Management of Chronic Gastrointestinal Ischemia

Gastrointestinal ischemia results from a mismatch of blood supply to the main gastrointestinal arteries and the oxygen demand to maintain adequate metabolism. Three aortic branches supply blood to the gastrointestinal tract: the celiac artery, the superior mesenteric artery, and the inferior mesenteric artery. One of the main causes of chronic gastrointestinal ischemia (CGI) is stenotic or occlusive disease of the supplying gastrointestinal arteries. For a long time it was thought that only occlusive disease of two or more gastrointestinal arteries could lead to CGI. The introduction of functional testing has played a pivotal role in the diagnosis of CGI. Functional testing has shown that CGI is more common than previously thought because it can also be caused by single vessel disease. Further studies showed that a majority of patients with single vessel disease had sustained response after adequate treatment. Moreover, functional testing seems to be pivotal to select patients who will benefit from treatment, whether the cause is single- or multi-vessel disease. In this thesis we aimed to study different aspects of diagnosis and treatment of CGI. We studied the predictive value of functional testing in diagnosis of CGI, and determined the diagnostic accuracy of a new minimally invasive technique to detect ischemia in order to optimize the diagnosis of CGI. Furthermore, we assessed the risk factors for atherosclerotic disease of the abdominal arteries, being one of the main causes of CGI. We also evaluated the clinical success of revascularization in single vessel disease and response to vasodilation therapy in patients with non-occlusive CGI

Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality

Objectives: We determined the prevalence of classical risk factors for atherosclerosis and mortality risk in patients with CGI. Methods: A case-control study was conducted. Patients referred with suspected CGI underwent a standard work-up including risk factors for atherosclerosis, radiological imaging of abdominal vessels and tonometry. Cases were patients with confirmed atherosclerotic CGI. Controls were healthy subjects previously not known with CGI. The mortality risk was calculated as standardized mortality ratio derived from observed mortality, and was estimated with ten-year risk of death using SCORE and PREDICT. Results: Between 2006 and 2009, 195 patients were evaluated for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender, diabetes, hypercholesterolemia, a personal and family history of cardiovascular disease (CVD), and current smoking are highly associated with CGI. After adjustment, female gender (OR 2.14 95% CI 1.05-4.36), diabetes (OR 5.59, 95% CI 1.95-16.01), current smoking (OR 5.78, 95% CI 2.27-14.72), and history of CVD (OR 21.61, 95% CI 8.40-55.55) remained significant. CGI patients >55 years had a higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to controls. During follow-up of 116 person-years, standardized mortality rate was higher in CGI patients (3.55; 95% CI 1.70-6.52). Conclusions: Patients with atherosclerotic CGI have an increased estimated CVD risk, and severe excess mortality. S

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Waarde van combinatie iFOBT en calprotectine

__Vraagstelling__ Er is steeds meer aandacht voor fecesonderzoeken in de eerste lijn. Calprotectine, een eiwit dat bij ontstekingen wordt aangemaakt door neutrofielen en monocyten, lijkt te correleren met de aanwezigheid van een darmontsteking bij inflammatory bowel disease (IBD) zoals de ziekte van Crohn en colitis ulcerosa. De immunochemische fecaaloccultbloedtest (iFOBT) wordt gebruikt voor het opsporen van bloed, zoals bij het bevolkingsonderzoek darmkanker. De NHG-Standaarden bevelen beide onderzoeken niet aan. Desondanks vragen huisartsen de laatste jaren steeds vaker iFOBT aan. Wat is de diagnostische waarde van deze fecesonderzoeken in vergelijking met endoscopie en histologisch onderzoek voor het uitsluiten (negatief voorspellende waarde) van ernstige darmziekten, zoals IBD en colorectaal carcinoom (CRC)? __Zoekstructuur__ We zochten in PubMed met de zoektermen: (‘calprotectin’) AND (‘hemoglobin’ OR ‘haemoglobin’ OR ‘haemoglobulin’ OR ‘occult blood’) AND (‘bowel disease’ OR ‘bowel symptoms’ OR ‘intestinal symptoms’ OR ‘gastrointestinal symptoms’). __Resultaten__ We vonden een recent en relevant prospectief cohortonderzoek waarbij huisartsen gedurende zes maanden werd gevraagd om calprotectine en iFOBT te bepalen bij patiënten bij wie zij een darmziekte vermoedden en die zij verwezen naar de tweede lijn.5 Combinatie van calprotectine en iFOBT was hierbij de indextest, de referentietest was endoscopie met pathologisch-anatomisch onderzoek. Van de 2173 patiënten retourneerden 1043 patiënten (48%) hun feces en 755 (35%) ondergingen endoscopie. Afkappunt voor iFOBT was iedere detecteerbare hoeveelheid bloed en voor calprotectine ≥ 50 microg/g. De negatief voorspellende waarde (NVW) van iFOBT voor colorectaal carcinoom, hooggradige adenomen en IBD was respectievelijk 100%, 97,8% en 98,4% (gemist: 0 CRC en 5 IBD). De NVW van calprotectine was respectievelijk 98,2%, 93,8% en 98,9% (gemist: 5 CRC en 1 IBD). Bij combinatie van beide tests steeg de NVW voor een ernstige darmziekte van 96,2% naar 97,3% ten opzichte van iFOBT alleen (gemist: 0 CRC en 3 IBD). Bij het afkappunt van 10 microg/g voor iFOBT (afkappunt bij darmkankerscreening is 75 mg/ml ~15 microg/g (6)) werden drie gevallen (11%) van CRC gemist. Bij 1,3% (n = 28) van 2173 patiënten werd CRC gediagnosticeerd. __Bespreking__ Mowat et al. beschrijven een prospectief cohortonderzoek waarin bij een groot aantal patiënten werd gekeken naar de diagnostische waarde van iFOBT en calprotectine in de eerste lijn.5 Het is een nauwkeurig uitgevoerd en beschreven onderzoek, maar er zijn ook een aantal kanttekeningen. Van de patiënten die werden verwezen naar de tweede lijn heeft 52% geen feces ingeleverd en uiteindelijk ondering 35% van alle patiënten een endoscopie. Wij missen de patiëntkenmerken, de uiteindelijke diagnose en de reden waarom de helft van patiënten geen feces heeft ingeleverd. Ook is er bij een deel van de patiënten besloten om geen endoscopie uit te voeren zonder dat wordt uitgelegd waarom. Hierdoor kan er sprake zijn geweest van selectiebias en kan de sensitiviteit en de NVW overschat worden als met name zieke patiënten hebben deelgenomen aan het onderzoek. __Conclusie__ iFOBT geeft een betrouwbare uitsluiting van CRC. Calprotectine kan gebruikt worden voor het uitsluiten van IBD, maar kan CRC missen. Een combinatie van beide tests geeft een minimale stijging van de negatief voorspellende waarde. __Betekenis__ Vanwege de komst van het bevolkingsonderzoek coloncarcinoom en langere wachttijden voor endoscopie is er behoefte aan niet-invasieve tests in de eerste lijn om patiënten te kunnen selecteren die waarschijnlijk geen ernstige darmziekte hebben en die niet direct verwezen hoeven te worden. Deze fecesonderzoeken lijken een goede potentie te hebben om in de toekomst in het diagnostisch pakket van de huisarts opgenomen te worden. Gezien de mogelijke selectiebias moeten de resultaten van het besproken onderzoek echter met voorzichtigheid worden geïnterpreteerd en moeten we vooralsnog de huidige NHG-Standaarden blijven volgen