Publications by authors named "Mario Fernández-Ruiz"

162 Publications

Interleukin-6-based mortality prediction model for COVID-19: validation and update in multicentre and second wave cohorts.

J Allergy Clin Immunol 2021 Mar 1. Epub 2021 Mar 1.

Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) is a highly variable condition. Validated tools to assist in the early detection of patients at high risk of mortality can help guide medical decisions.

Objective: To validate externally, as well as in patients from the second pandemic wave in Europe, our previously developed mortality prediction model for hospitalized COVID-19 patients.

Methods: Three validation cohorts were generated: two external with 185 and 730 patients from the first wave and one internal with 119 patients from the second wave. The probability of death was calculated for all subjects using our prediction model, which includes SpO/FiO ratio, neutrophil-to-lymphocyte ratio, LDH, interleukin-6 and age. Discrimination and calibration were evaluated in the validation cohorts. The prediction model was updated by re-estimating individual risk factor effects in the overall cohort (N=1477).

Results: The mortality prediction model showed good performance in the external validation cohorts 1 and 2, and in the second wave validation cohort 3 (AUC 0.94, 0.86 and 0.86, respectively), with excellent calibration (calibration slope 0.86, 0.94 and 0.79; intercept 0.05, 0.03 and 0.10, respectively). The updated model accurately predicted mortality in the overall cohort (AUC 0.91), which included patients from both the first and second COVID-19 waves. The updated model was also useful to predict fatal outcome in patients without respiratory distress at the time of evaluation.

Conclusions: This is the first COVID-19 mortality prediction model validated in patients from the first and second pandemic waves. The COR+12 online calculator is freely available to facilitate its implementation (https://utrero-rico.shinyapps.io/COR12_Score/).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919507PMC
March 2021

Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: a single-center retrospective study.

Int J Infect Dis 2021 Feb 26. Epub 2021 Feb 26.

Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain.

Background: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.

Methods: We 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.

Results: Overall, 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 <0.001). The occurrence of secondary infection was similar between both groups.

Conclusions: The combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.02.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908857PMC
February 2021

Effectiveness of anakinra for tocilizumab-refractory severe COVID-19. A single centre retrospective comparative study.

Int J Infect Dis 2021 Feb 13. Epub 2021 Feb 13.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense, Spain.

Objetives: A subgroup of patients with SARS-CoV-2 infection is considered to develop a cytokine release syndrome and have been treated with tocilizumab, but a significant percentage of patients evolve. Our objective was to determine the usefulness of anakinra as rescue treatment for patients with tocilizumab-refractory COVID-19 disease.

Methods: A prospective cohort of patients with COVID19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) to selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a six-point ordinal scale, from baseline to day 21.

Results: The study included 20 cases and 20 controls (mean age 65.3±12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. In-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P=0.527).

Conclusions: Treatment with anakinra was not useful to improve the prognosis of patients with tocilizumab-refractory severe COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.02.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881693PMC
February 2021

Efficacy and safety of oral fosfomycin for asymptomatic bacteriuria in kidney transplant recipients: Results from a Spanish multicenter cohort.

Antimicrob Agents Chemother 2021 Feb 8. Epub 2021 Feb 8.

Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Biomédica Hospital "12 de Octubre" (imas12), Madrid, Spain.

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum β-lactamase-producing [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; -value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; -value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02267-20DOI Listing
February 2021

Eradication of Staphylococcus aureus post-sternotomy mediastinitis following the implementation of universal pre-operative nasal decontamination with mupirocin: an interrupted time-series analysis.

Clin Infect Dis 2021 Jan 29. Epub 2021 Jan 29.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Complutense University, Madrid, Spain.

Background: Although pre-surgical nasal decontamination with mupirocin (NDM) has been advocated as a measure for preventing post-surgical mediastinitis (PSM) due to Staphylococcus aureus, this strategy is not universally recommended due to the lack of robust supporting evidence. We aimed to evaluate the role of pre-operative NDM in the annual incidence of S. aureus PSM at our institution.

