A super-resolution proof of concept in a cycloidal coded aperture miniature mass spectrometer.

RATIONALE: Higher resolution in fieldable mass spectrometers (MS) is desirable in space flight applications to enable resolving isobaric interferences at m/z < 60 u. Resolution in portable cycloidal MS coupled with array detectors could be improved by reducing the slit width and/or by reducing the width of the detector pixels. However, these solutions are expensive and can result in reduced sensitivity. In this paper, we demonstrate high-resolution spectral reconstruction in a cycloidal coded aperture miniature mass spectrometer (C-CAMMS) without changing the slit or detector pixel sizes using a class of signal processing techniques called super-resolution (SR). METHODS: We developed an SR reconstruction algorithm using a sampling SR approach whereby a set of spatially shifted low-resolution measurements are reconstructed into a higher-resolution spectrum. This algorithm was applied to experimental data collected using the C-CAMMS prototype. It was then applied to synthetic data with additive noise, system response variation, and spatial shift nonuniformity to investigate the source of reconstruction artifacts in the experimental data. RESULTS: Experimental results using two ½ pixel shifted spectra resulted in a resolution of ¾ pixel full width at half maximum (FWHM) at m/z = 28 u. This resolution is equivalent to 0.013 u, six times better than the resolution previously published at m/z = 28 for N2 + using C-CAMMS. However, the reconstructed spectra exhibited some artifacts. The results of the synthetic data study indicate that the artifacts are most likely caused by the system response variation. CONCLUSIONS: This paper demonstrates super-resolution spectral reconstruction in C-CAMMS without changing the slit or detector pixel sizes using a sampling SR approach. With improvements, this technique could be used to resolve isobaric interferences in a portable cycloidal MS for space flight applications.

The Long Neglected Cycloidal Mass Analyzer.

In 1938, Walker Bleakney and John A. Hipple first described the cycloidal mass analyzer as the only mass analyzer configuration capable of "perfect" ion focusing. Why has their geometry been largely neglected for many years and how might it earn a respectable place in the world of modern chemical analysis? This Perspective explores the properties of the cycloidal mass analyzer and identifies the lack of suitable ion array detectors as a significant reason why cycloidal mass analyzers are not widely used. The recent development of capacitive transimpedance amplifier array detectors can enable several techniques using cycloidal mass analyzers including spatially coded apertures and single particle mass analysis with a "virtual-slit", helping the cycloidal mass analyzer earn a respectable place in chemical analysis.

Is phosphate solubilizing ability in plant growth-promoting rhizobacteria isolated from chickpea linked to their ability to produce ACC deaminase?

AIMS: Since most phosphate solubilizing bacteria (PSB) also produce 1-aminocyclopropane-1-carboxylate (ACC) deaminase, we investigated if there was an association between these two plant growth-promoting properties under in vitro conditions. METHODS AND RESULTS: A total of 841 bacterial isolates were obtained using selective and enrichment isolation methods. ACC deaminase was investigated using in vitro methods and by sequencing the acdS gene. The effect of ACC deaminase on P solubilization was investigated further using five efficient PSB. ACC deaminase production ability was found amongst a wide range of bacteria belonging to the genera Bacillus, Burkholderia, Pseudomonas and Variovorax. The amount of ACC deaminase produced by PSB was significantly associated with the liberation of Pi from Ca-P when ACC was the sole N source. Ca-P solubilization was associated with the degree of acidification of the medium. Additionally, the P solubilization potential of PSB with (NH4 )2 SO4 was determined by the type of carboxylates produced. An in-planta experiment was conducted using Burkholderia sp. 12F on chickpea cv. Genesis-863 in sand : vermiculite (1 : 1 v/v) amended with rock phosphate and inoculation of this efficient PSB significantly increased growth, nodulation and P uptake of chickpea fertilized with rock phosphate. CONCLUSION: ACC deaminase activity influenced the capacity of PSB to solubilize P from Ca-P when ACC was the sole N source and Burkholderia sp. 12F promoted the chickpea-Mesorhizobium symbiosis. SIGNIFICANCE AND IMPACT OF THE STUDY: ACC deaminase activity could enhance the P solubilizing activity of rhizobacteria that improve plant growth.

