MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T cell responses.

Although intestinal epithelial cells (IECs) can express major histocompatibility complex class II (MHC II), especially during intestinal inflammation, it remains unclear if antigen presentation by IECs favours pro- or anti-inflammatory CD4+ T cell responses. Using selective gene ablation of MHC II in IECs and IEC organoid cultures, we assessed the impact of MHC II expression by IECs on CD4+ T cell responses and disease outcomes in response to enteric bacterial pathogens. We found that intestinal bacterial infections elicit inflammatory cues that greatly increase expression of MHC II processing and presentation molecules in colonic IECs. Whilst IEC MHC II expression had little impact on disease severity following Citrobacter rodentium or Helicobacter hepaticus infection, using a colonic IEC organoid-CD4+ T cell co-culture system, we demonstrate that IECs can activate antigen-specific CD4+ T cells in an MHC II-dependent manner, modulating both regulatory and effector Th cell subsets. Furthermore, we assessed adoptively transferred H. hepaticus-specific CD4+ T cells during intestinal inflammation in vivo and report that IEC MHC II expression dampens pro-inflammatory effector Th cells. Our findings indicate that IECs can function as non-conventional antigen presenting cells and that IEC MHC II expression fine-tunes local effector CD4+ T cell responses during intestinal inflammation.

Temporal Changes in Photoreducible Mercury, Photoreduction Rates, and the Role of Dissolved Organic Matter in Freshwater Lakes.

Total photoreducible mercury [Hg(II)RED] and photoreduction rates in the surface waters of four lakes in Kejimkujik National Park, Nova Scotia were measured monthly over a summer. The percent of THg that was photoreducible [%Hg(II)RED] decreased significantly in two of the four lakes from early to late summer: North Cranberry (maximum 42% to minimum 14%) and Big Dam East (maximum 51% to minimum 6%). Hg(II)RED was found to have a linear relationship with THg for all combined site data. THg and Hg(II)RED were found to have positive linear relationships with DOC concentrations (R2 = 0.97; n = 36; p < 0.01 and R2 = 0.75; n = 36; p < 0.01, respectively). A smaller proportion of THg was found to be photoreducible with increasing DOC concentration.

The Map of Need: identifying and predicting the spatial distribution of financial hardship in Scotland's veteran community.

INTRODUCTION: During military service, many household costs for both married and single service personnel are subsidised, and transition can leave veterans unprepared for the financial demands of civilian life. Armed Forces organisations such as Sailor, Soldier, Air Force Association (SSAFA) play a central role in understanding the financial challenges that UK veterans face and provide an insight into the financial hardship experienced by veterans. The aim of this study was to use SSAFA beneficiary data as a proxy to identify the nature of financial benefit, the spatial distribution of financial hardship in the Scottish SSAFA beneficiary community and explore factors that might predict where those recipients are located. METHODS: Using an anonymised data set of Scottish SSAFA financial beneficiaries between 2014 and 2019, this study used a geographical methodology to identify the geospatial distribution of SSAFA benefit recipients and exploratory regression analysis to explore factors to explain where SSAFA beneficiaries are located. RESULTS: Over half of benefit applicants (n=10 735) were concentrated in only 50 postcode districts, showing evidence of a clustered pattern, and modelling demonstrates association with area-level deprivation. The findings highlight strong association between older injured veterans and need for SSAFA beneficiary assistance. CONCLUSION: The findings demonstrate that beneficiaries were statistically clustered into areas of high deprivation, experiencing similar challenges to that of the wider population in these areas. Military service injury or disability was strongly associated with areas of high SSAFA benefit use and in those areas high unemployment was also a significant factor to consider.

Nursing practice and global refugee migration: initial impressions from an Intergovernmental-Academic Partnership.

