Risk factors for hospital-acquired bacteraemia - an explorative case-control study of hospital interventions.

BACKGROUND: Knowledge on hospital-related interventions as risk factors for hospital-acquired bacteraemia (HAB) is sparse. AIM: We aimed to investigate hospital interventions as risk factors for HAB. METHODS: Prospectively through one year, we identified episodes of HAB in a single tertiary hospital. We used a matched incidence density sampled case-control design. Matching on sex and age group, we sampled controls (1:2) from the adult hospital population with ongoing hospitalization for ≥48 h. Using conditional logistic regression, we estimated odds ratios (OR) with 95% confidence intervals (CI). For adjusted ORs (aOR), adjustments were made for length of hospital stay, type and urgency of admission, and Charlson Comorbidity Index score level. FINDINGS: From 15th October 2019 through 14th October 2020, we identified 115 incident episodes of HAB and matched them with 230 controls. HAB patients were more often admitted as 'medicine or emergency surgery'-patients (94% vs 87%) and had a longer hospital stay before inclusion (median days 20 vs 12). They were more frequently categorized as having a 'low level comorbidity' (58% vs 39%) but had higher prevalence of haematologic (15% vs 6%) or metastatic cancer (13% vs 10%). Our estimates for central venous catheters were aOR of 3.46 (95% CI 1.92-6.23), haemodialysis; aOR 5.05 (95% CI 1.41-18.06), immunosuppressive treatment including chemotherapy; aOR of 1.72 (95% CI 1.00-2.96). CONCLUSION: Central venous catheters and haemodialysis were the most prominent risk factors. Immunosuppressive treatment including therapy may play an important role in the development of HAB.

Hydrochloric acid treatment of tunneled central venous catheter infections in children with cancer.

BACKGROUND: Long-term tunneled central venous catheters (CVCs) are often the source of catheter-associated bloodstream infections (CABSIs), which may be difficult to eradicate and may lead to premature catheter removal. PROCEDURE: This prospective controlled study used instillation of 2 M hydrochloric acid (HCl) as an adjuvant to the intravenous antibiotic treatment of children with bacteremia and compared the results with those from the immediate preceding period. The primary outcome variable was infection-related CVC removal within 100 days of bacteremia. Only patients with double lumen Hickman CVC with external tubings were included. RESULTS: During a period of 36 months, 109 episodes of bacteremia were treated, 51 during the period where HCl was not used and 58 during the period where HCl was used. Forty-two out of 58 bacteremias were treated with HCl during the "HCl period." An intention-to-treat analysis showed that the median time to infection-related CVC removal was significantly longer during the HCl period compared with the non-HCl period (94 d vs. 12.5 d). At day 100 significantly more CVCs remained in place compared with the non-HCl period. Of the 42 CVCs treated with HCl, 2 had to be removed because of infection before day 30 and further 7 CVCs were removed before day 100. There was no difference in the occurrence of new bacteremias within the first 30 days of bacteremia in the 2 groups. CONCLUSION: HCl may successfully supplement intravenous antibiotics in the treatment of CABSI and contribute to CVC salvage.

Clinical evaluation of 3D/3D MRI-CBCT automatching on brain tumors for online patient setup verification - A step towards MRI-based treatment planning.