A call for more science in forensic science.

Forensic science is critical to the administration of justice. The discipline of forensic science is remarkably complex and includes methodologies ranging from DNA analysis to chemical composition to pattern recognition. Many forensic practices developed under the auspices of law enforcement and were vetted primarily by the legal system rather than being subjected to scientific scrutiny and empirical testing. Beginning in the 1990s, exonerations based on DNA-related methods revealed problems with some forensic disciplines, leading to calls for major reforms. This process generated a National Academy of Science report in 2009 that was highly critical of many forensic practices and eventually led to the establishment of the National Commission for Forensic Science (NCFS) in 2013. The NCFS was a deliberative body that catalyzed communication between nonforensic scientists, forensic scientists, and other stakeholders in the legal community. In 2017, despite continuing problems with forensic science, the Department of Justice terminated the NCFS. Just when forensic science needs the most support, it is getting the least. We urge the larger scientific community to come to the aid of our forensic colleagues by advocating for urgently needed research, testing, and financial support.

Mechanisms in plant growth-promoting rhizobacteria that enhance legume-rhizobial symbioses.

Nitrogen fixation is an important biological process in terrestrial ecosystems and for global crop production. Legume nodulation and N2 fixation have been improved using nodule-enhancing rhizobacteria (NER) under both regular and stressed conditions. The positive effect of NER on legume-rhizobia symbiosis can be facilitated by plant growth-promoting (PGP) mechanisms, some of which remain to be identified. NER that produce aminocyclopropane-1-carboxylic acid deaminase and indole acetic acid enhance the legume-rhizobia symbiosis through (i) enhancing the nodule induction, (ii) improving the competitiveness of rhizobia for nodulation, (iii) prolonging functional nodules by suppressing nodule senescence and (iv) upregulating genes associated with legume-rhizobia symbiosis. The means by which these processes enhance the legume-rhizobia symbiosis is the focus of this review. A better understanding of the mechanisms by which PGP rhizobacteria operate, and how they can be altered, will provide opportunities to enhance legume-rhizobial interactions, to provide new advances in plant growth promotion and N2 fixation.

Impact of seed-applied pesticides on rhizobial survival and legume nodulation.

AIMS: Compatibility of seed-applied pesticides and rhizobial inoculants is an important consideration for farmers when sowing legumes. Some of the seed-applied pesticides may influence rhizobial growth and nodulation, but there is currently little available information on the potential inhibitory effects. Therefore, common seed fungicidal and insecticidal treatments were assessed to determine adverse impacts on rhizobial inoculants both in vitro, on treated seed, and in the field. METHODS AND RESULTS: Initially, the in vitro toxicity of the seed-applied fungicides Thiram 600, P-Pickel T (PPT), their active ingredients (thiram and thiabendazole) and the insecticide Gaucho to rhizobia was measured with filter discs containing varying concentrations of the pesticides. Pea and chickpea seed was then coated with the same pesticides and inoculated with rhizobia in different inoculant substrates to determine bacterial survival and nodulation. Finally, a field trial using the fungicide PPT and commercial inoculants was conducted. Some seed fungicide treatments were found to be inhibitory to rhizobia and reduce nodulation under monoxenic conditions and in the field. SIGNIFICANCE AND IMPACT OF THE STUDY: These data provide more detailed information on the compatibility of specific rhizobial inoculants with common seed-applied pesticides. This research will provide information on the compatibility of rhizobia and seed-applied pesticides, and assist farmers to select sowing practices which reduce the risk of crop nodulation failures.

Use of ceftazidime/avibactam for the treatment of MDR Pseudomonas aeruginosa and Burkholderia cepacia complex infections in cystic fibrosis: a case series.