AIM: This report from the field describes impressions of the initial impact of bilateral, multi-sectoral field-based activities undertaken to strengthen International Organization for Migration/United Nations Migration Agency and US-based nurses' capacity to address complex clinical, social and cultural challenges experienced by refugees in resettlement. Authors comment on the defined and thorough health assessment process that refugees go through prior to resettlement, and focus on the essential nursing role in the health assessment process and continuum of care. The development of the interdisciplinary and collaborative partnership is described as well as next steps to move the partnership forward. BACKGROUND: In 2017, International Organization for Migration/United Nations Migration Agency and the University of Minnesota, guided by experts from the United States Centers for Disease Control and Prevention, began a unique bilateral Intergovernmental-Academic partnership to enhance the health care of refugees. A key component was to strengthen nursing care of refugees through the standardization of clinical practice and nursing leadership. SOURCES OF EVIDENCE: Listening sessions, direct interaction between International Organization for Migration/United Nations Migration Agency and US-based refugee resettlement stakeholders, patterns in resettlement. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The report highlights the potential public health impact of a bilateral and collaborative initiative that develops and bridges key points in the migration and health trajectory of people with refugee status. Separated by geography, context and scope of work, health professionals in different roles in varied worldwide settings with a spectrum of resources may not fully understand the work of each other. Project activities were a platform through which US-based and internationally based nurses established mutuality, reciprocity and equity as partners. By strengthening systems and resources, the partnership reinforces the abilities of nurses who engage in this important work, to optimize health and wellbeing of people with refugee status.

Gut microbiota of the European Brown Hare (Lepus europaeus).

Diseases of the gastrointestinal tract due to changes in the bacterial flora have been described with increasing incidence in the European brown hare. Despite extensive demographic and phylogeographic research, little is known about the composition of its gut microbiota and how it might vary based on potential environmental or host factors. We analysed the intestinal and faecal microbiota of 3 hare populations by Illumina MiSeq 16S rRNA gene amplicon sequencing. The phyla and OTU abundance composition differed significantly between intestinal and faecal samples (PERMANOVA: P = 0.002 and P = 0.031, respectively), but in both sample types Firmicutes and Bacteroidetes dominated the microbial community composition (45.51% and 19.30% relative abundance). Intestinal samples contained an enrichment of Proteobacteria compared with faecal samples (15.71-fold change, P < 0.001). At OTU level, a significant enrichment with best BLAST hits to the Escherichia-Shigella group, Eubacterium limosum, Sphingomonas kyeonggiensis, Flintibacter butyricus and Blautia faecis were detected in intestinal samples (P < 0.05). In our statistical model, geographic location and possibly associated environmental factors had a greater impact on the microbiota composition than host factors. Population had a significant effect on the composition of abundant intestinal and faecal OTUs, and on the abundance of potential pathogenic bacteria of the family Enterobacteriaceae, regularly associated with intestinal dysbiosis in hares, in faecal samples. Our study is the first to describe the microbiota in brown hares and provides a foundation to generate hypothesis aiming to test the role of gut health in population fluctuations of the species.

Increasing chloride concentration causes retention of mercury in melted Arctic snow due to changes in photoreduction kinetics.

Mercury (Hg) in the Arctic is a significant concern due to its bioaccumulative and neurotoxic properties, and the sensitivity of Arctic environments. Previous research has found high levels of Hg in snowpacks with high chloride (Cl-) concentrations. We hypothesised that Cl- would increase Hg retention by decreasing Hg photoreduction to Hg(0) in melted Arctic snow. To test this, changes in Hg photoreduction kinetics in melted Alert, NU snow were quantified with changing Cl- concentration and UV intensity. Snow was collected and melted in Teflon bottles in May 2014, spiked with 0-10µg/g Cl-, and irradiated with 3.52-5.78W·m-2 UV (280-400nm) radiation in a LuzChem photoreactor. Photoreduction rate constants (k) (0.14-0.59hr-1) had positive linear relationships with [Cl-], while photoreduced Hg amounts (Hg(II)red) had negative linear relationships with [Cl-] (1287-64pg in 200g melted snow). Varying UV and [Cl-] both altered Hg(II)red amounts, with more efficient Hg stabilisation by Cl- at higher UV intensity, while k can be predicted by Cl- concentration and/or UV intensity, depending on experimental parameters. Overall, with future projections for greater snowpack Cl- loading, our experimental results suggest that more Hg could be delivered to Arctic aquatic ecosystems by melted snow (smaller Hg(II)red expected), but the Hg in the melted snow that is photoreduced may do so more quickly (larger k expected).

High-grain diets supplemented with phytogenic compounds or autolyzed yeast modulate ruminal bacterial community and fermentation in dry cows.

