SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3, and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

The cGAS-STING signaling pathway is modulated by urolithin A.

During aging, general cellular processes, including autophagic clearance and immunological responses become compromised; therefore, identifying compounds that target these cellular processes is an important approach to improve our health span. The innate immune cGAS-STING pathway has emerged as an important signaling system in the organismal defense against viral and bacterial infections, inflammatory responses to cellular damage, regulation of autophagy, and tumor immunosurveillance. These key functions of the cGAS-STING pathway make it an attractive target for pharmacological intervention in disease treatments and in controlling inflammation and immunity. Here, we show that urolithin A (UA), an ellagic acid metabolite, exerts a profound effect on the expression of STING and enhances cGAS-STING activation and cytosolic DNA clearance in human cell lines. Animal laboratory models and limited human trials have reported no obvious adverse effects of UA administration. Thus, the use of UA alone or in combination with other pharmacological compounds may present a potential therapeutic approach in the treatment of human diseases that involves aberrant activation of the cGAS-STING pathway or accumulation of cytosolic DNA and this warrants further investigation in relevant transgenic animal models.

Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/-, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.

Increased expression of interleukin-6 gene in gastritis and gastric cancer.

Helicobacter pylori (H. pylori) induces an intense inflammatory response, mediated by proinflammatory cytokines, including interleukin (IL)-6 and its membrane receptor (IL-6R), which activates important signaling pathways in the development of gastric disease and cancer. We investigated the gene and protein expression of IL-6 and IL-6R and the influence of polymorphisms rs1800795, rs1800796, and rs1800797 on its gene expression together with H. pylori infection. Furthermore, an in-silico analysis was performed to support our results. Gastric biopsies were obtained from patients with gastric symptoms and patients with gastric cancer (GC) and were divided into groups (Control, Gastritis, and Cancer). H. pylori was detected by PCR. Real-time-qPCR was employed to determine gene expression, and western blot assay was used to analyze protein expression levels. PCR-RFLP was used to characterize IL-6 polymorphisms. Bioinformatics analyses were performed using the Gene Expression Omnibus (GEO) database and GEO2R to screen out differentially expressed genes (DEGs). H. pylori was detected in 43.3% of the samples. Statistically significant differences were found for IL-6 (P=0.0001) and IL-6R (P=0.0005) genes among the three groups, regardless of the presence of H. pylori. Among patients with H. pylori infection, the IL-6 and IL-6R gene and protein expressions were significantly increased, highlighting IL-6 gene overexpression in patients with GC. No statistically significant differences were found for the rs1800795, rs1800796, and rs1800797 polymorphisms compared to IL-6 gene expression. The results indicated that the IL-6 polymorphisms do not influence its expression, but IL-6 and IL-6R expression seems to be altered by the presence of H. pylori.

Intraoperative ultrasound imaging in the surgical treatment of congenital hyperinsulinism: prospective, blinded study.

BACKGROUND: In congenital hyperinsulinism (CHI), preoperative prediction of the histological subtype (focal, diffuse, or atypical) relies on genetics and 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine (18F-DOPA) PET-CT. The scan also guides the localization of a potential focal lesion along with perioperative frozen sections. Intraoperative decision-making is still challenging. This study aimed to describe the characteristics and potential clinical impact of intraoperative ultrasound imaging (IOUS) during CHI surgery. METHODS: This was a prospective, observational study undertaken at an expert centre over a 2-year interval. IOUS was performed blinded to preoperative diagnostic test results (genetics and 18F-DOPA PET-CT), followed by unblinding and continued IOUS during pancreatic resection. Characteristics and clinical impact were assessed using predefined criteria. RESULTS: Eighteen consecutive, surgically treated patients with CHI, with a median age of 5.5 months, were included (focal 12, diffuse 3, atypical 3). Focal lesions presented as predominantly hypoechoic, oval lesions with demarcated or blurred margins. Patients with diffuse and atypical disease had varying echogenicity featuring stranding and non-shadowing hyperechoic foci in three of six, whereas these characteristics were absent from those with focal lesions. The blinded IOUS-based subclassification was correct in 17 of 18 patients; one diffuse lesion was misclassified as focal. IOUS had an impact on the surgical approach in most patients with focal lesions (9 of 12), and in those with diffuse (2 of 3) and atypical (2 of 3) disease when the resection site was close to the bile or pancreatic duct. CONCLUSION: Uniform IOUS characteristics made all focal lesions identifiable. IOUS had a clinical impact in 13 of 18 patients by being a useful real-time supplementary modality in terms of localizing focal lesions, reducing the need for frozen sections, and preserving healthy tissue and delicate structures.