Methods: An interrupted time-series analysis, with autoregressive error model, was applied to our single-center cohort by comparing pre-intervention (1990-2003) and post-intervention period (2005 to 2018). Logistic regression was performed to analyze risk factors for S. aureus PSM.

Findings: 12,236 sternotomy procedures were analyzed (6,370 [52.1%] and 5,866 [47.9%] in the pre-intervention and post-intervention periods, respectively). The mean annual percentage adherence to NDM estimated over the post-interventional period was 90.2%. Only four out of 127 total cases of S. aureus PSM occurred during the 14-years post-intervention period (0.68/1,000 sternotomies vs. 19.31/1,000 in pre-interventional period [p<0.0001]). Interrupted time-series analysis demonstrated a statistically significant annual reduction of S. aureus PSM trend of -9.85 cases per 1,000 sternotomies (-13.17 to -6.5, P-value< 0·0001) in 2005, with a decreasing trend maintained over the following five years with an estimated relative reduction of 84.8% (95% CI: 89·25 to 74·09). Chronic obstructive pulmonary disease was the single independent risk factor for S. aureus PSM (odds ratio: 3.7; 95% CI: 1.72-7.93) and was equally distributed in patients undergoing sternotomy during pre or post-intervention periods.

Interpretation: Our experience suggests that the implementation of pre-operative NDM reduces significantly the incidence of S. aureus PSM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab073DOI Listing
January 2021

Tocilizumab for the treatment of COVID-19.

Expert Opin Biol Ther 2021 Jan 27:1-4. Epub 2021 Jan 27.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (Imas12) , Madrid, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14712598.2021.1880563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852257PMC
January 2021

Impact of viral load at admission on the development of respiratory failure in hospitalized patients with SARS-CoV-2 infection.

Eur J Clin Microbiol Infect Dis 2021 Jan 7. Epub 2021 Jan 7.

Department of Internal Medicine, Hospital Universitario ''12 de Octubre'', Instituto de Investigación Sanitaria Hospital ''12 de Octubre'' (imas12), Madrid, Spain.

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 < 25), intermediate viral load (Ct: 25-30) and low 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 < 25 was associated with a higher risk of respiratory failure during admission (OR: 2.99, 95%IC: 1.57-5.69). SARS-CoV-2 viral load, measured through the Ct value on admission, is a valuable tool to predict the development of respiratory failure in COVID-19 inpatients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10096-020-04150-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787698PMC
January 2021

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015.

Emerg Infect Dis 2021 Jan;27(1)

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2701.190782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774531PMC
January 2021

Is there a real risk of bacterial infection in patients receiving targeted and biological therapies?

Enferm Infecc Microbiol Clin 2020 Dec 15. Epub 2020 Dec 15.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; School of Medicine, Universidad Complutense. Madrid, Spain.

Over the past decades, the advent of targeted and biological therapies has revolutionized the management of cancer and autoimmune, hematological and inflammatory conditions. Although a large amount of information is now available on the risk of opportunistic infections associated with some of these agents, the evidence regarding the susceptibility to bacterial infections is more limited. Biological agents have been shown to entail a variable risk of bacterial infections in pivotal randomized clinical trials and post-marketing studies. Recommendations on risk minimization strategies and therapeutic interventions are therefore scarce and often based on expert opinion, with only a few clear statements for some particular agents (i.e. meningococcal vaccination for patients receiving eculizumab). In the present review the available information regarding the incidence of and risk factors for bacterial infection associated with the use of different groups of biological agents is summarized according to their mechanisms of action, and recommendations based on this evidence are provided. Additional information coming from clinical research and real-world studies is required to address unmet questions in this emerging field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eimc.2020.10.019DOI Listing
December 2020

Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

Transpl Infect Dis 2020 Nov 22:e13520. Epub 2020 Nov 22.

Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.

