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Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7) for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1) for occlusions. Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

Background Energy deficit is a common and serious problem in intensive care units and is associated with increased rates of complications, length of stay, and mortality. Parenteral nutrition (PN), either alone or in combination with enteral nutrition, can improve nutrient delivery to critically ill patients. Lipids provide a key source of calories within PN formulations, preventing or correcting energy deficits and improving outcomes. Discussion In this article, we review the role of parenteral lipid emulsions (LEs) in the management of critically ill patients and highlight important biologic activities associated with lipids. Soybean-oil-based LEs with high contents of polyunsaturated fatty acids (PUFA) were the first widely used formulations in the intensive care setting. However, they may be associated with increased rates of infection and lipid peroxidation, which can exacerbate oxidative stress. More recently developed parenteral LEs employ partial substitution of soybean oil with oils providing medium-chain triglycerides, ω-9 monounsaturated fatty acids or ω-3 PUFA. Many of these LEs have demonstrated reduced effects on oxidative stress, immune responses, and inflammation. However, the effects of these LEs on clinical outcomes have not been extensively evaluated. Conclusions Ongoing research using adequately designed and well-controlled studies that characterize the biologic properties of LEs should assist clinicians in selecting LEs within the critical care setting. Prescription of PN containing LEs should be based on available clinical data, while considering the individual patient’s physiologic profile and therapeutic requirements.

Background Bioelectrical impedance analysis (BIA) is commonly used to evaluate body composition as part of nutritional assessment. Current guidelines recommend performing BIA measurements in a fasting state of at least 2 h in a clinical setting and 8 h in a research setting. However, since asking patients with malnutrition or sarcopenia to fast is not desirable and literature to support the strategy in the guidelines is lacking, this study aimed to assess the impact of breakfast on BIA measurements. Methods We performed an explorative, prospective study in healthy volunteers aged between 18 and 70 years, with a normal fluid balance and a body mass index between 18.5 and 30 kg/m 2 . BIA measurements were performed according to the standard operating procedure in the fasting state, and 1, 2, 3, and 4 h after ingesting a standardized breakfast meal of about 400 kcal with a 150 mL drink, using the hand-to-food single-frequency BIA (Bodystat500 ®). The Kyle formula was used to calculate the primary outcome, i.e. fat-free mass (FFM, kg). A linear mixed model was used to compare baseline values with other time points. A difference of 1 kg in FFM was considered clinically relevant. Results Thirty-nine (85% female) volunteers were included, with a median age of 28 years (IQR 24–38). In 90% of the participants, having breakfast had no clinically relevant impact on the estimated FFM. For the group, the most pronounced mean difference, a statistically but not clinically significant higher value of 0.2 kg (0.4%), was observed after 3 h of fasting compared to baseline. No statistically significant differences were found at the other time points. Conclusion Eating affects single-frequency BIA measurements, but differences in FFM remain below clinical relevance for most participants when using a standardized breakfast. Thus, the current study suggests performing a BIA measurement in a fasting state is not required.

Crohn's disease (CD) is a chronic inflammatory disease in which cytokines play a pivotal role in the induction and maintenance of inflammation. Innate cytokine production is genetically determined and varies largely between individuals; this might impact the severity of inflammation. We aimed to assess whether ex-vivo endotoxin-stimulated levels of cytokines could be associated with disease phenotype. Patients with quiescent CD (Harvey-Bradshaw Index ≤ 4 and negative inflammation markers) who were not using immunomodulating drugs or biologicals were eligible. Historical disease characteristics (localization, behavior, number of bowel resections, drug history, extra-intestinal symptoms) were extracted from medical records. We measured cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10) in supernatants of lipopolysaccharide (LPS) -stimulated whole blood cultures and correlated these with disease characteristics and age- and sex-matched healthy controls. In addition, we analyzed whether single nucleotide polymorphisms (SNPs) in the promoter region of the TNF-α gene were related to TNF-α levels. We included 75 patients with CD and 24 healthy controls. Six patients were excluded because of increased inflammation markers resulting in a total of 69 patients. The mean age (SD) of patients with CD was 51.2 (12.3) years with a mean (SD) disease duration of 24.1 (11.5) years. Disease localization, peri-anal involvement and behavior were not related to LPS-stimulated TNF-α, IL-1β, IL-6 or IL-10 levels. In addition, combination of localization with behavior to differentiate mild from severe disease type showed no significant differences. TNF-α levels were higher in patients with CD (428 pg/ml IQR [267-468]) compared to healthy controls (459 pg/ml IQR [364-570], p=0.02). We found no associations between SNPs in the promoter region and TNF-α levels. In this study, innate cytokine production of TNF-α, IL-1β, IL-6 and IL-10 was not related to historical disease characteristics or disease severity in patients with quiescent CD. These findings suggest that genetically determined levels of these cytokines obtained from LPS-stimulated whole blood cultures are not linked with disease behavior or severity.

