Leaning in and moving forward: a call to action and review of diversity initiatives in SAGES.

BACKGROUND: Diversity, equity, and inclusion have been an intentional focus for SAGES well before the COVID-19 pandemic and the coincident societal recognition of social injustices and racism. Longstanding inequities within our society, healthcare, and the surgery profession have come to light in the aftermath of events that rose to attention around the time of Covid. In so doing, they have brought into focus disparities, injustices, and inequalities that have long been present in the field of surgery, selectively affecting the most vulnerable. METHODS: This White paper examines the current state of diversity within the field of surgery and SAGES (Society of American Gastrointestinal and Endoscopic Surgeons) approach and effort to pave the way forward to meaningful change. We delineate the imperative for diversity, equity, and inclusion for all. By all, we mean to be inclusive of the diversity of gender and sexual orientation, race, ethnicity, geography, sex, and disability in the field of surgery. RESULTS: SAGES is an organization that lives at the intersection of education and innovation. It has a vital role in assisting the surgical profession in addressing these issues and needs and being a force alongside others for sustained and necessary change. SAGES can only realize these goals through a commitment across all aspects of the organization to embed diversity, equity, and inclusion into our very fabric. CONCLUSION: True diversity, equity, and inclusion within a surgical organization is vital for its longevity, growth, relevance, and impact. Unfortunately, the absence of DEI limits opportunity, robs the organization of collective intelligence in an environment in which its presence is critical, contributes to health inequities, and impoverishes all within the society and its value to all with whom it interfaces. SAGES is an organization that lives at the intersection of education and innovation. It has a vital role in assisting the surgical profession in addressing these issues and needs and being a force alongside others for sustained and necessary change. SAGES can only realize these goals through a commitment across all aspects of the organization to embed diversity, equity, and inclusion into our very fabric. Strategies like those highlighted in this White Paper, may be within our grasp and we can learn yet more if we remain in a place of humility and teachability in the future.

Pentraxin-3 - a potential biomarker in ANCA-associated vasculitis.

OBJECTIVE: The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at baseline and 6 month follow-up in a longitudinal cohort. METHOD: Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up. RESULTS: Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (ρ = 0.45, p < 0.001, and ρ = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline. CONCLUSION: Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.

Association between acetaminophen use and vitiligo in US women and men.

BACKGROUND/OBJECTIVES: Exposure to chemical phenols, which can act as tyrosine analogues and result in anti-melanocyte autoimmunity, has been associated with vitiligo. Acetaminophen (N-acetyl-p-aminophenol) is an over-the-counter analgesic of phenolic origin. The risk of vitiligo with systemic exposure to acetaminophen has not yet been evaluated. METHODS: We examined the risk of vitiligo with regular use acetaminophen in women, the Nurses' Health Study (NHS) and in men, the Health Professionals Follow-up Study (HPFS). Regular acetaminophen use was asked biennially from 1990 in NHS and from 1986 in HPFS, and the year of clinician-diagnosed vitiligo was asked retrospectively in 2012 in the cohorts. RESULTS: In NHS, a total of 161 vitiligo cases were identified during a follow-up of 571,724 person-years; in HPFS, a total of 183 vitiligo cases were identified during a follow-up of 680,313 person-years. Regular use of acetaminophen was associated with an increased vitiligo risk in NHS but not HPFS. The multivariable relative risk (RR) was 1.52 (95% confidence interval [CI] 1.03-2.25) in NHS and 1.09 (95% CI 0.76-1.55) in HPFS. The higher risk of vitiligo was similar by duration of acetaminophen use in women; the multivariable RRs were 1.47 (95% CI 0.98-2.21) for acetaminophen use under 5 years, and 1.78 (95% CI 1.11-2.84) for acetaminophen use over 5 years. CONCLUSIONS: Acetaminophen may be associated with a higher risk of vitiligo in women.

A systematic review of point-of-care abdominal ultrasound scans performed by general surgeons in paediatric patients.