BACKGROUND: Magnetic Resonance Imaging (MRI) is often used in modern day radiotherapy (RT) due to superior soft tissue contrast. However, treatment planning based solely on MRI is restricted due to e.g. the limitations of conducting online patient setup verification using MRI as reference. In this study 3D/3D MRI-Cone Beam CT (CBCT) automatching for online patient setup verification was investigated. MATERIAL AND METHODS: Initially, a multi-modality phantom was constructed and used for a quantitative comparison of CT-CBCT and MRI-CBCT automatching. Following the phantom experiment three patients undergoing postoperative radiotherapy for malignant brain tumors received a weekly CBCT. In total 18 scans was matched with both CT and MRI as reference. The CBCT scans were acquired using a Clinac iX 2300 linear accelerator (Varian Medical Systems) with an On-Board Imager (OBI). RESULTS: For the phantom experiment CT-CBCT and MRI-CBCT automatching resulted in similar results. A significant difference was observed only in the longitudinal direction where MRI-CBCT resulted in the best match (mean and standard deviations of 1.85±2.68 mm for CT and -0.05±2.55 mm for MRI). For the clinical experiment the absolute difference in couch shift coordinates acquired from MRI-CBCT and CT-CBCT automatching, were ≤2 mm in the vertical direction and ≤3 mm in the longitudinal and lateral directions. For yaw rotation differences up to 3.3 degrees were observed. Mean values and standard deviations were 0.8±0.6 mm, 1.5±1.2 mm and 1.2±1.2 mm for the vertical, longitudinal and lateral directions, respectively and 1.95±1.12 degrees for the rotation (n=17). CONCLUSION: It is feasible to use MRI as reference when conducting 3D/3D CBCT automatching for online patient setup verification. For both the phantom and clinical experiment MRI-CBCT performed similar to CT-CBCT automatching and significantly better in the longitudinal direction for the phantom experiment.

Salmonella or Campylobacter gastroenteritis prior to a cancer diagnosis does not aggravate the prognosis: a population-based follow-up study.

We hypothesized that preceding zoonotic Salmonella or Campylobacter gastroenteritis aggravated the prognosis in cancer patients. Exposed patients comprised all of those diagnosed with first-time Salmonella/Campylobacter gastroenteritis from 1991 and with first-time cancer diagnosis thereafter (through 2003) in two Danish counties. These patients were matched for main cancer type, gender, age and calendar period to unexposed cancer patients, i.e. those without Salmonella/Campylobacter gastroenteritis. We compared cancer stage by age- and comorbidity-adjusted logistic regression analysis, survival by comorbidity-adjusted Cox's regression analysis and mortality dependent on the time period between Salmonella/Campylobacter gastroenteritis and cancer by spline regression curves. The study cohort comprised 272 Salmonella/Campylobacter-exposed cancer patients and 2681 unexposed cancer patients. Prevalence odds ratios [95% confidence intervals (CI)] in exposed as compared with unexposed patients were 0.96 (0.74-1.25) for localized tumours, 1.15 (0.87-1.54) for regional spread and 1.14 (0.84-1.55) for metastases. Adjusted mortality rate ratios (95% CI) were 0.93 (0.75-1.16) for 0-1 year, 1.08 (0.84-1.39) for 2-5 years and 1.02 (0.60-1.73) for the remaining period. Mortality estimates did not change in relation to the time period between gastroenteritis and cancer. Salmonella/Campylobacter gastroenteritis prior to cancer was associated with neither the cancer stage nor a poorer prognosis.

Increased risk of zoonotic Salmonella and Campylobacter gastroenteritis in patients with haematological malignancies: a population-based study.

We hypothesised that haematological malignancies increase the risk of acquiring zoonotic Salmonella or Campylobacter gastroenteritis. The population-based study comprised all first-time Salmonella/Campylobacter gastroenteritis cases in two Danish counties (1991-2003), with age- and gender-matched controls from the background population. We linked the study cohort to registries to obtain data on malignancies, chemotherapy (yes/no), and main comorbidities diagnosed before Salmonella/Campylobacter gastroenteritis. Based on this design, we determined incidence rate ratios (IRR) in conditional logistic regression analyses, and we used weighted mean regression curves to evaluate fluctuations in risk 0-5 years after the malignancy diagnosis. Sixty-eight of 13,324 cases (0.5%) and 29 of 26,648 controls (0.1%) had haematological malignancy before their Salmonella/Campylobacter gastroenteritis. Comorbidity-adjusted IRR for Salmonella/Campylobacter gastroenteritis in patients with haematological malignancy as compared to patients without malignancy were 4.46 [95% confidence intervals (CI), 2.88-6.90] for all individuals, 8.33 (95% CI, 4.31-16.1) for Salmonella, and 2.17 (95% CI, 1.15-4.08) for Campylobacter. Stratification on chemotherapy treatment did not change these estimates. In time-related analyses, IRR were 7-8 in the first 2 years after the haematological malignancy diagnosis and 4-5 in the following 3 years. Patients with haematological malignancy had increased long-term risk of enquiring Salmonella or Campylobacter gastroenteritis.

