Ambient air pollution, covert cerebrovascular disease and cognition: results from the ISSYS study.

BACKGROUND AND PURPOSE: Although air pollution (AP) has been associated with stroke and dementia, data regarding its relationship with covert cerebrovascular disease (cCVD) and cognition over time are sparse. The aim of this study was to explore these relationships. METHODS: A prospective population-based study of 976 stroke-free and non-demented individuals living in Barcelona, Spain, was conducted during 2010-2016. A land use regression model was used to estimate the exposure of each participant to AP: NOx, NO2, PM2.5, PM10, PMcoarse and PM2.5 absorbance. Cognitive function and cCVD were assessed at baseline (n = 976) and 4 years after (n = 317). Multivariate-adjusted models were developed. RESULTS: At baseline, 99 participants (10.1%) had covert brain infarcts and 91 (9.3%) had extensive periventricular white matter hyperintensities (WMHs). Marked subcortical WMH progression was seen in 19.7%; the incidence of other covert cerebrovascular lessons ranged between 5% and 6% each. PM2.5 was related to higher odds of having a covert brain infarct (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.06-4.60). PM2.5 absorbance was related to higher odds of having extensive subcortical WMHs (OR 1.72; 95% CI 1.13-2.60), whereas NO2 was related to higher odds of having extensive subcortical (OR 1.66; 95% CI 1.17-2.35) or periventricular (OR 1.96; 95% CI 1.10-3.50) WMHs and to higher odds of developing marked subcortical WMH progression (OR 1.40; 95% CI 1.05-1.90). NOx was related to incident cerebral microbleeds (OR 1.36; 95% CI 1.04-1.79). There was no association between AP and cognition. CONCLUSIONS: Air pollutant predicts the presence and accumulation of cCVD. Its impact on cognitive impairment remains to be determined.

Prevalence and commonality of non-technical skills and human factors in airway management guidelines: a narrative review of the last 5 years.

The primary aim of this review was to identify, analyse and codify the prominence and nature of human factors and ergonomics within difficult airway management algorithms. A directed search across OVID Medline and PubMed databases was performed. All articles were screened for relevance to the research aims and according to predetermined exclusion criteria. We identified 26 published airway management algorithms. A coding framework was iteratively developed identifying human factors and ergonomic specific words and phrases based on the Systems Engineering Initiative for Patient Safety model. This framework was applied to the papers to delineate qualitative and quantitative results. Our results show that human factors are well represented within recent airway management guidelines. Human factors associated with work systems and processes featured more prominently than user and patient outcome measurement and adaption. Human factors are an evolving area in airway management and our results highlight that further considerations are necessary in further guideline development.

AllergoOncology: ultra-low IgE, a potential novel biomarker in cancer-a Position Paper of the European Academy of Allergy and Clinical Immunology (EAACI).

Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra-low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra-low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti-tumour surveillance, indicating the importance of a balanced IgE-mediated immune function. Ultra-low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in-depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co-factors are warranted.

Comparison of survival of stage I-III colon cancer by travel distance and hospital volume.

BACKGROUND: Previous studies have demonstrated improved outcomes at high-volume colorectal surgery centers; however, the benefit for patients who live far from such centers has not been assessed relative to local, low-volume facilities. METHODS: The 2010-2015 National Cancer Database (NCDB) was queried for patients with stage I-III colon adenocarcinoma undergoing treatment at a single center. A 'local, low-volume' cohort was constructed of 12,768 patients in the bottom quartile of travel distance at the bottom quartile of institution surgical volume and a 'travel, high-volume' cohort of 11,349 patients in the top quartile of travel distance at the top quartile of institution surgical volume. RESULTS: In unadjusted analysis, patients in the travel cohort had improved rates of positive resection margins (3.7% vs. 5.5%, p < 0.001), adequate lymph-node harvests (92% vs. 83.6%, p < 0.001), and 30- (2.2% vs. 3.9%, p < 0.001) and 90-day mortality (3.7% vs. 6.4%, p < 0.001). On multivariable logistic regression analysis adjusting for patient demographic, tumor, and facility characteristics, the cohorts demonstrated equivalent overall survival (HR: 0.972, p = 0.39), with improved secondary outcomes in the 'travel' cohort of adequate lymph-node harvesting (OR: 0.57, p < 0.001), and 30- (OR 0.79, p = 0.019) and 90-day mortality (OR 0.80, p = 0.004). CONCLUSIONS: For patients with stage I-III colon cancer, traveling to high-volume institutions compared to local, low-volume centers does not convey an overall survival benefit. However, given advantages including 30- and 90-day mortality and adequate lymph-node harvest, nuanced patient recommendations should consider both these differences and the unquantified benefits to local care, including cost, travel time, and support systems.