BACKGROUND: The efficacy of antibiotic treatment in pulmonary and systemic infections in cystic fibrosis (CF) is limited by the increased prevalence of MDR strains of Pseudomonas aeruginosa and Burkholderia cepacia complex. Ceftazidime/avibactam is a new combination which, in vitro, appears to have good activity against MDR strains of P. aeruginosa and B. cepacia complex. METHODS: A retrospective analysis was performed including adult patients with CF who received at least one course of ceftazidime/avibactam owing to pulmonary exacerbations not responding to conventional antibiotic treatment. RESULTS: Treatment with ceftazidime/avibactam was associated with reduction in inflammatory markers and improvement in lung function. No episodes of acute kidney injury or elevation in transaminase were observed. CONCLUSIONS: Ceftazidime/avibactam appeared to be well tolerated and improved patients' outcomes. Further studies are needed to better assess the role of this new combination in CF.

Hip abductor muscle volumes are smaller in individuals affected by patellofemoral joint osteoarthritis.

OBJECTIVE: The aims of this study were twofold: firstly, to compare hip abductor muscle volumes in individuals with patellofemoral joint (PFJ) osteoarthritis (PFJ OA) against those of healthy controls; and secondly, to determine whether hip muscle volumes and hip kinematics during walking are related in individuals with PFJ OA and healthy controls. METHODS: Fifty-one individuals with PFJ OA and thirteen asymptomatic, age-matched healthy controls ≥40 years were recruited. Volumes of the gluteus medius, gluteus minimus and tensor fasciae latae were obtained from magnetic resonance (MR) images. Video motion capture was used to measure three-dimensional hip joint kinematics during overground walking. RESULTS: Significantly smaller gluteus medius (P = 0.017), gluteus minimus (P = 0.001) and tensor fasciae latae (P = 0.027) muscle volumes were observed in PFJ OA participants compared to controls. Weak correlations were observed between smaller gluteus minimus volume and larger hip flexion angle at contralateral heel strike (CHS) (r = -0.279, P = 0.038) as well as between smaller gluteus minimus volume and increased hip adduction angle at CHS (r = -0.286, P = 0.046). CONCLUSION: Reduced hip abductor muscle volume is a feature of PFJ OA and is associated with increased hip flexion and adduction angles during the late stance phase of walking for PFJ OA participants and healthy controls.

Intravenous fosfomycin for pulmonary exacerbation of cystic fibrosis: Real life experience of a large adult CF centre.

BACKGROUND: The increased prevalence of multi-drug resistant strains of P.aeruginosa and allergic reactions among adult patients with cystic fibrosis (CF) limits the number of antibiotics available to treat pulmonary exacerbations. Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an alternative therapeutic option in such cases. AIM: To describe the clinical efficacy, safety and tolerability of intravenous fosfomycin in combination with a second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult patients with CF. METHOD: A retrospective analysis of data captured prospectively, over a 2-years period, on the Unit electronic medical records for patients who received IV fosfomycin was performed. Baseline characteristics in the 12 months prior treatment, lung function, CRP, renal and liver function and electrolytes at start and end of treatment were retrieved. RESULTS: 54 patients received 128 courses of IV fosfomycin in combination with a second antibiotic, resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable. 4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved at the end of the course. Electrolyte supplementation was required in 18% of cases for potassium and magnesium and 7% for phosphate. Nausea was the most common side effect (48%), but was well controlled with anti-emetics. CONCLUSION: Antibiotic regimens including fosfomycin appear to be clinically effective and safe. Fosfomycin should, therefore, be considered as an add-on therapy in patients who failed to respond to initial treatment and with multiple drug allergies.

Epidemiology and microbiological characterization of clinical isolates of Staphylococcus aureus in a single healthcare region of the UK, 2015.