Background Patients with long-term intestinal failure are usually treated by means of home parenteral nutrition (HPN) where they administer their nutritional formulation intravenously via a central venous access device (mostly a catheter). This implies that such patients are exposed to a lifelong risk of developing Staphylococcus aureus bacteremia (SAB). SAB poses a threat to both catheter and patient survival and may lead to frequent hospitalization and a permanent loss of vascular access. In other clinical settings, S. aureus carriage eradication has been proven effective in the prevention of S. aureus infections. Unfortunately, there is a complete lack of evidence in HPN support on the most effective and safe S. aureus decolonization strategy in S. aureus carriers. We hypothesized that long-term S. aureus decolonization in HPN patients can only be effective if it is aimed at the whole body (nasal and extra-nasal) and is given chronically or repeatedly on indication. Besides this, we believe that S. aureus carriage among caregivers, who are in close contact with the patient, are of great importance in the S. aureus transmission routes. Methods/design The CARRIER trial is a randomized, open-label, multicenter clinical trial in Dutch and Danish hospitals that treat patients on HPN. A total of 138 adult HPN patients carrying S. aureus will be randomly assigned to a search and destroy (SD) strategy, a quick and short, systemic antibiotic treatment, or a continuous suppression (CS) strategy, a repeated chronic topical antibiotic treatment. The primary outcome measure is the proportion of patients in whom S. aureus is totally eradicated during a 1-year period. Secondary outcomes are time to successful eradication, long-term antimicrobial resistance, adverse events, patient compliance, incidence of ( S. aureus ) infections, catheter removals, mortality rates, S. aureus transmission routes, quality of life, and health care costs. Discussion The CARRIER trial is designed to identify the most safe and effective long-term S. aureus carriage decolonization strategy in HPN patients. This will eventually lead to a better understanding of long-term S. aureus decolonization treatments in general. The results of this study will have a great impact on our daily clinical practice, which eventually may result in less S. aureus- related infections. Trial registration ClinicalTrials.gov; NCT03173053 . Registered on 1 June 2017.

Summary The droplet digital polymerase chain reaction (ddPCR) is a novel molecular technique that allows rapid quantification of rare target DNA sequences. Aim of this study was to explore the feasibility of the ddPCR technique to detect pathogen DNA in whole blood and to assess the diagnostic accuracy of ddPCR to detect bloodstream infections (BSIs), benchmarked against blood cultures. Broad‐range primers and probes were designed to detect bacterial 16S rRNA (and Gram stain for differentiation) and fungal 28S rRNA. To determine the detection limit of ddPCR, 10‐fold serial dilutions of E. coli and C. albicans were spiked in both PBS and whole blood. The diagnostic accuracy of ddPCR was tested in historically collected frozen blood samples from adult patients suspected of a BSI and compared with blood cultures. Analyses were independently performed by two research analysts. Outcomes included sensitivity and specificity of ddPCR. Within 4 h, blood samples were drawn, and DNA was isolated and analysed. The ddPCR detection limit was approximately 1–2 bacteria or fungi per ddPCR reaction. In total, 45 blood samples were collected from patients, of which 15 (33%) presented with positive blood cultures. The overall sensitivity of ddPCR was 80% (95% CI 52–96) and specificity 87% (95% CI 69–96). In conclusion, the ddPCR technique has considerable potential and is able to detect very low amounts of pathogen DNA in whole blood within 4 h. Currently, ddPCR has a reasonable sensitivity and specificity, but requires further optimization to make it more useful for clinical practice. The droplet digital polymerase chain reaction (ddPCR) is a novel molecular technique that allows rapid quantification of rare target DNA sequences. Aim of this study was to explore the feasibility of the ddPCR technique to detect pathogen DNA in whole blood, and to assess the diagnostic accuracy of ddPCR to detect bloodstream infections, benchmarked against blood cultures. The ddPCR technique showed considerable potential and was able to detect very low amounts of pathogen DNA in whole blood within 4 h. Currently, ddPCR has a reasonable sensitivity and specificity, but requires further optimization to make it more useful for clinical use.

Introduction The use of thiopurines is frequently accompanied by hepatotoxicity. Studies on hepatocyte cultures showed a time- and dose-dependent increase of thiopurine toxicity. 5-Aminosalicylic acid (5-ASA) and allopurinol can influence thiopurine metabolism; however, it is unknown whether this affects in vitro cytotoxicity. Methods Human hepatoma cells (Huh7, HepG2 and HepaRG) were incubated with increasing concentrations of thiopurines, 5-ASA or allopurinol. Water-soluble tetrazolium salt-1 (WST-1) cytotoxicity assays were used to calculate cell survival curves and half maximal inhibitory concentrations (IC 50 ). Combination experiments with thiopurines with a fixed dose of 200 μM 5-ASA or 100 μM allopurinol were conducted in HepaRG cells. Caspase-3/7 activation was evaluated, and single cell electrophoresis analysis was performed. Results A time- and dose-related cytotoxic effect was seen with azathioprine (AZA) in all hepatoma cells, whereas Huh7 and HepG2 cells did not show toxicity to 6-mercaptopurine (6-MP). HepaRG cells expressed the highest levels of drug metabolising enzymes, and therefore, combination experiments were conducted in HepaRG cells. Addition of a non-toxic dose of allopurinol resulted in a twofold to threefold increased cytotoxicity of all thiopurines, which seemed to be mediated by apoptosis/DNA damage. Conclusion The addition of allopurinol to thiopurines leads to a two–threefold increased cytotoxicity in HepaRG cells.

