Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000

To examine shifts in the etiology, incidence, evolution, susceptibility, and patient mortality of bacterial and fungal bloodstream isolates (BSIs) from hematopoietic stem cell transplantation (HSCT) recipients, we reviewed the BSIs of 796 patients who underwent an HSCT in our institution during a 10-year period. Four hundred eighty-nine episodes of bacterial and fungal BSI were detected in 330 patients (41%). Three hundred ten isolates (63%) were gram-positive bacteria, 142 (29%) were gram-negative, and 18 and 19 isolates were different species of anaerobic organism and Candida spp. (both 4%). Coagulase-negative staphylococci (CoNS), with 210 isolates, were the organism most frequently isolated in each year of study and during the three phases of immune recovery after HSCT. The ratio of gram-positive to gram-negative has declined from 3.3 (1991–1992) to 1.8 (1999–2000). Crude mortality occurred in 47 cases of 489 BSI episodes (10%). Mortality according to groups was gram-negative, 7%; gram-positive, 9%; and anaerobic bacteria, 11%. Candida spp. was the group that accounted for the highest crude mortality, with 42%. Gram-positive microorganisms were isolated more often than gram-negative organisms, but the trend is reversing. CoNS were the leading pathogen during the 10 years of study and during the three phases of immune recovery after HSCT. Crude mortality of HSCT patients with BSI was low except for infections caused by Candida spp.Disclosures. Conflict of interest: none. Redundant publications: no substantial overlapping with previous papers. This study was presented at the 43rd ICAAC (K-1370).     

Zidovudine/lamivudine/abacavir plus tenofovir in HIV-infected naive patients: a 96-week prospective one-arm pilot study

We evaluated a single-class quadruple nucleoside/nucleotide regimen in a 96-week prospective one-arm pilot study in adult HIV-infected naive patients with CD4 >100 cells/microl. Standard zidovudine/lamivudine/abacavir and tenofovir doses were given. Virologic efficacy was evaluated by intent-to-treat (ITT), switch = failure and on-treatment (OT) analyses. A total of 54 patients were included (median CD4 count 254 cells/microl, VL 79,706 copies/ml). A median drop in VL of 2 log at 14 days and >3 log since week 12 was observed. A total of 34/54 (63%) patients (ITT) and 34/39 (87%) patients (OT) had VL <50 copies/ml at 96 weeks. Four (7%) patients switched therapy due to adverse events, 5 (9%) had virologic failure, and 1 died. Similar efficacy results were observed irrespective of baseline VL (> or <5 log) or CD4 cells (> or <250/microl). A median CD4 gain of +223 cells/microl was achieved. K65R + 41L + 219Q were detected in one patient at virologic failure. Only two patients presented fat loss on clinical evaluation. A decrease in total cholesterol (p = 0.007) and LDLc (p = 0.016) was observed. Our data suggest that zidovudine/lamivudine/abacavir plus tenofovir is a simple, effective, and well-tolerated NNRTI/PI-sparing regimen, even for patients with high viral loads. Larger trials comparing this option with standard initial antiretroviral regimens should be conducted.     

Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non-infectious febrile episodes (n = 10). On first day of fever, mean (+/- SD) PCT level was 0.3 ng/ml (0.2) in neutropenic fever of unknown origin, 0.5 ng/ml (0.7) in microbiologically confirmed infections, 0.2 ng/ml (0.2) in clinically documented infections and 1.7 (4.2) in non-infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10.1 ng/ml (6.7)] than all remaining groups (P = 0.027; Kruskal-Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values > or = 3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.     

Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes

In this multicenter retrospective study, the outcomes of 234 patients with myelodysplastic syndrome (MDS) who underwent transplantation between 1995 and 1999 from HLA-identical siblings were analyzed according to the hematopoietic stem cell source used, that is, bone marrow (BM, n = 132) or granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells (PBPCs, n = 102). There were 69 cases of refractory anemia (RA), 86 RA with excess blasts (RAEB), 75 RAEB in transformation (RAEB-t), and 4 unclassified MDS at diagnosis. The International Prognostic Scoring System was intermediate-2 or high in 104 of the 158 available scores. Multivariate analyses focused on transplantation-related mortality (TRM), 2-year treatment failure incidence, and survival. Use of PBPCs reduced the median duration of neutropenia and thrombocytopenia by 4 and 12 days, respectively. The incidence of acute GVHD was similar whatever the graft type used. Chronic GVHD was more likely to have occurred with PBPCs (odds ratio [OR], 1.62; 95% confidence interval [CI], 0.87-3.02). Two-year TRM was significantly reduced with PBPCs (relative risk [RR], 0.33; 95% CI, 0.15-0.73; P <.007), except for patients who had either RA or high-risk cytogenetics. The 2-year treatment failure incidence was significantly decreased with PBPCs, from 38% to 13% (RR, 0.22; 95% CI, 0.10-0.48; P <.001). Estimate of the 2-year event-free survival was 50% with PBPCs versus 39% with BM. In multivariate analysis, the outcome was significantly improved with PBPCs (RR, 0.27; 95% CI, 0.13-0.52; P <.001), except for patients with either RA or high-risk cytogenetics. In conclusion, PBPCs might be preferred for allogeneic transplantation in MDS patients at high risk for relapse on the basis of morphologic criteria because the use of this hematopoietic stem cell was associated with lower treatment failure incidence and improved survival.     

Community-wide distribution of predator-prey interaction strength in kelp forests

The strength of interactions between predators and their prey (interaction strength) varies enormously among species within ecological communities. Understanding the community-wide distribution of interaction strengths is vital, given that communities dominated by weak interactions may be more stable and resistant to invasion. In the oceans, previous studies have reported log-normal distributions of per capita interaction strength. We estimated the distribution of predator-prey interaction strengths within a subtidal speciose herbivore community (45 species). Laboratory experiments were used to determine maximum per capita interaction strengths for eight species of herbivores (including amphipods, isopods, gastropods, and sea urchins) that graze on giant kelp (Macrocystis pyrifera) microscopic stages. We found that maximum per capita interaction strength saturated as a function of individual herbivore biomass, likely caused by predator/prey size thresholds. Incorporating this nonlinearity, we predicted maximum per capita interaction strength for the remaining herbivore species. The resulting distribution of per capita interaction strengths was bimodal, in striking contrast to previous reports from other communities. Although small herbivores often had per capita interaction strengths similar to larger herbivores, their tendency to have greater densities in the field increased their potential impact as grazers. These results indicate that previous conclusions about the distributions of interaction strength in natural communities are not general, and that intermediate-sized predators can under realistic circumstances represent the most effective consumers in natural communities.     

Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft-versus-host disease after allogeneic transplantation

The graft-versus-host disease (GVHD) characteristics of 150 consecutive patients undergoing reduced intensity conditioning allogeneic (allo-RIC) transplants and 88 patients undergoing myeloablative conditioning regimen were analysed. All patients received the same GVHD prophylaxis and peripheral blood stem cells from a human leucocyte antigen identical sibling. The cumulative incidence of acute GVHD (aGVHD) was 67% and 44% in the myeloablative and allo-RIC regimen groups, respectively (P < 0.001), and was 39% vs. 29%, respectively (P = 0.043), for grades 2-4 aGVHD. Only conditioning type (myeloablative versus allo-RIC) significantly influenced the incidence of aGVHD in multivariate analysis: Hazard ratio (HR) = 2.16 [95% confidence interval (CI): 1.52-3.07], P < 0.0001. The cumulative incidence of chronic GVHD (cGVHD) was 63% and 71% among myeloablative and allo-RIC patients respectively (P = 0.084). This trend was because of the higher incidence of limited cGVHD, but not extensive cGVHD among allo-RIC recipients [HR = 3.3 (95% CI: 1.42-8.08), P = 0.0017]. Moreover, among patients who developed cGVHD, the cumulative incidence of limited cGVHD was significantly lower in the myeloablative group than in the allo-RIC group (7% vs. 25%, P = 0.007). Duration of immunosuppression was shorter among allo-RIC patients (35.5% vs. 68.8% required systemic immunosuppression 36 months after transplant, P = 0.028). Although prospective controlled trials are required to further evaluate the effect of the conditioning regimen on GVHD, our results suggest that RIC modifies the incidence and characteristics of both acute and cGVHD after allogeneic transplantation, and decreases the immunosuppression requirements in long-term follow up when compared with myeloablative conditioning.     