A 7-day high-fat, high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle.

KEY POINTS: We have recently shown that a high-fat, high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days' HFHC diet on (1) skeletal muscle concentration of lipid metabolites, and (2) potential changes in the perilipin (PLIN) content of the lipid droplets storing intramuscular triglyceride (IMTG). The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to lipid droplet stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists in reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. ABSTRACT: A high-fat, high-calorie (HFHC) diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LDs) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LDs has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (11 males, 2 females) healthy lean individuals (age: 23 ± 2.5 years; body mass index: 24.5 ± 2.4 kg m-2 ), following an overnight fast, before and after consuming a high-fat (64% energy), high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+101%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (+80%; P < 0.01), also in type I fibres only. We propose that these adaptations of LDs support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days' HFHC diet.

The side of the primary tumor affects overall survival in colon adenocarcinoma: an analysis of the national cancer database.

BACKGROUND: Due to conflicting study results on the effect of laterality on overall survival in primary colon cancers, we sought to examine the impact of left compared to right-sided primary tumors on overall survival for stage I-III colon cancer using the largest dataset to date. METHODS: The 2006-2013 NCDB was queried for patients with single primary, stage I-III colon adenocarcinoma and grouped by stage and tumor location. RESULTS: For stage I-II tumors, 114,839 patients had resection (62% right:38% left). After adjustment, patients with right-sided tumors had superior survival ([HR right as reference]: 1.13, 95% CI 1.09-1.17, p < 0.001). For stage III tumors, 71,024 patients had resection, (59% right:41% left). After adjustment, patients with left-sided tumors had superior survival with chemotherapy (HR 0.85, p < 0.001) and no difference in survival without chemotherapy (HR 0.97, p = 0.18). CONCLUSIONS: The side of the primary tumor impacts overall survival across stages for colon adenocarcinoma. Patients with right-sided tumors have superior survival for stage I-II disease while patients with left-sided stage III disease demonstrate a survival advantage, suggesting an opportunity for investigators to use sidedness as a surrogate for prognosis and chemoresponsiveness.

Disparities in colostomy reversal after Hartmann's procedure for diverticulitis.

BACKGROUND: Hartmann's procedure for diverticulitis is a common procedure, with highly variable rates and timing of colostomy reversal. The aim of this study was to evaluate the impact of race and insurance coverage on reversal within 2 years of Hartmann's procedure for diverticulitis. METHODS: The Healthcare Cost and Utilization Project (HCUP) State Inpatient Database of five states (2007-2010) was queried for patients who had Hartmann's procedure in the setting of diverticulitis. Patients were grouped by race and insurance status, and multivariable adjustment was performed to evaluate rate and timing of colostomy takedown at 2 years. RESULTS: Among 11,019 patients who had Hartmann's procedure for diverticulitis, 6900 (69%) patients had colostomy reversal by 2 years, with a median time to reversal of 19 weeks. Compared to white patients with private insurance, combinations of black race and non-private insurance significantly reduced likelihood of colostomy reversal at 2 years across all combinations. Black patients without insurance had the lowest likelihood of reversal at 2 years (OR 0.27, 95% CI 0.14-0.51, p < 0.001). For patients who had colostomy reversal within 2 years, black patients without insurance had a significant delay in time to reversal (11 weeks, 95% CI 6-16, p < 0.001) compared to white patients with private insurance, and delays persisted across all other groups. CONCLUSIONS: Black patients and those without private insurance experienced significantly lower rates of, and delayed time to, colostomy reversal compared to white patients with private insurance. These disparities must be considered for allocation of resources in marginalized communities.