Glutathione S-transferases (GSTs) are important in the detoxification of many compounds, including reactive oxygen species. Polymorphisms in GSTs resulting in a decreased enzyme activity might enhance the risk for inflammatory bowel disease by eliciting a state of oxidative stress. Previous case-control studies showed divergent results and were frequently limited in sample size; therefore we conducted a meta-analysis including results from our case-control study. For the case-control study, we genotyped 552 patients with Crohn's disease (CD), 223 patients with ulcerative colitis (UC) and 972 healthy controls by PCR for functional deletions in GST Mu and GST Theta. Both were not analyzed in recent genome-wide association studies. For the meta-analysis, PubMed, EMBASE and Web of Science were searched. In this meta-analysis, we show an enhanced susceptibility for UC in individuals with the GSTT1null genotype (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.31-3.92). In our case-control study, a reduced risk for CD was seen with the GSTT1null genotype (OR 0.58, 95% CI 0.43-0.77); however, pooled analysis showed an OR of 1.67, 95% CI 0.81-3.45. In this meta-analysis, we showed an increased risk for UC in individuals with the GSTT1null genotype.

Although in other groups Staphylococcus aureus eradication has proven to be an effective infection prevention measure, to our knowledge, no such studies have been performed in patients on home parenteral nutrition (HPN). The aim of this study was to investigate the efficacy of chronic nasal mupirocin use on S. aureus eradication and prevention of catheter related infections in patients on HPN. This was a cohort study with data collected from adult patients on HPN who were screened for S. aureus carriage. In case of carriage, the patient was instructed to apply mupirocin nasal ointment monthly. Outcomes were the percentage of successful S. aureus eradication and the effect on the incidence of catheter-related infections and development of mupirocin resistance. S. aureus nasal carriage was found in 54% of the patients. Eradication was successful in 66% (70 of 106) of patients treated with mupirocin. Overall S. aureus catheter-related infection rates decreased by 50% (P = 0.02). The decrease was mostly due to a drop in central line-associated bloodstream infection (CLABSI) rates (0.26versus 0.1 per 1000 central venous catheter days; P = 0.04). The overall CLABSI rates decreased as well (incidence ratio rate, 0.43; 95% confidence interval. 0.24–0.76; P < 0.01). Low-level mupirocin resistance was observed in four patients. Findings from the present study highlighted the potential usefulness of mupirocin ointment prophylaxis to establish S. aureus eradication in patients on HPN. However, awareness for the development of mupirocin resistance is prudent. Further research needs to be carried out to validate these findings. •Staphylococcus aureus is a leading cause of difficult-to-treat catheter-related infections.•S. aureus carriage is known for a two- to fourfold increased risk for S. aureus infections.•Mupirocin nasal ointment eradicated S. aureus in 66% of the patients on home parenteral nutrition.•A 50% decrease in S. aureus infections was observed post-mupirocin commencement.•Further research to validate these findings is necessary.

Enteral tube feeding remains an indispensible strategy to treat disease-related malnutrition. In the present study we evaluated in clinical practice whether prescribed feeding volumes correspond with administered quantities and we highlight possible causes for discrepancies. During a 4-month observation period data from all patients fully depending on tube feeding (1·5–2·5 litres/d) were collected in a Dutch 900-bed academic hospital. The range for administered feeds to be adequate was set at 100 ± 10 % of the prescribed dose. Fifty-five patients (mean age 57 (sd 30) years) were included. Tube feeding was given continuously via pump (n 37) or drip (n 3), in portions (n 14) or by combined modes (n 1). Administered tube feeding amounts were significantly lower than prescribed in 40 % of all patients (P ≤ 0·001). The mean ratio of administered v. prescribed energy was 87 (sd 21) % (all modes), 85 (sd 24) % (pump), 94 (sd 12) % (portions) and 88·3 (sd 18·1) % (drip), respectively. The mean energy deficit amounted to 1089 kJ/d (range − 7955 to +795). Only on intensive care unit wards did feeding administration meet the set goal. Feeding interruptions because of diagnostic or therapeutic procedures were the main reason for decreased intakes. Our findings show that many patients relying on tube feeding do not meet their nutritional goals during hospital stay. This problem can be addressed by adapting feeding schedules and the use of formulations with a higher energy density.