Search

Transcatheter aortic valve implantation is a fast-growing procedure. Expanding to low-risk patients, it has surpassed surgical aortic valve implantation in frequency and has been associated with excellent outcomes. Stroke is a devastating complication after transcatheter aortic valve implantation. Silent brain infarcts identified by diffusion-weighted magnetic resonance imaging are present in most patients following transcatheter aortic valve implantation. Postoperative delirium and cognitive dysfunction are common neurologic complications. The stroke and silent brain infarcts are likely caused by particulate emboli released during the procedure. Intravascularly positioned cerebral embolic protection devices are designed to prevent debris from entering the aortic arch vessels to avoid stroke. Despite promising design, randomized clinical trials have not demonstrated a reduction in stroke in patients receiving cerebral embolic protection devices. Similarly, the association of cerebral embolic protection devices with silent brain infarcts, post-operative delirium and cognitive dysfunction is uncertain. Monitored anesthesia care or conscious sedation is as safe as general anesthesia and is associated with lower cost but different anesthetic techniques have not been shown to decrease stroke risk, postoperative delirium, or cognitive dysfunction. Anesthesiologists play important roles in providing perioperative care including management of neurologic events in patients undergoing transcatheter aortic valve implantation. Large randomized clinical trials are needed that focus on the correlation between perioperative interventions and neurologic outcomes.

Rates of pregnancies affected by nonalcoholic fatty liver disease (NAFLD) in the United States have nearly tripled in the last decade and NAFLD confers increased perinatal risks, such as hypertensive complications, postpartum hemorrhage, and preterm birth.1 Rates of cirrhosis in pregnancy are also rising,2 although estimates specific to NAFLD cirrhosis are lacking. Whether NAFLD cirrhosis confers differential perinatal risks than other causes of cirrhosis in pregnancy is also unknown.

ispartof: INTENSIVE CARE MEDICINE vol:47 issue:3 pages:344-348 ispartof: location:United States status: published

Positron emission tomography (PET) offers an incredible wealth of diverse research applications in vascular disease, providing a depth of molecular, functional, structural, and spatial information. Despite this, vascular PET imaging has not yet assumed the same clinical use as vascular ultrasound, CT, and MR imaging which provides information about late-onset, structural tissue changes. The current clinical utility of PET relies heavily on visual inspection and suboptimal parameters such as SUVmax; emerging applications have begun to harness the tool of whole-body PET to better understand the disease. Even still, without automation, this is a time-consuming and variable process. This review summarizes PET applications in vascular disorders, highlights emerging AI methods, and discusses the unlocked potential of AI in the clinical space.

PURPOSE: Further diagnostic testing may be required after a coronary computed tomography angiography (CTA) showing suspected coronary stenosis. Whether myocardial perfusion imaging (MPI) provides further prognostic information post-CTA remains debated. We evaluated the prognosis for patients completing CTA stratified for post-CTA diagnostic work-up using real-world data.METHODS: We identified all patients in our uptake area with angina symptoms undergoing first-time CTA over a 10-year period. Follow-up time was a median of 3.7 years [1.9-5.8]. The primary endpoint was a composite of myocardial infarction or death. The secondary endpoint was late revascularization.RESULTS: During the study period 53,351 patients underwent CTA. Of these, 24% were referred for further down-stream testing, 3,547 (7%) to MPI and 9,135 (17%) to invasive coronary angiography (ICA). The primary and secondary endpoints occurred in 2,026 (3.8%) and 954 (1.8%) patients. Patient-characteristic-adjusted hazard ratios for the primary and secondary endpoint using patients with a normal CTA as reference were 1.37 (1.21-1.55) and 2.50 (1.93-3.23) for patient treated medically, 1.68 (1.39-2.03) and 6.13 (4.58-8.21) for patients referred to MPI and 1.94 (1.69-2.23) and 9.18 (7.16-11.78) for patients referred for ICA, respectively. Adjusted analysis with stratification for disease severity at CTA showed similar hazard ratios for patients treated medically after CTA and patients referred for MPI and treated medically after the MPI.CONCLUSION: In patients completing coronary CTA, second-line MPI testing seems to identify patients at low risk of future events. MPI seems to have the potential to act as gatekeeper for ICA after coronary CTA.

OBJECTIVES: The aim of this study was to examine prevalence, predictors, and impact of coronary artery calcium (CAC) across different risk factor burdens on the prevalence of obstructive coronary artery disease (CAD) and future coronary heart disease (CHD) risk in young patients.BACKGROUND: The interplay of risk factors and CAC for predicting CHD in young patients aged ≤45 years is not clear.METHODS: The study included 3,691 symptomatic patients (18-45 years of age) from the WDHR (Western Denmark Heart Registry) undergoing coronary computed tomographic angiography. CHD events were myocardial infarction and late revascularization.RESULTS: During a median of 4.1 years of follow-up, 57 first-time CHD events occurred. In total, 3,180 patients (86.1%) had CAC = 0 and 511 patients (13.9%) had CAC > 0. Presence of CAC increased with number of risk factors (odds ratio: 4.5 [95% CI: 2.7-7.3] in patients with >3 vs 0 risk factors). The prevalence of obstructive CAD at baseline and the rate of future CHD events increased in a stepwise manner with both higher CAC and number of risk factors. The CHD event rate was lowest at 0.5 (95% CI: 0.1-3.6) per 1,000 person-years in patients with 0 risk factors and CAC = 0. Among patients with >3 risk factors, the event rate was 3.1 (95% CI: 1.0-9.7) in patients with CAC = 0 compared with 36.3 (95% CI: 17.3-76.1) in patients with CAC >10.CONCLUSIONS: In young patients, there is a strong interplay between CAC and risk factors for predicting the presence of obstructive CAD and for future CHD risk. In the presence of risk factors, even a low CAC score is a high-risk marker. These results demonstrate the importance of assessing risk factors and CAC simultaneously when assessing risk in young patients.