BACKGROUND/PURPOSE: Bedside point-of-care ultrasound scans are a cheap, quick and safe diagnostic tool. There is increasing evidence for the use of point-of-care surgeon-performed ultrasound scans in adults, however there are fewer studies of its use in children. This systematic review aims to provide an up-to-date summary of the evidence behind surgeon-performed ultrasound scans in paediatric surgery. METHODS: The PubMed database was used to conduct this systematic review between the dates 1 Jan 1980 to 1 June 2020 (last search: 1 June 2020). Seven primary research studies were included in this review. RESULTS: There is good evidence for the use of ultrasound scans in appendicitis and hypertrophic pyloric stenosis. Training times are easily achievable and transferable within a surgical department. CONCLUSIONS: Although the use of surgeon-performed bedside ultrasound scans has been described in appendicitis and hypertrophic pyloric stenosis, more research is required to embed this into clinical practice, particularly in low volume centres such as district general hospitals. A robust training programme is also recommended to incorporate ultrasound scans into clinical practice.

In-silico analysis of interacting pathways through KIM-1 protein interaction in diabetic nephropathy.

BACKGROUND: Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1. METHODS: This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated by this protein. These genes were then further considered in pathway analysis to discover the dysregulated pathways in diabetic nephropathy. The long list of differentially expressed genes is meaningless without pathway analysis. RESULTS: Critical pathways that are dysregulated in diabetic nephropathy patients have been identified. These include Immune System (Total = 237, P < 0.05), Innate Immune System (Total = 140, P < 0.05), Cytokine Signaling Immune system (Total = 116, P < 0.05), Adaptive Immune System (Total = 85) and Neutrophil degranulation (Total = 78). CONCLUSION: The top 5 genes that are interacting directly with HIVCR1 include CASP3, CCL2, SPP1, B2M, and TIMP1 with degrees 161, 144, 108, 107, and 105 respectively for Immune system pathways (Innate Immune System, Cytokine Signaling Immune system, Adaptive Immune System and Neutrophil degranulation).

Time-dependent lipid profile inversely associates with mortality in hemodialysis patients - independent of inflammation/malnutrition.

BACKGROUND: Patients with end-stage kidney disease have an extremely high cardiovascular mortality rate, but there is a paradoxical relationship between lipid profile and survival in haemodialysis patients. To investigate whether inflammation/malnutrition confounds the associations between lipids and mortality, we studied a full lipid profile comprising of five clinically well-established lipid parameters and its associations with mortality in a large, multinational European cohort with a median follow-up >3 years. METHODS: The association between quartiles of total, high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, as well as triglyceride, levels and the end-points of all-cause, cardiovascular and non-cardiovascular mortality was assessed in a cohort of 5,382 incident, adult haemodialysis patients from >250 Fresenius Medical Care dialysis centres out of 14 participating countries using baseline and time-dependent Cox models. Analyses were fully adjusted and stratified for inflammation/malnutrition status and other patient-level variables. RESULTS: Time-dependent quartiles of total, HDL, non-HDL and LDL cholesterol were inversely associated with the hazard for all-cause, cardiovascular and non-cardiovascular mortality. Compared with the lowest quartile of the respective lipid parameter, hazard ratios of other quartiles were <0.86. Similar, albeit weaker, associations were found with baseline lipid profile and mortality. Neither time-dependent nor baseline associations between lipid profile and mortality were affected by inflammation/malnutrition, statin use or geography. CONCLUSIONS: Baseline and time-dependent lipid profile are inversely associated with mortality in a large, multicentre cohort of incident haemodialysis patients. Inflammation/malnutrition is not a confounder nor effect modificator of the associations between lipid profile and mortality in European haemodialysis patients.

Development of a shared decision-making tool in vitiligo: an international study.

BACKGROUND: Shared decision-making tools (SDMt) are visual tools developed to promote joint medical decisions between physicians and patients. There is a paucity of such tools in dermatology. OBJECTIVES: To develop and validate a SDMt for use in specialized consultation for vitiligo. METHODS: A prospective cross-sectional study was carried out from March 2019 to March 2020. We first conducted a qualitative study of topics discussed by patients and clinicians during therapeutic decision-making in the setting of a specialized consultation for vitiligo using an anchored-theory method, which allowed conceptualization of the SDMt. The usefulness of the SDMt was evaluated by a working group of multidisciplinary health workers and patients with vitiligo. Consensus on the final tool was obtained through an e-Delphi method. RESULTS: We recruited 30 patients with vitiligo for the qualitative study, which identified 91 topics related to therapeutic decision-making. Hierarchical clustering analysis confirmed the distribution of these topics in two subgroups (general treatment goals and priorities, and topics specific to each treatment). The consensus of a multidisciplinary group was used to develop the SDMt. The tool was comprised of eight A5 cards, which addressed face repigmentation; body repigmentation (limited area); body repigmentation (extended area); partial or complete depigmentation; coping with the disease; stabilization of disease; maintaining repigmentation; and disease information. Cognitive interviews confirmed the satisfaction, readability and usefulness of the SDMt. The SDMt was then translated and culturally validated in English. CONCLUSIONS: We developed a tool for shared decision-making in nonsegmental vitiligo, which we translated and cross-culturally validated in a US patient population with vitiligo to ensure its generalizability.