Association between neoadjuvant chemoradiation and survival for patients with locally advanced rectal cancer.

AIM: To examine the overall survival differences for the following neoadjuvant therapy modalities - no therapy, chemotherapy alone, radiation alone and chemoradiation - in a large cohort of patients with locally advanced rectal cancer. METHOD: Adults with clinical Stage II and III rectal adenocarcinoma were selected from the National Cancer Database and grouped by type of neoadjuvant therapy received: no therapy, chemotherapy only, radiotherapy only or chemoradiation. Multivariable regression methods were used to compare adjusted differences in perioperative outcomes and overall survival. RESULTS: Among 32 978 patients included, 9714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1170 (3.5%) radiotherapy only and 21 204 (64.3%) chemoradiation. Compared with no therapy, chemotherapy or radiotherapy alone were not associated with any adjusted differences in surgical margin positivity, permanent colostomy rate or overall survival (all P > 0.05). With adjustment, neoadjuvant chemoradiation vs no therapy was associated with a lower likelihood of surgical margin positivity (OR 0.74, P < 0.001), decreased rate of permanent colostomy (OR 0.77, P < 0.001) and overall survival [hazard ratio (HR) 0.79, P < 0.001]. When compared with chemotherapy or radiotherapy alone, chemoradiation remained associated with improved overall survival (vs chemotherapy alone HR 0.83, P = 0.04; vs radiotherapy alone HR 0.83, P < 0.019). CONCLUSION: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter preservation, R0 resection and survival for patients with locally advanced rectal cancer. Despite this finding, one-third of patients in the United States with locally advanced rectal cancer fail to receive stage-appropriate chemoradiation.

AllergoOncology - the impact of allergy in oncology: EAACI position paper.

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment.

Injury surveillance in Trinidad: an accident and emergency based injury surveillance system at the San Fernando General Hospital.

OBJECTIVE: Injuries are a significant cause of morbidity and mortality worldwide. Injuries disproportionately affect people living in low and middle income countries, including the Caribbean; however little is known about the epidemiology of injuries in these areas. An accident and emergency (A&E) department injury surveillance system was established at the San Fernando General Hospital, Trinidad and Tobago, to address this important data gap. METHODS: A detailed overview of the objectives, data collection methods, and inherent strengths and limitations of this surveillance system are presented, along with results of an analysis of data collected during the first three years of operations (from 2002 to 2004). RESULTS: Trained hospital staff collect a variety of injury/poisoning, demographic and clinical data on nearly 20,000 patients presenting each year with injury to the A&E Department. The total number of injuries in men was almost twice that in women. The majority of injuries were seen in those 25-44-years of age. Falls, other blunt force, stab/cut, traffic injury and poisoning represented the leading causes of injury. Nearly half of all the injuries occurred in the home, with the street/highway and work environments also accounting for an appreciable number of injuries. The majority of injuries were reported as unintentional. CONCLUSION: Injuries represent an important population health and health services issue in South Trinidad. Data from the A&E Department injury surveillance system represent an important resource to inform evidence-based health policy decisions on injury prevention and public health resource allocation.

AllergoOncology: the role of IgE-mediated allergy in cancer.

Epidemiological studies have suggested inverse associations between allergic diseases and malignancies. As a proof of concept for the capability of immunoglobulin E (IgE) to destruct tumor cells, several experimental strategies have evolved to specifically target this antibody class towards relevant tumor antigens. It could be demonstrated that IgE antibodies specific to overexpressed tumor antigens have been superior to any other immunoglobulin class with respect to antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) reactions. In an alternative approach, IgE nonspecifically attached to tumor cells proved to be a powerful adjuvant establishing tumor-specific immune memory. Active Th2 immunity could also be achieved by applying an oral immunization regimen using mimotopes, i.e. epitope mimics of tumor antigens. The induced IgE antibodies could be cross-linked by live tumor cells leading to tumoricidic mediator release. Thus, IgE antibodies may not only act in natural tumor surveillance, but could possibly also be exploited for tumor control in active and passive immunotherapy settings. Thereby, eosinophils, mast cells and macrophages can be armed with the cytophilic IgE and become potent anti-tumor effectors, able to trace viable tumor cells in the tissues. It is strongly suggested that the evolving new field AllergoOncology will give new insights into the role of IgE-mediated allergy in malignancies, possibly opening new avenues for tumor therapy.