Background: Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.

Methods: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively.

Results: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes.

Conclusions: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13520DOI Listing
November 2020

Invasive pulmonary aspergillosis associated with COVID-19 in a kidney transplant recipient.

Transpl Infect Dis 2020 Nov 13:e13501. Epub 2020 Nov 13.

Department of Nephrology, University Hospital "12 de Octubre", Madrid, Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might increase the risk of invasive pulmonary aspergillosis (IPA). Although several case reports and small series have been reported in the general population, scarce information is available regarding coronavirus disease 2019 (COVID-19)-associated IPA in the setting of solid organ transplantation. We describe a case of a kidney transplant recipient with severe COVID-19 that was subsequently diagnosed with probable IPA on the basis of the repeated isolation of Aspergillus fumigatus in sputum cultures, repeatedly increased serum (1 → 3)-β-d-glucan levels, and enlarging cavitary nodules in the CT scan. The evolution was favorable after initiation of isavuconazole and nebulized liposomal amphotericin B combination therapy and the withdrawal of immunosuppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13501DOI Listing
November 2020

Organ Donation and Transplantation During the COVID-19 Pandemic: A Summary of the Spanish Experience.

Transplantation 2021 01;105(1):29-36

Intensive Care Unit, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.

Background: Spain has been amongst the countries most affected by the COVID-19 pandemic, which has posed significant challenges to the donation and transplantation program. Despite a dramatic decrease of donation and transplantation activities during the critical early weeks of the outbreak, the program has recovered and is learning to cope with COVID-19.

Methods: We describe the 4 pillars upon which the Spanish donation and transplantation program has been rebuilt.

Results: (1) Standards have been developed and progressively updated for the evaluation and selection of potential donors and recipients with regards to SARS-CoV-2 infection. (2) Spain has been actively generating evidence to assess the validity of our standards and to understand the natural history of the infection in transplant recipients. No case of donor-derived COVID-19 has been reported to date. COVID-19 has been more frequent and has had a more aggressive course in recipients of solid organ transplants than in the general population, but this seems largely explained by the demographics and comorbidity of transplant patients. (3) As a result of this evidence and experience, recommendations have been issued for the management of COVID-19 in solid organ transplant recipients and candidates on the waiting list. (4) Finally, concrete guidance has been issued for centers to manage the donation and transplantation programs in relation to a dynamic and heterogeneous epidemiologic scenario.

Conclusions: The Spanish experience confronting the impact of COVID-19 upon donation and transplantation may help serve the needs of a broader community in other countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003528DOI Listing
January 2021

Immunomodulatory Therapies for COVID-19 in Solid Organ Transplant Recipients.

Curr Transplant Rep 2020 Oct 23:1-11. Epub 2020 Oct 23.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Centro de Actividades Ambulatorias, 2ª planta, bloque D. Avda. de Córdoba, s/n, 28041 Madrid, Spain.

Purpose Of Review: Severe coronavirus disease 2019 (COVID-19) is characterized by the development of a deleterious hyperinflammatory response, in which the pleiotropic cytokine interleukin (IL)-6 plays a pivotal role. The administration of immunomodulatory therapies has been proposed to revert the tissue damage induced by COVID-19-related cytokine release syndrome (CRS). The present review summarizes the biological rationale and available clinical experience with this therapeutic strategy in the specific scenario solid organ transplantation (SOT).

Recent Findings: A number of case reports, case series, and non-controlled cohort studies have assessed the efficacy and safety of the anti-IL-6-receptor monoclonal tocilizumab in SOT (namely kidney transplantation) recipients with COVID-19 pneumonia and CRS. Although the heterogeneity in patient management and the lack of a control group limit the interpretation of these results, tocilizumab therapy appears to provide some clinical benefit in post-transplant COVID-19 and to be reasonably safe in terms of bacterial superinfection. A large randomized clinical trial (RCT) has shown survival benefit with adjuvant corticosteroids in non-transplant patients, but supporting evidence is scarce for SOT recipients and confounded by the variable adjustment of baseline immunosuppression. Anecdotal experiences have been reported with the use of the anti-IL-1 agent anakinra and the NLRP3 inflammasome inhibitor colchicine in this population.