The feeding of concentrate-rich diets may lead to microbial imbalances and dysfermentation in the rumen. The main objective of this study was to determine the effects of supplementing phytogenic compounds (PHY) or autolyzed yeast (AY) on rumen fermentation and microbial abundance in cows intermittently fed concentrate-rich diets. The experiment was carried out as an incomplete 3 × 4 Latin square design, with 8 nonlactating rumen-fistulated Holstein-Friesian cows. The cows were randomly assigned to a concentrate diet that was either not supplemented (CON), or supplemented with PHY or AY. Each of the 4 consecutive experimental periods was composed of a 1-wk roughage-only diet (RD), 6-d gradual concentrate increase, followed by 1 wk of 65% concentrate (dry matter basis; Conc I), and 1 wk of RD and a final 2-wk 65% concentrate (dry matter basis; Conc II) phase. Digesta samples were collected from the rumen mat for bacterial 16S rRNA gene Illumina MiSeq (Illumina, Balgach, Switzerland) sequencing, and samples of particle-associated rumen liquid were obtained for measuring short-chain fatty acids, lactate, ammonia, and pH during RD (d 6), Conc I (d 19), and Conc II (d 39). The concentrate feeding caused a decrease of overall bacterial diversity indices, especially during Conc I. The genera Ruminococcus, Butyrivibrio, and Coprococcus were decreased, whereas Prevotella, Megasphaera, Lachnospira, and Bacteroides were increased in abundance. Supplementation of both feed additives increased the abundance of gram-positive and decreased that of gram-negative bacteria. Supplementation of AY enhanced cellulolytic bacteria such as Ruminococcus spp., whereas PHY decreased starch and sugar fermenters including Bacteroides spp., Shuttleworthia spp., and Syntrophococcus spp. Moreover, PHY supplementation increased butyrate percentage in the rumen in both concentrate phases. In conclusion, intermittent high-concentrate feeding altered the digesta-associated rumen bacterial community and rumen fermentation with more significant alterations found in Conc I than in Conc II. The data also showed that both feed additives had the most significant modulatory effects on the bacterial community, and their subsequent fermentation, during periods of low pH.

Epimural bacterial community structure in the rumen of Holstein cows with different responses to a long-term subacute ruminal acidosis diet challenge.

Subacute ruminal acidosis (SARA) is a prevalent metabolic disorder in cattle, characterized by intermittent drops in ruminal pH. This study investigated the effect of a gradual adaptation and continuously induced long-term SARA challenge diet on the epimural bacterial community structure in the rumen of cows. Eight rumen-cannulated nonlactating Holstein cows were transitioned over 1 wk from a forage-based baseline feeding diet (grass silage-hay mix) to a SARA challenge diet, which they were fed for 4 wk. The SARA challenge diet consisted of 60% concentrates (dry matter basis) and 40% grass silage-hay mix. Rumen papillae biopsies were taken at the baseline, on the last day of the 1-wk adaptation, and on the last day of the 4-wk SARA challenge period; ruminal pH was measured using wireless sensors. We isolated DNA from papillae samples for 16S rRNA gene amplicon sequencing using Illumina MiSeq. Sequencing results of most abundant key phylotypes were confirmed by quantitative PCR. Although they were fed similar amounts of concentrate, cows responded differently in terms of ruminal pH during the SARA feeding challenge. Cows were therefore classified as responders (n = 4) and nonresponders (n = 4): only responders met the SARA criterion of a ruminal pH drop below 5.8 for longer than 330 min/d. Data showed that Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant phyla, and at genus level, Campylobacter and Kingella showed highest relative abundance, at 15.5 and 7.8%, respectively. Diversity analyses revealed a significant increase of diversity after the 1-wk adaptation but a decrease of diversity and species richness after the 4-wk SARA feeding challenge, although without distinction between responders and nonresponders. At the level of the operational taxonomic unit, we detected diet-specific shifts in epimural community structure, but in the overall epimural bacterial community structure, we found no differences between responders and nonresponders. Correlation analysis revealed significant associations between grain intake and operational taxonomic unit abundance. The study revealed major shifts in the 3 dominating phyla and, most importantly, a loss of diversity in the epimural bacterial communities during a long-term SARA diet challenge, in which 60% concentrate supply for 4 wk was instrumental rather than the magnitude of the drop of ruminal pH below 5.8.

Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning.

Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (follicle-stimulating hormone (FSH) level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12-45 years were evaluated (7 in the intervention group and 10 in the observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at a median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure.

Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis.

Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

High diversity of viable bacteria isolated from lymph nodes of slaughter pigs and its possible impacts for food safety.

AIMS: Ileocaecal lymph nodes (ICLNs) of pigs, the key immune inductive site for bacterial systemic invasion, were examined in this study with emphasis on viable and cultivable bacteria. METHODS AND RESULTS: Asymptomatic and pathologically altered ICLNs of slaughter pigs (n = 16) with hyperplasia, purulence or granulomatous formations were aerobically and anaerobically cultivated. In total, 209 isolates were collected and the near full-length 16S rRNA gene from each isolate was sequenced. Taxonomic classification revealed that 68% of the isolates belonged to Proteobacteria, 27% to Firmicutes and 5% to Actinobacteria. Purulent and granulomatous ICLNs generally tended to contain more Proteobacteria than asymptomatic and enlarged ICLNs (P = 0·061). The isolates could be assigned to 25 species belonging to 17 genera including Escherichia, Carnobacterium, Lactobacillus, Staphylococcus and Acinetobacter. Furthermore, pathogens such as Streptococcus suis and Salmonella enterica were detected. The most abundant isolate (57%) was most similar (>99%) to Escherichia coli. Random amplified polymorphic DNA (RAPD) profiling revealed a high genetic diversity among E. coli isolates and 24% of these isolates were positive for at least one gene associated with enterohemorrhagic disease (eae, fliC, stx1 or hlyA). Compared with a recently published DNA-based high-throughput sequencing data set including the same ICLNs, 4% of species detected were cultivable. CONCLUSIONS: The presence of viable, commensal and pathogenic bacterial phylotypes could be proven in ICLNs with Proteobacteria being dominant. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that broadly characterizes viable bacteria from ICLNs of pigs. The presence of bacteria in lymph nodes of farm animals has practical relevance for host colonization and possible chronic infection. It is also of great interest for basic research investigating translocation of bacteria from the gastrointestinal tract to ICLNs.

Dark Matter Search Results from the PICO-2L C3F8 Bubble Chamber.

New data are reported from the operation of a 2 liter C3F8 bubble chamber in the SNOLAB underground laboratory, with a total exposure of 211.5 kg days at four different energy thresholds below 10 keV. These data show that C3F8 provides excellent electron-recoil and alpha rejection capabilities at very low thresholds. The chamber exhibits an electron-recoil sensitivity of <3.5×10(-10) and an alpha rejection factor of >98.2%. These data also include the first observation of a dependence of acoustic signal on alpha energy. Twelve single nuclear recoil event candidates were observed during the run. The candidate events exhibit timing characteristics that are not consistent with the hypothesis of a uniform time distribution, and no evidence for a dark matter signal is claimed. These data provide the most sensitive direct detection constraints on WIMP-proton spin-dependent scattering to date, with significant sensitivity at low WIMP masses for spin-independent WIMP-nucleon scattering.

Pyrosequencing reveals shifts in the bacterial epimural community relative to dietary concentrate amount in goats.