Background Few reports have evaluated prognostic modelling studies of tools used for surgical decision-making. This systematic review aimed to describe and critically appraise studies that have developed or validated multivariable prognostic models for post-operative liver decompensation following partial hepatectomy. Methods This study was designed using the CHARMS checklist. Following a comprehensive literature search, two reviewers independently screened candidate references for inclusion and abstracted relevant study details. Qualitative assessment was performed using the PROBAST tool. Results We identified 36 prognostic modelling studies; 25 focused on development only, 3 developed and validated models, and 8 validated pre-existing models. None compared routine use of a prognostic model against standard clinical practice. Most studies used single-institution, retrospective cohort designs, conducted in Eastern populations. In total, 15 different outcome definitions for post-operative liver decompensation events were used. Statistical concerns surrounding model overfitting, performance assessment, and internal validation led to high risk of bias for all studies. Conclusions Current prognostic models for post-operative liver decompensation following partial hepatectomy may not be valid for routine clinical use due to design and methodologic concerns. Landmark resources and reporting guidelines such as the TRIPOD statement may assist researchers, and additionally, model impact assessment studies represent opportunities for future research.

Background The ratio of early mitral inflow velocity to early diastolic strain rate (E/e'sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure. We hypothesize that E/e'sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e'. Methods & results Consecutive patients undergoing isolated CABG at Gentofte Hospital (n = 652) were included. The mean age of the study population was 67 ± 9 years, 84% were male, mean LVEF was 50 ± 11%. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11.2%) died. Both E/e' and E/e'sr were significant predictors in univariable models. In a multivariable model, E/e'sr remained an independent predictor of outcome (HR:1.05 [1.01–1.10], p = 0.049, per 10 cm increase) whereas E/e' did not (HR:1.05 [0.99–1.11], p = 0.053, per 1-unit increase). The relationship between E/e'sr, and the outcome was significantly modified by GLS (p for interaction = 0.043). In the multivariable model, E/e'sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02–1.36], p = 0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99–1.10], p = 0.14). E/e' was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e'sr improved net reclassification with 33% when added to EuroSCOREII. Conclusion Following CABG, preoperative E/e'sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e'.

Country- and ethnicity-specific reference values for echocardiographic parameters are necessary for decision making. No prior studies have examined reference values in adults from the Amazon Basin of Brazil. We performed echocardiographic examinations in 290 healthy adults (mean age 37 ± 14 years, 40% male) from the Brazilian Amazon. Left ventricular (LV) dimensions and volumes were obtained and indexed to body surface area. We also assessed systolic (LV ejection fraction [LVEF] and global longitudinal strain [GLS]) and diastolic function. LV dimensions and volumes were larger in males compared to females, but after indexation only volumes remained larger (P

To examine local practice for non-malignant polyps and to calculate morbidity and mortality associated with bowel resection for this indication. This retrospective cohort study was conducted by reviewing our local gastrointestinal pathology database over a five-year period to identify colonic resections performed for benign polyps. Using search terms “polyp” and “adenoma,” 272 cases were identified. Exclusion criteria included: cancer diagnosis, emergency surgeries, multiple resections, and subtotal colectomies for polyposis. 106 patients were included in the study. Primary outcome was perioperative mortality. Secondary outcomes included patient morbidity, characteristics of polyps requiring surgery, and the number of patients referred for a second endoscopic opinion prior to proceeding with surgery. 64 male and 42 female patients with a mean age of 65.3 years (± 8.6 years) underwent colon resection for benign polyps. The mean polyp size was 32.7 mm (± 19.5 mm). 30 patients (28.6%) had polyps equal to or less than 2 cm. Most of the polyps described were sessile (n = 55, 51.9%) and located in the right colon (n = 84, 79.3%). Endoscopic resection was attempted in 31 patients (29.2%), and five cases (4.7%) were referred for a second endoscopic opinion prior to proceeding with surgery. Endoscopists incorrectly felt that polyps were malignant in 62 cases (58.5%). Using Clavien-Dindo classification, most patients had no complications n = 36 (34.0%) or minor complications n = 41 (38.7%). Twelve patients (11.3%) had complications that required antibiotics, blood transfusions, or total parental nutrition. Nine patients (8.5%) required surgical or endoscopic management. Six patients (5.7%) required ICU admission. Mortality rate was 1.9% (n = 2). Surgery for benign colonic polyps is associated with significant morbidity and mortality. These findings reveal a gap in endoscopic management of benign colonic polyps.