Exploring the limits of prolonged apnoea with high-flow nasal oxygen: an observational study.

High-flow nasal oxygen is increasingly used for oxygenation during apnoea. Extending apnoea duration using this technique has mainly been investigated during minor laryngeal surgery, but it is unclear how long it can be administered for before it should be discontinued due to acidosis. We aimed to describe the dynamics of arterial blood gases during apnoeic oxygenation with high-flow nasal oxygen with jaw thrust only, to explore the limits of this technique. We included adult orthopaedic patients scheduled for general anaesthesia. After pre-oxygenation, anaesthesia with neuromuscular blockade was induced and high-flow nasal oxygen (70 l.min-1 ) was continued with jaw thrust as the only means of airway management, with monitoring of vital signs and arterial blood gas sampling every 5 minutes. Apnoeic oxygenation with high-flow nasal oxygen was discontinued when arterial carbon dioxide tension (PaCO2 ) exceeded 12 kPa or pH fell to 7.15. This technique was used in 35 patients and median (IQR [range]) apnoea time was 25 (20-30 [20-45]) min and was discontinued in all patients when pH fell to 7.15. The mean (SD) PaCO2 increase was 0.25 (0.06) kPa.min-1 but it varied substantially (range 0.13-0.35 kPa.min-1 ). Mean (SD) arterial oxygen tension was 48.6 (11.8) kPa when high-flow nasal oxygen was stopped. Patients with apnoea time > 25 minutes were significantly older (p = 0.025). We conclude that apnoeic oxygenation with high-flow nasal oxygen resulted in a significant respiratory acidosis that varies substantially on the individual level, but oxygenation was maintained.

Increased expression of interleukin-6 gene in gastritis and gastric cancer

Helicobacter pylori (H. pylori) induces an intense inflammatory response, mediated by proinflammatory cytokines, including interleukin (IL)-6 and its membrane receptor (IL-6R), which activates important signaling pathways in the development of gastric disease and cancer. We investigated the gene and protein expression of IL-6 and IL-6R and the influence of polymorphisms rs1800795, rs1800796, and rs1800797 on its gene expression together with H. pylori infection. Furthermore, an in-silico analysis was performed to support our results. Gastric biopsies were obtained from patients with gastric symptoms and patients with gastric cancer (GC) and were divided into groups (Control, Gastritis, and Cancer). H. pylori was detected by PCR. Real-time-qPCR was employed to determine gene expression, and western blot assay was used to analyze protein expression levels. PCR-RFLP was used to characterize IL-6 polymorphisms. Bioinformatics analyses were performed using the Gene Expression Omnibus (GEO) database and GEO2R to screen out differentially expressed genes (DEGs). H. pylori was detected in 43.3% of the samples. Statistically significant differences were found for IL-6 (P=0.0001) and IL-6R (P=0.0005) genes among the three groups, regardless of the presence of H. pylori. Among patients with H. pylori infection, the IL-6 and IL-6R gene and protein expressions were significantly increased, highlighting IL-6 gene overexpression in patients with GC. No statistically significant differences were found for the rs1800795, rs1800796, and rs1800797 polymorphisms compared to IL-6 gene expression. The results indicated that the IL-6 polymorphisms do not influence its expression, but IL-6 and IL-6R expression seems to be altered by the presence of H. pylori.

Influence of Nodal signalling on pluripotency factor expression, tumour cell proliferation and cisplatin-sensitivity in testicular germ cell tumours.

