The Impact of Homemade Laparoscopic Box Trainers on Medical Student Surgical Skills: A Randomized Control Pilot Study.

Objective: While instructional videos are commonly used in surgical education, there is a paucity of data on home laparoscopic box trainers. This pilot study evaluated impacts of augmenting instructional videos with these devices. Design: This was a randomized controlled pilot study evaluating laparoscopic surgical performance on the LapSim virtual surgical simulator before and after a 2 week curriculum of instructional videos alone (n = 8, 47.1%) vs videos plus a home laparoscopic box trainer (n = 9, 52.9%). The LapSim recorded mistake number, time, and instrument path length to complete each task. Participants completed surveys about their perceptions of surgery before and after the course. Participants: Preclinical medical students were recruited. Those with extensive surgical experience or did not complete the course were excluded. Results: For the box trainer group vs the videos alone group: mean change in mistakes was -10.0 (standard deviation [SD]:17.1) vs +.5 (SD:21.59) (P = .28); mean change in time was -433.24 (SD:304.67) seconds vs -366.16 (SD:240.10) seconds (P = .62); mean change in instrument path length was -4.27 (SD:4.38) meters vs -3.19 (SD:4.86) meters (P = .64). The box trainer group ranked "I feel as though surgery comes naturally" 1.58 points higher (95% confidence interval [CI]: .85, 2.32; P < .01) and "I am worried about being skilled at surgery" 1.26 points lower (95% CI: 2.29, -.24; P = .02) upon completing the study. The videos alone group reported no significant changes in survey responses. Conclusion: Home laparoscopic box trainers can generate confidence and reduce anxiety regarding surgical fields. This study provides a framework for future larger scale works.

FOXO3a and the MAPK p38 are activated by cetuximab to induce cell death and inhibit cell proliferation and their expression predicts cetuximab efficacy in colorectal cancer.

BACKGROUND: Cetuximab, a monoclonal antibody against EGFR used for the treatment of colorectal cancer (CRC), is ineffective in many patients. The aim of this study was to identify the signalling pathways activated by cetuximab in CRC cells and define new biomarker of response. METHODS: We used in vitro, in vivo models and clinical CRC samples to assess the role of p38 and FOXO3a in cetuximab mechanism of action. RESULTS: We show that cetuximab activates the MAPK p38. Specifically, p38 inhibition reduced cetuximab efficacy on cell growth and cell death. At the molecular level, cetuximab activates the transcription factor FOXO3a and promotes its nuclear translocation via p38-mediated phosphorylation, leading to the upregulation of its target genes p27 and BIM and the subsequent induction of apoptosis and inhibition of cell proliferation. Finally, we found that high FOXO3a and p38 expression levels are associated with better response rate and improved outcome in cetuximab-treated patients with CRC harbouring WT KRAS. CONCLUSIONS: We identify FOXO3a as a key mediator of cetuximab mechanism of action in CRC cells and define p38 as its activator in this context. Moreover, high FOXO3a and p38 expression could predict the response to cetuximab in patients with CRC harbouring WT KRAS.

Reducing sibling conflict in maltreated children placed in foster homes.

Sibling aggression among maltreated children placed in foster homes is linked to other externalizing problems and placement disruption. The reduction of sibling conflict and aggression may be achieved via a multicomponent ecologically focused intervention for families in the foster care system. The focus of the study is to evaluate the feasibility and short-term effectiveness of a transtheoretical intervention model targeting sibling pairs and their foster parent that integrates family systems, social learning theory, and a conflict mediation perspective. In this pilot study, sibling pairs (N = 22) and their foster parent were randomized into a three-component intervention (n = 13) or a comparison (n = 9) group. Promoting Sibling Bonds (PSB) is an 8-week prevention intervention targeting maltreated sibling pairs ages 5-11 years placed together in a foster home. The siblings, parent, and joint components were delivered in a program package at the foster agency by a trained two-clinician team. Average attendance across program components was 73 %. Outcomes in four areas were gathered at pre- and postintervention: observed sibling interaction quality (positive and negative) including conflict during play, and foster parent reports of mediation strategies and sibling aggression in the foster home. At postintervention, adjusting for baseline scores and child age, intervention pairs showed higher positive (p < 0.001) and negative (p < 0.05) interaction quality and lower sibling conflict during play (p < 0.01) than comparison pairs. Foster parents in the intervention group reported a higher number of conflict mediation strategies than those in the comparison group (p < 0.001). Foster parents in the intervention group reported lower sibling physical aggression from the older toward the younger child than those in the comparison group (p < 0.05). Data suggest that the PSB intervention is a promising approach to reduce conflict and promote parental mediation, which together may reduce sibling aggression in the foster home.