We investigated the impact of genetic variants in OCT1 (SLC22A1) on morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) pharmacokinetics in adult patients scheduled for major surgery. Blood samples were taken before and 5, 10, 15, 30, 45, 60 and 90 min after a bolus of morphine (0.15 mg/kg). Patients were genotyped for the genetic variants (rs12208357, rs34059508, rs72552763 and rs34130495) in OCT1. Eighty-six patients completed the trial. The mean difference (95% confidence interval) for dose adjusted morphine, M3G and M6G AUC was 0.9 (−0.7–2.4), −5.9 (−11.8 to −0.03) and −1.1 (−2.5–0.4) h/L*10 −6, respectively, in patients with two reduced function alleles compared to patients with no reduced function alleles in OCT1. Accordingly, the (AUC M3G/Dose)/(AUC morphine/Dose) and (AUC M6G/Dose)/(AUC morphine/Dose) ratio was reduced, −1.8 (−3.2 to −0.4) and −0.4 (−0.7 to −0.03), respectively, when comparing the same groups. OCT1 variants had no influence on the experience of pain, adverse events or the number of PCA doses used. In conclusion, genetic variants in OCT1 had a small and clinically unimportant impact on the exposure of morphine after intravenous administration. Our results do not support pre-emptive genotyping for OCT1 prior to morphine administration in patients scheduled for major surgery.

ObjectiveTo assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality.MethodsIn the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia.ResultsOut of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb ConclusionModerate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.

Fat oxidation decreases with age, yet no studies have previously investigated if aging affects the maximal fat oxidation rate (MFO) during exercise in men and women differently. We hypothesized that increased age would be associated with a decline in MFO and this would be more pronounced in women due to menopause, compared with men. In this cross-sectional study design, 435 (247/188, male/female) subjects of varying ages performed a DXA scan, a submaximal graded exercise test and a maximal oxygen uptake test, to measure MFO and cardiorespiratory fitness (CRF) by indirect calorimetry. Subjects were stratified into 12 groups according to sex (male/female), age (55 years), CRF (below average and above average). Women aged 55 years. In summary, we found that women aged Novelty: Maximal fat oxidation rate is higher in young women compared with men. This sex-related difference is attenuated after the age of 45 years. Cardiorespiratory fitness does not influence this sex-related difference.

Physical exercise results in a duration and intensity-dependent vascular response in healthy human tendon. In overused (tendinopathy) and damagedtendon, angiogenic pathways are activated and neovascularization is observed.Whereas no direct relationship exists between the amount of neovessels and degree of tendinopathy symptoms, almost all tendinopathic patients have elevated neovascularization and tendon blood flow, as assessed by Doppler ultrasound methodology. The enhanced flow in tendinopathy can be successfully abolished by heavy resistance training. Already in the early time-phase of tendinopathy (

Appropriate patient selection for liver resection in hepatocellular carcinoma (HCC) is critical to mitigation of major liver-related postoperative complications. Currently, no standard prognostic tool exists to predict the risk of postoperative liver decompensation events (POLDEs) after partial hepatectomy for patients with cirrhosis and HCC. This study aimed to identify independent preoperative predictors of POLDEs for future development of prognostic tools to improve surgical decision-making. This population-based, retrospective cohort study investigated patients with cirrhosis and incident HCC between 2007 and 2017, identified using administrative health data from Ontario, Canada. The occurrence of a POLDE or death within 2 years after surgery was described. Multivariable Cox regression identified independent predictors of POLDE-free survival, as well as cause-specific hazards for POLDEs and death. Among 611 patients with cirrhosis and HCC who underwent liver resection, 160 (26.2%) experienced at least one POLDE, and 189 (30.9%) died within 2 years after surgery. Diabetes, cirrhosis etiology, major liver resection, and previous non-malignant decompensation were independent predictors of POLDE-free survival. Except for extent of resection, the same risk factors were associated with POLDEs in the cause-specific analysis. In contrast, only age and history of previous non-malignant decompensation were independent predictors of mortality. Among patients with cirrhosis undergoing resection for HCC, patient and disease-related factors are associated with POLDEs and POLDE-free survival. These factors can be used both to inform clinical practice and to advance the development of preoperative prognostic tools, which may lead to improved outcomes for this population.

Context Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, although not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown. Objective To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and to elucidate the potential role of serum-prolactin concentrations in pregnancy. Materials and Methods Pregnant women from the Odense Child Cohort provided blood samples for analysis of 5 major PFAS (n = 1300) and prolactin concentrations (n = 924). They subsequently provided information about the duration of breastfeeding in questionnaires at 3 and 18 months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations. Results Increased serum concentrations of perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorononanoic acid, and ∑PFAS were associated with a 16% (95% CI: 4%-30%), 14% (95% CI: 2%-26%), 14% (95% CI: 3%-27%), and 20% (95% CI: 6%-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations. Conclusions These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences.

Aims Aortic valve calcification (AVC) detected by non-contrast computed tomography (NCCT) associates with morbidity and mortality in patients with aortic valve stenosis. However, the importance of AVC in the general population is sparsely evaluated. We intend to describe the associations between AVC score on NCCT and echocardiographic findings as left atrial (LA) dilatation, left ventricular (LV) hypertrophy, aortic valve area (AVA), peak velocity, mean gradient, and aortic valve replacement (AVR) in a population with AVC scores ≥300 AU. Methods and results Of 10 471 males aged 65–74 years from the Danish Cardiovascular Screening trial (DANCAVAS), participants with AVC score ≥300 AU were invited for transthoracic echocardiography and 828 (77%) of 1075 accepted the invitation. AVC scores were categorized (300–599, 600–799, 800–1199, and ≥1200 AU). AVR was obtained from registries. AVC was significantly associated with a steady increase in LA dilation (10.5%, 16.3%, 15.8%, 19.6%, P = 0.031), LV hypertrophy (3.9%, 6.6%, 8.9%, 10.1%, P = 0.021), peak velocity (1.7, 1.9, 2.1, 2.8 m/s, P = 0001), mean gradient (6, 8, 11, 19 mmHg, P = 0.0001), and a decrease in AVA (2.0, 1.9, 1.7, 1.3 cm2, P = 0.0001). The area under the curve was 0.79, 0.93, and 0.92 for AVA ≤1.5 cm2, peak velocity ≥3.0 m/s, and mean gradient ≥20 mmHg, respectively, and the associated optimal AVC score thresholds were 734, 1081, and 1019 AU. AVC > 1200 AU was associated with AVR (P Conclusion Among males from the background population, increasing AVC scores were associated with LA dilatation, LV hypertrophy, AVA, peak aortic velocity, mean aortic gradient, and AVR.