We investigated the epidemiology and characterization of isolates of Staphylococcus aureus within the Yorkshire and Humber (YH) region in the UK. In July 2015, each laboratory within YH (n = 14) was assigned two consecutive days during which all clinical isolates of S. aureus were collected. Isolates were tested for antibiotic susceptibilities and the presence of genes encoding methicillin resistance (mecA and mecC), Panton-Valentine leukocidin (PVL) (lukS-PV), and efflux-mediated chlorhexidine resistance (qacA); isolates were also characterized by spa-types. Minimum inhibitory concentrations (MICs) to chlorhexidine were determined by the broth dilution method. Of 520 isolates collected, 6·2% were methicillin-resistant S. aureus (MRSA, all mecA-positive) and mupirocin resistance was low [0·8%, 95% confidence interval (CI) 0·3-2·0] and only found in MRSA. Carriage of the qacA gene was identified in 1·7% (95% CI 0·8-3·3) of isolates and 3·5% (95% CI 2·2-5·4) had a chlorhexidine MIC of 4 mg/l. The PVL gene was infrequent (3·7%, 95% CI 2·4-5·6). Genotyping identified 234 spa-types that mapped to 22 clonal complexes. Comparison of these current data with previous work suggest that the widespread use of staphylococcal decolonization regimens over the past decade or more has not had an adverse impact on resistance rates, PVL carriage or the prevalence of specific S. aureus lineages.

Spinal cord protection in aortic endovascular surgery.

A persistent neurological deficit, such as paraplegia or paraparesis, secondary to spinal cord injury remains one of the most feared complications of surgery on the descending thoracic or abdominal aorta. This is despite sophisticated advances in imaging and the use of less invasive endovascular procedures. Extensive fenestrated endovascular aortic graft prostheses still carry a risk of spinal cord injury of up to 10%; thus, this risk should be identified and strategies implemented to protect the spinal cord and maintain perfusion. The patients at highest risk are those undergoing extensive thoracic aortic stenting including thoracic, abdominal, and pelvic vessels. Although many techniques are available, lumbar cerebrospinal fluid drainage remains the most frequent intervention, along with maintenance of perfusion pressure and possibly staged procedures to allow collateral vessel stabilization. Many questions remain regarding other technical aspects, spinal cord monitoring and cooling, pharmacological protection, and the optimal duration of interventions into the postoperative period.

Rat Cytomegalovirus Vaccine Prevents Accelerated Chronic Rejection in CMV-Naïve Recipients of Infected Donor Allograft Hearts.

Cytomegalovirus accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in solid organ transplants; however, the mechanisms involved are unclear. We determined the efficacy of a CMV vaccine in preventing CMV-accelerated rat cardiac allograft rejection in naïve recipients of CMV+ donor hearts. F344 donor rats were infected with RCMV 5 days prior to heterotopic cardiac transplantation into CMV-naïve or H2 O2 -inactivated RCMV-vaccinated Lewis recipients. Recipients of RCMV-infected donor hearts rejected at POD59, whereas vaccinated recipients exhibited a significantly prolonged time to rejection-POD97, similar to recipients of uninfected donor hearts (POD108). Although all of the donor hearts were preinfected, the vaccinated recipients had lower graft and PBMC viral loads at POD 7 compared to unvaccinated controls. Adoptive T cell and passive antibody transfers from vaccinated Lewis rats into naïve recipients demonstrate that both T-cell and B-cell arms of the adaptive immune response provide protection against CMV-accelerated rejection. Similar findings were obtained when testing three different adjuvants in passive transfer experiments. We have determined that the timing of the vaccine prior to transplantation and the specific adjuvant play critical roles in mediating anti-viral responses and promoting graft survival. CMV vaccination prior to transplantation may effectively increase graft survival.

Escherichia coli bacteraemia: 2 years of prospective regional surveillance (2010-12).

