The contribution of the anaesthetist to risk-adjusted mortality after cardiac surgery

It is widely accepted that the performance of the operating surgeon affects outcomes, and this has led to the publication of surgical results in the public domain. However, the effect of other members of the multidisciplinary team is unknown. We studied the effect of the anaesthetist on mortality after cardiac surgery by analysing data collected prospectively over ten years of consecutive cardiac surgical cases from ten UK centres. Casemix-adjusted outcomes were analysed in models that included random-effects for centre, surgeon and anaesthetist. All cardiac surgical operations for which the EuroSCORE model is appropriate were included, and the primary outcome was in-hospital death up to three months postoperatively. A total of 110 769 cardiac surgical procedures conducted between April 2002 and March 2012 were studied, which included 127 consultant surgeons and 190 consultant anaesthetists. The overwhelming factor associated with outcome was patient risk, accounting for 95.75% of the variation for in-hospital mortality. The impact of the surgeon was moderate (intra-class correlation coefficient 4.00% for mortality), and the impact of the anaesthetist was negligible (0.25%). There was no significant effect of anaesthetist volume above ten cases per year. We conclude that mortality after cardiac surgery is primarily determined by the patient, with small but significant differences between surgeons. Anaesthetists did not appear to affect mortality. These findings do not support public disclosure of cardiac anaesthetists' results, but substantially validate current UK cardiac anaesthetic training and practice. Further research is required to establish the potential effects of very low anaesthetic caseloads and the effect of cardiac anaesthetists on patient morbidity

BAFF and MyD88 signals promote a lupuslike disease independent of T cells

Systemic lupus erythernatosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, the underlying cause of disease appears to relate to defects in T cell tolerance or T cell help to 13 cells. Transgenic (Tg) mice over-expressing the cytokine 13 cell-activating factor of the tumor necrosis factor family (BAFF) develop an autoimmune disorder similar to SLE and show impaired B cell tolerance and altered T cell differentiation. We generated BAFF Tg mice that were completely deficient in T cells, and, surprisingly, these mice developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did, however, require 13 cell-intrinsic signals through the Toll-like receptor (TLR)-associated signaling adaptor MyD88, which controlled the production of proinflammatory autoantibody isotypes. TLR7/9 activation strongly up-regulated expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), which is a receptor for BAFF involved in 13 cell responses to T cell-independent antigens. Moreover, BAFF enhanced TLR7/9 expression on 13 cells and TLR-mediated production of autoantibodies. Therefore, autoirnmunity in BAFF Tg mice results from altered 13 cell tolerance, but requires TLR signaling and is independent of T cell help. It is possible that SLE patients with elevated levels of BAFF show a similar basis for disease

The diagnosis of colorectal cancer in patients with symptoms: finding a needle in a haystack

Patients often see primary care physicians with symptoms that might signal colorectal cancer but are also common in adults without cancer. Physicians and patients must then make a difficult decision about whether and how aggressively to evaluate the symptom. Favoring referral is that missed diagnoses lead to unnecessary testing, prolonged uncertainty, and continuing symptoms; also, the physician will suffer chagrin. It is not clear that diagnostic delay leads to progression to a more advanced stage. Against referral is that proper evaluation includes colonoscopy, with attendant inconvenience, discomfort, cost, and risk. The article by Hamilton et al, published this month in BMC Medicine, provides strong estimates of the predictive value of the various symptoms and signs of colorectal cancer and show how much higher predictive values are with increasing age and male sex. Unfortunately, their results also make clear that most colorectal cancers present with symptoms with low predictive values, < 1.2%. Models that include a set of predictive variables, that is, risk factors, age, sex, screening history, and symptoms, have been developed to guide primary prevention and clinical decision-making and are more powerful than individual symptoms and signs alone. Although screening for colorectal cancer is increasing in many countries, cancers will still be found outside screening programs so primary care physicians will remain at the front line in the difficult task of distinguishing everyday symptoms from life-threatening cancer