Intervening to Improve Outcomes for Siblings in Foster Care: Conceptual, Substantive, and Methodological Dimensions of a Prevention Science Framework.

In recent years, the child welfare field has devoted significant attention to siblings in foster care. Policymakers and practitioners have supported efforts to connect siblings via shared foster placements and visitation while researchers have focused on illuminating the empirical foundations of sibling placement and sibling intervention in child welfare. The current paper synthesizes literature on sibling relationship development and sibling issues in child welfare in the service of presenting a typology of sibling-focused interventions for use with foster youth. The paper provides two examples of current intervention research studies focused on enhancing sibling developmental processes and understanding their connection to child welfare outcomes. The paper concludes by presenting an emerging agenda informing policy, practice, and research on siblings in foster care.

Child maltreatment, dating perpetration of physical assault, and cortisol reactivity among disadvantaged female adolescents.

OBJECTIVE: Few studies have examined hypothalamic-pituitary-adrenal axis stress reactivity and its relationship to histories of child maltreatment and physical aggression. We examined the relation of a history of childhood sexual abuse (CSA) and perpetration of dating violence to patterns of cortisol change before (resting) and after (reactivity) exposure to a laboratory stressor. METHODS: In a sample of 40 disadvantaged sexually active female adolescent patients (ages 14-17 years), we collected self-reports of lifetime child maltreatment (5 types) and past-year female perpetration of physical assault (PA) acts toward a romantic partner. We assessed changes in salivary cortisol trajectories during resting and reactivity phases following the viewing of a teen dating violence vignette. RESULTS: Reports of CSA (CSA+ group) were associated with reports of perpetration of severe dating PA (PA+ group), but the relation of these reports to laboratory-assessed patterns of cortisol changes following the stressor was opposite. As compared with subjects without victimization or perpetration histories (referent group), the CSA+ group showed the most pronounced positive slope (reactivity), whereas the PA+ group showed the least positive slope following the laboratory stressor after the overlap between these groups was statistically adjusted. While showing less reactivity to the laboratory stressor, the PA+ group had higher levels of resting cortisol, which stayed high during reactivity as compared to the referent group. CONCLUSION: The laboratory paradigm to elicit neuroendocrine stress-related cortisol reactivity appears to be a promising tool for identifying altered cortisol physiology among female adolescents with mixed histories of CSA and perpetration of dating PA.

The Role of Cultural Dissimilarity Factors on Child Adjustment Following Foster Placement.

Understanding the cultural factors associated with children's experiences in foster care is important because they may contribute to child psychological adjustment to foster placement. Despite considerable public policy debate of the role of ethnicity on foster placement decisions, there are virtually no empirical studies about the contribution of cultural dissimilarity factors on child psychological adjustment such as internalizing and externalizing problems shortly after children enter non-kinship placement. Using a sample of N =106 ethnic minority children (clustered in 62 families), we hypothesized that the number (ranging from 0 to 5) and types (i.e., ethnic status, country of birth, and spoken language) of cultural dissimilarity factors between biological and foster families contribute to child internalizing symptoms (CDI depression and LSD loneliness) and externalizing problems (ECBI conduct) after considering family and agency clustering and adjusting for confound variables (child age, gender, and severity of child maltreatment). Results showed that a higher number of dissimilar types and certain types contributed to lower scores in child psychological adjustment. Dissimilar ethnic status between caregivers contributes to CDI depression and LSD loneliness symptoms while dissimilar spoken language between caregivers contributed to ECBI conduct problems in the foster home. These results inform the public policy debate of transethnic placements for children involved in the foster care system.