Summary: Immunomodulation has emerged as a promising option for SOT recipients with COVID-19-related CRS, with available experience mainly restricted to the anti-IL-6 agent tocilizumab. However, the supporting evidence is scarce and of low quality. In the absence of RCT, observational studies including well-matched control groups should be designed in future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40472-020-00306-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581948PMC
October 2020

COVID-19 in transplant recipients: The Spanish experience.

Am J Transplant 2020 Oct 23. Epub 2020 Oct 23.

Organización Nacional de Trasplantes (Spanish National Transplant Organization), Madrid, Spain.

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16369DOI Listing
October 2020

Infectious complications of rheumatoid arthritis and psoriatic arthritis during targeted and biological therapies: a viewpoint in 2020.

Ann Rheum Dis 2020 12 22;79(12):1532-1543. Epub 2020 Sep 22.

Oregon Health Sciences University, Portland, Oregon, USA.

Biological therapies have improved the outcomes of several major inflammatory, autoimmune and also neoplastic disorders. Those directed towards cytokines or other soluble mediators, cell-surface molecules or receptors or various components of intracellular signalling pathways may be associated with the occurrence of infections whose diversity depends on the particular immune target. In this context and following a keynote lecture given by one of us at the European League Against Rheumatism meeting on June 2018, a multidisciplinary group of experts deeply involved in the use of targeted and biological therapies in rheumatoid and psoriatic arthritis decided to summarise their recent vision of the immunological basis and epidemiology of infections occurring during targeted and biological therapies, and provide useful indications for their management and prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-217092DOI Listing
December 2020

Tocilizumab use in Kidney Transplant Patients with COVID-19.

Clin Transplant 2020 11 27;34(11):e14072. Epub 2020 Sep 27.

Department of Nephrology, Hospital Universitario, Madrid, Spain.

A potential benefit of immunomodulatory agents such as tocilizumab (TCZ) has been reported in patients with coronavirus disease 2019 (COVID-19) and severe pulmonary involvement. However, this therapy has been scarcely studied in kidney transplant (KT) recipients. Herein, we describe the clinical course and outcome of 10 KT patients with severe COVID-19 that were treated with TCZ. Mean age of the study group was 54 ± 10 years (70% females), and 30% of the cases were within 6 months from transplant. Mycophenolate mofetil was discontinued in all cases upon admission, whereas baseline steroids were maintained and tacrolimus dose was reduced. Initial treatment included hydroxychloroquine, antibiotics, and prophylactic anticoagulation. Before treatment with TCZ, 3 patients were receiving high-flow oxygen, 4 patients low-flow oxygen and 1 case non-invasive ventilation. All patients received a single dose of intravenous TCZ within a mean time of 7 ± 4 days since admission. During a median follow-up of 16 days (IQR: 10-29), 7 patients (70%) gradually improved and were finally discharged while three cases (30%) did not exhibited clinical improvement and ultimately died. In conclusion, although treatment with TCZ could be associated with improved clinical outcomes in a subset of KT recipients with COVID-19, further studies are warranted before drawing firm conclusions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ctr.14072DOI Listing
November 2020

Risk factors for the development of invasive aspergillosis after kidney transplantation: Systematic review and meta-analysis.

Am J Transplant 2021 02 4;21(2):703-716. Epub 2020 Sep 4.

Unit of Infectious Diseases, Department of Internal Medicine, University Hospital 12 de Octubre, Madrid, Spain.

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16248DOI Listing
February 2021

Pretransplant CMV-specific T-cell immunity but not dose of antithymocyte globulin is associated with recovery of specific immunity after kidney transplantation.

J Infect Dis 2020 Aug 11. Epub 2020 Aug 11.

