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

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.

Antibiotic susceptibility trend before and after long-term use of selective digestive decontamination: a 16 year ecological study.

OBJECTIVES: The aim of this study was to compare antimicrobial susceptibility rates in a Spanish ICU before and after the introduction of selective digestive decontamination (SDD) and also to compare these with susceptibility data from other Spanish ICUs without SDD. METHODS: We performed a retrospective study in the ICU of the University Hospital of Alava, where SDD was implemented in 2002. The SDD protocol consisted of a 2% mixture of gentamicin, colistin and amphotericin B applied on the buccal mucosa and a suspension of the same drugs in the gastrointestinal tract; additionally, for the first 3 days, systemic ceftriaxone was administered. From 1998 to 2013 we analysed the susceptibility rates for 48 antimicrobial/organism combinations. Interrupted time series using a linear dynamic model with SDD as an intervention was used. Data from other ICUs were obtained from the ENVIN-HELICS national registry. RESULTS: Only amoxicillin/clavulanic acid against Escherichia coli and Proteus mirabilis, and a high concentration of gentamicin against Enterococcus faecalis, resulted in a significant decrease in the susceptibility rate after the implementation of SDD, with a drop of 20%, 27% and 32%, respectively. Compared with other Spanish ICUs without SDD, the susceptibility rate was higher in the ICU of our hospital in most cases. When it was lower, differences were <10%, except for a high concentration of streptomycin against Enterococcus faecium, for which the difference was 19%. CONCLUSIONS: No relevant changes in the overall susceptibility rate after the implementation of SDD were detected. Susceptibility rates were not lower than those in the Spanish ICUs without SDD.

Utility of Real-Time 3-Dimensional Transesophageal Echocardiography in the Assessment of Mitral Paravalvular Leak.

BACKGROUND: Mitral paravalvular leak (PVL) is a potential complication of surgical valve replacement procedures. Real-time 3D transesophageal echocardiography (RT-3DTEE) has emerged as an efficient tool for providing essential information about the anatomy of mitral PVLs compared with 2DTEE findings. The purpose of this study was to evaluate the utility of RT-3DTEE in the assessment of mitral PVLs. METHODS AND RESULTS: The 3D characteristics of PVLs were recorded and compared with 2D findings. We included 34 consecutive patients with clinical suspicion of mitral PVL in the study. Mitral PVLs were detected in 26 patients (76%); 26 PVLs were identified by 2DTEE and 37 by RT-3DTEE. Moderate or severe mitral regurgitation was present in 23 patients (88%). The most common PVL locations were the septal and posterior regions. The median PVL size measured by RT-3DTEE was 7 mm long×4 mm wide. The median vena contracta of defect measured by 2DTEE and RT-3DTEE was 5 mm and 4 mm, respectively. The median effective regurgitant orifice area of defect measured by RT-3DTEE was 0.36 cm(2). The defect types were "oval" (54%), "round" (35%), "crescentic" (8%) and highly irregular (3%). CONCLUSIONS: Compared with 2DTEE, RT-3DTEE provided detailed descriptions of the number, location, size and morphology of PVLs, which is essential for planning and guiding the potential corrective techniques. (Circ J 2016; 80: 738-744).

A randomized trial of intravenous glutamine supplementation in trauma ICU patients.

PURPOSE: To evaluate the effect of the intravenous (i.v.) L-alanyl-L-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit (ICU). METHODS: This was a prospective, randomized, double-blind, multicenter trial. Glutamine was not given as a component of nutrition but as an extra infusion. The primary outcome variable was the number of new infections within the first 14 days. RESULTS: We included 142 patients. There were no differences between groups in baseline characteristics. Up to 62 % of the patients in the placebo group and 63 % in the treatment group presented confirmed infections (p = 0.86). ICU length of stay was 14 days in both groups (p = 0.54). Hospital length of stay was 27 days in the placebo group and 29 in the treatment group (p = 0.88). ICU mortality was 4.2 % in both groups (p = 1). Sixty percent of the patients presented low glutamine levels before randomization. At the end of the treatment (6th day), 48 % of the patients maintained low glutamine levels (39 % of treated patients vs. 57 % in the placebo group). Patients with low glutamine levels at day 6 had more number of infections (58.8 vs. 80.9 %; p = 0.032) and longer ICU (9 vs. 20 days; p < 0.01) and hospital length of stay (24 vs. 41 days; p = 0.01). CONCLUSIONS: There was no benefit with i.v. L-alanyl-L-glutamine dipeptide supplementation (0.5 g/kg body weight/day of the dipeptide) during 5 days in trauma patients admitted to the ICU. The i.v. glutamine supplementation was not enough to normalize the plasma glutamine levels in all patients. Low plasma glutamine levels at day 6 were associated with a worse outcome.