BACKGROUND: Testicular germ cell tumours (TGCTs) are characterised by an overall high cisplatin-sensitivity which has been linked to their continued expression of pluripotency factors. Recently, the Nodal signalling pathway has been implicated in the regulation of pluripotency factor expression in fetal germ cells, and the pathway could therefore also be involved in regulating expression of pluripotency factors in malignant germ cells, and hence cisplatin-sensitivity in TGCTs. METHODS: We used in vitro culture of the TGCT-derived cell line NTera2, ex vivo tissue culture of primary TGCT specimens and xenografting of NTera2 cells into nude mice in order to investigate the consequences of manipulating Nodal and Activin signalling on pluripotency factor expression, apoptosis, proliferation and cisplatin-sensitivity. RESULTS: The Nodal signalling factors were markedly expressed concomitantly with the pluripotency factor OCT4 in GCNIS cells, seminomas and embryonal carcinomas. Despite this, inhibition of Nodal and Activin signalling either alone or simultaneously did not affect proliferation or apoptosis in malignant germ cells in vitro or ex vivo. Interestingly, inhibition of Nodal signalling in vitro reduced the expression of pluripotency factors and Nodal pathway genes, while stimulation of the pathway increased their expression. However, cisplatin-sensitivity was not affected following pharmacological inhibition of Nodal/Activin signalling or siRNA-mediated knockdown of the obligate co-receptor CRIPTO in NTera2 cells in vitro or in a xenograft model. CONCLUSION: Our findings suggest that the Nodal signalling pathway may be involved in regulating pluripotency factor expression in malignant germ cells, but manipulation of the pathway does not appear to affect cisplatin-sensitivity or tumour cell proliferation.

Red blood cell transfusion in surgery: an observational study of the trends in the USA from 2011 to 2016.

Guidelines recommend restrictive red blood cell transfusion strategies. We conducted an observational study to examine whether the rate of peri-operative red blood cell transfusion in the USA had declined during the period from 01 January 2011 to 31 December 2016. We included 4,273,168 patients from all surgical subspecialties. We examined parallel trends in rates of the following: pre-operative transfusion; prevalence of bleeding disorders and coagulopathy; and minimally invasive procedures. To account for changes in population and procedure characteristics, we performed multivariable logistic regression to assess whether the risk of receiving a transfusion had declined over the study period. Clinical outcomes included peri-operative myocardial infarction, stroke and all-cause mortality at 30 days. Peri-operative red blood cell transfusion rates declined from 37,040/441,255 (8.4%) in 2011 to 46,845/1,000,195 (4.6%) in 2016 (p < 0.001) across all subspecialties. Compared with 2011, the corresponding adjusted OR (95%CI) for red blood cell transfusion decreased gradually from 0.88 (0.86-0.90) in 2012 to 0.51 (0.50-0.51) in 2016 (p < 0.001). Pre-operative red blood cell transfusion rates and the prevalence of bleeding disorders decreased, whereas haematocrit levels and the proportion of minimally invasive procedures increased. Compared with 2011, the adjusted hazard ratios (95%CI) in 2012 and 2016 were 0.96 (0.90-1.02) and 1.05 (0.99-1.11) for myocardial infarction, 0.91 (0.83-0.99) and 0.99 (0.92-1.07) for stroke and 0.98 (0.94-1.02) and 0.99 (0.96-1.03) for all-cause mortality. Use of peri-operative red blood cell transfusion declined from 2011 to 2016. This was not associated with an increase in adverse clinical outcomes.

The EuroSIDA study: 25 years of scientific achievements.

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

Baseline findings of the population-based, randomized, multifaceted Danish cardiovascular screening trial (DANCAVAS) of men aged 65-74 years.