Obesity has been associated with increased production of reactive oxygen species (ROS), which may be involved in the development of cardiovascular disease and type 2 diabetes (T2D). Endurance exercise lowers ROS production and increases antioxidant capacity in muscle cells, but it is currently unknown whether high intensity interval training (HIT) elicits the same effects. Twelve sedentary obese subjects at risk of developing T2D took part in a six-week intervention, performing three HIT sessions per week (five 1-min sets of high-intensity cycling (125% of VO2peak), with 90 s recovery in between sets). Muscle biopsies were obtained for assessment of ROS production (H2O2 emission), mitochondrial respiratory capacity, and antioxidant protein levels before and after the intervention. H2O2 emission decreased 60.4% after the intervention (Succinate 3 mmol･l−1), concurrent with a 35.1% increase in protein levels of the antioxidant manganese superoxide dismutase (MnSOD) and a trend towards increased levels of the antioxidant catalase (p = 0.06, 72.9%). These findings were accompanied by a 19% increased mitochondrial respiratory capacity (CI + II), a 6.9% increased VO2peak and a 1.7% lower body fat percentage. These effects were achieved after just 15 min of high-intensity work and 40 min of total time spent per week. Overall, this suggests that a relatively small amount of HIT is sufficient to induce beneficial effects on ROS production and antioxidant status in muscle cells, which may lower oxidative stress and potentially protect against the development of cardiovascular disease.

The effect of oral glutathione (GSH) supplementation was studied in obese subjects with and without type 2 diabetes (T2DM) on measures of glucose homeostasis and markers of oxidative stress. Twenty subjects (10 patients with T2DM and 10 obese subjects) were recruited for the study, and randomized in a double-blinded placebo-controlled manner to consume either 1000 mg GSH per day or placebo for 3 weeks. Before and after the 3 weeks insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp and a muscle biopsy was obtained to measure GSH and skeletal muscle mitochondrial hydrogen peroxide (H2O2) emission rate. Whole body insulin sensitivity increased significantly in the GSH group. Skeletal muscle GSH was numerically increased (∼19%) in the GSH group; no change was seen in GSH to glutathione disulfide ratio. Skeletal muscle mitochondrial H2O2 emission rate did not change in response to the intervention and neither did the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine or the DNA oxidation product 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), although 8-oxodG decreased as a main effect of time. Oral GSH supplementation improves insulin sensitivity in obese subjects with and without T2DM, although it does not alter markers of oxidative stress. The study has been registered in clinicaltrials.gov (NCT02948673). Novelty: Reduced glutathione supplementation increases insulin sensitivity in obese subjects with and without T2DM. H2O2 emission rate from skeletal muscle mitochondria was not affected by GSH supplementation.

Background Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Primary-care physicians (PCPs) play a key role in identifying patients requiring specialist referral. In this study, we aim to determine PCPs’ practice patterns for paediatric NAFLD, as knowledge gaps have been reported for adult NAFLD. Methods A survey was sent to 60 PCPs in the Eastern Ontario Network from July 2019 to January 2020. Results Thirty-seven (62%) PCPs responded to the survey. Twenty-one incorrectly considered the prevalence of paediatric NAFLD to be ≤10%. The majority (35/36) cared for less than five paediatric NAFLD patients. Thirty-four (92%) were only ‘slightly familiar’ or ‘not familiar at all’ with paediatric NAFLD. Only one PCP routinely screens for NAFLD. Only one PCP was aware of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) clinical guidelines for paediatric NAFLD. Twenty-five (68%) correctly selected lifestyle modifications as a treatment option. Lack of confidence in the knowledge of NAFLD was the most common barrier for managing paediatric cases. Conclusion The majority of PCPs are not screening for paediatric NAFLD and are not familiar with its clinical spectrum, citing a lack of knowledge regarding NAFLD as the greatest barrier. This may cause delays in diagnosis and a presentation with advanced fibrosis at the time of specialist referral. Dissemination and implementation of clinical guidelines have the potential to improve knowledge and screening rates for NAFLD in children at the primary-care level.

Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of layer-specific GLS has not yet been investigated in patients with suspected stable angina pectoris (SAP). We sought to investigate the prognostic value of layer-specific and whole wall GLS in patients with suspected SAP. From September 2008 to March 2011, 296 consecutive patients with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were enrolled in a prospective cohort study. Patients underwent echocardiography including two-dimensional speckle tracking at rest, exercise stress test, and coronary angiography. The end-point was a composite of incident heart failure, acute myocardial infarction, and cardiovascular death (MACE). Out of the 285 included patients (mean age 61 years, 50% male), 24 (8%) developed MACE during a median follow-up of 3.5 years. Both endocardial [hazard ratio (HR) 1.21, 95% CI 1.08–1.35, p = 0.001], epicardial (HR 1.29, 95% CI 1.12–1.50, p = 0.001) and whole wall GLS (HR 1.25, 1.10–1.42, p = 0.001) were significantly associated with an increased risk of developing MACE during follow-up in univariable Cox regression analysis. In multivariable analysis, only epicardial (HR 1.23, 95% CI 1.00–1.51, p = 0.046) and whole wall GLS (HR 1.20, 95% CI 1.00–1.43, p = 0.049) remained significantly associated with an increased risk of MACE independent of various baseline clinical variables, left ventricular ejection fraction (LVEF), E/eʹ and Duke Score. Layer-specific and whole wall GLS were significant predictors of MACE in this cohort of patients with suspected SAP independent of various baseline clinical variables, LVEF, E/eʹ and Duke Score.

