Showing papers by "Mario Fernández-Ruiz published in 2020"

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

Abstract: 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 (SpO2/FiO2). A multivariable mortality risk model including the SpO2/FiO2 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.

Invasive Aspergillosis Due to Aspergillus Section Usti: A Multicenter Retrospective Study.

Abstract: Aspergillus spp. of section Usti (A.ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. Clinical report forms were obtained for 90 patients, of which 27 had proven/probable IA. Additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing anti-mold prophylaxis was present in 47% cases. Pulmonary IA represented 67% cases. Primary or secondary extra-pulmonary sites of infection were observed in 46% cases, with skin being affected in 28% cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16 and 4 µg/mL for amphotericin B, voriconazole, posaconazole and isavuconazole, respectively. Aspergillus ustus IA mainly occurred in non-neutropenic transplant patients and was frequently associated with extra-pulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.

Tocilizumab use in Kidney Transplant Patients with COVID-19.

Abstract: 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.

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

Abstract: 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.

Kidney transplantation in the extremely elderly from extremely aged deceased donors: a kidney for each age.

Abstract: BACKGROUND Advances in life expectancy have led to an increase in the number of elderly people with end-stage renal disease (ESRD). Scarce information is available on the outcomes of kidney transplantation (KT) in extremely elderly patients based on an allocation policy prioritizing donor-recipient age matching. METHODS We included recipients ≥75 years that underwent KT from similarly aged deceased donors at our institution between 2002 and 2015. Determinants of death-censored graft and patient survival were assessed by Cox regression. RESULTS We included 138 recipients with a median follow-up of 38.8 months. Median (interquartile range) age of recipients and donors was 77.5 (76.3-79.7) and 77.0 years (74.7-79.0), with 22.5% of donors ≥80 years. Primary graft non-function occurred in 8.0% (11/138) of patients. Cumulative incidence rates for post-transplant infection and biopsy-proven acute rejection (BPAR) were 70.3% (97/138) and 15.2% (21/138), respectively. One- and 5-year patient survival were 82.1 and 60.1%, respectively, whereas the corresponding rates for death-censored graft survival were 95.6 and 93.1%. Infection was the leading cause of death (46.0% of fatal cases). The occurrence of BPAR was associated with lower 1-year patient survival [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.64-10.82; P = 0.003]. Diabetic nephropathy was the only factor predicting 5-year death-censored graft survival (HR = 4.82, 95% CI 1.08-21.56; P = 0.040). CONCLUSIONS ESRD patients ≥75 years can access KT and remain dialysis free for their remaining lifespan by using grafts from extremely aged deceased donors, yielding encouraging results in terms of recipient and graft survival.

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

Abstract: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02). Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.

Early kinetics of Torque Teno virus DNA load and BK polyomavirus viremia after kidney transplantation.

Abstract: Growing evidence supports the role of the replication kinetics of Torque Teno virus (TTV) as a convenient surrogate marker of immunosuppression after solid organ transplantation.1,2 Human BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) constitutes one of the leading causes of graft lost after kidney transplantation (KT), a circumstance that has prompted the search for improved risk stratification strategies.3 Since the host's control of both TTV and BKPyV infection mainly relies on the cell-mediated immunity, it could be hypothesized that the presence of high TTV DNA levels could identify those recipients at greatest risk of BKPyVAN.1,4 However, contradictory results on this issue have been recently reported.

An evidence-based bundle improves the quality of care and outcomes of patients with candidaemia.

Abstract: Background Candidaemia is a leading cause of bloodstream infections in hospitalized patients all over the world. It remains associated with high mortality. Objectives To assess the impact of implementing an evidence-based package of measures (bundle) on the quality of care and outcomes of candidaemia. Methods A systematic review of the literature was performed to identify measures related to better outcomes in candidaemia. Eight quality-of-care indicators (QCIs) were identified and a set of written recommendations (early treatment, echinocandins in septic shock, source control, follow-up blood culture, ophthalmoscopy, echocardiography, de-escalation, length of treatment) was prospectively implemented. The study was performed in 11 tertiary hospitals in Spain. A quasi-experimental design before and during bundle implementation (September 2016 to February 2018) was used. For the pre-intervention period, data from the prospective national surveillance were used (May 2010 to April 2011). Results A total of 385 and 263 episodes were included in the pre-intervention and intervention groups, respectively. Adherence to all QCIs improved in the intervention group. The intervention group had a decrease in early (OR 0.46; 95% CI 0.23-0.89; P = 0.022) and overall (OR 0.61; 95% CI 0.4-0.94; P = 0.023) mortality after controlling for potential confounders. Conclusions Implementing a structured, evidence-based intervention bundle significantly improved patient care and early and overall mortality in patients with candidaemia. Institutions should embrace this objective strategy and use the bundle as a means to measure high-quality medical care of patients.

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

Abstract: 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.

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

Abstract: 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.

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

Abstract: 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.