BACKGROUND: The challenge of managing age-related diseases is increasing; routine checks by the general practitioner do not reduce cardiovascular mortality. The aim here was to reduce cardiovascular mortality by advanced population-based cardiovascular screening. The present article reports the organization of the study, the acceptability of the screening offer, and the relevance of multifaceted screening for prevention and management of cardiovascular disease. METHODS: Danish men aged 65-74 years were invited randomly (1 : 2) to a cardiovascular screening examination using low-dose non-contrast CT, ankle and brachial BP measurements, and blood tests. RESULTS: In all, 16 768 of 47 322 men aged 65-74 years were invited and 10 471 attended (uptake 62·4 per cent). Of these, 3481 (33·2 per cent) had a coronary artery calcium score above 400 units. Thoracic aortic aneurysm was diagnosed in the ascending aorta (diameter 45 mm or greater) in 468 men (4·5 per cent), in the arch (at least 40 mm) in 48 (0·5 per cent) and in the descending aorta (35 mm or more) in 233 (2·2 per cent). Abdominal aortic aneurysm (at least 30 mm) and iliac aneurysm (20 mm or greater) were diagnosed in 533 (5·1 per cent) and 239 (2·3 per cent) men respectively. Peripheral artery disease was diagnosed in 1147 men (11·0 per cent), potentially uncontrolled hypertension (at least 160/100 mmHg) in 835 (8·0 per cent), previously unknown atrial fibrillation confirmed by ECG in 50 (0·5 per cent), previously unknown diabetes mellitus in 180 (1·7 per cent) and isolated severe hyperlipidaemia in 48 men (0·5 per cent). In all, 4387 men (41·9 per cent), excluding those with potentially uncontrolled hypertension, were referred for additional cardiovascular prevention. Of these, 3712 (35·5 per cent of all screened men, but 84·6 per cent of those referred) consented and were started on medication. CONCLUSION: Multifaceted cardiovascular screening is feasible and may optimize cardiovascular disease prevention in men aged 65-74 years. Uptake is lower than in aortic aneurysm screening.

Association of preoperative anaemia with postoperative morbidity and mortality: an observational cohort study in low-, middle-, and high-income countries.

BACKGROUND: Anaemia is associated with poor postoperative outcomes, but few studies have described the impact of preoperative anaemia in low- and middle- (LMICs), and high-income countries (HICs). METHODS: This was a planned analysis of data collected during an international 7 day cohort study of adults undergoing elective inpatient surgery. The primary outcome was in-hospital death, and the secondary outcomes were in-hospital complications. Anaemia was defined as haemoglobin <12 g dl-1 for females and <13 g dl-1 for males. Hierarchical three-level mixed-effect logistic regression models were constructed to examine the associations between preoperative anaemia and outcomes. RESULTS: We included 38 770 patients from 474 hospitals in 27 countries of whom 11 675 (30.1%) were anaemic. Of these, 6886 (17.8%) patients suffered a complication and 198 (0.5%) died. Patients from LMICs were younger with lower ASA physical status scores, but a similar prevalence of anaemia [LMIC: 5072 (32.5%) of 15 585 vs HIC: 6603 (28.5%) of 23 185]. Patients with moderate [odds ratio (OR): 2.70; 95% confidence interval (CI): 1.88-3.87] and severe anaemia (OR: 4.09; 95% CI: 1.90-8.81) were at an increased risk of death in both HIC and LMICs. Complication rates increased with the severity of anaemia. Compared with patients in LMICs, those in HICs experienced fewer complications after an interaction term analysis [LMIC (OR: 0.92; 95% CI: 0.87-0.97) vs HIC (OR: 0.86; 95% CI: 0.84-0.87); P<0.01]. CONCLUSIONS: One-third of patients undergoing elective surgery are anaemic. These patients have an increased risk of complications and death. The prevalence of anaemia is similar amongst patients in LMICs despite their younger age and lower risk profile. CLINICAL TRIAL REGISTRATION: ISRCTN51817007.

Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the Nomenclature of Cognitive Change Associated With Anaesthesia and Surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the Nomenclature of Cognitive Change Associated with Anaesthesia and Surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines (Diagnostic and Statistical Manual for Mental Disorders, fifth edition [DSM-5] and National Institute for Aging and the Alzheimer Association [NIA-AA]) are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the Nomenclature of Cognitive Change Associated with Anaesthesia and Surgery-20181.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

High intraoperative inspiratory oxygen fraction and risk of major respiratory complications.

BACKGROUND: High inspiratory oxygen fraction ( FIO2 ) may improve tissue oxygenation but also impair pulmonary function. We aimed to assess whether the use of high intraoperative FIO2 increases the risk of major respiratory complications. METHODS: We studied patients undergoing non-cardiothoracic surgery involving mechanical ventilation in this hospital-based registry study. The cases were divided into five groups based on the median FIO2 between intubation and extubation. The primary outcome was a composite of major respiratory complications (re-intubation, respiratory failure, pulmonary oedema, and pneumonia) developed within 7 days after surgery. Secondary outcomes included 30-day mortality. Several predefined covariates were included in a multivariate logistic regression model. RESULTS: The primary analysis included 73 922 cases, of whom 3035 (4.1%) developed a major respiratory complication within 7 days of surgery. For patients in the high- and low-oxygen groups, the median FIO2 was 0.79 [range 0.64-1.00] and 0.31 [0.16-0.34], respectively. Multivariate logistic regression analysis revealed that the median FIO2 was associated in a dose-dependent manner with increased risk of respiratory complications (adjusted odds ratio for high vs low FIO2 1.99, 95% confidence interval [1.72-2.31], P -value for trend <0.001). This finding was robust in a series of sensitivity analyses including adjustment for intraoperative oxygenation. High median FIO2 was also associated with 30-day mortality (odds ratio for high vs low FIO2 1.97, 95% confidence interval [1.30-2.99], P -value for trend <0.001). CONCLUSIONS: In this analysis of administrative data on file, high intraoperative FIO2 was associated in a dose-dependent manner with major respiratory complications and with 30-day mortality. The effect remained stable in a sensitivity analysis controlled for oxygenation. CLINICAL TRIAL REGISTRATION: NCT02399878.

Insulin resistance in vascular endothelial cells promotes intestinal tumour formation.

The risk of several cancers, including colorectal cancer, is increased in patients with obesity and type 2 diabetes, conditions characterised by hyperinsulinaemia and insulin resistance. Because hyperinsulinaemia itself is an independent risk factor for cancer development, we examined tissue-specific insulin action in intestinal tumour formation. In vitro, insulin increased proliferation of intestinal tumour epithelial cells by almost two-fold in primary culture of tumour cells from ApcMin/+ mice. Surprisingly, targeted deletion of insulin receptors in intestinal epithelial cells in ApcMin/+ mice did not change intestinal tumour number or size distribution on either a low or high-fat diet. We therefore asked whether cells in the tumour stroma might explain the association between tumour formation and insulin resistance. To this end, we generated ApcMin/+ mice with loss of insulin receptors in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules and increased the frequency of neutrophils in tumours. We conclude that although insulin is mitogenic for intestinal tumour cells in vitro, impaired insulin action in the tumour microenvironment may be more important in conditions where hyperinsulinaemia is secondary to insulin resistance. Insulin resistance in tumour endothelial cells produces an activated, proinflammatory state that promotes tumorigenesis. Improvement of endothelial dysfunction may reduce colorectal cancer risk in patients with obesity and type 2 diabetes.

Ventilation via the 2.4 mm internal diameter Tritube® with cuff - new possibilities in airway management.

BACKGROUND: A small tube may facilitate tracheal intubation and improve surgical access. We describe our initial experience with the Tritube® that is a novel cuffed endotracheal tube with a 2.4 mm internal diameter. METHODS: The Tritube® was used in seven adult Ear-Nose-and Throat surgical patients with airway narrowing or whose surgical access was facilitated by this small-bore endotracheal tube. Ventilation through Tritube® is performed with the manually operated Ventrain® -ventilator that allows active suctioning during expiration, therefore facilitating normoventilation through small diameter airways. RESULTS: The small diameter of Tritube® seemed to improve glottis visualisation during intubations and gave excellent working conditions for surgery. Two patients were intubated awake with a flexible scope and a guide wire or with an angulated video laryngoscope. One patient had almost complete glottic occlusion that just allowed for passage of the Tritube® . Adequate ventilation was achieved in all patients and intratracheal pressure was kept between 5 and 20 cm H2 O. The tube was well tolerated after emergence from anaesthesia and kept intratracheally in five awake patients in the post-operative recovery unit, in one case for more than 1 h. Ventilating with Ventrain® through Tritube® demands meticulous breath by breath measurement and adjustment of the intratracheal pressure. CONCLUSION: The 2.4 mm internal diameter Tritube® seems to facilitate tracheal intubation and to provide unprecedented view of the intubated airway during oral, pharyngeal, laryngeal or tracheal procedures in adults. This technique has the potential to replace temporary tracheostomy, jet-ventilation or extra-corporal membrane oxygenation in selected patients.