Mortality secondary to cirrhosis in North America is increasing. We describe the incidence of cirrhosis stratified by birth cohort and cirrhosis etiology and project disease burden to 2040.This is a retrospective cohort study in Ontario, Canada, using population-based administrative health care data. Individuals with incident cirrhosis (2000-2017) were identified, and etiology was defined as HCV, HBV, NAFLD, alcohol-associated liver disease (ALD), or autoimmune liver disease/other using validated case definitions. Annual age/sex-adjusted cirrhosis incidence rate per 100,000 person-years was calculated with incidence projection to 2040 using age-period-cohort modeling along with average annual percent change (AAPC) in cirrhosis incidence stratified by birth cohort and etiology. In total, 159,549 incident cases of cirrhosis were identified. Incidence increased by 26% with an AAPC of 2%/year (95% CI, 1.6-2.4; P 0.001). The largest increases were for HCV (AAPC, 4.1%/year; 95% CI, 2.6-5.7; P 0.001) and NAFLD (AAPC, 3.3%/year; 95% CI, 2.6-4.1%; P 0.001). ALD and HCV cirrhosis in those born1980 increased by 11.6%/year (95% CI, 9.3-13.9; P 0.001) and 9.5%/year (95% CI, 6.2-13.0; P 0.001), respectively. However, by 2040, cirrhosis incidence is projected to continue to increase, driven mostly by NAFLD, especially in postmenopausal women, and ALD in individuals born1980.Cirrhosis incidence will continue to increase over the next two decades secondary to NAFLD with a worrisome rapid rise in ALD cirrhosis among young adults. Public education, policy, and intervention targeting NAFLD risk factors and alcohol use in young adults are urgently needed.

ObjectiveAortic valve calcification (AVC) and coronary artery calcification (CAC) are predictors of cardiovascular disease (CVD), presumably sharing risk factors. Our objectives were to determine the prevalence and extent of AVC in a large population of men aged 60–74 years and to assess the association between AVC and cardiovascular risk factors including CAC and biomarkers.MethodsParticipants from the DANish CArdioVAscular Screening and intervention trial (DANCAVAS) with AVC and CAC scores and without previous valve replacement were included in the study. Calcification scores were calculated on non-contrast CT scans. Cardiovascular risk factors were self-reported, measured or both, and further explored using descriptive and regression analysis for AVC association.Results14 073 men aged 60–74 years were included. The AVC scores ranged from 0 to 9067 AU, with a median AVC of 6 AU (IQR 0–82). In 8156 individuals (58.0%), the AVC score was >0 and 215 (1.5%) had an AVC score ≥1200. In the regression analysis, all cardiovascular risk factors were associated with AVC; however, after inclusion of CAC ≥400, only age (ratio of expected counts (REC) 1.07 (95% CI 1.06 to 1.09)), hypertension (REC 1.24 (95% CI 1.09 to 1.41)), obesity (REC 1.34 (95% CI 1.20 to 1.50)), known CVD (REC 1.16 (95% CI 1.03 to 1.31)) and serum phosphate (REC 2.25 (95% CI 1.66 to 3.10) remained significantly associated, while smoking, diabetes, hyperlipidaemia, estimated glomerular filtration rate and serum calcium were not.ConclusionsAVC was prevalent in the general population of men aged 60–74 years and was significantly associated with all modifiable cardiovascular risk factors, but only selectively after adjustment for CAC ≥400 AU.Trial registration numberNCT03946410 and ISRCTN12157806.

Rationale and Objectives Contrast-enhanced ultrasound (CEUS) has increasingly gained acceptance in the postoperative evaluation of kidney-transplantation recipients. Our meta-analysis aims to evaluate the diagnostic accuracy of CEUS in identifying post-transplantation complications. Materials and Methods PubMed, Scopus, Ovid Medline, and Cochrane databases were searched from their inception until February 28, 2020, for diagnostic test accuracy studies comparing CEUS to a reference standard for monitoring complications after kidney transplantation. A meta-analysis was conducted to calculate the pooled sensitivity, specificity, accuracy, and diagnostic odds ratio using a bivariate random effects model. Sensitivity analysis was performed using R software by stratifying the studies based on study design, sample size, age, and origin of the study to evaluate the influence of these factors on the overall effect. Results Two independent reviewers analyzed 285 publications, out of which 29 were determined directly relevant and 12 (with a total of 542 cases) contained all required data for the meta-analysis. The overall sensitivity of included studies was estimated to be 0.86 (95% confidential interval (CI); 0.78-–0.92). Similarly, the overall specificity was estimated to be 0.90 (95% CI; 0.82–0.94). Log diagnostic odds ratio was 4.25 (95% CI; 3.43–5.07), and the area under the curve of the pooled receiver operating characteristic was 0.94. Stratified sensitivity analyses showed study design, sample size, age group, and origin of the study had no significant impact on the overall diagnostic value of CEUS. Conclusion Evidence suggests that CEUS is a potentially effective and accurate method to evaluate a variety of complications such as rejection, vascular complications, and malignancies after kidney transplantation.