Maimónides Institute for Biomedical Research of Cordoba (IMIBIC)/Reina Sofía University Hospital/University of Cordoba, Cordoba, Spain.

Background: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time as well as the impact of the dose-dependent ATG.

Methods: CMV-CMI was assessed at days +30, +45, +60 and +90 after transplantation with the QuantiFERON-CMV assay. A "Reactive" result (IFNG ≥0.2 UI/mL) indicated a positive CMV-CMI.

Results: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that the ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFNG level (>12 IU/mL vs. ≤12 IU/mL) was associated with having positive CMV-CMI at day +30 (OR 12.9; 95% CI 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFNG level ≤12 IU/mL.

Conclusion: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation The pretransplant IFNG level, but not the ATG dose, shows a strong association with the kinetics of this recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa503DOI Listing
August 2020

IL-6-based mortality risk model for hospitalized patients with COVID-19.

J Allergy Clin Immunol 2020 10 22;146(4):799-807.e9. Epub 2020 Jul 22.

Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación, Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; Department of Immunology, Ophthalmology and ENT, Universidad Complutense de Madrid, Madrid, Spain.

Background: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed.

Objective: Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital.

Methods: We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model.

Results: High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, d-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO/FiO). A multivariable mortality risk model including the SpO/FiO ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity.

Conclusion: This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375283PMC
October 2020

Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study.

J Med Virol 2021 02 27;93(2):831-842. Epub 2020 Jul 27.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

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/FiO 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.26308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404673PMC
February 2021

Incidence and clinical profiles of COVID-19 pneumonia in pregnant women: A single-centre cohort study from Spain.

EClinicalMedicine 2020 Jun 15;23:100407. Epub 2020 Jun 15.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Complutense University, 2ª planta, bloque D. Avda. de Córdoba, s/n. Madrid, Spain.

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%; -value = 0·003) and serum C-reactive protein (CRP) levels >10 mg/dL (33·0% vs. 0·0%; -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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295514PMC
June 2020

Impact of duration of antibiotic therapy in central venous catheter-related bloodstream infection due to Gram-negative bacilli.

J Antimicrob Chemother 2020 10;75(10):3049-3055

Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (imas12), Madrid, Spain.

Background: A progressive increase in the incidence of catheter-related bloodstream infection (CRBSI) due to Gram-negative bacilli (GNB) has been reported. Current guidelines recommend antibiotic treatment for at least 7-14 days, although the supporting evidence is limited.

Methods: We performed a retrospective single-centre study including all patients with a definite diagnosis of GNB CRBSI from January 2012 to October 2018 in which the central venous catheter (CVC) was removed. The occurrence of therapeutic failure [clinical failure (persistence of symptoms and laboratory signs of infection), microbiological failure (persistent bacteraemia or relapse) and/or all-cause 30 day mortality] was compared between episodes receiving short [≤7 days (SC)] or long courses [>7 days (LC)] of appropriate antibiotic therapy following CVC removal.

Results: We included 54 GNB CRBSI episodes with an overall rate of therapeutic failure of 27.8% (15/54). Episodes receiving SC therapy were more frequently due to MDR GNB [60.9% (14/23) versus 34.5% (10/29); P = 0.058] and had higher Pitt scores [median (IQR) 1 (0-4) versus 0 (0-2); P = 0.086]. There were no significant differences in the rate of therapeutic failure between episodes treated with SC or LC therapy [30.4% (7/23) versus 27.6% (8/29); OR 1.15; 95% CI 0.34-3.83; P = 0.822]. The use of SCs was not associated with increased odds of therapeutic failure in any of the exploratory models performed.

Conclusions: The administration of appropriate antibiotic therapy for ≤7 days may be as safe and effective as longer courses in episodes of GNB CRBSI once the CVC has been removed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa244DOI Listing
October 2020

Varied clinical presentation and outcome of SARS-CoV-2 infection in liver transplant recipients: Initial experience at a single center in Madrid, Spain.