A characteristic eruption associated with ifosfamide, carboplatin, and etoposide chemotherapy after pretreatment with recombinant interleukin-1 alpha.

BACKGROUND: Patients who received recombinant interleukin-1 alpha (IL-1 alpha) before chemotherapy followed by autologous bone marrow transplantation had a characteristic intertriginous cutaneous eruption that has not previously been described. OBJECTIVE: Our aim was to document these skin changes and to determine whether IL-1 alpha as a sole agent caused recognizable changes in the skin. METHODS: A prospective study of the skin changes in eight patients was performed. We characterized the clinical, histologic, and immunohistochemical features of the patient's skin after IL-1 alpha infusions and after chemotherapy. RESULTS: No specific clinical or histologic changes were seen immediately after IL-1 alpha infusions. Immunohistochemical studies showed significant upregulation of endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Within 1 day of the initiation of chemotherapy (ifosfamide, carboplatin, and etoposide), a cutaneous eruption consisting of mucositis and varying degrees of erythema progressing to painful erosions in body folds and under adhesive tape developed in all patients. Histologic features were consistent with a chemotherapeutic effect on the epidermis as well as eccrine and apocrine glands. Expression of keratinocyte intercellular adhesion molecule-1 and HLA-DR as well as of ELAM-1 on dermal endothelial cells was increased. The perivascular lymphocytic infiltrate consisted mainly of CD4+ T cells. CONCLUSION: High-dose chemotherapy with ifosfamide, carboplatin, and etoposide resulted in a characteristic cutaneous eruption that is consistent with a toxic reaction to chemotherapeutic agents. Its accentuation in skin folds and under taped areas suggests that eccrine excretion of the drugs or a toxic metabolite is an important contributing factor. IL-1 alpha may induce the expression of ELAM-1 but does not cause a cutaneous eruption.

Kidney in Galloway-Mowat syndrome: clinical spectrum with description of pathology.

The Galloway-Mowat syndrome, a rare inherited disorder, is characterized by congenital microcephaly with hypotonia and developmental delay, often hiatus hernia, and nephrotic syndrome manifested in infancy or in early childhood. The glomerular lesion has been poorly characterized in the few previous reports of this syndrome. We studied three siblings with microcephaly and nephrotic syndrome occurring during the first two weeks of life. Hematuria, glycosuria and renal failure were also present. Renal biopsy and postmortem specimens of two patients were studied. Glomerular structure was disorganized; capillary lumina were of varying calibers, capillary walls were adherent to one another, and mesangial zones were poorly demarcated. Glomerular basement membrane ultrastructure was markedly altered. The normal trilaminar structure was obscured or replaced by flocculent material; furthermore, 6 to 8 nm fibrils of unknown nature permeated the space between endothelial and epithelial cells. Non-glomerular basement membranes were unaltered in appearance. This syndrome apparently represents, in part, a new disorder of glomerular basement membrane formation and function.

The perioperative management of pheochromocytoma in children.

The perioperative experiences of 15 children and adolescents who underwent a total of 18 surgical procedures for resection of a pheochromocytoma were analyzed to determine clinical or hemodynamic events associated with intraoperative or postoperative complications. Of the pre- and intraoperative factors assessed, only preoperative resolution of symptoms and normalization of blood pressure were predictive of uncomplicated outcome. No intraoperative factors were statistically associated with outcome, but the four patients with complicated outcomes had had aggressively administered intraoperative fluids. Noninvasive measures of cardiac function did not help predict outcome; however, echocardiography results were available only for six patients. Two of the patients with complicated outcomes had cardiac dysfunction, suggesting undiagnosed catecholamine-induced cardiomyopathy in the other two with complicated outcomes. Intraoperative fluids should be given based on intraoperative blood pressures, the presence or absence of prior adrenergic blockade, and assessment of preoperative myocardial function. If preoperative myocardial dysfunction is revealed, intraoperative measurement of right atrial and pulmonary capillary wedge pressures may be indicated.