Die SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-Pandemie hat zu weitreichenden Veranderungen in die Versorgungsrealitat praktisch aller medizinischen Fachbereiche gefuhrt. Empfehlungen zum perioperativen Management in Bezug auf SARS-CoV‑2 und Darstellung von Auswirkungen auf die kolorektale Chirurgie. Es wurde eine systematische Literaturrecherche durchgefuhrt. Perioperative Infektionen mit SARS-CoV‑2 fuhren zu einer deutlich erhohten postoperativen Mortalitat und mussen durch ein strukturiertes Masnahmenbundel verhindert werden. Die weltweiten Einschrankungen bei Vorsorgeuntersuchungen und Therapieangeboten konnen mittelfristig eine erhohte Mortalitat durch kolorektale Karzinome zur Folge haben. Auch in der Notfallversorgung zeigt sich ein erheblicher Ruckgang der Fallzahlen mit der Gefahr verspateter Interventionen. Eine rasche Normalisierung der klinischen Behandlungspfade in der Kolorektalchirurgie ist erforderlich, um langfristige negative Folgen fur die Patienten zu vermeiden.

Introduction Oral delivery of proteins, including glucagon-like peptide 1 (GLP-1) receptor agonists, is impeded by low gastrointestinal permeation. Oral semaglutide has been developed for once-daily oral administration by co-formulation of the GLP-1 analogue semaglutide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC, 300 mg). A randomised, partially double-blind, placebo-controlled thorough QT/corrected QT (QTc) trial was conducted to confirm the absence of unacceptable QTc interval prolongation with SNAC. QT is defined as interval on the electrocardiogram, measured from the start of the QRS complex to the end of the T wave. Methods Part A of the study sought to identify an appropriate dose of SNAC (which was substantially higher than that used in the oral semaglutide co-formulation) for QTc assessment. Three sequential healthy volunteer cohorts were randomised to escalating single oral doses of SNAC (1.2, 2.4 or 3.6 g) or placebo. Following identification of an appropriate dose, a cross-over trial was conducted (Part B). Healthy volunteers received one of four treatment sequences, including single oral doses of SNAC, moxifloxacin (positive control) and placebo. Primary objectives were to (1) assess adverse events (AEs) with escalating SNAC doses and (2) confirm that SNAC does not cause unacceptable QTc interval prolongation versus placebo, using the Fridericia heart rate-corrected QT interval (QTcF). Results All subjects completed Part A (N = 36) and 46 subjects completed Part B. In Part A, all AEs were mild to moderate in severity; no relationship was identified between AE incidence and SNAC dose. SNAC 3.6 g, the maximum investigated SNAC dose, was selected for Part B. There was no unacceptable prolongation of the QTcF interval with SNAC 3.6 g, and assay sensitivity was demonstrated with moxifloxacin as the positive control. There was no significant exposure–response relationship between SNAC concentration and QTcF interval, and no instances of QTc interval > 450 ms or increases > 30 ms. Conclusion This QT/QTc trial demonstrates that SNAC doses 12-fold higher than the 300 mg dose used in the oral formulation of semaglutide do not cause unacceptable prolongation of the QTcF interval. Trial Registration Clinicaltrials.gov identifier: NCT02911870., Plain Language Summary Medications that are taken orally can be broken down by acid in the stomach before they are absorbed and therefore be less effective. Oral semaglutide is a novel type 2 diabetes medication that is formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), which helps to protect against semaglutide degradation in the stomach. Regulatory authority guidelines recommend that new therapies should be tested for prolongation of the QT interval, an important part of the heart’s electrical cycle. A previous trial demonstrated that semaglutide alone, which is currently available as an injectable diabetes therapy, did not prolong the QT interval when given in doses higher than those used in patients. Therefore, the current trial was conducted to assess whether the SNAC component of oral semaglutide has any relevant prolonging effect on the QT interval. Following regulatory guidelines for trials evaluating prolongation of the QT interval, the first part of the trial aimed to find a suitably high dose of SNAC. The second part of the trial aimed to confirm that SNAC does not prolong the QT interval. The results of this trial demonstrated that a 3.6 g dose of SNAC, which is 12-fold higher than the amount contained in oral semaglutide, does not prolong the QT interval. The safety and tolerability of SNAC 1.2 g, 2.4 g and 3.6 g were assessed in this trial and no concerns were identified. These results, taken alongside those of the previous QT interval study with subcutaneous semaglutide, indicate no relevant effect of oral semaglutide on the QT interval.

Objective The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved. Design A randomized, double-blinded, placebo-controlled, crossover study. Methods Ten patients with overweight/obesity and type 2 diabetes (mean±s.d.; HbA1c 52 ± 11 mmol/mol; BMI 32.5 ± 4.8 kg/m2) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1200 pmol/kg/min), or placebo (saline) during two separate, 230-min, standardized, liquid mixed meal tests followed by a meal ad libitum. Subcutaneous adipose tissue biopsies were analyzed. Results Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Δbaseline-subtracted area under the curve (bsAUC)C-peptide% ± s.e.m.; −14 ± 6%, P = 0.021) and peak glucagon (Δ% ± s.e.m.; −11 ± 6%, P = 0.046) but had no effect on plasma glucose (P = 0.692). Suppression of bone resorption (assessed by circulating carboxy-terminal collagen crosslinks (CTX)) was impaired during GIP(3-30)NH2 infusion compared with placebo (ΔbsAUCCTX; ±s.e.m.; −4.9 ± 2 ng/mL × min, P = 0.005) corresponding to a ~50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, meal consumption ad libitum or adipose tissue triglyceride content. Conclusions Using a selective GIP receptor antagonist during a meal, we show that endogenous GIP increases postprandial insulin secretion with little effect on postprandial glycaemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.