Early mandated social distancing is a strong predictor of reduction in peak daily new COVID-19 cases.

OBJECTIVES: Mandated social distancing has been applied globally to reduce the spread of coronavirus disease 2019 (COVID-19). However, the beneficial effects of this community-based intervention have not been proven or quantified for the COVID-19 pandemic. STUDY DESIGN: This is a regional population-level observational study. METHODS: Using publicly available data, we examined the effect of timing of mandated social distancing on the rate of COVID-19 cases in 119 geographic regions, derived from 41 states within the United States and 78 other countries. The highest number of new COVID-19 cases per day recorded within a geographic unit was the primary outcome. The total number of COVID-19 cases in regions where case numbers had reached the tail end of the outbreak was an exploratory outcome. RESULTS: We found that the highest number of new COVID-19 cases per day per million persons was significantly associated with the total number of COVID-19 cases per million persons on the day before mandated social distancing (ß = 0.66, P < 0.0001). These findings suggest that if mandated social distancing is not initiated until the number of existing COVID-19 cases has doubled, the eventual peak would result in 58% more COVID-19 cases per day. Subgroup analysis on those regions where the highest number of new COVID-19 cases per day has peaked showed increase in ß values to 0.85 (P < 0.0001). The total number of cases during the outbreak in a region was strongly predicted by the total number of COVID-19 cases on the day before mandated social distancing (ß = 0.97, P < 0.0001). CONCLUSIONS: Initiating mandated social distancing when the numbers of COVID-19 cases are low within a region significantly reduces the number of new daily COVID-19 cases and perhaps also reduces the total number of cases in the region.

Phenotypic features of vascular calcification in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease stage 5 (CKD5) are predisposed to vascular calcification (VC), but the combined effect of factors associated with VC was sparsely investigated. We applied the relaxed linear separability (RLS) feature selection model to identify features that concomitantly associate with VC in CKD5 patients. METHODS: Epigastric arteries collected during surgery from living donor kidney transplant recipients were examined to score the histological extent of medial VC. Sixty-two phenotypic features in 152 patients were entered into RLS model to differentiate between no-minimal VC (n = 93; score 0-1) and moderate-extensive VC (n = 59; score 2-3). The subset of features associated with VC was selected on the basis of cross-validation procedure. The strength of association of the selected features with VC was expressed by the absolute value of 'RLS factor'. RESULTS: Among 62 features, a subset of 17 features provided optimal prediction of VC with 89% of patients correctly classified into their groups. The 17 features included traditional risk factors (diabetes, age, cholesterol, BMI and male sex) and markers of bone metabolism, endothelial function, metabolites, serum antibodies and mitochondrial-derived peptide. Positive RLS factors range from 1.26 to 4.05 indicating features associated with increased risk of VC, and negative RLS factors range from -0.95 to -1.83 indicating features associated with reduced risk of VC. CONCLUSION: The RLS model identified 17 features including novel biomarkers and traditional risk factors that together concomitantly associated with medial VC. These results may inform further investigations of factors promoting VC in CKD5 patients.

Different subclasses and isotypes of antibodies against phosphorylcholine in haemodialysis patients: association with mortality.