Ecological balance in the rumen is highly sensitive to concentrate-rich diets. Yet the effects of these feeding practices on the caprine bacterial epimural microbiome (CBEM), a microbial community with putative important physiological functions in the rumen, are largely unexplored. This study aimed to investigate the effect of dietary concentrate amount on ruminal CBEM. Seventeen growing goats were fed diets with 0 [n=5; 6.2MJ of metabolizable energy (ME)/d], 30 (n=6; 7.3MJ of /d), or 60% (n=6; 10.2MJ of ME/d) concentrate for 6 wk. Two hours after their last feeding, goats were euthanized and tissue samples of the ventral rumen wall were collected, washed in phosphate-buffered saline to detach loosely attached bacteria, and stored at -20°C for further processing. Genomic DNA was isolated from thawed rumen mucosa samples and used for Roche/454 Life Science (Branford, CT) 16S rRNA gene amplicon pyrosequencing yielding 122,458 reads. Pyrosequencing data were clustered into 1,879 operational taxonomic units (OTU; 0.03 distance level). Pyrosequencing revealed Proteobacteria, Bacteroidetes, Firmicutes, and Spirochaetes as the most abundant phyla (97.7%). Compared with the 30% group, both the 60 and 0% concentrate groups harbored significantly more Firmicutes and SR1, respectively. On an OTU level, a Bergeriella-related OTU was most abundant in the CBEM, followed by 2 Campylobacter OTU, which responded differently to diets: 1 OTU was significantly increased whereas the other significantly decreased with highest concentrate amount in the diet. At the genus level, the 0% concentrate group harbored increased Kingella-like sequences compared with the other feeding groups. Furthermore, the 0% concentrate group tended to have more Bergeriella than the 30 and 60% concentrate groups. The genus Bergeriella was significantly decreased in the 60% feeding group compared with the other diets. In conclusion, this is the first report of CBEM using deep-sequencing methods on the genus and OTU level, and our study revealed major shifts in the CBEM in response to concentrate-rich diets with potential health relevance in goats.

Mercury in Arctic snow: quantifying the kinetics of photochemical oxidation and reduction.

Controlled experiments were performed with frozen and melted Arctic snow to quantify relationships between mercury photoreaction kinetics, ultra violet (UV) radiation intensity, and snow ion concentrations. Frozen (-10°C) and melted (4°C) snow samples from three Arctic sites were exposed to UV (280-400 nm) radiation (1.26-5.78 W · m(-2)), and a parabolic relationship was found between reduction rate constants in frozen and melted snow with increasing UV intensity. Total photoreduced mercury in frozen and melted snow increased linearly with greater UV intensity. Snow with the highest concentrations of chloride and iron had larger photoreduction and photooxidation rate constants, while also having the lowest Hg(0) production. Our results indicate that the amount of mercury photoreduction (loss from snow) is the highest at high UV radiation intensities, while the fastest rates of mercury photoreduction occurred at both low and high intensities. This suggests that, assuming all else is equal, earlier Arctic snow melt periods (when UV intensities are less intense) may result in less mercury loss to the atmosphere by photoreduction and flux, since less Hg(0) is photoproduced at lower UV intensities, thereby resulting in potentially greater mercury transport to aquatic systems with snowmelt.

Dual bolus intravenous contrast injection technique for multiregion paediatric body CT.

OBJECTIVES: Optimal vascular and parenchymal enhancement for multi-region paediatric body computed tomography (CT) has many challenges. A variety of approaches are currently employed, associated with varying image quality and radiation dose implications. We present a dual bolus intravenous (DBI) contrast technique for single-acquisition imaging of the chest, abdomen and pelvis, with evaluation of multi-compartmental vascular enhancement. METHODS: A DBI regime was designed for use with a programmable dual head pump injector. A larger initial bolus (two-thirds volume) is followed by a smaller bolus (one-third volume) before imaging the chest, abdomen and pelvis in a single acquisition, 45-65 seconds from the start of initial injection. Flow rates and second bolus timing were tailored to patient weight and contrast volume, using five weight categories. Multi-compartmental vascular opacification was graded and image quality was assessed in a cohort of 130 patients. RESULTS: The DBI technique resulted in concordant multi-compartmental (thoracic aortic, pulmonary arterial, abdominal aortic and portal venous) vascular enhancement. Early splenic parenchymal enhancement artefacts and alterations to renal enhancement were observed. CONCLUSION: We present a weight-stratified dual bolus intravenous contrast technique to improve image quality in paediatric multi-region body CT. KEY POINTS: • In children, optimal vascular and parenchymal enhancement in multi-region CT is challenging. • A dual bolus contrast technique offers concordant arterial and portal venous opacification. • Adaptation to patient size is achieved by stratification into five weight categories. • Dose penalties of 'overlap' and 'dual phase' imaging techniques can be avoided.

Lost therapeutic potential of monocyte-derived dendritic cells through lost tissue homing: stable restoration of gut specificity with retinoic acid.

