EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. Funding: Bill & Melinda Gates Foundation

Reversibilidad de la desnaturacion parcial en DNA

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Diverticulitis: An Update From the Age Old Paradigm

For a disease process that affects so many, we continue to struggle to define optimal care for patients with diverticular disease. Part of this stems from the fact that diverticular disease requires different treatment strategies across the natural history- acute, chronic and recurrent. To understand where we are currently, it is worth understanding how treatment of diverticular disease has evolved. Diverticular disease was rarely described in the literature prior to the 1900’s. In the late 1960’s and early 1970’s, Painter and Burkitt popularized the theory that diverticulosis is a disease of Western civilization based on the observation that diverticulosis was rare in rural Africa but common in economically developed countries. Previous surgical guidelines focused on early operative intervention to avoid potential complicated episodes of recurrent complicated diverticulitis (e.g., with free perforation) that might necessitate emergent surgery and stoma formation. More recent data has challenged prior concerns about decreasing effectiveness of medical management with repeat episodes and the notion that the natural history of diverticulitis is progressive. It has also permitted more accurate grading of the severity of disease and permitted less invasive management options to attempt conversion of urgent operations into the elective setting, or even avoid an operation altogether. The role of diet in preventing diverticular disease has long been debated. A high fiber diet appears to decrease the likelihood of symptomatic diverticulitis. The myth of avoid eating nuts, corn, popcorn, and seeds to prevent episodes of diverticulitis has been debunked with modern data. Overall, the recommendations for “diverticulitis diets” mirror those made for overall healthy lifestyle – high fiber, with a focus on whole grains, fruits and vegetables. Diverticulosis is one of the most common incidental findings on colonoscopy and the eighth most common outpatient diagnosis in the United States. Over 50% of people over the age of 60 and over 60% of people over age 80 have colonic diverticula. Of those with diverticulosis, the lifetime risk of developing diverticulitis is estimated at 10–25%, although more recent studies estimate a 5% rate of progression to diverticulitis. Diverticulitis accounts for an estimated 371,000 emergency department visits and 200,000 inpatient admissions per year with annual cost of 2.1–2.6 billion dollars per year in the United States. The estimated total medical expenditure (inpatient and outpatient) for diverticulosis and diverticulitis in 2015 was over 5.4 billion dollars. The incidence of diverticulitis is increasing. Besides increasing age, other risk factors for diverticular disease include use of NSAIDS, aspirin, steroids, opioids, smoking and sedentary lifestyle. Diverticula most commonly occur along the mesenteric side of the antimesenteric taeniae resulting in parallel rows. These spots are thought to be relatively weak as this is the location where vasa recta penetrate the muscle to supply the mucosa. The exact mechanism that leads to diverticulitis from diverticulosis is not definitively known. The most common presenting complaint is of left lower quadrant abdominal pain with symptoms of systemic unwellness including fever and malaise, however the presentation may vary widely. The gold standard cross-sectional imaging is multi-detector CT. It is minimally invasive and has sensitivity between 98% and specificity up to 99% for diagnosing acute diverticulitis. Uncomplicated acute diverticulitis may be safely managed as an out-patient in carefully selected patients. Hospitalization is usually necessary for patients with immunosuppression, intolerance to oral intake, signs of severe sepsis, lack of social support and increased comorbidities. The role of antibiotics has been questioned in a number of randomized controlled trials and it is likely that we will see more patients with uncomplicated disease treated with observation in the future Acute diverticulitis can be further sub classified into complicated and uncomplicated presentations. Uncomplicated diverticulitis is characterized by inflammation limited to colonic wall and surrounding tissue. The management of uncomplicated diverticulitis is changing. Use of antibiotics has been questioned as it appears that antibiotic use can be avoided in select groups of patients. Surgical intervention appears to improve patient’s quality of life. The decision to proceed with surgery is recommended in an individualized manner. Complicated diverticulitis is defined as diverticulitis associated with localized or generalized perforation, localized or distant abscess, fistula, stricture or obstruction. Abscesses can be treated with percutaneous drainage if the abscess is large enough. The optimal long-term strategy for patients who undergo successful non-operative management of their diverticular abscess remains controversial. There are clearly patients who would do well with an elective colectomy and a subset who could avoid an operation all together however, the challenge is appropriate risk-stratification and patient selection. Management of patients with perforation depends greatly on the presence of feculent or purulent peritonitis, the extent of contamination and hemodynamic status and associated comorbidities. Fistulas and strictures are almost always treated with segmental colectomy. After an episode of acute diverticulitis, routine colonoscopy has been recommended by a number of societies to exclude the presence of colorectal cancer or presence of alternative diagnosis like ischemic colitis or inflammatory bowel disease for the clinical presentation. Endoscopic evaluation of the colon is normally delayed by about 6 weeks from the acute episode to reduce the risk associated with colonoscopy. Further study has questioned the need for endoscopic evaluation for every patient with acute diverticulitis. Colonoscopy should be routinely performed after complicated diverticulitis cases, when the clinical presentation is atypical or if there are any diagnostic ambiguity, or patient has other indications for colonoscopy like rectal