The risk of premature death is high among patients on haemodialysis (HD patients). We previously determined that immunoglobulin (Ig)M antibodies against phosphorylcholine (anti-PC) are negatively associated with increased risk of cardiovascular disease (CVD), atherosclerosis, some autoimmune diseases and mortality among HD patients in this cohort. Here, we also study other subclasses and isotypes of anti-PC in HD patients in relation to mortality, inflammation and gender. The study group is a cohort of 209 prevalent HD patients [median age = 66 years, interquartile range (IQR) = 51-74], vintage time = 29 months (IQR = 15-58; 56% men) with a mean follow-up period of 41 months (IQR = 20-60). Fifty-six per cent were men. We also divided patients into inflamed C-reactive protein (CRP) > 5·6 mg/ml and non-inflamed CRP. Antibody levels were determined by in-house enzyme-linked immunosorbent assay. IgG1 anti-PC below median was significantly associated with increased all-cause mortality (after adjustment for confounders: P = 0·02), while IgG, IgA and IgG2 anti-PC were not associated with this outcome. Among non-inflamed patients, IgM and IgG1 anti-PC were significantly associated with mortality (P = 0·047 and 0·02). IgG1 anti-PC was significantly associated with mortality among men (P = 0·03) and trending among women (P = 0·26). IgM (as previously reported) and IgG1 anti-PC are negatively associated with survival among HD patients and non-inflamed HD patients, but among inflamed patients there were no associations. IgG, IgA or IgG2 anti-PC were not associated with survival in these groups and subgroups. Further studies are needed to determine if raising anti-PC levels, especially IgM and IgG1 anti-PC, through immunization is beneficial.

Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin.

BACKGROUND: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. METHODS: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. RESULTS: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4-5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. CONCLUSION: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.

ANTECEDENTES: El papel del tratamiento adyuvante en pacientes con adenocarcinoma esofagogástrico tratados con quimioterapia neoadyuvante es polémico. En la práctica del Reino Unido, el estado del margen de resección quirúrgico se utiliza a menudo para identificar a los pacientes que reciben tratamiento adyuvante. El objetivo de este estudio fue evaluar el beneficio en la supervivencia del tratamiento adyuvante en pacientes con márgenes de resección positivos (R1). MÉTODOS: Se combinaron dos bases de datos de instituciones del Reino Unido que recogen información de forma prospectiva para identificar pacientes elegibles. Se utilizaron análisis de regresión de Cox ajustados para comparar la supervivencia global y la supervivencia libre de recidiva según el tratamiento adyuvante. Los patrones de recidiva se evaluaron como resultado secundario. También se realizó un análisis de emparejamiento por puntaje de propensión. RESULTADOS: De 616 pacientes incluidos en la base de datos combinada, se incluyeron en el estudio 242 pacientes con resección R1. De estos pacientes, 112 (46%) recibieron quimiorradioterapia adyuvante, 46 (19%) pacientes fueron tratados con quimioterapia adyuvante y 84 (35%) pacientes no recibieron ningún tratamiento. En el análisis ajustado, la quimiorradioterapia adyuvante mejoró la supervivencia libre de recidiva (cociente de riesgos instantáneos, hazard ratio, HR 0,59, i.c. del 95% 0,38-0,94; P = 0,026) con un beneficio tanto para la recidiva local (HR 0,48, i.c. del 95% 0,24-0,99; P = 0,047) como para la sistémica (HR 0,56, i.c. del 95% 0,33-0,94; P = 0,027). Cuando los pacientes se clasificaron según la respuesta tumoral a la quimioterapia neoadyuvante, los no respondedores (Mandard Grado 4/5) tratados con quimiorradioterapia adyuvante obtuvieron un beneficio en la supervivencia (HR 0,61, i.c. del 95% 0,38-0,97; P = 0,037). En el análisis por emparejamiento por puntaje de propensión, se observó un beneficio en la supervivencia global (HR 0,62, i.c. del 95% 0,39-0,98; P = 0,042) y en la supervivencia libre de recidiva (HR 0,51.i.c. del 95% 0,30-0,87; P = 0,004) con la quimiorradioterapia adyuvante frente a no recibir tratamiento adyuvante. CONCLUSIÓN: El tratamiento adyuvante puede mejorar la supervivencia global y la supervivencia libre de recidiva en pacientes con margen de resección positivo. Este patrón parece más pronunciado con la quimiorradioterapia adyuvante en pacientes que no responden a la quimioterapia.

Association of blood mercury levels with nonmelanoma skin cancer in the U.S.A. using National Health and Nutrition Examination Survey data (2003-2016).