Human monocyte-derived dendritic cells (DC) (MoDC) are utilized for immunotherapy. However, in-vitro immunological effects are often not mirrored in vivo. We studied the tissue-homing potential of MoDC. Circulating monocytes and DC expressed different tissue-homing markers and, during in-vitro development of MoDC, homing marker expression was lost resulting in a 'homeless' phenotype. Retinoic acid (RA) induced gut-homing markers (ß7 and CCR9) and a regulatory phenotype and function [decreased human leucocyte antigen D-related (HLA-DR) and increased ILT3 and fluorescein isothiocyanate (FITC-dextran uptake) in MoDC]. RA-MoDC were less stimulatory and primed conditioned T cells with a gut-homing profile (ß7(+)CLA(-)). Unlike the normal intestinal microenvironment, that from inflamed colon of ulcerative colitis (UC) patients did not induce regulatory properties in MoDC. However, RA-MoDC maintained their regulatory gut-specific properties even in the presence of UC microenvironment. Therefore, MoDC may be ineffectual for immunotherapy because they lack tissue-homing and tissue-imprinting specificity. However, MoDC rehabilitation with gut-homing potential by RA could be useful in promoting immunotherapy in pathologies such as UC.

Effectiveness of non-cardiac preoperative testing in non-cardiac elective surgery: a systematic review.

Elective surgery is usually preceded by preoperative diagnostics to minimize risk. The results are assumed to elicit preventive measures or even cancellation of surgery. Moreover, physicians perform preoperative tests as a baseline to detect subsequent changes. This systematic review aims to explore whether preoperative testing leads to changes in management or reduces perioperative mortality or morbidity in unselected patients undergoing elective, non-cardiac surgery. We systematically searched all relevant databases from January 2001 to February 2011 for studies investigating the relationship between preoperative diagnostics and perioperative outcome. Our methodology was based on the manual of the Ludwig Boltzmann Institute for Health Technology Assessment, the Scottish Intercollegiate Guidelines Network (SIGN) handbook, and the PRISMA statement for reporting systematic reviews. One hundred and one of the 25 281 publications retrieved met our inclusion criteria. Three test grid studies used a randomized controlled design and 98 studies used an observational design. The test grid studies show that in cataract surgery and ambulatory surgery, there are no significant differences between patients with indicated preoperative testing and no testing regarding perioperative outcome. The observational studies do not provide valid evidence that preoperative testing is beneficial in healthy adults undergoing non-cardiac surgery. There is no evidence derived from high-quality studies that supports routine preoperative testing in healthy adults undergoing non-cardiac surgery. Testing according to pathological findings in a patient's medical history or physical examination seems justified, although the evidence is scarce. High-quality studies, especially large randomized controlled trials, are needed to explore the effectiveness of indicated preoperative testing.

Clinicopathological differences between breast cancer in patients with primary metastatic disease and those without: a multicentre study.

OBJECTIVE: Approximately 6% of breast cancer (BC) patients present with primary metastatic disease (pmBC) at first diagnosis. The clinicopathological differences between tumours from patients who have metastatic disease and those who do not are unclear. METHODS: This study was an exploratory analysis of patients with pmBC treated in 8 German breast cancer centres between 1998 and 2010. Phenotypes were defined using the following immunohistochemical markers: oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). The control arm included the group of patients who had neither local recurrence nor distant metastases at a follow-up of at least 30 months after initial diagnosis. RESULTS: A total of 2214 patients were included. Of these, 1642 had non metastatic BC, and 572 had pmBC. Eighty-five patients (15%) with pmBC were diagnosed at stage T1. On multivariate analysis, factors associated with pmBC were as follows: positive lymph node status, grade 3, lobular histology and Luminal B phenotype (Her 2 positive). Of the sample, 197 patients (34%) with pmBC were diagnosed as stage T2, 90 patients (16%) were diagnosed as stage T3, and 200 patients (35%) were diagnosed as stage T4. Only positive lymph node status and grade 3 were reported as risk factors for distant metastases in patients with stage T3 and T4 cancer. CONCLUSION: There are differences in the clinicopathological features among breast cancer patients with primary metastases and those without. Receptor expression and histological type play a minor role in the risk for metastasis in patients with stage T3 and T4 disease when compared to patients with T1 pmBC tumours. On initial diagnosis, lobular histology and Luminal B positivity (Her 2 positive) in T1 pmBC were determined to be risk factors for primary metastatic disease.