Context The maximal fat oxidation rate (MFO) is higher in aerobically fit vs unfit young men, but this training-related increase in MFO is attenuated in middle-aged men. Further, it has also been found that unfit men with obesity may have an elevated MFO compared to unfit normal-weight men. Objective Based hereupon, we aimed to investigate whether a fitness-related higher MFO were attenuated in middle-aged women compared to young women. Also, we aimed to investigate if unfit women with obesity have a higher MFO compared to unfit normal-weight women. We hypothesized that the training-related elevated MFO was attenuated in middle-aged women, but that unfit women with obesity would have an elevated MFO compared to unfit normal-weight women. Methods We recruited 70 women stratified into 6 groups: young fit (n = 12), young unfit (n = 12) middle-aged fit (n = 12), middle-aged unfit (n = 12), unfit young women with obesity (n = 12), and unfit middle-aged women with obesity (n = 10). Body composition and resting blood samples were obtained and MFO was measured by a graded exercise test on a cycle ergometer via indirect calorimetry. Subsequently, a maximal exercise test was performed to establish peak oxygen uptake (V̇O2peak). Results Young and middle-aged fit women had a higher MFO compared to age-matched unfit women, and young fit women had a higher MFO compared to fit middle-aged women. Unfit women with obesity, independent of age, had a higher MFO compared to their normal-weight and unfit counterparts. Conclusion The training-related increase in MFO seems maintained in middle-aged women, and we find that unfit women with obesity, independent of age, have a higher MFO compared to unfit normal-weight women.

Aims Coronary artery calcification (CAC) measured on cardiac computed tomography (CT) is an important risk marker for cardiovascular disease (CVD) and has been included in the prevention guidelines. The aim of this study was to describe CAC score reference values in the middle-aged and elderly population and to develop a freely available CAC calculator. Methods and results All participants from two population-based cardiac CT screening cohorts (DanRisk and DANCAVAS) were included. The CAC score was measured as a part of a screening session. Positive CAC scores were log-transformed and non-parametrically regressed on age for each gender, and percentile curves were transposed according to proportions of zero CAC scores. Men had higher CAC scores than women, and the prevalence and extend of CAC increased steadily with age. An online CAC calculator was developed, http://flscripts.dk/cacscore. After entering sex, age, and CAC score, the CAC score percentile and the coronary age are depicted including a figure with the specific CAC score and 25%, 50%, 75%, and 90% percentiles. The specific CAC score can be compared to the entire background population or only those without prior CVD. Conclusion This study provides modern population-based reference values of CAC scores in men and woman and a freely accessible online CAC calculator. Physicians and patients are very familiar with blood pressure and lipids, but unfamiliar with CAC scores. Using the calculator makes it easy to see if a CAC value is low, moderate, or high, when a physician in the future communicate and discusses a CAC score with a patient.

The ability to provide prompt, real-time, easily accessible and radiation-free diagnostic assessments makes ultrasound (US) one of the most versatile imaging modalities. The introduction and development of stable microbubble-based ultrasound contrast agents (UCAs) in the early 1990s improved visualization of complex vascular structures, overcoming some of the limitations of B-mode and Doppler imaging. UCAs have been used extensively in the adult population to visualize vasculature and to evaluate perfusion and blood flow dynamics in organs and lesions. Since the first observations that air bubbles within a liquid can generate a strong echogenic effect, to the early makeshift approaches with agitated saline, and later to the development of industrially produced and federally approved UCAs, these agents have evolved to become both clinically and commercially viable. Perhaps the most exciting potential of UCAs is being uncovered by current research that explores the use of these agents for molecular imaging and therapeutic applications. As contrast-enhanced ultrasound (CEUS) becomes more widely available, it is important for pediatric radiologists to understand the physics of the interaction between the US signal and the microbubbles in order to properly utilize them for the highest level of diagnostic imaging and interventions. In this article we introduce the composition of UCAs and the physics of their behavior in US, and we offer a brief history of their development over the last decades.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Background Assessment of maximal LA volume (LAVmax) is recommended in imaging guidelines but evidence suggests additional value of functional LA measures. How extended measures of LA function associate to left ventricular filling pressure has not been fully explored. Purpose To investigate the association between functional LA measures and left ventricular end-diastolic pressure (LVEDP) Methods Patients suspected of coronary artery disease referred for angiography had simultaneous left heart catheterization performed for invasive pressure measurements. LVEDP > 12mmHg was considered elevated. LA measurements by echocardiography included: LAVmax, minimal LA volume (LAVmin), total LA emptying fraction (total LAEF), passive LA emptying fraction (passive LAEF), and active LA emptying fraction (active LAEF). Results Of 43 patients, 28 (65%) had elevated LVEDP. These patients more frequently had coronary vessel disease (VD) and impaired LA mechanics by all accounts except by LAVmax. All LA measures except LAVmax were associated with LVEDP in unadjusted linear regression analyses, however, only LA emptying fractions remained associated with LVEDP after adjusting for age and VD (2.6 (1.2-4.0) mmHg increase, p = 0.001, per 5% decrease in total LAEF; 1.4 (0.1-2.8) mmHg increase, p = 0.040, per 5% decrease in active LAEF; 1.8 (0.1-3.4) mmHg increase, p = 0.038, per 5% decrease in passive LAEF). In logistic regression, passive LAEF was significantly associated with elevated LVEDP (figure), and this was also the case after adjusting for age and VD (OR = 1.11 (1.01-1.21), p = 0.023, per 1% decrease). Similar findings were made in subgroup analyses among patients without dilated LA and patients without conventional indicators of elevated filling pressure. Conclusion Left ventricular end-diastolic pressure is significantly associated with LA functional measures but not LA volumes. Additionally, passive LAEF is associated with elevated LVEDP. Future studies examining LA function should include all components of LAEF. Abstract Figure.