BACKGROUND: Some studies have reported increased incidence or mortality of lung and brain cancers associated with occupations involving potential mercury exposure. Epidemiological evidence related to skin cancer is also limited. OBJECTIVES: To investigate the association between blood mercury (Hg) levels and nonmelanoma skin cancer (NMSC). METHODS: We used National Health and Nutrition Examination Survey data from 2003 to 2016. The exposures were blood total (tHg), inorganic (iHg) and methylmercury (MeHg). The outcome was a self-reported diagnosis of NMSC. We included participants aged ≥ 20 years who had information on blood mercury and sociodemographic factors. We conducted a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of NMSC associated with quartiles of blood Hg, after adjusting for the sociodemographic factors and survey year. RESULTS: The number of participants was 29 413; mean age was 49 years and 52% were female. Compared with those with a tHg ≤ 0·47 µg L-1 (Q1), those with a tHg > 1·74 µg L-1 (Q4) had nearly double the odds of NMSC (OR 1·79, 95% CI 1·19-2·71; Ptrend = 0·004). Similarly, those in the highest quartile of MeHg (> 1·44 µg L-1 ) had 1·7 times greater odds of NMSC (OR 1·74, 95% CI 1·13-2·70; Ptrend = 0·01) than those in the lowest quartile (≤ 0·21 µg L-1 ). iHg levels were nonsignificantly positively associated with NMSC (Ptrend = 0·08). CONCLUSIONS: We found that higher blood tHg and MeHg levels were associated with a higher prevalence of NMSC. Linked Comment: Taylor. Br J Dermatol 2020; 183:413-414.

You ≠ me: individual differences in the structure of social cognition.

This study investigated the structure of social cognition, and how it is influenced by personality; specifically, how various socio-cognitive capabilities, and the pattern of inter-relationships and co-dependencies among them differ between divergent personality styles. To measure social cognition, a large non-clinical sample (n = 290) undertook an extensive battery of self-report and performance-based measures of visual perspective taking, imitative tendencies, affective empathy, interoceptive accuracy, emotion regulation, and state affectivity. These same individuals then completed the Personality Styles and Disorders Inventory. Latent Profile Analysis revealed two dissociable personality profiles that exhibited contrasting cognitive and affective dispositions, and multivariate analyses indicated further that these profiles differed on measures of social cognition; individuals characterised by a flexible and adaptive personality profile expressed higher action orientation (emotion regulation) compared to those showing more inflexible tendencies, along with better visual perspective taking, superior interoceptive accuracy, less imitative tendencies, and lower personal distress and negativity. These characteristics point towards more efficient self-other distinction, and to higher cognitive control more generally. Moreover, low-level cognitive mechanisms served to mediate other higher level socio-emotional capabilities. Together, these findings elucidate the cognitive and affective underpinnings of individual differences in social behaviour, providing a data-driven model that should guide future research in this area.

Domination of Filamentous Anoxygenic Phototrophic Bacteria and Prediction of Metabolic Pathways in Microbial Mats from the Hot Springs of Al Aridhah.

Microbial mats in hot springs form a dynamic ecosystem and support the growth of diverse communities with broad-ranging metabolic capacity. In this study, we used 16S rRNA gene amplicon sequencing to analyse microbial communities in mat samples from two hot springs in Al Aridhah, Saudi Arabia. Putative metabolic pathways of the microbial communities were identified using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). Filamentous anoxygenic phototrophic bacteria associated with phylum Chloroflexi were abundant (> 50 %) in both hot springs at 48 °C. Chloroflexi were mainly represented by taxa Chloroflexus followed by Roseiflexus. Cyanobacteria of genus Arthrospira constituted 3.4 % of microbial mats. Heterotrophic microorganisms were mainly represented by Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes. Archaea were detected at a lower relative abundance (< 1 %). Metabolic pathways associated with membrane transport, carbon fixation, methane metabolism, amino acid biosynthesis, and degradation of aromatic compounds were commonly found in microbial mats of both hot springs. In addition, pathways for production of secondary metabolites and antimicrobial compounds were predicted to be present in microbial mats. In conclusion, microbial communities in the hot springs of Al Aridhah were composed of diverse bacteria, with taxa of Chloroflexus being dominant.

Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease.

BACKGROUND: Chemerin is an adipokine that signals through the G protein-coupled receptor ChemR23 and is associated with inflammation, glucose homeostasis, lipid metabolism and renal function, all of which strongly influence cardiovascular risk. However, elevated chemerin provides a survival advantage in patients with chronic kidney disease (CKD), but how this relates to the cardiovascular phenotype is unknown. OBJECTIVES: The aim of the present study was to establish the association of chemerin with coronary calcification and to determine the effects of chemerin signalling, through ChemR23, in vascular smooth muscle cell (VSMC) calcification. METHODS: Plasma chemerin was measured in 113 patients with CKD and 50 healthy controls. All patients underwent computed tomography to determine coronary artery calcium (CAC) score. VSMCs were isolated from wild-type and ChemR23 knock-out mice and treated with chemerin. RESULTS: Multivariate analyses established creatinine, cholesterol, body mass index and tumour necrosis factor as significant confounders for circulating chemerin levels. Despite these positive associations with renal function, cardiometabolic risk factors and inflammation, chemerin was inversely associated with CAC both in an age- and sex-adjusted analysis and in a multivariate analysis adjusting for the aforementioned confounders. In addition, circulating chemerin levels were associated with the calcification inhibitors matrix gla protein (MGP) and fetuin-A. Finally, chemerin significantly reduced phosphate-induced calcification and increased MGP expression in VSMCs, whereas chemerin was devoid of these effects in VSMCs lacking ChemR23. CONCLUSION: In conclusion, these results suggest that chemerin signalling through ChemR23 in VSMCs protects against vascular calcification in CKD.

Effectiveness of premedication protocol using intravenous fentanyl to reduce pain associated with femoral artery closure device placement.

AIM: To test the effectiveness of a premedication protocol using intravenous bolus of 100 µg fentanyl to reduce pain associated with femoral artery closure device placement for neuro-endovascular procedures. MATERIALS AND METHODS: The severity of pain associated with femoral artery closure device placement was analysed using a numerical rating scale score ranging from 0 (no pain) to 10 (most severe pain) in two cohorts of consecutive adult patients (n=118), those who were (n=64) or were not (n=54) treated with premedication protocol. The primary endpoints were the proportion of patients with excellent (score ≤1) and failed pain control (score ≥8). Stepwise logistic regression analysis was performed to identify the effect of premedication on pain control after adjustment for potential confounders. RESULTS: The median numerical pain rating score at femoral artery closure device placement was significantly lower in patients treated with premedication protocol compared with those who underwent closure without premedication (1 versus 5, p<0.001). There was a significantly higher rate of excellent (56.2% versus 14.8%, p<0.001) and good (68.7% versus 31.2%, p<0.001) pain control at closure device placement among patients treated with premedication protocol. None of the patients treated with premedication protocol reported failed pain control compared with 33.4% of those who underwent closure device placement without premedication. In the multivariate analysis, treatment with the premedication protocol was significantly associated with an increased rate of excellent pain control (odds ratio 2.3; 95% confidence interval 1.9-3.1). CONCLUSION: Premedication with intravenous fentanyl injection prior to femoral artery closure device placement can reduce the intensity of pain associated with closure.

Gender differences, UV exposure and risk of lentigo maligna in a nationwide healthcare population cohort study.

BACKGROUND: Our understanding of the relationship between ultraviolet (UV) radiation exposure and lentigo maligna (LM) has been largely derived from epidemiologic/clinical studies based on invasive melanoma. Recent studies have shown gender differences in melanocytic tumours incidence. OBJECTIVE: To examine the association of UV light with LM by gender remains unclear. METHODS: Two prospective cohort study [Nurses' Health Study (1980-2012)] and [Health Professionals Follow-up Study (1986-2010)] were analysed. All participants with LM or MIS, non-LM type were included in analysis. UV index at birth, age 15, and age 30 were calculated by gender. Lifetime UV flux was calculated. Hazard ratios (HRs) were calculated. RESULTS: A total of 110 485 women from NHS and 41 015 men from HPFS were examined. A total of 281 LM and 776 melanoma in situ (MIS), non-LM cases were reported. Risk of LM increased with increasing UV flux exposure in multivariate-adjusted models for men (P for trend = 0.04), but not for women (P for trend = 0.91). CONCLUSIONS: UV flux may be associated with LM in men but not in women.

