Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of ...adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.
Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters.
First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.
Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.
None.
We are witnessing the dramatic consequences of the COVID-19 pandemic which, unfortunately, go beyond the impact on the health system. Until herd immunity is achieved with vaccines, the only available ...mechanisms for controlling the pandemic are quarantines, perimeter closures and social distancing with the aim of reducing mobility. Governments only apply these measures for a reduced period, since they involve the closure of economic activities such as tourism, cultural activities, or nightlife. The main criterion for establishing these measures and planning socioeconomic subsidies is the evolution of infections. However, the collapse of the health system and the unpredictability of human behavior, among others, make it difficult to predict this evolution in the short to medium term. This article evaluates different models for the early prediction of the evolution of the COVID-19 pandemic to create a decision support system for policy-makers. We consider a wide branch of models including artificial neural networks such as LSTM and GRU and statistically based models such as autoregressive (AR) or ARIMA. Moreover, several consensus strategies to ensemble all models into one system are proposed to obtain better results in this uncertain environment. Finally, a multivariate model that includes mobility data provided by Google is proposed to better forecast trend changes in the 14-day CI. A real case study in Spain is evaluated, providing very accurate results for the prediction of 14-day CI in scenarios with and without trend changes, reaching 0.93 Formula: see text, 4.16 RMSE and 1.08 MAE.
The effect of β-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered ...early (intravenously before reperfusion).
Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean ± SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6 ± 15.3 versus 32.0 ± 22.2 g; adjusted difference, -6.52; 95% confidence interval, -11.39 to -1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was -8.13 (95% confidence interval, -13.10 to -3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21).
In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI.
http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.
In the context of the International GNSS Service (IGS), several IGS Ionosphere Associated Analysis Centers have developed different techniques to provide global ionospheric maps (GIMs) of vertical ...total electron content (VTEC) since 1998. In this paper we present a comparison of the performances of all the GIMs created in the frame of IGS. Indeed we compare the
classical
ones (for the ionospheric analysis centers CODE, ESA/ESOC, JPL and UPC) with the new ones (NRCAN, CAS, WHU). To assess the quality of them in fair and completely independent ways, two assessment methods are used: a direct comparison to altimeter data (VTEC-altimeter) and to the difference of slant total electron content (STEC) observed in independent ground reference stations (dSTEC-GPS). The main conclusion of this study, performed during one solar cycle, is the consistency of the results between so many different GIM techniques and implementations.
The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored.
This was an international, multicenter, retrospective cohort study conducted between February and December 2020. ...Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31-365 days).
A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 0.56-2.91; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 1.99-4.0; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 1.02-4.99; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 2.93-29.70; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 1.35-8.46; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 0.25-1.80; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001).
At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.
Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact ...of NRP on the short‐term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012–2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high‐volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p = .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 95% CI 1.43–2.72; p < .001) and 1‐year graft loss (OR 1.77 95% CI 1.01–3.17; p = .034). In conclusion, compared with RR, NRP appears to improve the short‐term outcomes of cDCDD kidney transplants.
This multicenter, nationwide, retrospective study that uses propensity score matching shows lower delayed graft function and higher 1‐year graft survival rates for transplants using kidneys from controlled donation after circulatory determination of death donors procured with normothermic regional perfusion versus through rapid recovery.
Abstract
Background
The role of vitamin D status in COVID-19 patients is a matter of debate.
Objectives
To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and ...to analyze the possible influence of vitamin D status on disease severity.
Methods
Retrospective case–control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated.
Results
Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, mean ± standard deviation 25OHD levels were 13.8 ± 7.2 ng/mL, compared with 20.9 ± 7.4 ng/mL in controls (P < .0001). 25OHD values were lower in men than in women. Vitamin D deficiency was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (P < .0001). 25OHD inversely correlates with serum ferritin (P = .013) and D-dimer levels (P = .027). Vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay than those with serum 25OHD levels ≥20 ng/mL. No causal relationship was found between vitamin D deficiency and COVID-19 severity as a combined endpoint or as its separate components.
Conclusions
25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease.
This study sought to analyze the clinical impact of the degree and improvement of mitral regurgitation in TAVR recipients, validate the main imaging determinants of this improvement, and assess the ...potential candidates for double valve repair with percutaneous techniques.
Many patients with severe aortic stenosis present with concomitant mitral regurgitation (MR). Cardiac imaging plays a key role in identifying prognostic factors of MR persistence after transcatheter aortic valve replacement (TAVR) and for planning its treatment.
A total of 1,110 patients with severe aortic stenosis from 6 centers who underwent TAVR were included. In-hospital to 6-month follow-up clinical outcomes according to the degree of baseline MR were evaluated. Off-line analysis of echocardiographic and multidetector computed tomography images was performed to determine predictors of improvement, clinical outcomes, and potential percutaneous alternatives to treat persistent MR.
Compared with patients without significant pre-TAVR MR, 177 patients (16%) presented with significant pre-TAVR MR, experiencing a 3-fold increase in 6-month mortality (35.0% vs. 10.2%; p < 0.001). After TAVR, the degree of MR improved in 60% of them. A mitral annular diameter of >35.5 mm (odds ratio: 9.0; 95% confidence interval: 3.2 to 25.3; p < 0.001) and calcification of the mitral apparatus by multidetector computed tomography (odds ratio: 11.2; 95% confidence interval: 4.03 to 31.3; p < 0.001) were independent predictors of persistent MR. At least 14 patients (1.3% of the entire cohort, 13.1% of patients with persistent MR) met criteria for percutaneous mitral repair with either MitraClip (9.3%) or a balloon-expandable valve (3.8%).
Significant MR is not uncommon in TAVR recipients and associates with greater mortality. In more than one-half of patients, the degree of MR improves after TAVR, which can be predicted by characterizing the mitral apparatus with multidetector computed tomography. According to standardized imaging criteria, at least 1 in 10 patients whose MR persists after TAVR could benefit from percutaneous mitral procedures, and even more could be treated with MitraClip after dedicated pre-imaging evaluation.
As the skin is the main protective organ of the body, it is exposed to wounds or injuries which carry out a healing process during a period of approximately 15 days depending on the severity of the ...injury. In the present research, the development of chitosan-based hydrogels loaded with silver nanoparticles and calendula extract (Ch-AgNPs-Ce) was proposed. This can be used to fulfill the hemostatic, anti-infective, antibacterial, healing and anti-inflammatory functions through controlled release of the nanoparticles and calendula extract in substitution of commonly used drugs. The physical properties of the silver nanoparticles were analyzed by UV–visible spectroscopy, scanning and transmission electron microscopy, showing a size between 50 and 100 nm. The antibacterial properties were evaluated by the agar well diffusion method. Antimicrobial testing of the hydrogels showed that the inclusion of silver nanoparticles provides concentration-dependent antibacterial behavior against E. coli and S. aureus. The healing properties of the system were tested in two diabetic patients to whom said hydrogels were placed, obtaining a positive curative result after a few weeks. Therefore, it can be concluded that Ch-AgNPs-Ce hydrogels can achieve healing in chronic or exposed wounds after a period of time which can be used in alternative treatments in patients with poor healing capacity.
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