Predictors of blood transfusion in patients undergoing elective surgery for degenerative conditions of the spine

Background

The requirement of blood in the surgery of degenerative conditions of lumbar spine is around 10?%. Preoperative autologous blood donation is an effective method that is used in surgeries with an important blood loss. This is an expensive method because of the great number of predonated blood units not used in the postoperative period (around 70?% in our practice).

Objective

To know the risk factors associated with transfusion in the postoperative period in patients who undergo surgeries of degenerative conditions of the lumbar spine.

Methods

We designed a retrospective study of 142 cases of patients operated for degenerative conditions of the lumbar spine (not including simple disk hernia or adult degenerative scoliosis).

Results

Female sex, age >60?years, preoperative ASA score 3 and preoperative hemoglobin ≤136?g/L are the risk factors related to the need of blood transfusion in the postoperative period. After application of a statistical study, female sex and preoperative ASA score 3 were the most important variables to explain transfusional risk. A woman with ASA score 3 has a 61?% foretold probability to be transfused in the postoperative period, while a man with ASA?Conclusions Females, ASA 3, preoperative hemoglobin ≤136?g/L and age older than 60?years increase the risk to be transfused in the postoperative period for degenerative conditions of the spine.     

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift,Spain, 2007 to 2019

BackgroundCatheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death.AimTo analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat).MethodsA cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007–2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000 patient days. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000 patient days and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported.ResultsDuring the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate: 0.20 episodes/1,000 patient days). Patients’ median age was 64.1 years; 36.6% (3,403/9,290) were female. In total, 73.7% (n = 6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n = 5,822) were related to central venous catheter (CVC), 24.1% (n = 2,236) to peripheral venous catheters (PVC) and 13.3% (n = 1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR: 0.94; 95%CI: 0.93–0.96), especially in the ICU (IRR: 0.88; 95%CI: 0.87–0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR: 0.88; 95%CI: 0.87–0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC: 1.08; 95%CI: 1.05–1.11; IRR PVC: 1.03; 95% 1.00-1.05).ConclusionsOver the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards.     

BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes

Recently, it was shown that the oncogenic activation of BRAF, a member of the RAS/RAF family of kinases, by the V600E mutation is characteristic for sporadic colon tumors with microsatellite instability. Further, it was shown to associate with the silencing of the mismatch repair (MMR) gene MLH1 by hypermethylation. Moreover, BRAF mutations proved to be absent in tumors from hereditary nonpolyposis colorectal cancer syndrome (HNPCC) families with germline mutations in the MMR genes MLH1 and MSH2. These data suggest that the oncogenic activation of BRAF is involved only in sporadic colorectal tumorigenesis. In order to further support this hypothesis, we have extended the analysis of the BRAF gene to a different subset of HNPCC families without germline mutations in MLH1 and MSH2. BRAF-V600E mutations were analysed by automatic sequencing in 38 tumors from HNPCC families with germline mutations in the MSH6 gene and also in HNPCC (suspected) families that do not have mutations in the MMR genes MLH1, MSH2 and MSH6. All patients belong to different families. No mutations were detected in 14 tumors from HNPCC patients with germline mutations in MSH6. Further, no mutations of BRAF were found in tumors from 23 MMR-negative families, from which 13 fulfilled the Amsterdam criteria (HNPCC) and 10 were suspected for HNPCC as they were positive for the Bethesda criteria. Overall, our data reinforce the concept that BRAF is not involved in the colorectal tumorigenesis of HNPCC. The detection of a positive BRAF-V600E mutation in a colorectal cancer suggests a sporadic origin of the disease and the absence of germline alterations of MLH1, MSH2 and also of MSH6. These findings have a potential impact in the genetic testing for HNPCC diagnostics and suggest a potential use of BRAF as exclusion criteria for HNPCC or as a molecular marker of sporadic cancer.