Dosimetric and geometric evaluation of an open low-field magnetic resonance simulator for radiotherapy treatment planning of brain tumours.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) imaging is superior to computed tomography (CT) in radiotherapy of brain tumours. In this study an open low-field MR-simulator is evaluated in order to eliminate the cost of and time spent on additional CT scanning. MATERIALS AND METHODS: Eleven patients with brain tumours are both CT and MR scanned and the defined tumour volumes are compared. Image distortions and dose calculations based on CT density correction, MR unit density and MR bulk density, bone segmentation are performed. Monte Carlo simulations using 4 and 8 MV beams on homogeneous and bone segmented mediums are performed. RESULTS: Mean MR and CT tumour volumes of approximately the same size (V MR =55+/-34 cm3 and V CT =51+/-32 cm3) are observed, but for individual patients, small intersection volumes are observed. The MR images show negligible distortion within radial distances below 12 cm (<1.5 mm). On unit density mediums, dose errors above 2% are observed in low dose areas. Monte Carlo simulations with 4 MV photons show large deviations in dose (>2%) just behind the skull if bone is not segmented. CONCLUSIONS: It is feasible to use an MR-simulator for radiotherapy planning of brain tumours if bone is segmented or a careful choice of beam energy (>4 MV) is selected.

The role of alternative oxidase in modulating carbon use efficiency and growth during macronutrient stress in tobacco cells.

When wild-type (wt) tobacco (Nicotiana tabacum cv. Petit Havana SR1) cells are grown under macronutrient (P or N) limitation, they induce large amounts of alternative oxidase (AOX), which constitutes a non-energy-conserving branch of the respiratory electron transport chain. To investigate the significance of AOX induction, wt cells were compared with transgenic (AS8) cells lacking AOX. Under nutrient limitation, growth of wt cell cultures was dramatically reduced and carbon use efficiency (g cell dry weight gain g(-1) sugar consumed) decreased by 42-63%. However, the growth of AS8 was only moderately reduced by the nutrient deficiencies and carbon use efficiency values remained the same as under nutrient-sufficient conditions. As a result, the nutrient limitations more severely compromised the tissue nutrient status (P or N) of AS8 than wt cells. Northern analyses and a comparison of the mitochondrial protein profiles of wt and AS8 cells indicated that the lack of AOX in AS8 under P limitation was associated with increased levels of proteins commonly associated with oxidative stress and/or stress injury. Also, the level of electron transport chain components was consistently reduced in AS8 while tricarboxylic acid cycle enzymes did not show a universal trend in abundance in comparison to the wt. Alternatively, the lack of AOX in AS8 cells under N limitation resulted in enhanced carbohydrate accumulation. It is concluded that AOX respiration provides an important general mechanism by which plant cells can modulate their growth in response to nutrient availability and that AOX also has nutrient-specific roles in maintaining cellular redox and carbon balance.

Protein oxidation in plant mitochondria as a stress indicator.