bleeding or is above 50 years of age without recent colonoscopy. For patients in whom elective colectomy is indicated, it is imperative to identify a wide range of modifiable patient co-morbidities. Every attempt should be made to improve a patient’s chance of successful surgery. This includes optimization of patient risk factors as well as tailoring the surgical approach and perioperative management. A positive outcome depends greatly on thoughtful attention to what makes a complicated patient “complicated”. Operative management remains complex and depends on multiple factors including patient age, comorbidities, nutritional state, severity of disease, and surgeon preference and experience. Importantly, the status of surgery, elective versus urgent or emergent operation, is pivotal in decision-making, and treatment algorithms are divergent based on the acuteness of surgery. Resection of diseased bowel to healthy proximal colon and rectal margins remains a fundamental principle of treatment although the operative approach may vary. For acute diverticulitis, a number of surgical approaches exist, including loop colostomy, sigmoidectomy with colostomy (Hartmann’s procedure) and sigmoidectomy with primary colorectal anastomosis. Overall, data suggest that primary anastomosis is preferable to a Hartman’s procedure in select patients with acute diverticulitis. Patients with hemodynamic instability, immunocompromised state, feculent peritonitis, severely edematous or ischemic bowel, or significant malnutrition are poor candidates. The decision to divert after colorectal anastomosis is at the discretion of the operating surgeon. Patient factors including severity of disease, tissue quality, and comorbidities should be considered. Technical considerations for elective cases include appropriate bowel preparation, the use of a laparoscopic approach, the decision to perform a primary anastomosis, and the selected use of ureteral stents. Management of the patient with an end colostomy after a Hartmann’s procedure for acute diverticulitis can be a challenging clinical scenario. Between 20 – 50% of patients treated with sigmoid resection and an end colostomy after an initial severe bout of diverticulitis will never be reversed to their normal anatomy. The reasons for high rates of permanent colostomies are multifactorial. The debate on the best timing for a colostomy takedown continues. Six months is generally chosen as the safest time to proceed when adhesions may be at their softest allowing for a more favorable dissection. The surgical approach will be a personal decision by the operating surgeon based on his or her experience. Colostomy takedown operations are challenging surgeries. The surgeon should anticipate and appropriately plan for a long and difficult operation. The patient should undergo a full antibiotic bowel preparation. Preoperative planning is critical; review the initial operative note and defining the anatomy prior to reversal. When a complex abdominal wall closure is necessary, consider consultation with a hernia specialist. Open surgery is the preferred surgical approach for the majority of colostomy takedown operations. Finally, consider ureteral catheters, diverting loop ileostomy, and be prepared for all anastomotic options in advance. Since its inception in the late 90’s, laparoscopic lavage has been recognized as a novel treatment modality in the management of complicated diverticulitis; specifically, Hinchey III (purulent) diverticulitis. Over the last decade, it has been the subject of several randomized controlled trials, retrospective studies, systematic reviews as well as cost-efficiency analyses. Despite being the subject of much debate and controversy, there is a clear role for laparoscopic lavage in the management of acute diverticulitis with the caveat that patient selection is key. Segmental colitis associated with diverticulitis (SCAD) is an inflammatory condition affecting the colon in segments that are also affected by diverticulosis, namely, the sigmoid colon. While SCAD is considered a separate clinical entity, it is frequently confused with diverticulitis or inflammatory bowel disease (IBD). SCAD affects approximately 1.4% of the general population and 1.15 to 11.4% of those with diverticulosis and most commonly affects those in their 6th decade of life. The exact pathogenesis of SCAD is unknown, but proposed mechanisms include mucosal redundancy and prolapse occurring in diverticular segments, fecal stasis, and localized ischemia. Most case of SCAD resolve with a high-fiber diet and antibiotics, with salicylates reserved for more severe cases. Relapse is uncommon and immunosuppression with steroids is rarely needed. A relapsing clinical course may suggest a diagnosis of IBD and treatment as such should be initiated. Surgery is extremely uncommon and reserved for severe refractory disease. While sigmoid colon involvement is considered the most common site of colonic diverticulitis in Western countries, diverticular disease can be problematic in other areas of the colon. In Asian countries, right-sided diverticulitis outnumbers the left. This difference seems to be secondary to dietary and genetic factors. Differential diagnosis might be difficult because of similarity with appendicitis. However accurate imaging studies allow a precise preoperative diagnosis and management planning. Transverse colonic diverticulitis is very rare accounting for less than 1% of colonic diverticulitis with a perforation rate that has been estimated to be even more rare. Rectal diverticula are mostly asymptomatic and diagnosed incidentally in the majority of patients and rarely require treatment. Giant colonic diverticula (GCD) is a rare presentation of diverticular disease of the colon and it is defined as an air-filled cystic diverticulum larger than 4 cm in diameter. The pathogenesis of GCD is not well defined. Overall, the management of diverticular disease depends greatly on patient, disease and surgeon factors. Only by tailoring treatment to the patient in front of us can we achieve optimal outcomes

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): Study protocol for a multicentre, observational trial

Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369.

Impact of COVID-19 on Cardiovascular Testing in the United States Versus the Rest of the World

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection