Engineered interleukin-6-derived cytokines recruit artificial receptor complexes and disclose CNTF signaling via the OSMR.

Ciliary neurotrophic factor (CNTF) activates cells via the non-signaling α-receptor CNTF receptor (CNTFR) and the two signaling ß-receptors glycoprotein 130 (gp130) and leukemia inhibitory factor receptor (LIFR). The CNTF derivate, Axokine, was protective against obesity and insulin resistance, but clinical development was halted by the emergence of CNTF antibodies. The chimeric cytokine IC7 used the framework of interleukin (IL-)6 with the LIFR-binding site from CNTF to activate cells via IL-6R:gp130:LIFR complexes. Similar to CNTF/Axokine, IC7 protected mice from obesity and insulin resistance. Here, we developed CNTF-independent chimeras that specifically target the IL-6R:gp130:LIFR complex. In GIL-6 and GIO-6, we transferred the LIFR binding site from LIF or OSM to IL-6, respectively. While GIO-6 signals via gp130:IL-6R:LIFR and gp130:IL-6R:OSMR complexes, GIL-6 selectively activates the IL-6R:gp130:LIFR receptor complex. By re-evaluation of IC7 and CNTF, we discovered the Oncostatin M receptor (OSMR) as an alternative non-canonical high-affinity receptor leading to IL-6R:OSMR:gp130 and CNTFR:OSMR:gp130 receptor complexes, respectively. The discovery of OSMR as an alternative high-affinity receptor for IC7 and CNTF designates GIL-6 as the first truly selective IL-6R:gp130:LIFR cytokine, whereas GIO-6 is a CNTF-free alternative for IC7.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Morphea mimicking facial capillary malformations: Two new cases and review of the literature.

Morphea and facial capillary malformations (port-wine stains) are distinct conditions that can affect the pediatric population. Early localized morphea mimicking a capillary malformation is an uncommon clinical presentation. We present two new cases of girls, aged 2 and 3 years, who presented with erythematous patches, initially diagnosed as capillary malformations, which were later diagnosed as morphea. We also performed a literature review, yielding 12 additional cases that underscore that the unusual presentation of morphea may delay correct diagnosis. Although early management of morphea reduces long-term sequelae, it is important to delay laser treatment for selected acquired vascular malformations, until the diagnosis of morphea is excluded.

Novel SLC12A2-ROS1 Fusion in Non-Small Cell Lung Cancer with a Significant Response to Crizotinib: The Importance of Choosing the Appropriate Next-Generation Sequencing Assay.

Identifying the druggable target is crucial for patients with nonsquamous advanced non-small cell lung cancer (NSCLC). This article adds to the spectrum of ROS1 fusion cases described in NSCLC. We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers: a fusion that has clinical and radiological sensitivity to crizotinib. Fluorescence in situ hybridization detected the SLC12A2-ROS1 fusion and it was confirmed through hybrid capture-based next-generation sequencing (NGS); however, the fusion could not be detected by amplicon-based assay. The success of implementing NGS into routine clinical practice depends on the accuracy of testing. The test's methodological features should then be considered because they significantly affect the results. Given this patient's response to crizotinib, identifying patients with undescribed ROS1 fusions has important therapeutic implications. KEY POINTS: This is the first known description of an SLC12A2-ROS1 fusion. Considering the patient's clinical features and tumor response observed after crizotinib therapy, the authors confirm that this new rearrangement has relevant clinical impact for patients with non-small cell lung cancer. The success of implementing next-generation sequencing (NGS) into routine clinical practice depends on the accuracy of the testing. Different assays and NGS platforms can achieve differing results. Each assay's limitations need to be considered to ensure the quality of precision medicine in clinical practice.

Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery.

AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.

Predicting Chemotherapy Toxicity in Older Patients with Cancer: A Multicenter Prospective Study.

BACKGROUND: Standard oncology tools are inadequate to distinguish which older patients are at higher risk of developing chemotherapy-related complications. MATERIALS AND METHODS: Patients over 70 years of age starting new chemotherapy regimens were prospectively included in a multicenter study. A prechemotherapy assessment that included sociodemographics, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and the development of grade 3-5 toxicity was examined by using logistic regression. RESULTS: A total of 551 patients were accrued. Chemotherapy doses (odds ratio [OR] 1.834; 95% confidence interval [CI] 1.237-2.719) and creatinine clearance (OR 0.989; 95% CI 0.981-0.997) were the only factors independently associated with toxicity. Only 19% of patients who received reduced doses of chemotherapy and had a creatinine clearance ≥40 mL/minute had grade 3-4 toxicity, compared with 38% of those who received standard doses or had a creatinine clearance <40 mL/minute (p < .0001). However, no satisfactory multivariate model was obtained using different selection approaches. CONCLUSION: Chemotherapy doses and renal function were identified as the major risk factors for developing severe toxicity in the older patient. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up in these patients. IMPLICATIONS FOR PRACTICE: Older patients are more vulnerable to chemotherapy toxicity. However, standard tools are inadequate to identify who is at higher risk of developing chemotherapy-related complications. Chemotherapy doses (standard vs. reduced) and renal function were identified as the major risk factors for developing severe toxicity in the elderly. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up.

Hydrobiogeochemistry of Two Catchments in Brazil Under Forest Recovery in an Environmental Services Payment Program.

We investigated the fluvial geochemistry of two catchments at different stages in the forest recovery process which have been a focus of an Environmental Services Payment (ESP) program in Brazil. The Posses (PS) and Salto de Cima (SC) catchments (1200 ha and 1500 ha, respectively) are situated in the municipality of Extrema, Minas Gerais state. Their streams flow into the Jaguari River that supplies part of the water demand of the São Paulo metropolitan area. Samples were collected for chemical analysis and physical-chemical field measures every 2 weeks from January to December 2017. An important pollution point source was discovered in the PS stream related to bovine urine and feces, as well another unidentified source that can be related to a small food processing industry and/or a small fish farm. At the SC stream, on the other hand, there was clear evidence of domestic sewage input. This preliminary study confirmed a limited improvement of the stream water quality in response to recovery of the forest vegetation. Therefore, we recommend that in addition to enhanced monitoring to help distinguish biogeochemical sources and the benefits of land conservation practices, the ESP program should consider controlling point source pollution to accomplish its purpose.

Cellular glycosylation senses metabolic changes and modulates cell plasticity during epithelial to mesenchymal transition.

Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin, and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward hexosamine biosynthesis pathway (HBP), which fuels aberrant glycosylation patterns that are extensively observed in cancer cells. HBP depends on nutrient availability to produce its end product UDP-GlcNAc, and for this reason is considered a metabolic sensor pathway. UDP-GlcNAc is the substrate used for the synthesis of major types of glycosylation, including O-GlcNAc and cell surface glycans. In general, the rate limiting enzyme of HBP, GFAT, is overexpressed in many cancer types that present EMT features as well as aberrant glycosylation. Moreover, altered levels of O-GlcNAcylation can modulate cell morphology and favor EMT. In this review, we summarize some of the current knowledge that correlates glucose metabolism, aberrant glycosylation and hyper O-GlcNAcylation supported by HBP that leads to EMT activation. Developmental Dynamics 247:481-491, 2018. © 2017 Wiley Periodicals, Inc.

Myocardial Injury After Noncardiac Surgery (MINS) in Vascular Surgical Patients: A Prospective Observational Cohort Study.

OBJECTIVE: To determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in vascular surgical patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described. METHODS: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03 ng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring. RESULTS: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4). CONCLUSIONS: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Epithelial Mesenchymal Transition Induces Aberrant Glycosylation through Hexosamine Biosynthetic Pathway Activation.

Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been focused on the importance of glycolysis and pentose phosphate pathway. However, a neglected but very important branch of glucose metabolism is the hexosamine biosynthesis pathway (HBP). The HBP is a branch of the glucose metabolic pathway that consumes ∼2-5% of the total glucose, generating UDP-GlcNAc as the end product. UDP-GlcNAc is the donor substrate used in multiple glycosylation reactions. Thus, HBP links the altered metabolism with aberrant glycosylation providing a mechanism for cancer cells to sense and respond to microenvironment changes. Here, we investigate the changes of glucose metabolism during epithelial mesenchymal transition (EMT) and the role of O-GlcNAcylation in this process. We show that A549 cells increase glucose uptake during EMT, but instead of increasing the glycolysis and pentose phosphate pathway, the glucose is shunted through the HBP. The activation of HBP induces an aberrant cell surface glycosylation and O-GlcNAcylation. The cell surface glycans display an increase of sialylation α2-6, poly-LacNAc, and fucosylation, all known epitopes found in different tumor models. In addition, modulation of O-GlcNAc levels was demonstrated to be important during the EMT process. Taken together, our results indicate that EMT is an applicable model to study metabolic and glycophenotype changes during carcinogenesis, suggesting that cell glycosylation senses metabolic changes and modulates cell plasticity.

Effective interventions to improve young adults' linkage to HIV care in Sub-Saharan Africa: a systematic review.

HIV/AIDS remains a major public health problem despite the efforts to prevent and decrease its spread. Sub-Saharan Africa (SSA) represents 70% of the global number of people living with HIV and 73% of all HIV/AIDS-related deaths. Young adults age 15-24 years are disproportionately impacted by HIV/AIDS in SSA with 34% of people living with HIV (PLWHIV) and 37% of newly diagnosed individuals being in this age group. It is important that PLWHIV be linked to care to facilitate antiretroviral therapy (ART) initiation and limit the spread of infection. We conducted a systematic literature review to identify effective interventions designed to improve linkage to care among HIV-infected young adults in SSA. One hundred and forty-six titles and abstracts were screened, 28 full-texts were reviewed, and 6 articles met the inclusion and exclusion criteria. Home-based HIV counseling and testing, home-based HIV self-testing, and mobile HIV counseling and testing followed by proper referral of HIV-positive patients to HIV care were effective for improving linkage of young adults to care. Other factors such as referral forms, transportation allowance, home initiation of HIV care, and volunteer escort to the HIV treatment clinic were effective in reducing time to linkage to care. There is a vast need for research and interventions that target HIV-positive young adults in SSA which aim to improve their linkage and access to HIV care. The results of this study illustrate effective interventions in improving linkage to care and reducing time to linkage to care of young adults in SSA.

Hemobilia related to cystic artery pseudoaneurysm as a cause of acute pancreatitis.

Hemobilia is a rare cause of upper gastrointestinal bleeding (UGIB). It is commonly iatrogenic, and is more rarely caused by tumors, lithiasis, and inflammatory or vascular disease. We describe a case of cystic artery pseudoaneurysm, which caused acute pancreatitis as an unusual complication.

Systemic and alveolar inflammatory response in the dependent and nondependent lung in patients undergoing lung resection surgery: A prospective observational study.

BACKGROUND: Measurement of inflammatory mediators in bronchoalveolar lavage (BAL) during lung resection surgery with periods of one-lung ventilation (OLV) has revealed an intense local pulmonary response. The role of each lung in the inflammation that occurs during this procedure has never been investigated. OBJECTIVE(S): The primary objective of our study was to compare the inflammatory response in the dependent lung with that of the nondependent lung by measuring inflammatory markers in BAL. Our secondary objective was to assess the behaviour of these inflammatory mediators in patients with and without postoperative pulmonary complications (PPCs). DESIGN: A prospective, observational study. SETTING: Department of Anaesthesiology in a university hospital. PATIENTS: Forty-six consecutive patients undergoing lung resection surgery. INTERVENTION(S): BAL samples were taken from dependent and nondependent lung 10 min before initiating OLV and at the end of OLV (once two-lung ventilation was established). All patients were followed up until 30 days after surgery. MAIN OUTCOME MEASURES: The concentration of cytokines [interleukin (IL)-1, IL-2, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α)], nitric oxide, carbon monoxide and matrix metalloproteinase 2 (MMP-2) was analysed in both lungs before and after OLV. PPCs were recorded. RESULTS: In BAL fluid, all measured biomarkers, apart from IL-10, were significantly greater (P < 0.05) at the end of OLV than those obtained before OLV, both for the dependent and nondependent lung. The increase in measured biomarkers was similar in both lungs. Eight patients developed PPC. Patients who developed PPC had higher levels of TNF-α (P < 0.05) in BAL from the nondependent lung before and after OLV than patients who did not have PPC. Patients who developed PPC had a smaller increase in MMP-2 levels (P < 0.05) in the dependent lung than patients who did not have PPC. CONCLUSION: In lung resection surgery, the inflammatory response is similar in both lungs. However, the greater increase in TNF-α levels in the nondependent lung and the smaller increase of MMP-2 concentration in the dependent lung may increase the susceptibility to develop PPC.

Development of a polymerase chain reaction assay for the rapid detection of the oral pathogenic bacterium, Selenomonas noxia.

BACKGROUND: In recent studies, periodontal health has been linked to being overweight and/or obese. Among common oral bacteria, Selenomonas noxia has been implicated in converting periodontal health to disease, and Selenomonas species have also been found in gastric ulcers. The objective of this study was to develop and validate a quantitative polymerase chain reaction (qPCR) assay for the specific and rapid detection of S. noxia. METHODS: Two oligonucleotide primer pairs and one probe were designed and tested to determine optimal amplification signal with three strains of S. noxia. The PCR assay was tested against fourteen non-target organisms, including closely related oral Selenomonads, one phylogenetically closely related bacterium, and two commonly isolated oral bacteria. RESULTS: One of the primer sets was more sensitive at detecting the target organism and was selected for optimization and validation experiments. The designed primers and probe amplified the target organism with 100% specificity. PCR inhibition was observed with an internal positive control, and inhibition was resolved by diluting the DNA extract. CONCLUSIONS: The qPCR assay designed in this study can be used to specifically detect S. noxia in the clinical setting and in future research involving the enhanced detection of S. noxia. The assay can also be used in epidemiological studies for understanding the role of S. noxia in disease processes including, but not limited to, oral health and obesity of infectious origin.

Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Incidence of Postoperative Delirium among Elderly Patients after Elective Surgeries under Anesthesia in the Charity Services of the Philippine General Hospital.

Background: Due to the increasing number of elderly patients being referred to anesthesia for surgical procedures, there is a growing interest with regard to the incidence of postoperative delirium and its contributing factors. Objectives: The primary objective of this study is to determine the incidence of postoperative delirium in the charity elderly patients at the Philippine General Hospital (PGH). Methods: The incidence of postoperative delirium was assessed in an analytic prospective study conducted at the PGH among elderly patients undergoing elective surgeries. Through interviews and chart reviews, the collected data focused on baseline intellectual status, age, gender, ASA classification, level of education, comorbidities, vices, previous surgeries, maintenance medications, preoperative diagnostics, duration of surgery, duration of anesthesia, type of anesthetic technique, and pain scores at the recovery room and 24 hours postoperatively. Responses to the Short Portable Mental Status Questionnaire (SPMSQ), the Preoperative and Postoperative assessment forms and the Confusion Assessment Method (CAM) instrument were analyzed. Results: It was observed that there was a 2.5% incidence of postoperative delirium in the study population and among the risk factors assessed, polypharmacy and presence of moderate to severe pain scores on the first day following surgery were significant contributors in its occurrence. Conclusion: In this preliminary study, the incidence of postoperative delirium as well as the significant contributing factors were described. In succeeding investigations, it is recommended to extend the observation and follow-up periods.

Mortality and major postoperative complications within 1 year after vascular surgery: a prospective cohort study.

INTRODUCTION: Patients undergoing vascular procedures are prone to developing postoperative complications affecting their short­term mortality. Prospective reports describing the incidence of long­term complications after vascular surgery are lacking. OBJECTIVES: We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1­year mortality. PATIENTS AND METHODS: This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications. RESULTS: We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1­year follow­up. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1­year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1­year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1­year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001). CONCLUSIONS: The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3­fold increase in 1­year mortality.

Self-association of okadaic acid: structural and pharmacological significance.

Okadaic acid (OA) has been an invaluable pharmacological tool in the study of cellular signaling. The great affinity of this polyether for its targets together with its high specificity to inhibit certain protein phosphatases enables the differential study of these proteins. Crystallographic structures of protein phosphatases in complex with OA show a 1:1 protein to toxin ratio. Nevertheless, it has been found that OA is able to self-associate under certain conditions although very little is known about the importance of this phenomenon. Here we review the available knowledge on the latter topic and we report on the existence of an unusual self-associated tetrameric form. The structure of these oligomers is proposed based on spectroscopic data and molecular modeling calculations.