Plant mitochondria produce reactive oxygen species (ROS) as an unavoidable side product of aerobic metabolism, but they have mechanisms for regulating this production such as the alternative oxidase. Once produced, ROS can be removed by several different enzyme systems. Finally, should the first two strategies fail, the ROS produced can act as a signal to the rest of the cell and/or cause damage to DNA, lipids and proteins. Proteins are modified in a variety of ways by ROS, some direct, others indirect e.g. by conjugation with breakdown products of fatty acid peroxidation. Reversible oxidation of cysteine and methionine side chains is an important mechanism for regulating enzyme activity. Mitochondria from both mammalian and plant tissues contain a number of oxidised proteins, but the relative abundance of these post-translationally modified forms is as yet unknown, as are the consequences of the modification for the properties and turnover time of the proteins. Specific proteins appear to be particularly vulnerable to oxidative carbonylation in the matrix of plant mitochondria; these include several enzymes of the Krebs cycle, glycine decarboxylase, superoxide dismutase and heat shock proteins. Plant mitochondria contain a number of different proteases, but their role in removing oxidatively damaged proteins is, as yet, unclear.

Three differentially expressed basic peroxidases from wound-lignifying Asparagus officinalis.

The activity of ionically bound peroxidases from an asparagus spear increased from 5-24 h post-harvest. Isoelectric focusing showed that the post-harvest increase of the total peroxidase activity was due to the increase of several distinct isoperoxidases. Concomitantly, a decrease in the activity of two anionic peroxidases was observed. Peroxidases with pI 5.9, 6.4 and 9.2 were detected only at 24 h post-harvest, whereas four peroxidases, with pI 8.7, 8.1, 7.4, and 6.7, detected throughout the time-course, increased in their activity. Histochemical staining demonstrated that lignin and peroxidase activity were located in the vascular bundles throughout the period of measurement. Lignin was detected in the cell walls of the protoxylem in the vascular bundles of the asparagus stem. A cDNA library of mRNA isolated from asparagus spears 24 h post-harvest was screened for peroxidases using homologous and heterologous probes. Three clones were isolated and the corresponding mature asparagus peroxidases displayed 70%, 76% and 81% amino acid sequence identity to each other. These new asparagus peroxidases are typical class III plant peroxidases in terms of conserved regions with a calculated pI >9.2, which is consistent with most basic peroxidases. One of the genes was shown to be a constitutively expressed single-copy gene, whereas the others showed an increased expression at post-harvest. The highest similarity in the amino acid sequence (71-77%) was found in peroxidases from roots of winter grown turnip TP7, to Arabidopsis AtP49, to an EST sequence from cotton fibres and to TMV-infected tobacco.

A new class of N-hydroxycinnamoyltransferases. Purification, cloning, and expression of a barley agmatine coumaroyltransferase (EC 2.3.1.64).

Agmatine coumaroyltransferase (ACT), which catalyzes the first step in the biosynthesis of antifungal hydroxycinnamoylagmatine derivatives, was purified to apparent homogeneity from 3-day-old etiolated barley (Hordeum vulgare L.) seedlings. The enzyme was highly specific for agmatine as acyl acceptor and had the highest specificity for p-coumaroyl-CoA among various acyl donors with a specific activity of 29.7 nanokatal x mg(-1) protein. Barley ACT was found to be a single polypeptide chain of 48 kDa with a pI of 5.20 as determined by isoelectric focusing. The 15 N-terminal amino acid residues were identified by micro-sequencing of the native protein and were used to clone a full-length barley ACT cDNA that predicted a protein of 439 amino acid residues. The sequence was devoid of N-terminal signal peptide, suggesting a cytosolic localization of barley ACT. Recombinant ACT produced and affinity-purified from Escherichia coli had a specific activity of 189 nanokatal x mg(-1) protein, thus confirming the identity of the purified native protein. A partial cDNA sequence for ACT was obtained from wheat that predicted a protein of 353 amino acid residues and had 95% sequence identity to barley ACT. Two motifs in the amino acid sequence reveal that barley ACT represents a new class of N-hydroxycinnamoyltransferases belonging to the transferase superfamily. The barley ACT is unique in producing the precursor of hordatine, a proven antifungal factor that may be directed toward Blumeria graminis.