OBJECTIVES: To determine the prevalence of antibiotic resistance and the epidemiology of Escherichia coli bacteraemia isolates across the Yorkshire and Humber National Health Service region over 2 years. METHODS: Ten percent of all E. coli blood culture isolates were collected per month from 14 laboratories across the Yorkshire and Humber region. Individual laboratories submitted antibiotic susceptibility data and isolates were re-tested centrally using the VITEK2(®) system (bioMérieux, France). Isolates were also characterized using PCR to test for the presence of sequences encoding extended-spectrum ß-lactamases (ESBLs) and genotyped using amplified fragment length polymorphism (AFLP). Selected isolates were further characterized using multilocus sequence typing. RESULTS: Between July 2010 and June 2012, 770 isolates were examined: 63%, 40%, 14% and 7% of isolates were non-susceptible to ampicillin, trimethoprim, ciprofloxacin and gentamicin, respectively. Eight percent of isolates (n = 63) were ESBL positive; CTX-M group 1 enzymes were the most common (68%). There was a fluctuating trend in the prevalence of resistance to amoxicillin/clavulanic acid (MIC >8 mg/L): July-September 2010, 16%; July-September 2011, 38%; and April-June 2012, 22%. AFLP identified 106 types. The majority of isolates belonged to one of two AFLP types: AFLP 1 [sequence type (ST) 131; 17%] and AFLP 2 (ST73; 18%). ST131 and ST73 were both associated with hospital- and community-onset bacteraemia, and with urinary, hepatobiliary and gastrointestinal sources of infection. ESBL-positive isolates were predominantly ST131 (60%). CONCLUSIONS: Continued surveillance of antibiotic resistance among E. coli bacteraemia isolates is necessary to enhance these early baseline data. The variable prevalence of resistance to amoxicillin/clavulanic acid raises concerns, as both E. coli bacteraemia and empirical use of this antibiotic are common.

Surveillance of antibiotic susceptibility of Enterobacteriaceae isolated from urine samples collected from community patients in a large metropolitan area, 2010-2012.

Antibiotic susceptibilities of large cohorts of Enterobacteriaceae isolated from urine collected in the community are scarce. We report the susceptibilities of Enterobacteriaceae isolated from urine of non-selected community populations in a metropolitan area (Leeds and Bradford, UK) over 2 years. Isolates (n = 6614) were identified as follows: Escherichia coli (n = 5436), Klebsiella spp. (n = 525), Proteus mirabilis (n = 305), and 15 other species (n = 290); 58 isolates were unidentified. Ampicillin resistance was observed in 53% E. coli and 28% P. mirabilis; ≥34% E. coli and P. mirabilis were non-susceptible to trimethoprim compared to 20% Klebsiella spp.; nitrofurantoin resistance was observed in 3% E. coli and 15% Klebsiella spp. The occurrence of extended-spectrum ß-lactamases (ESBL) was low (6%), as was non-susceptibility to carbapenems, cefipime and tigecycline (<2%). Further surveillance is required to monitor this level of resistance and additional clinical studies are needed to understand the impact on the outcome of current empirical prescribing decisions.

Spectral Reconstruction Improvement in a Cycloidal Coded-Aperture Mass Spectrometer.

Spatial aperture coding is a technique used to improve throughput without sacrificing resolution both in optical spectroscopy and sector mass spectrometry (MS). Previous work demonstrated that aperture coding combined with a position-sensitive array detector in a miniature cycloidal mass spectrometer was successful in providing high-throughput, high-resolution measurements. However, due to poor alignment and field nonuniformities, reconstruction artifacts were present. Recently, significant progress was made in eliminating most of the reconstruction artifacts with improved field uniformity and alignment. However, artifacts as large as 1/3 of the main peak were still observed at low mass (<17 u). Such artifacts will reduce accuracy in identification and quantification of analytes, reducing the impact of the throughput advantage gained by using a coded aperture. The artifacts were hypothesized to be a result of a mass dependent in curvature of ions in the ion source. Ions with higher mass (m/z > 17 u) and a larger curvature did not pass through all slits in the coded aperture. Therefore, when reconstructing with a system response derived from the aperture image from a higher mass m/z = 32 u ion, reconstruction artifacts appeared for m/z < 17 u. In this work, two methods were implemented to significantly reduce the presence of artifacts in reconstructed data. First, we modified the reconstruction algorithm to incorporate a mass-dependent system response function across the mass range (10-110 u). This method reduced the size of the artifacts by 82%. Second, to validate the hypothesis that the mass-dependent system response function was a result of differences in curvature of ions in the ion source, we modified the design of the ion source by shifting the coded aperture slits relative to the center of the ionization volume. This method resulted in ions of all masses passing through all slits in the coded aperture, a constant system response function across the entire mass range. Artifacts were reduced by 94%.

Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.

Autosomal recessive childhood-onset severe retinal dystrophy (arCSRD) designates a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), while the less aggressive forms are usually considered juvenile retinitis pigmentosa. Recently, mutations in the retinal-specific guanylate cyclase gene were found in patients with LCA. Disease genes implicated in other forms of arCSRD are expected to encode proteins present in the neuroretina or in the retinal pigment epithelium (RPE). The RPE, a monolayer of cells separating the vascular-rich choroid and the neuroretina, is in intimate contact with the outer segments of rods and cones via the microvilli surrounding the photoreceptors. The RPE expresses a tissue-specific and evolutionarily highly conserved 61 kD protein (RPE65) present at high levels in vivo. Although the function of RPE65 is not yet known, an important role in the RPE/photoreceptor vitamin-A cycle is suggested by the fact that RPE65 associates both with serum retinol-binding protein and with the RPE-specific 11-cis retinol dehydrogenase, an enzyme active in the synthesis of the visual pigment chromophore 11-cis retinal. Here we report that the analysis of RPE65 in a collection of about 100 unselected retinal-dystrophy patients of different ethnic origin revealed five that are likely to be pathogenic mutations, including a missense mutation (Pro363Thr), two point mutations affecting splicing (912 + 1G-->T and 65 + 5G-->A) and two small re-arrangements (ins144T and 831del8) on a total of nine alleles of five patients with arCSRD. In contrast to other genes whose defects have been implicated in degenerative retinopathies, RPE65 is the first disease gene in this group of inherited disorders that is expressed exclusively in the RPE, and may play a role in vitamin-A metabolism of the retina.

Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa.

Inadequate levels of all-trans-retinol in the blood cause retinal dysfunction; hence, genes implicated in retinal vitamin-A metabolism represent candidates for inherited retinal degenerations. In the current study, molecular genetic analysis of a consanguineous pedigree segregating for non-syndromic autosomal recessive retinitis pigmentosa (arRP) indicated that the affected siblings were homozygous by descent for a G4763A nucleotide substitution in RLBP1, the gene encoding cellular retinaldehyde-binding protein (CRALBP). This substitution is predicted to replace an arginine with glutamine at residue 150. CRALBP is not expressed in photoreceptors but is abundant in the retinal pigment epithelium (RPE) and Müller cells of the neuroretina, where it carries 11-cis-retinol and 11-cis-retinaldehyde. When expressed in bacteria, recombinant CRALBP (rCRALBP) containing the R150Q substitution was less soluble than wild-type rCRALBP. Mutant rCRALBP was purified from the soluble cell lysate and the protein structure was verified by mass spectrometry. The mutant protein lacked the ability to bind 11-cis-retinaldehyde. These findings suggest that arRP in the current pedigree results from a lack of functional CRALBP, presumably leading to disruption of retinal vitamin-A metabolism.

Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa.