Predictive tools to determine risk of infection in kidney transplant recipients

Abstract: Introduction: Infection represents a major complication after kidney transplantation (KT). Therapeutic drug monitoring is essentially the only approach for the adjustment of immunosuppression in current practice, with suboptimal results. The implementation of immune monitoring strategies may contribute to minimizing the risk of adverse events attributable to over-immunosuppression without compromising graft outcomes.Areas covered: The present review (based on PubMed/MEDLINE searches from database inception to November 2019) is focused on immune biomarkers with no antigen specificity (non-pathogen-specific), including serum levels of immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, soluble CD30, intracellular ATP production by stimulated CD4+ T-cells, and other cell-based immune assays. We also summarized recent advances in the use of replication kinetics of latent viruses to assess the functionality of T-cell immunity, with focus on the nonpathogenic anelloviruses. Finally, the composite risk scores reported in the literature are critically discussed.Expert opinion: Notable efforts have been made to develop an enlarging repertoire of immune biomarkers and prediction models, although most of them still lack technical standardization and external validation. Preventive interventions based on these tools (prolongation of prophylaxis, tapering of immunosuppression, or immunoglobulin replacement therapy in hypogammaglobulinemic patients) remain to be defined, ideally in the context of controlled trials.

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

Abstract: 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). 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. 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.

Early Posttransplant Mobilization of Monocytic Myeloid-derived Suppressor Cell Correlates With Increase in Soluble Immunosuppressive Factors and Predicts Cancer in Kidney Recipients.

Abstract: BACKGROUND Myeloid-derived suppressor cells (MDSCs) increase in patients with cancer and are associated with poor prognosis; however, their role in transplantation is not yet understood. Here we aimed to study the MDSC effects on the evolution of kidney transplant recipients (KTRs). METHODS A cohort of 229 KTRs was prospectively analyzed. Two myeloid cells subsets. CD11bCD33CD14CD15HLA-DR (monocytic MDSC [M-MDSC]) and CD11bCD33CD14CD15HLA-DR (monocytes), were defined by flow cytometry. The suppressive capacity of myeloid cells was tested in cocultures with autologous lymphocytes. Suppressive soluble factors, cytokines, anti-HLA antibodies, and total antioxidant capacity were quantified in plasma. RESULTS Pretransplant, M-MDSC, and monocytes were similar in KTRs and healthy volunteers. M-MDSCs increased immediately posttransplantation and suppressed CD4 and CD8 T cells proliferation. M-MDSCs remained high for 1 y posttransplantation. Higher M-MDSC counts at day 14 posttransplant were observed in patients who subsequently developed cancer, and KTRs with higher M-MDSC at day 14 had significantly lower malignancy-free survival. Day 14 M-MDSC >179.2 per microliter conferred 6.98 times (95% confidence interval, 1.28-37.69) more risk to develop cancer, independently from age, gender, and immunosuppression. Early posttransplant M-MDSCs were lower in patients with enhanced alloimmune response as represented by anti-HLA sensitization. M-MDSC counts correlated with higher circulatory suppressive factors arginase-1 and interleukin-10, and lower total antioxidant capacity. CONCLUSIONS Early posttransplant mobilization of M-MDSCs predicts cancer and adds risk as an independent factor. M-MDSC may favor an immunosuppressive environment that promotes tumoral development.

A critical review of the relationship between post-transplant atherosclerotic events and cytomegalovirus exposure in kidney transplant recipients.

Abstract: Introduction: Cytomegalovirus (CMV) infection after kidney transplantation (KT) has been implicated in the so-called ‘indirect effects’ attributable to the viral ability to evade host’s immunity an...

Peripherally inserted central venous catheter placed and maintained by a dedicated nursing team for the administration of antimicrobial therapy vs. another type of catheter: a retrospective case–control study

Abstract: Introduction Data concerning the use of peripherally inserted central catheters (PICC) for the administration of intravenous (IV) antimicrobials in the acute care setting is scarce. Methods We performed a single-center retrospective case–control study (1:1). Case subjects were defined as patients who received IV antimicrobial treatment through a PICC line placed and maintained by specifically trained nurses (PICC group). Control subjects were defined as patients who received antimicrobial therapy by a peripheral or a central venous catheter (CVC) (control group). Control subjects were matched by type of antimicrobial, causative microorganism of the infection that was being treated and duration of treatment. An event leading to undesired catheter removal (ELUCR) was defined as any circumstance which lead to the removal of the indwelling catheter other than the completion of the scheduled course of antimicrobial therapy. Results The study included 50 patients in each group. The total follow-up time was 1376 catheter-days for the PICC group and 1362 catheter-days for the control group. We observed a significantly lower incidence of ELUCR in the PICC group (0.2 versus 7.7 events per 100 catheter-days; P Conclusions A PICC placed and maintained by a dedicated nursing team is an excellent alternative to peripheral venous catheters or CVCs for administrating antimicrobial therapy for both short and long periods of treatment.

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

Abstract: 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.

Congenital cutaneous candidiasis associated with maternal peripartum candidemia

Abstract: 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.