Diagnosis validation and clinical characterization of atopic dermatitis in Nurses' Health Study 2.

BACKGROUND: Epidemiologic studies of atopic dermatitis (AD) are often limited by case definitions that have not been validated. OBJECTIVE: In this study, we assessed the accuracy of self-report of AD in a large cohort of US female nurses, the Nurses' Health Study 2 (NHS2). We also provide clinical characteristics of AD in the cohort. METHODS: We sent an electronic questionnaire to NHS2 participants who previously reported ever having a diagnosis of AD. This questionnaire was designed to confirm cases of AD using previously validated algorithms with >85% specificity. We assessed the association of AD with asthma, comparing the results when different definitions of AD were applied. We also inquired about various aspects of participants' AD. RESULTS: Responses were received from 2509 of 5126 (49%) nurses who were sent the questionnaire, with an average age of 62. Most participants (1996/2509, 80%) reiterated their previously reported clinician diagnosis of AD. Application of the two diagnostic algorithms yielded confirmation of 1538 and 1293 prevalent cases, respectively. The association of AD with asthma was stronger when more stringent AD case definitions were applied. Participants generally reported mild disease (92% with ≤10% maximal body surface area involved) and a high proportion (57%) reported adult-onset disease. CONCLUSIONS: Self-report of AD diagnosis has good reliability, and future analyses will be strengthened by our ability to conduct sensitivity analyses with refined confirmed AD subgroups.

Mercury and Organochlorines in the Terrestrial Environment of Schirmacher Hills, Antarctica.

We report the levels of mercury (Hg) and nine organochlorine pesticides [OCPs: α-hexachlorocyclohexane (HCH), ß-HCH, γ-HCH, δ-HCH, α-Endosulfan, ß-Endosulfan, Endosulfan sulfate, p,p'-dichlorodiphenyldichloroethylene (DDE) and p,p'-dichlorodiphenyldichloroethane (DDD)] in the terrestrial environment (moss and soil) and water (OCPs only) of Schirmacher Hills, Antarctica. This area has never been studied for mercury and not for OCPs since 1988. Mercury levels in moss, 66 ± 37 ng/g dry weight (dw), are comparable to other Antarctic locations. Levels of α-HCH, below detection to 4.48 ng/g dw, and p,p'-DDE, below detection to 31 ng/g dw, in mosses are lower or marginally higher than other Antarctic locations. No other OCPs were detected in moss. None of the OCPs were detected in soil. This suggests that Schirmacher Hills may be considered as a background site with respect to mercury and analyzed OCPs, despite the operation of two old research stations (Maitri, est. 1989, and Novolazarevskaya, est. 1961) in the region.

Pressure flow pattern of varicocele veins and its correlation with testicular blood flow and semen parameters.

The pressure pattern in varicocele veins of infertile patients and its correlation with semen quality and testicular blood flow was determined. Consecutive patients at andro-urology clinic of a teaching hospital undergoing microsurgical varicocelectomy were included. Their semen quality and testicular blood flow were determined. Peak systolic velocity (PSV) and resistive index (RI) of subcapsular and intraparenchymal branches of testicular artery were noted by colour Doppler ultrasonography. During surgery before ligation of varicocele veins, intravenous pressures of internal spermatic (ISV) and external spermatic (ESV) veins were determined at baseline and after Valsalva manoeuvre. Thirty patients, 20-45 years old, were evaluated. Baseline pressure for maximum dilated ISV (A), less dilated ISV (B) and ESV was 15.93 ± 6.34, 12.38 ± 4.60 and 12.92 ± 5.65 mm. Hg, respectively, which increased after Valsalva by 104.4%, 116.2% and 38.22% respectively. Correlation (r = -.71; p < .05) was appreciated between percentage increase in pressure of ISV B with PSV of intraparenchymal testicular arteries and progressive motility (r = -.759; p < .05), nonprogressive motility (r = -.738; p < .05) and morphology (r = -.653; p = .07) of spermatozoa. In conclusion, ISV develops higher pressure on Valsalva as compared to ESV and has correlation with semen quality and testicular blood flow.