Transpl Infect Dis 2020 Oct 1;22(5):e13372. Epub 2020 Jul 1.

Department of Internal Medicine, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital ", Universidad Complutense de Madrid, Madrid, Spain.

Background: Which are the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant (LT) recipients?

Methods: We attempted to address this question by reviewing our single-center experience during the first 2 months of the pandemics at a high incidence area.

Results: Nineteen adult patients (5 females) were diagnosed by May 5, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323090PMC
October 2020

Derivation and external validation of the SIMPLICITY score as a simple immune-based risk score to predict infection in kidney transplant recipients.

Kidney Int 2020 10 12;98(4):1031-1043. Epub 2020 Jun 12.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain. Electronic address:

Existing approaches for infection risk stratification in kidney transplant recipients are suboptimal. Here, we aimed to develop and validate a weighted score integrating non-pathogen-specific immune parameters and clinical variables to predict the occurrence of post-transplant infectious complications. To this end, we retrospectively analyzed a single-center derivation cohort of 410 patients undergoing kidney transplantation in 2008-2013 in Madrid. Peripheral blood lymphocyte subpopulations, serum immunoglobulin and complement levels were measured at one-month post-transplant. The primary and secondary outcomes were overall and bacterial infection through month six. A point score was derived from a logistic regression model and prospectively applied on a validation cohort of 522 patients undergoing kidney transplantation at 16 centers throughout Spain in 2014-2015. The SIMPLICITY score consisted of the following variables measured at month one after transplantation: C3 level, CD4 T-cell count, CD8 T-cell count, IgG level, glomerular filtration rate, recipient age, and infection within the first month. The discrimination capacity in the derivation and validation cohorts was good for overall (areas under the receiver operating curve of 0.774 and 0.730) and bacterial infection (0.767 and 0.734, respectively). The cumulative incidence of overall infection significantly increased across risk categories in the derivation (low-risk 13.7%; intermediate-risk, 35.9%; high-risk 77.6%) and validation datasets (10.2%, 28.9% and 50.4%, respectively). Thus, the SIMPLICITY score, based on easily available immune parameters, allows for stratification of kidney transplant recipients at month one according to their expected risk of subsequent infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.04.054DOI Listing
October 2020

Congenital cutaneous candidiasis associated with maternal peripartum candidemia.

Rev Iberoam Micol 2020 Apr - Jun;37(2):68-71. Epub 2020 May 31.

Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain; Unit of Pediatric Infectious Diseases, Department of Pediatrics, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), School of Medicine, Universidad Complutense, Madrid, Spain; Spanish Translational Research Network in Pediatric Infectious Diseases (RITIP), Spain.

Background: Cutaneous congenital candidiasis (CCC) is a rare condition consisting of invasive fungal infection of the epidermis and dermis that mostly affects preterm infants. Maternal vaginal candidiasis is present in half of the cases, although the occurrence of invasive candidiasis during pregnancy or peripartum period is exceptional.

Case Report: We present the case of a full-term infant that was born by vacuum-assisted vaginal delivery to an apparently healthy 33 year-old woman with no history of intravenous drug use or vaginal candidiasis during pregnancy. The newborn showed a diffuse maculopapular rash with respiratory distress and bilateral interstitial lung infiltrates, requiring nasal continuous positive airway pressure support. Blood cultures obtained from the mother due to intrapartum fever yielded Candida albicans. Cultures of vaginal discharge and neonate skin also yielded C. albicans with the same in vitro susceptibly pattern. No alternative source for candidemia was identified. The clinical course after starting a systemic antifungal therapy was favorable in both the mother and the neonate, with clearance of candidemia and resolution of the skin lesions.