Epidemiology and risk factors for late infection in solid organ transplant recipients.

BACKGROUND: Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce. METHODS: We prospectively analyzed all patients undergoing SOT from July 2003 to March 2008, who survived the first 6 months after surgery and with a minimum 1-year follow-up. Risk factors associated with the development of bacterial and cytomegalovirus (CMV) LI and survival were identified. RESULTS: Overall, 942 SOT recipients (491 kidney, 280 liver, 65 heart, and 106 double transplants) were included. During the study period 147 patients (15.6%) developed 276 episodes of LI (incidence rate, 0.43 per 1000 transplantation-days). Bacteria were the most prevalent etiology (88.0%). Primary sources of infection included urinary tract (36.9%), intra-abdominal (16.7%), and sepsis without source (13.4%). Independent risk factors for late bacterial infection were: age (hazard ratio [HR] [per year] 1.0; 95% confidence interval [CI]: 1.0-1,0), female gender (HR 1.7; 95%CI: 1.1-2.6), anti-hepatitis C virus (HCV) positive serostatus (HR 1.8; 95%CI: 1.1-3.0), chronic allograft dysfunction (HR 3.2; 95%CI: 1.7-6.1), early CMV disease (HR 2.2; 95%CI 1.2-4.1), and early bacterial infection (HR 2.5; 95%CI 1.6-3.8). The occurrence of chronic allograft dysfunction was an independent risk factor for late CMV disease (HR 6.5; 95%CI: 1.7-24.6), whereas immunosuppression based on mammalian target of rapamycin inhibitors protected against the development of late CMV disease (HR 0.3; 95%CI: 0.1-1.0). Cox model selected anti-HCV positive serostatus (adjusted HR [aHR] 2.67; 95%CI: 1.27-5.59), age (aHR [per year] 1.06; 95%CI: 1.02-1.10), and the occurrence of LI (aHR 9.12; 95%CI: 3.90-21.33) as independent factors for mortality. CONCLUSIONS: LI did not constitute an uncommon complication in our cohort, and patients at risk may benefit from close clinical monitoring.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

Predictive modelling of the physical demands during training and competition in professional soccer players.

OBJECTIVES: The present study aimed to predict the cut-off point-values that best differentiate the physical demands of training and competition tasks including friendly matches (FM), small sided games (SSG), large sided games (LSG), mini-goal games (MG) and ball circuit-training (CT) in professional soccer players. DESIGN: Experimental randomized controlled trial. METHODS: Fourteen professional players participated in all tasks with the CT, SSG and MG consisting of 8 repetitions of 4-min game play, interspersed by 2-min of active recovery. The training data were compared to the first 32-min of the LSG and two competitive FM per player. All movement patterns from walking to sprint running were recorded using 10Hz GPS devices while player perception of exertion was recorded via a visual analogue scale, post-task. Decision tree induction was applied to the dataset to assess the cut-off point-values from four training drills (SSG, LSG, MG, and CT) and FM for every parameter combination. RESULTS: Distance covered during jogging (2.3-3.3m/s; >436m), number of decelerations (≤730.5) and accelerations (≤663), and maximum velocity reached (>5.48m/s) characterized the physical demands during competition (FM) with great variability amongst training drills. CONCLUSION: The use of these novel, cut-off points may aid coaches in the design and use of training drills to accurately prepare athletes for soccer competition.

In vitro redox activity of haemozoin and ß-haemozoin interacting with the following antimalarials: artemether, lumefantrine and quinine.