Descontaminación digestiva selectiva: repercusión en la carga de trabajo y el coste del laboratorio de microbiología y tendencias en la resistencia bacteriana / Selective decontamination of the digestive tract: Repercussions on microbiology laboratory workload and costs, and antibiotic resistance trends

Introducción Determinar la carga de trabajo y el coste para el laboratorio de microbiología así como el impacto en la flora microbiana y las tendencias de la resistencia bacteriana en el servicio de medicina intensiva (SMI) a partir de la introducción de la descontaminación digestiva selectiva. Métodos Se cuantificó la carga de trabajo y el coste total de microbiología así como la parte imputada al servicio peticionario en el año anterior y posterior a la introducción del procedimiento. Se valoró el cambio en la flora microbiana y se analizaron las tendencias de resistencia bacteriana durante 12 años en 21 combinaciones centinela antimicrobiano/microorganismo. Resultados La carga de trabajo imputada al SMI aumentó un 10% y el coste un 1,8% en el período posterior a la introducción del procedimiento (diferencias no significativas). El aumento de la carga de trabajo a costa de los cultivos de vigilancia epidemiológica se compensó con disminuciones significativas de broncoaspirados cuantitativos, hemocultivos, exudados, identificaciones y antibiogramas, y serología. El procedimiento se ha asociado a una disminución significativa de aislados de Acinetobacter y a un ascenso significativo de Enterococcus. Se han detectado 3 tendencias significativas de aumento de resistencia, las 3 en Pseudomonas aeruginosa (imipenem, tobramicina y ciprofloxacino).Conclusiones En este hospital, la implantación de este procedimiento no ha supuesto un aumento significativo de la carga de trabajo y el coste del laboratorio de microbiología, y se ha asociado a una marcada disminución de Acinetobacter y a un aumento de Enterococcus y de la resistencia a imipenem, tobramicina y ciprofloxacino en P. aeruginosa (AU)

Introduction This study determines the workload and cost of implementing selective digestive decontamination in the microbiology laboratory, and reports the impact on microbial flora and bacterial resistance trends in the intensive care unit (ICU).Methods The total microbiological workload and cost were quantified, as well as the part charged to the petitioning service, in the year before and the year after introducing the procedure. Changes in microbial flora were evaluated and bacterial resistance trends were analyzed over 12 years in 21 sentinel antimicrobial/microorganism combinations. Results The workload ascribed to the ICU increased by 10% and cost increased by 1.8% in the period after introduction of the procedure (non-significant differences). The increased workload resulting from epidemiological surveillance cultures was compensated by significant reductions in quantitative endotracheal aspirate cultures, blood cultures, exudate cultures, identification tests with antibiograms, and serologies. The procedure has been associated with a significant decrease in Acinetobacter isolates and a significant increase in Enterococcus. Three significant trends of increased resistance were detected, all of them in Pseudomonas aeruginosa (imipenem, tobramycin, and ciprofloxacin).Conclusions In our hospital, implementation of selective digestive decontamination did not cause a significant increase in the workload or costs in the microbiology laboratory. Selective digestive decontamination was associated with a significant decrease in Acinetobacter, an increase in Enterococcus, and higher resistance to imipenem, tobramycin and ciprofloxacin in P. aeruginosa(AU)

[Selective decontamination of the digestive tract: repercussions on microbiology laboratory workload and costs, and antibiotic resistance trends]. / Descontaminación digestiva selectiva: repercusión en la carga de trabajo y el coste del laboratorio de microbiología y tendencias en la resistencia bacteriana.