Conclusions: CCC must be considered in full-term newborns with maculopapular rash at birth or during the first days of life. The absence of alternative sources for bloodstream infection in the present case suggests a potential etiopathogenic relationship between CCC and maternal candidemia. It is reasonable to rule out postpartum candidemia when CCC is suspected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.riam.2020.02.002DOI Listing
May 2020

COVID-19 in Spain: Transplantation in the midst of the pandemic.

Am J Transplant 2020 09 27;20(9):2593-2598. Epub 2020 May 27.

Nephrology Service, Hospital Regional Universitario de Málaga, Málaga, Spain.

Spain has been one of the most affected countries by the COVID-19 outbreak. As of April 28, 2020, the number of confirmed cases is 210 773, including 102 548 patients recovered, more than 10 300 admitted to the ICU, and 23 822 deaths, with a global case fatality rate of 11.3%. From the perspective of donation and transplantation, the Spanish system first focused on safety issues, providing recommendations for donor evaluation and testing, and to rule out SARS-CoV-2 infection in potential recipients prior to transplantation. Since the country entered into an epidemiological scenario of sustained community transmission and saturation of intensive care, developing donation and transplantation procedures has become highly complex. Since the national state of alarm was declared in Spain on March 13, 2020, the mean number of donors has declined from 7.2 to 1.2 per day, and the mean number of transplants from 16.1 to 2.1 per day. Increased mortality on the waiting list may become a collateral damage of this terrible pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267131PMC
September 2020

Direct T-cell Inhibition and Agents Targeting T-cell Migration and Chemotaxis.

Infect Dis Clin North Am 2020 06 23;34(2):191-210. Epub 2020 Apr 23.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0002), Instituto de Salud Carlos III, Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain.

Lymphocyte depletion and blockade of T-cell activation and trafficking serve as therapeutic strategies for an enlarging number of immune-mediated diseases and malignancies. This review summarizes the infection risks associated to monoclonal antibodies that bind to the α chain of the interleukin-2 receptor, the cell surface glycoprotein CD52, and members of α4- and β2-integrin families acting as cell-adhesion molecules. An outline of the mechanisms of action, approved indications and off-label uses, expected impact on the host immune response, and available clinical evidence is provided for each of these agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.idc.2020.02.002DOI Listing
June 2020

COVID-19 in solid organ transplant recipients: A single-center case series from Spain.

Am J Transplant 2020 07 10;20(7):1849-1858. Epub 2020 May 10.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.

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-β (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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15929DOI Listing
July 2020

Variations in Circulating Active MMP-9 Levels During Renal Replacement Therapy.

Biomolecules 2020 03 26;10(4). Epub 2020 Mar 26.

Cardiorenal Translational Laboratory, Institute of Research i+12 (imas12), Hospital Universitario 12 de Octubre, 28041, Madrid, Spain.

Renal replacement therapy (RRT) is complicated by a chronic state of inflammation and a high mortality risk. However, different RRT modalities can have a selective impact on markers of inflammation and oxidative stress. We evaluated the levels of active matrix metalloproteinase (MMP)-9 in patients undergoing two types of dialysis (high-flux dialysis (HFD) and on-line hemodiafiltration (OL-HDF)) and in kidney transplantation (KT) recipients. Active MMP-9 was measured by zymography and ELISA before (pre-) and after (post-) one dialysis session, and at baseline and follow-up (7 and 14 days, and 1, 3, 6, and 12 months) after KT. Active MMP-9 decreased post-dialysis only in HFD patients, while the levels in OL-HDF patients were already lower before dialysis. Active MMP-9 increased at 7 and 14 days post-KT and was restored to baseline levels three months post-KT, coinciding with an improvement in renal function and plasma creatinine. Active MMP-9 correlated with pulse pressure as an indicator of arterial stiffness both in dialysis patients and KT recipients. In conclusion, active MMP-9 is better controlled in OL-HDF than in HFD and is restored to baseline levels along with stabilization of renal parameters after KT. Active MMP-9 might act as a biomarker of arterial stiffness in RRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom10040505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226477PMC
March 2020