OBJECTIVE: Malaria parasites invade, grow and multiply inside erythrocytes and obtain nourishment from haemoglobin. Then, the released haem group is oxidized to haematin and inert dimeric haemozoin bio-crystals form, which provides the parasite a unique way to avoid the toxicity associated with the haem group. Therefore, antimalarial drugs are designed to inhibit dimer formation; however, recent electrochemical studies indicate that an inert dimer also promotes a toxic oxidizing environment. Therefore, this work explores drug reactivity in the presence of monomers and dimers to evaluate their contribution to redox activity. MATERIALS AND METHODS: Three medicines mixed with haemozoin or ß-haemozoin in carbon paste electrodes were tested using cyclic voltammetry. RESULTS: The data indicated again that the substances modify the natural redox state of haemozoin and ß-haemozoin. This effect could be attributed to the natural oxidation potential of the drugs. In addition, it was found that the oxidation potential decreased through quinine, lumefantrine and artemether with the same tendency in the presence of haemozoin but with less current density. Additionally, it was observed that the oxidation response between the monomer haemozoin and antimalarial drugs is carried out at more negative potentials. CONCLUSIONS: Together, the total results indicate that antimalarials per se can contribute to oxidation processes and that in combination with monomeric or dimeric haemozoin can increase or decrease the oxidizing power of the haemozoin forms. The various oxidizing environments suggest that the cell membranes can also be damaged by the unique presence of the antimalarial.

Performance of differential time to positivity as a routine diagnostic test for catheter-related bloodstream infections: a single-centre experience.

OBJECTIVE: To assess the performance of differential time to positivity (DTP) for the diagnosis of catheter-related bloodstream infections (CRBSI). METHODS: From all episodes of bloodstream infections (BSI) diagnosed during a 15-year period (2003-17) those in which a paired set of blood cultures drawn from a catheter and a peripheral vein were positive for the same microorganism and had a clinically and/or microbiologically defined source were selected. To assess diagnostic discrimination ability and accuracy of DTP for CRBSI, area under the receiver operating characteristic curves (AUC) and performance characteristics of a DTP ≥2 h were computed. RESULTS: A total of 512 BSI were included, of which 302 (59%) were CRBSI. Discrimination ability of DTP was low for Staphylococcus aureus (AUC 0.656 ± 0.06), coagulase-negative staphylococci (AUC 0.618 ± 0.081), enterococci (AUC 0.554 ± 0.117) and non-AmpC-producing Enterobacteriaceae (AUC 0.653 ± 0.053); moderate for Pseudomonas aeruginosa (AUC 0.841 ± 0.073), and high for AmpC-producing Enterobacteriaceae (AUC 0.944 ± 0.039). For the entire sample, DTP had a low-to-moderate discrimination ability (AUC 0.698 ± 0.024). A DTP ≥2 h has a low sensitivity for coagulase-negative staphylococci (60%) and very low for S. aureus (34%), enterococci (40%) and non-AmpC-producing Enterobacteriaceae (42%). A DTP cut-off of 1 h improved sensitivity (90%) for AmpC-producing Enterobacteriaceae. CONCLUSIONS: Differential time to positivity performs well for diagnosing CRBSI only when AmpC-producing Enterobacteriaceae and P. aeruginosa are involved. Performance is low for common Gram-positive organisms and non-AmpC-producing enteric bacilli; a negative test should not be used to rule out CRBSI due to these microorganisms. A DTP ≥1 h may improve accuracy for AmpC-producing Enterobacteriaceae, particularly Enterobacter spp.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

Risk factors for infection with extended-spectrum and AmpC beta-lactamase-producing gram-negative rods in renal transplantation.