Exploratory analysis of a phase III trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment

<p>Abstract</p> <p>Background</p> <p>A phase III trial in Japan showed that pirfenidone is effective for idiopathic pulmonary fibrosis (IPF). To find out which patients specifically benefit from pirfenidone, we analyzed in an exploratory manner the data from the phase III trial.</p> <p>Methods</p> <p>The patients in the phase III trial were stratified by baseline percentage predicted vital capacity (%VC), arterial oxygen partial pressure (PaO₂), and the lowest oxygen saturation by pulse oximetry (SpO₂) during the 6-minute steady-state exercise test (6MET). In the subpopulations, changes in VC and subjective symptoms (cough and dyspnea on the Fletcher, Hugh-Jones [F, H-J] Classification scale) were evaluated in patients treated with high-dose (1800 mg/day) pirfenidone, low-dose (1200 mg/day) pirfenidone, and placebo at week 52.</p> <p>Results</p> <p>Significant efficacy of pirfenidone in reducing the decline in VC could be seen in a subpopulation having %VC ≥ 70% and SpO₂< 90% at baseline. This favorable effect was accompanied by categorical change in VC and progression-free survival time. In the subpopulation, pirfenidone significantly suppressed cough and dyspnea.</p> <p>Conclusions</p> <p>IPF patients having %VC ≥ 70% and SpO₂< 90% at baseline will most likely benefit from pirfenidone when evaluated using changes in VC (and %VC), and cough and dyspnea symptoms. This subpopulation could expect to benefit most from pirfenidone treatment.</p> <p>Trial Registration</p> <p>This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (Registration Number: JAPICCTI-050121).</p

The ACTA PORT-score for predicting perioperative risk of blood transfusion for adult cardiac surgery.

BACKGROUND: A simple and accurate scoring system to predict risk of transfusion for patients undergoing cardiac surgery is lacking. METHODS: We identified independent risk factors associated with transfusion by performing univariate analysis, followed by logistic regression. We then simplified the score to an integer-based system and tested it using the area under the receiver operator characteristic (AUC) statistic with a Hosmer-Lemeshow goodness-of-fit test. Finally, the scoring system was applied to the external validation dataset and the same statistical methods applied to test the accuracy of the ACTA-PORT score. RESULTS: Several factors were independently associated with risk of transfusion, including age, sex, body surface area, logistic EuroSCORE, preoperative haemoglobin and creatinine, and type of surgery. In our primary dataset, the score accurately predicted risk of perioperative transfusion in cardiac surgery patients with an AUC of 0.76. The external validation confirmed accuracy of the scoring method with an AUC of 0.84 and good agreement across all scores, with a minor tendency to under-estimate transfusion risk in very high-risk patients. CONCLUSIONS: The ACTA-PORT score is a reliable, validated tool for predicting risk of transfusion for patients undergoing cardiac surgery. This and other scores can be used in research studies for risk adjustment when assessing outcomes, and might also be incorporated into a Patient Blood Management programme

Use of Cooking Fuels and Cataract in a Population-Based Study: The India Eye Disease Study.

