/2754 Medicine (miscellaneous) No data IDR 2019 UEM

This paper analyzes a cost-effective modification of the power topology commonly found in small wind turbine systems based on a passive rectifier and a boost converter. The boost-converter inductor and the input filter capacitor often placed at the rectifier output can be replaced by the generator-phase inductance. Different controller structures have been proposed for this low-cost inverter, but they have been focused on the converter itself rather than the overall turbine control. Moreover, only steady-state behavior has been demonstrated. This paper proposes a control structure only requiring retuning of the boost-current controller found in systems equipped with boost inductance, with other control loops remaining unchanged. The inductorless converter dynamic performance is studied and compared with the conventional topology in terms of current- and torque-control capability. The system efficiency, including the losses’ distribution in the generator, is analyzed. Simulation and experimental results are presented to demonstrate the technical viability of this proposal.

Acute porphyria attacks are associated with the strong up-regulation of hepatic heme synthesis and over-production of neurotoxic heme precursors. First-line therapy is based on carbohydrate loading. However, altered glucose homeostasis could affect its efficacy. Our first aim was to investigate the prevalence of insulin resistance (IR) in an observational case-control study including 44 Spanish patients with acute intermittent porphyria (AIP) and 55 age-, gender- and BMI-matched control volunteers. Eight patients (18.2%) and one control (2.3%, p = 0.01) showed a high HOMA-IR index (cut-off ≥ 3.4). Patients with IR and hyperinsulinemia showed clinically stable disease. Thus, the second aim was to evaluate the effect of the co-administration of glucose and a fast-acting or new liver-targeted insulin (the fusion protein of insulin and apolipoprotein A-I, Ins-ApoAI) in AIP mice. The combination of glucose and the Ins-ApoAI promoted partial but sustained protection against hepatic heme synthesis up-regulation compared with glucose alone or co-injected with fast-acting insulin. In a prevention study, Ins-ApoAI improved symptoms associated with a phenobarbital-induced attack but maintained high porphyrin precursor excretion, probably due to the induction of hepatic mitochondrial biogenesis mediated by apolipoprotein A-I. In conclusion, a high prevalence of IR and hyperinsulinemia was observed in patients with AIP. The experimental data provide proof-of-concept for liver-targeted insulin as a way of enhancing glucose therapy for AIP.

Resumen Antecedentes y objetivo La hemophagocytic lymphohistiocytosis (HLH, «linfohistiocitosis hemofagocitica») es una entidad grave, producida por una incorrecta regulacion de la respuesta inmunologica frente a diversos estimulos del sistema inmunitario. Su diagnostico y tratamiento precoz suponen un reto para el clinico. Pacientes y metodo Hemos realizado un estudio descriptivo retrospectivo de los pacientes adultos diagnosticados de HLH, segun los criterios de la Histiocyte Society, entre los anos 2010 y 2015 en nuestra institucion, analizando sus caracteristicas clinicas, el estudio diagnostico-etiologico y su evolucion. Resultados Se analizaron 18 pacientes. La mediana de tiempo al diagnostico fue de 24 dias. La etiologia fue neoplasica en 8 casos (hematologica en 7), infecciosa en 6 (leishmaniasis visceral en 4), inflamatoria en uno, y en los 3 restantes, idiopatica. Se realizo tratamiento en 16 pacientes con corticoides, asociando ciclosporina en 2, inmunoglobulinas en uno, y etoposido con tacrolimus en otro. Conclusiones Destacamos la escasa utilizacion de etoposido en el tratamiento dirigido, el actualmente recomendado. La mortalidad global fue del 44%, asociada a la etiologia neoplasica principalmente (67 frente a 16,6% de mortalidad en la etiologia infecciosa, p

Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.

Microbiological spectrum and outcome of infectious complications following small bowel transplantation (SBT) have not been thoroughly characterized. We performed a retrospective analysis of all patients undergoing SBT from 2004 to 2013 in Spain. Sixty-nine patients underwent a total of 87 SBT procedures (65 pediatric, 22 adult). The median follow-up was 867 days. Overall, 81 transplant patients (93.1%) developed 263 episodes of infection (incidence rate: 2.81 episodes per 1000 transplant-days), with no significant differences between adult and pediatric populations. Most infections were bacterial (47.5%). Despite universal prophylaxis, 22 transplant patients (25.3%) developed cytomegalovirus disease, mainly in the form of enteritis. Specifically, 54 episodes of opportunistic infection (OI) occurred in 35 transplant patients. Infection was the major cause of mortality (17 of 24 deaths). Multivariate analysis identified retransplantation (hazard ratio [HR]: 2.21; 95% confidence interval [CI]: 1.02-4.80; p = 0.046) and posttransplant renal replacement therapy (RRT; HR: 4.19; 95% CI: 1.40-12.60; p = 0.011) as risk factors for OI. RRT was also a risk factor for invasive fungal disease (IFD; HR: 24.90; 95% CI: 5.35-115.91; p

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.