Increasing prevalence of infections caused by multiresistant gram-negative enteric bacilli due to synthesis of extended-spectrum beta-lactamase (ESBL) or to desrepressed chromosomic AmpC beta-lactamase (AmpC) is a major concern in the hospitalized patient population. Renal transplant recipients are especially susceptible to these infections. A cohort observational study in a 3-year period was performed. ESBL-production was determined by phenotypic analysis based on the CLSI recommendations. A multi-variate logistic regression analysis was performed to identify independent variables associated with multi-resistant gram-negative bacilli infection. The study included 417 patients (61 double kidney-pancreas recipients). The incidence of ESBL-producing and desrepressed chromosomic AmpC beta-lactamase resistance was 11.8% (49 patients). The most frequent bacteria isolated was E. coli (35/60 isolations), followed by Klebsiella spp(12/60 isolations). Double kidney-pancreas transplantation(OR 3.5, CI95% 1.6-7.8), previous use of antibiotics(OR 2.1,CI95% 1.1-4.1), posttransplant dialysis requirement (OR 3.1, CI95% 1.5-6.4) and posttransplant urinary obstruction (OR 5.8, CI95% 2.2-14.9) were independent variables associated with these multiresistant gram-negative enteric bacilli infections. The incidence of ESBL-producing and desrepressed AmpC beta-lactamase gram-negative enteric bacilli infection in our population was high. These infections are associated with significant morbidity after renal transplantation.

Severe Hepatitis C Recurrence as a Risk Factor for Opportunistic Infections in Liver Transplant Recipients.

OBJECTIVE: The aim of the study was to determine the clinical characteristics, frequency of opportunistic infections (OI), and the outcomes for liver transplant recipients with severe hepatitis C virus (HCV) recurrence. In addition, the objective was to evaluate HCV recurrence as a risk factor for developing an OI. METHODS: We conducted a retrospective observational study recording all liver transplant recipients from July 1, 2003, to December 31, 2012. Patients with liver disease due to HCV were selected. Active surveillance of infections was conducted periodically, and patients were classified according to presence of severe HCV recurrence. RESULTS: Three hundred seventy patients underwent liver transplantation because of chronic HCV. One hundred forty-seven patients presented severe recurrence (SR) (49%) and 50 (17%) of them had post-liver transplant cholestatic hepatitis C. Patients with SR presented OI, especially cytomegalovirus (CMV) infections and invasive fungal infections, more frequently than patients without SR (33% vs 13%; P < .001). From the diagnosis of SR to the presentation of OI, the median number of days was 169 (6-2083). Acute allograft rejection (OR 1.8 95% confidence interval [CI] 1.1-3.3) donor age ≥60 years (OR 2.9 95% CI 1.3-6.8), and SR (OR 2.8, 95% CI 1.6-5.1) were independently associated with the development of OI in liver transplant recipients. CONCLUSION: A high index of suspicion of opportunistic infections must be maintained when faced with severe HCV recurrence in liver transplant recipients. Moreover, active surveillance against CMV infection and other prophylactic strategies against opportunistic infections should be considered.

Infection-related mortality in a large cohort of renal transplant recipients.

INTRODUCTION: Infections represent a major cause of morbidity and mortality among renal transplant recipients. Our aim was to analyze the incidence and etiology of infection-related mortality among a large cohort of renal transplant recipients. METHODS: From 1995 to 2004, we collected all causes of mortality among patients receiving a renal transplantation. The date of transplant, the last follow-up/death, type of transplant, age, and cause of death were tabulated into a database. The incidence rate of mortality was calculated in events per 10,000 transplant months. RESULTS: Among the 1218 renal transplants performed in the study period the causes of mortality were: cardiovascular, 65 (38%); infection, 49 (29%); cancer, 21 (12%); other causes, 18 (10.5%); and unknown, 18 (10.5%). Infection-related mortality were: sepsis = 17 (35%), bacterial pneumonia = 9 (18%), abdominal bacterial infection = 2 (4%), invasive viral infection = 12 (24%), and invasive fungal infection = 9 (18%). There were no differences in the global causes of mortality according to the year of transplantation. The incidence rate of infection-related mortality was higher among aged patients and similar to cardiovascular-related mortality. Comparing the periods 1995 to 1999 with 2000 to 2004, bacterial infection-related mortality remained stable (57% vs 57%), while viral infection-related mortality decreased (31% vs 7%) and fungal infection-related mortality increased (11% vs 36%; P = .06). CONCLUSIONS: In the last decade, infection-related mortality among renal transplant recipients has not decreased. Although better control of invasive viral infections has been achieved, bacterial and fungal invasive infections remain important causes of mortality in this population.

Characterization of the organ donor with bacteremia.