INTRODUCTION: This study determines the workload and cost of implementing selective digestive decontamination in the microbiology laboratory, and reports the impact on microbial flora and bacterial resistance trends in the intensive care unit (ICU). METHODS: The total microbiological workload and cost were quantified, as well as the part charged to the petitioning service, in the year before and the year after introducing the procedure. Changes in microbial flora were evaluated and bacterial resistance trends were analyzed over 12 years in 21 sentinel antimicrobial/microorganism combinations. RESULTS: The workload ascribed to the ICU increased by 10% and cost increased by 1.8% in the period after introduction of the procedure (non-significant differences). The increased workload resulting from epidemiological surveillance cultures was compensated by significant reductions in quantitative endotracheal aspirate cultures, blood cultures, exudate cultures, identification tests with antibiograms, and serologies. The procedure has been associated with a significant decrease in Acinetobacter isolates and a significant increase in Enterococcus. Three significant trends of increased resistance were detected, all of them in Pseudomonas aeruginosa (imipenem, tobramycin, and ciprofloxacin). CONCLUSIONS: In our hospital, implementation of selective digestive decontamination did not cause a significant increase in the workload or costs in the microbiology laboratory. Selective digestive decontamination was associated with a significant decrease in Acinetobacter, an increase in Enterococcus, and higher resistance to imipenem, tobramycin and ciprofloxacin in P. aeruginosa.

Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study.

BACKGROUND: It is estimated that 5% of the hypertensive patients are resistant to conventional antihypertensive therapy. Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene have been associated with high blood pressure levels, but not with resistant hypertension. The aim of the present study was to investigate if the -786T>C and G894T (Glu298Asp) polymorphisms of the NOS3 gene were associated with resistant hypertension. METHODS: A prospective case-control observational study was performed. From a series of 950 consecutive patients followed up during 42 months, 48 patients with resistant hypertension were detected. 232 patients with controlled high blood pressure were also included. RESULTS: No differences were observed in the distribution of G894T (Glu298Asp) NOS3 genotypes between the resistant hypertension group and the controlled hypertension patients. However, genotype -786CC was more frequent in the group of patients with resistant hypertension (33.3%) than in the group of patients with controlled high blood pressure (17.7%) (p 0.03). Furthermore carriers of allele T (-786TC and -786TT) were more frequent in patients with controlled hypertension (82.3%) than those with resistant hypertension (66.7%) (Multivariate analysis; RR 2.09; 95% CI 1.03-4.24; p 0.004). CONCLUSION: Our results indicate that genotype -786CC of the NOS3 gene increase the susceptibility to suffer resistant hypertension, which suggest that resistance to conventional therapy could be determined at the endothelial level.

-511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone.

INTRODUCTION: Osteoclasts are the most important cells involved in the pathogenesis of Paget disease of bone (PDB). Cytokines stimulate osteoclast differentiation and activation, with some of them over-expressed in pagetic osteoclasts. We have assessed whether genetic variability in genes coding of proteins from the IL1 pathway clustered in chromosome 2 is associated with clinical characteristics and the therapeutic response of patients with PDB. METHODS: We have studied -511 C/T and +3953 T/C polymorphisms of the IL1B gene, a HinfI polymorphism in the 5'UTR of the IL1R1 gene, and a variable number of tandem repeats (VNTR) in the intron 2 of the IL1RN gene, in 165 patients diagnosed as suffering from PDB and in 122 healthy controls. Distribution of genotypes and alleles was studied for association with clinical and laboratory data and response to bisphosphonate (BSP) treatment. RESULTS: No differences were observed in the distribution of genotypes or alleles between PDB patients and control subjects. We also failed to detect differences concerning epidemiological, clinical and laboratory data in the series of PDB patients. However, the -511 CC genotype of the IL1B gene was associated with a higher percentage of resistance to BSP (49% vs. 20%; P = 0.00 for all BSP, 60% vs. 39%, P = 0.17 for etidronate, 50% vs. 37% P = 0.53 for clodronate, 48 vs. 34% P = 0.05 for tiludronate and 50% vs. 4% P = 0.01 for risedronate). CONCLUSIONS: Our results suggest that the -511 CC genotype of the IL1B gene could be related to resistance to bisphosphonates in patients with PDB.