Real-life cohorts have shown that the effectiveness of all-oral, direct-acting antivirals (DAA) for HCV treatment is > 90%. We aimed to explore the predictive factors of DAA success in HIV coinfection. This is an observational prospective study within the cohort BVIH-DOC^, Madrid, Spain. HIV/HCV-coinfected patients were included if they had been treated with DAAs between 9 January 2015 and 31 August 2016. The sustained virological response (SVR) was analysed in the intention-to-treat population. Binary logistic regression was used to study the impact of cirrhosis, anti-HCV therapy experience and the IL28B polymorphism on SVR, besides factors with a p value < 0.15 from the univariate analysis. DAA were prescribed to 423 patients. SVR was confirmed in 92.9%. The univariate analysis showed higher proportion of patients with SVR among those with DAA adherence ≥ 95% (difference + 10.3%, 95%CI 3.5–19.6) and a baseline CD4+ cell count ≥ 200/μL (difference + 14.7%, 95%CI 4.1–31.0). Logistic regression evinced that both DAA adherence and baseline CD4+ cell counts predicted the SVR (OR 3.9, 95% CI 1.8– 8.8, and OR 5.2, 95% CI 1.9–13.9, respectively). Moreover, men who reported having sex with other men (MSM) were less likely to achieve SVR (OR 4.2, 95% CI 1.1–16.1). Among MSM, three of three patients without SVR were suspected to have experienced HCV reinfection. DAA for HCV in HIV-coinfected patients is highly effective. DAA adherence ≥ 95% and a baseline CD4+ count ≥ 200/μL predicted a higher probability of SVR. A lower rate of SVR was found in MSM, presumably due to a higher frequency of HCV reinfection. Sin financiación 2.837 JCR (2019) Q2, 45/93 Infectious Diseases; Q3, 73/135 Microbiology 1.171 SJR (2019) Q1, 385/2754 Medicine (miscellaneous); Q2, 83/300 Infectious Diseases, 34/128 Microbiology (medical) No data IDR 2019 UEM

Functional status linked to a poor outcome in a broad spectrum of medical disorders. Barthel Activities of Daily Life Index (BADLI) is one of the most extended tools to quantify functional dependence. Whether BADLI can help to predict outcomes in elderly patients with acute venous thromboembolism (VTE) is unknown. The current study aimed to ascertain the influence of BADLI on 6-month all-cause mortality in aged patients with VTE. This is a prospective observational study. We included consecutive patients older than 75-year-old with an acute VTE between April 2015 and April 2017. We analyzed several variables as mortality predictors, including BADLI-measured functional status. Afterward, we performed a multivariate analysis, using logistic regression, to identify all-cause mortality independent predictive factors. Two hundred and two subjects were included. Thirty-five (17%) patients died in the first 6 months. The leading cause of death was cancer (59%). After multivariable logistic regression, we identified BADLI and Charlson index as independent predictors for 6-months mortality [BADLI (every decrease of 10 points) OR 1.21 95% CI (1.03-1.42) and Charlson index OR 1.71 95% CI (1.21-2.43)]. Body mass index (BMI) values were inversely related to mortality [OR 0.85 95% CI (0.75-0.95)]. In conclusion, BADLI, BMI, and Charlson index scores are independent predictive factors for 6-month all-cause mortality in old patients with VTE.

Hemophagocytic syndrome (HPS) is a rare, but increasingly reported disease characterized by severe dysfunction of cytotoxic T cells and NK cells, often associated with poor outcome. It has been related to multiple processes including a large variety of infections. Even though viral infections have been described as triggers of HPS, influenza associated hemophagocytic syndrome in adults has been rarely reported. Here, we present a case of an 85 year-old man with essential thrombocytemia who developed HPS triggered by influenza A H1N1 infection and a review of the literature with special emphasis on the importance of a prompt diagnosis and an early treatment to achieve a more favourable outcome. Hemophagocytic syndrome secondary to influenza virus infection is a rare condition with high mortality that should be suspected in patients with an aggressive disease course. Early diagnosis and initiation of antiviral treatment and in some cases immunomodulatory therapy are crucial for the prognosis.

Cardiac allograft vasculopathy (CAV) is a major cause of long-term morbidity and mortality after heart transplantation (HTx), whose relationship with CMV infection is uncertain. This study evaluated the influence of CMV infection in the development of CAV.We enrolled 166 consecutive HTx recipients who underwent their first transplant from January 1995 to July 2002. All patients received 14 days of intravenous ganciclovir and were prospectively monitored for CMV infection during the first year after HTx. CAV was diagnosed by coronary angiography performed at 1, 5, and 10 years after HTx, following the new criteria of the International Society for Heart and Lung Transplantation. We collected all variables potentially related with the development of CAV. Risk factors were studied using a complementary log-log model.After a median follow-up of 11 years (range, 1-17 years), 72 patients (43%) developed CAV (63.8% CAV(1), 15.2% CAV(2), 20.8% CAV(3)). Symptoms secondary to CAV were present in 32% of these patients, and 8% died because of it. In the regression multivariate analysis, independent variables associated with the development of CAV were donor age (hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.002-1.053; p0.028), presence of cellular acute rejection ≥ 2R (HR, 1.764; 95% CI, 1.011-3.078; p0.0414), CMV infection (HR, 2.334; 95% CI, 1.043-5.225; p0.0354), and not having been treated with a calcium channel blocker (HR, 0.472; 95% CI, 0.275-0.811; p0.0055).Standardized angiographic criteria show CMV infection is associated with the development of CAV.

Acute HIV infection is a challenging diagnosis that is easily missed due to the nonspecific symptoms of the HIV seroconversion syndrome; some patients might develop neurological symptoms, usually around three weeks after the onset of illness. A high HIV viral load in CSF (cerebrospinal fluid) has been associated with the presence of neurological symptoms, and a correlation between the CSF HIV RNA level and the severity of neurological symptoms has been described. We present the case of a patient who developed a peripheral facial palsy and a trigeminal neuralgia during an acute HIV infection, and the laboratory and microbiological findings, including the HIV viral load in CSF, which strongly suggest an HIV primary infection as the etiology of these neuropathies.

During a visceral leishmaniasis outbreak in an area of Madrid, Spain, the incidence of disease among solid organ transplant recipients was 10.3% (7/68). Being a black person from sub-Saharan Africa, undergoing transplantation during the outbreak, and residing