INTRODUCTION: The presence of bloodstream infection in the donor is a common finding that could be transmitted to the recipient. To safely expand the donor pool, we examined its relevance. MATERIALS AND METHODS: We described the clinical characteristics of organ donors grafted in our center between 1997 and 2006 who had bacteremia detected in blood cultures obtained during organ procurement. RESULTS: Among 1353 organ donors, 75 were non-heart-beating donors type II and the others brain-dead donors. Only 186 donors (14%) showed bacteremia during retrieval. This mean age was 49.8 years (range 12 to 86 years, SD 18) including 63% men. Causes of death were cerebrovascular accident in 60%; craneoencephalic trauma, 25%; and other causes, 15%. The average length of the intensive care unit stay was 3 days (interquartile range: 2 to 7 days). Twenty-nine percent of donors presented previous infectious complications (90% from respiratory origin). The most prevalent pathogen isolated in blood cultures was coagulase negative Staphylococci (46,2%), followed by S aureus (15%), Streptococcus group viridans (9.1%), enterobacteria (9%), Enterococcus faecalis (7.5%) and gram-negative bacilli nonfermentative (6.2%). In 3.1%, the bloodstream infections were polymicrobial. The bronchial aspiration cultures were positive in 50% of cases and the urine culture in 8,6%. In 17% of donors the isolated microorganism was coincident between blood and bronchial cultures. Pseudomonas spp and S aureus were more common than the others (P = .004 and P = .058, respectively). CONCLUSIONS: The incidence of bacteremia in our cohort was 14%. The respiratory tract was the most common clinical focus. Pseudomonas spp or S aureus isolated in bronchial cultures are risk factors to develop bacteremia. According to these findings, it is important to start specific antibiotics against those microorganisms in the donor and the recipients.

Epidemiology and outcomes of multiple antibiotic-resistant bacterial infection in renal transplantation.

BACKGROUND: Mutiresistant bacterial infections are an emerging problem in the nosocomial setting. Our objectives were to describe the incidence, outcome, and risk factors for acquisition of multiresistant bacteria among renal transplant recipients. METHODS: We prospectively followed patients undergoing kidney transplantation over a 3-year period. We collected demographic features, underlying chronic diseases, and main transplant characteristics and complications. Multiple antibiotic resistance was defined for the most important bacteria: Enteric gram-negative bacilli resistant to betalactamics, cephalosporins, and quinolones; Staphylococcus aureus resistant to methicillin, cotrimoxazole, and clindamcin; Enterococcus spp resistant to ampicillin and quinolones; nonfermentator bacilli resistant to all antibiotics except aminoglycosides and collistin. RESULTS: Overall, 416 patients included 65 double transplants (62 kidney-pancreas and three kidney-liver) of mean age 48.5 years, and 57% men. Infection with multiresistant bacteria was observed in 58 patients (14%). Most frequent multiresistant bacteria were: Escherichia coli (n = 33), Klebsiella spp (n = 15), Citrobacter spp (n = 8), Enterobacter spp (n = 5), Morganella morganii (n = 2), Pseudomonas aeruginosa (n = 16), Acinetobacter baumanii (n = 2), Enterococcus spp (n = 9) and methicillin-resistant S. aureus (MRSA, n = 2). Age greater than 50 years, hepatitis C virus infection, double kidney-pancreas transplantation, requirement for posttransplant hemodialysis, surgical reoperation, and requirement for nephrostomy were independent variables associated with multiresistant bacterial infection. Most used antibiotics for treatment were: carbapenems (65%), amikacin (12%), linezolid, piperacillin-tazobactam, vancomycin, collistin, and fosfomycin. Infection with multiresistant bacteria was associated with a worse prognosis (graft loss or death, 19% vs 8%, P = .009). CONCLUSIONS: The incidence of infection with multiresistant bacteria in our renal transplant cohort was high, being most frequently cephalosporin-resistant enteric gram-negative bacilli and multiresistant P aeruginosa. Methicillin-resistant S. aureus incidence was low. Infection with multiresistant bacteria conferred a worse prognosis.