Inherited retinal diseases are a common cause of visual impairment in children and young adults, often resulting in severe loss of vision in later life. The most frequent form of inherited retinopathy is retinitis pigmentosa (RP), with an approximate incidence of 1 in 3,500 individuals worldwide. RP is characterized by night blindness and progressive degeneration of the midperipheral retina, accompanied by bone spicule-like pigmentary deposits and a reduced or absent electroretinogram (ERG). The disease process culminates in severe reduction of visual fields or blindness. RP is genetically heterogeneous, with autosomal dominant, autosomal recessive and X-linked forms. Here we have identified two mutations in a novel retina-specific gene from chromosome 8q that cause the RP1 form of autosomal dominant RP in three unrelated families. The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans. Two families have a nonsense mutation in codon 677 of this gene (Arg677stop), whereas the third family has a nonsense mutation in codon 679 (Gln679stop). In one family, two individuals homozygous for the mutant gene have more severe retinal disease compared with heterozygotes.

Clinical determinants and impact of hemorrhagic lesions on intestinal pathology in preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: We sought to determine the clinical and histopathological factors associated with intestinal hemorrhage and its correlation with clinical outcomes in neonates with surgical necrotizing enterocolitis (NEC). METHODS: A retrospective study compared clinical and histopathology information in neonates following surgical NEC with severe hemorrhage and those with mild/moderate hemorrhagic lesions seen on resected intestine pathology. RESULTS: The infants with severe hemorrhage (Grade 3-4, 81/148, 54.7%) had significantly lower exposure to antenatal steroids (52.5 % vs 76.9 %; p = 0.004), had higher gestational age (28.5 weeks [7.14] vs. 26.58 [2.90]; p = 0.034), lost more bowel length (p = 0.045), had higher CRP levels at 2 weeks (p = 0.035), and had less intestinal failure ([30.3 % vs 52.5 %]; p = 0.014) than mild/moderate (Grade 0-2, 67/148, 45.2%) hemorrhage group. Those with severe hemorrhage had significantly higher mean inflammation score (2.67 [0.94] vs. 1.63 [0.92]; p = <0.001), higher necrosis scores (1.95 [1.28] vs. 1.49 [1.35]; p = 0.037), higher neovascularization (p = 0.01), higher fibroblasts (p = 0.023) and higher lymphocyte percentages up to 48 hours (p < 0.05) following NEC than mild/ moderate hemorrhage group.On multivariable regression, less exposure to antenatal steroids (OR 0.18 [95% CI 0.05-0.58]; p = 0.005), higher inflammation (OR 3.7 [95% CI 2.09-7.32]; p = 0.001), and lymphocyte count on the day of onset/24 hours following NEC (OR 1.06 [95% CI 1.02-1.11]; p = 0.005) were independently associated with a higher odd of severe intestinal hemorrhage. CONCLUSION: The surgical NEC infants with intestinal hemorrhage were less likely to have antenatal steroid exposure but had higher inflammation grade and lymphocyte counts following NEC onset on multivariable regression modeling.

A protracted outbreak of difficult-to-treat resistant Pseudomonas aeruginosa in a haematology unit: a matched case-control study demonstrating increased risk with use of fluoroquinolone.

BACKGROUND: Between September 2016 and November 2020, 17 cases of difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) were reported in haematology patients at a tertiary referral hospital in the North of England. AIM: A retrospective case-control study was conducted to investigate the association between DTR-PA infection and clinical interventions, patient movement, antimicrobial use and comorbidities. METHODS: Cases were patients colonized or infected with the outbreak strain of DTR-PA who had been admitted to hospital prior to their positive specimen. Exposures were extracted from medical records, and cases were compared with controls using conditional logistic regression. Environmental and microbiological investigations were also conducted. FINDINGS: Seventeen cases and 51 controls were included. The final model included age [>65 years, adjusted OR (aOR) 6.85, P=0.232], sex (aOR 0.60, P=0.688), admission under the transplant team (aOR 14.27, P=0.43) and use of ciprofloxacin (aOR 102.13, P=0.030). Investigations did not indicate case-to-case transmission or a point source, although a common environmental source was highly likely. CONCLUSION: This study found that the use of fluoroquinolones is an independent risk factor for DTR-PA in haematology patients. Antimicrobial stewardship and review of fluoroquinolone prophylaxis should be considered as part of PA outbreak investigations in addition to standard infection control interventions.