BACKGROUND: Biomass cooking fuels are commonly used in Indian households, especially by the poorest socioeconomic groups. Cataract is highly prevalent in India and the major cause of vision loss. The evidence on biomass fuels and cataract is limited. OBJECTIVES: To examine the association of biomass cooking fuels with cataract and type of cataract. METHODS: We conducted a population-based study in north and south India using randomly sampled clusters to identify people ≥ 60 years old. Participants were interviewed and asked about cooking fuel use, socioeconomic and lifestyle factors and attended hospital for digital lens imaging (graded using the Lens Opacity Classification System III), anthropometry, and blood collection. Years of use of biomass fuels were estimated and transformed to a standardized normal distribution. RESULTS: Of the 7,518 people sampled, 94% were interviewed and 83% of these attended the hospital. Sex modified the association between years of biomass fuel use and cataract; the adjusted odds ratio (OR) for a 1-SD increase in years of biomass fuel use and nuclear cataract was 1.04 (95% CI: 0.88, 1.23) for men and 1.28 (95% CI: 1.10, 1.48) for women, p interaction = 0.07. Kerosene use was low (10%). Among women, kerosene use was associated with nuclear (OR = 1.76, 95% CI: 1.04, 2.97) and posterior subcapsular cataract (OR = 1.71, 95% CI: 1.10, 2.64). There was no association among men. CONCLUSIONS: Our results provide robust evidence for the association of biomass fuels with cataract for women but not for men. Our finding for kerosene and cataract among women is novel and requires confirmation in other studies. Citation: Ravilla TD, Gupta S, Ravindran RD, Vashist P, Krishnan T, Maraini G, Chakravarthy U, Fletcher AE. 2016. Use of cooking fuels and cataract in a population-based study: the India Eye Disease Study. Environ Health Perspect 124:1857-1862; http://dx.doi.org/10.1289/EHP193

Genetic Variants at Chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 Influence the Risk of Breast Cancer in Men

Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleotide polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35) (odds ratio (OR)  = 1.30, p = 7.98×10−4), rs10941679 (5p12) (OR = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2) (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04×10−6). Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs—rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)—showed significant differences in ORs (p<0.05) between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

Preparation, structural characterisation and antibacterial properties of Ga-doped sol-gel phosphate-based glass

A sol-gel preparation of Ga-doped phosphate-based glass with potential application in antimicrobial devices has been developed. Samples of composition (CaO)(0.30)(Na2O)(0.20-x) (Ga2O3) (x) (P2O5)(0.50) where x = 0 and 0.03 were prepared, and the structure and properties of the gallium-doped sample compared with those of the sample containing no gallium. Analysis of the P-31 MAS NMR data demonstrated that addition of gallium to the sol-gel reaction increases the connectivity of the phosphate network at the expense of hydroxyl groups. This premise is supported by the results of the elemental analysis, which showed that the gallium-free sample contains significantly more hydrogen and by FTIR spectroscopy, which revealed a higher concentration of -OH groups in that sample. Ga K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure data revealed that the gallium ions are coordinated by six oxygen atoms. In agreement with the X-ray absorption data, the high-energy XRD results also suggest that the Ga3+ ions are octahedrally coordinated with respect to oxygen. Antimicrobial studies demonstrated that the sample containing Ga3+ ions had significant activity against Staphylococcus aureus compared to the control

Centrally concentrated molecular gas driving galactic-scale ionized gas outflows in star-forming galaxies

We perform a joint analysis of high spatial resolution molecular gas and star-formation rate (SFR) maps in main-sequence star-forming galaxies experiencing galactic-scale outflows of ionized gas. Our aim is to understand the mechanism that determines which galaxies are able to launch these intense winds. We observed CO(1→0) at 1-arcsec resolution with ALMA in 16 edge-on galaxies, which also have 2-arcsec spatial-resolution optical integral field observations from the SAMI Galaxy Survey. Half the galaxies in the sample were previously identified as harbouring intense and large-scale outflows of ionized gas (‘outflow types’) and the rest serve as control galaxies. The data set is complemented by integrated CO(1→0) observations from the IRAM 30-m telescope to probe the total molecular gas reservoirs. We find that the galaxies powering outflows do not possess significantly different global gas fractions or star-formation efficiencies when compared with a control sample. However, the ALMA maps reveal that the molecular gas in the outflow-type galaxies is distributed more centrally than in the control galaxies. For our outflow-type objects, molecular gas and star-formation are largely confined within their inner effective radius (reff), whereas in the control sample, the distribution is more diffuse, extending far beyond reff. We infer that outflows in normal star-forming galaxies may be caused by dynamical mechanisms that drive molecular gas into their central regions, which can result in locally enhanced gas surface density and star-formation