Impact of valganciclovir prophylaxis on the development of severe late-cytomegalovirus disease in high-risk solid organ transplant recipients.

BACKGROUND: With the introduction of prolonged prophylaxis with valganciclovir in cytomegalovirus (CMV) donor/recipient serodiscordance (D+/R-) patients, concerns about a high incidence of late and invasive CMV disease associated with mortality have emerged. We compared the characteristics of CMV disease in D+/R- patients receiving prolonged valganciclovir prophylaxis with R+ patients. METHODS: We prospectively followed all solid organ transplant recipients from January 2004 to December 2005. CMV prophylaxis with valganciclovir or ganciclovir was administered as follows: donor- recipient serodiscordance (D+/R-), 12 weeks; induction with antithymocyte globulin or acute rejection episodes requiring steroid pulses, 15 to 30 days; and CMV R+ double kidney-pancreas, 15 days. Transplant characteristics and the development of CMV disease variables were collected for all patients. We defined 2 groups according to the risk of CMV disease: CMV donor/recipient mismatch (D+/R-) and recipient CMV-positive (R+) groups. RESULTS: During the study period we performed 481 solid organ transplantations: 237 kidney, 34 kidney-pancreas, 157 liver, 38 heart, 13 liver-kidney, and 2 heart-kidney. Overall, 36 patients developed CMV disease (7.5%). CMV donor-recipient mismatch (D+/R-) was associated with a greater risk of CMV disease compared with CMV-positive recipients (16% vs 7%; P = .036). Prophylaxis against CMV was longer in the D+/R- group (mean days 73 vs 15; P < .001). CMV disease appeared later in the D+/R- than in R+ group (mean days 123 vs 59; P < .001). We observed a trend toward a lower incidence of tissue-invasive CMV disease among the D+/R- group compared with the R+ group without significance (14% vs 41%; P = .382). Three patients died in the first 30 days after the onset of CMV disease, all of them in the R+ group. CONCLUSIONS: In our setting, high-risk patients (D+/R-) receiving prolonged prophylaxis with valganciclovir developed later CMV disease, but this was neither more tissue-invasive nor more life-threatening than in the R+ group.

TH1/TH2 cytokine release pattern during in vivo cytomegalovirus disease in solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is associated with an increased net immunosuppressive state in solid organ transplant recipients, leading to more bacterial and fungal infections. The release of pro- and anti-inflammatory cytokines could be one of the responsible factors. METHODS: We prospectively included all patients undergoing solid organ transplantation between April and November 2004. During follow-up, plasma samples were collected in the immediate postsurgical period, at the first and second months, at the time of maximum antigenemia during CMV disease, and at 6 months posttransplantation. We determine the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Log-transformed data were compared by a nonparametric Wilcoxon test for related variables. RESULTS: During the study period, we monitored 146 recipients of solid organ transplantation: 77 kidneys, 8 kidney-pancreas, 46 liver, 11 heart, 2 liver-kidney, and 2 heart-kidney. No differences were observed between the TNF-alpha and IL-10 levels in the immediate postsurgical period or during CMV disease. TNF-alpha and IL-10 levels during CMV disease were higher than levels during the first month (mean TNF-alpha first month = 12.71 pg/mL vs CMV disease = 22.71 pg/mL, P = .028; mean IL-10 first month = 3.47 pg/mL vs CMV disease = 19.2 pg/mL, P = .018). Th1/Th2 ratio (measured as TNF-alpha/IL-10) was 1.75 in the immediate postsurgical period, 7.5 during the first month, 1.86 at the time of CMV disease, and 4.61 at the sixth month. The difference in Th1/Th2 ratio during CMV disease and in the first month was statistically significant (P = .043). CONCLUSION: During CMV disease, we observed an increase in TNF-alpha and IL-10 release, which was similar to that during the postsurgical period. An imbalance toward an anti-inflammatory pattern was noted in these two periods. This could reflect a cooperative factor increasing the net state of immunosuppression during CMV disease.