In vitro and in vivo evaluation of enoxaparin removal by continuous renal replacement therapies with acrylonitrile and polysulfone membranes.

BACKGROUND: Enoxaparin is a low-molecular-weight heparin for which the degree of elimination through hemofilters during continuous renal replacement therapy (CRRT) is not well established. OBJECTIVE: The elimination of enoxaparin by CRRT, using acrylonitrile (AN69) or polysulfone (PS) membranes, was studied in vitro and among critically ill patients. METHODS: In vitro procedures were carried out using Ringer's lactate, bovine albumin-containing Ringer's lactate, or fresh human plasma as enoxaparin vehicle, using AN69 or PS membranes, and following continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD). Prefilter and ultrafiltrate samples were collected over 60 minutes. All procedures were carried out in triplicate. Patients undergoing CRRT entered the in vivo study. Enoxaparin was administered subcutaneously once daily. The sieving coefficient (Sc) and saturation coefficient (Sa) were calculated as the relation between anti-factor Xa activity in simultaneously collected dialysate/ultrafiltrate samples and plasma samples. RESULTS: Mean Sc (for CVVH) or Sa (for CVVHD) values in the in vitro procedures ranged from 0.16 to 0.57. Sc values during CVVH were significantly higher than Sa values during CVVHD in the Ringer's lactate procedures for both membranes (AN69 membrane, P = 0.014; PS membrane, P < 0.001) and in the plasma procedures with the PS membrane (P < 0.001). Six male and 2 female patients (all white) participated in the in vivo study. Their mean body weight ranged from 55 to 80 kg, and their age ranged from 71 to 82 years. In patients, Sc or Sa achieved values between 0.26 and 0.67. No significant differences were found in vivo in the permeability of the 2 membranes to enoxaparin. CONCLUSIONS: In these studies, the Sc and Sa values suggested that enoxaparin passed through AN69 and PS membranes during CRRT. Further pharmacokinetic and clinical studies are needed to determine whether a dose adjustment for enoxaparin is needed for patients undergoing CRRT.

Meropenem and continuous renal replacement therapy: in vitro permeability of 2 continuous renal replacement therapy membranes and influence of patient renal function on the pharmacokinetics in critically ill patients.

The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 +/- 0.12) was similar to the unbound fraction (0.79 +/- 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.

Influence of renal function on the pharmacokinetics of piperacillin/tazobactam in intensive care unit patients during continuous venovenous hemofiltration.

The pharmacokinetics of piperacillin/tazobactam (4 g/0.5 g every 6 or 8 hours, by 20-minute intravenous infusion) were studied in 14 patients with acute renal failure who underwent continuous venovenous hemofiltration with AN69 membranes. Patients were grouped according to severity (CL(CR) < or =10 mL/min, 10 < CL(CR) < or =50 mL/min, and CL(CR) > 50 mL/min). A noncompartmental analysis was performed. The sieving coefficient (0.78 +/- 0.28) was similar to the unbound fraction (0.65 +/- 0.24) for tazobactam, but it was significantly different (0.34 +/- 0.25) from the unbound fraction (0.78 +/- 0.14) for piperacillin. Extracorporeal clearance was 37.0% +/- 28.8%, 12.7% +/- 12.6%, and 2.8% +/- 3.2% for piperacillin in each group and 62.5% +/- 44.9%, 35.4% +/- 17.0%, and 13.1% +/- 8.0% for tazobactam. No patients presented tazobactam accumulation. In patients with CL(CR) < 50 mL/min, t(%)ss >MIC90 values were 100% for a panel of 19 pathogens, but in those with CL(CR) > 50 mL/min, t(%)ss >MIC90 indexes were 55.5% and 16.6% for pathogens with MIC90 values of 32 and 64. The extracorporeal clearance of piperacillin/tazobactam is clinically significant in patients with CL(CR) > 50 mL/min, in which the risk of underdosing and clinical failure is important and extra doses are required.