Sex hormones are responsible for multiple physiologic processes by signalling through estrogen (ER) and androgen receptors (AR).(1) ERs and ARs are expressed in liver and biliary tract cells in normal and diseased states in both men and women. Thus, the liver is recognized as a sex hormone responsive organ. In general, estrogen is associated with hepatic "protection" while androgens associate with hepatic "progression".

Das transdiagnostische Konzept der Ich- bzw. Persönlichkeitsstruktur spielt in der psychodynamischen Krankheitslehre eine zentrale Rolle, gelten doch viele psychische und psychoso-matische Störungen als Ausdruck struktureller Vulnerabilitäten und Defizite. Daher kommt der Strukturdiagnostik eine besondere Bedeutung zu, gerade unter differenzialindikatorischen und behandlungstechnischen Aspekten. Weil Veränderungen der Persönlichkeitsstruktur auch als Therapieziel immer mehr Beachtung finden, sollten strukturdiagnostische Verfahren änderungssensitiv sein, um diese angemessen zu erfassen. Die Kurzform des OPD-Strukturfragebogens (OPD-SFK) wird zwar aufgrund ihrer Anwendungsökonomie klinisch und wissenschaftlich vielfach eingesetzt, ist bisher jedoch nicht auf ihre Eignung zur Veränderungsmessung analysiert worden. Zwei große, unabhängige und diagnostisch heterogene Stichproben stationärer Psychotherapiepatienten (N=1183 bzw. 967) wurden bei Aufnahme und Entlassung mit dem OPD-SFK untersucht. Als Indikatoren der Änderungssensitivität wurden die Standardized Effect Size (SES), der Standardized Response Mean (SRM) sowie die Smallest Real Difference (SRD) berechnet. Für den OPD-SFK Gesamtwert sowie die Subskalen wurden in beiden Stichproben Veränderungseffekte in niedriger Größenordnung gefunden (SES zwischen 0,23 und 0,48 sowie SRM zwischen 0,27 und 0,53). Zudem wurde gezeigt, dass mit dem OPD-SFK größere Veränderungen für Patienten mit strukturellen Störungen nachweisbar sind als für jene mit geringen Strukturdefiziten und dass die Gruppenunterschiede signifikant sind. Mittels der SRD wurde in beiden Stichproben ein Anteil von 22% signifikant strukturell verbesserter Patienten ermittelt. Trotz einiger methodenkritischer Aspekte legen die Befunde nahe, dass sich der OPD-SFK bei stationären Psychotherapiepatienten eignet, um Veränderungen persönlichkeitsstruktureller Fähigkeiten zwischen Beginn und Abschluss der Behandlung abzubilden. Da Untersuchungen zur Änderungssensitivität anderer strukturdiagnostischer Verfahren ausstehen, können bislang keine empirisch abgesicherten Empfehlungen formuliert werden, welches Instrument am besten therapeutisch induzierte Veränderungen in der Persönlichkeitsstruktur erfasst.

Background Gastric pull-up (GPU) procedures may be complicated by leaks, fistulas, or stenoses. These complications are usually managed by endoscopy, but in extreme cases multidisciplinary management including reoperation may be necessary. Here, we report a combined endoscopic and surgical approach to manage a failed secondary GPU procedure. Case summary A 70-year-old male with treatment-refractory cervical esophagocutaneous fistula with stenotic remnant esophagus after secondary GPU was transferred to our tertiary hospital. Local and systemic infection originating from the infected fistula was resolved by endoscopy. Hence, elective esophageal reconstruction with free-jejunal interposition was performed with no subsequent adverse events. Conclusion A multidisciplinary approach involving interventional endoscopists and surgeons successfully managed severe complications arising from a cervical esophagocutaneous fistula after GPU. Endoscopic treatment may have lowered the perioperative risk to promote primary wound healing after free-jejunal graft interposition.

There is growing evidence that sodium fluoride ([18F]fluoride) PET/CT can detect active arterial calcifications at the molecular stage. We investigated the relationship between arterial mineralization in the left common carotid artery (LCC) assessed by [18F]fluoride PET/CT and cardiovascular/thromboembolic risk. In total, 128 subjects (mean age 48 ± 14 years, 51% males) were included. [18F]fluoride uptake in the LCC was quantitatively assessed by measuring the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice. Average SUVmax (aSUVmax) was calculated over all slices and correlated with 10-year risk of cardiovascular events estimated by the Framingham model, CHA2DS2-VASc score, and level of physical activity (LPA). The aSUVmax was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA, p < 0.01) and thromboembolic (one-way ANOVA, p < 0.01) events, and it was significantly lower in patients with greater LPA (one-way ANOVA, p = 0.02). On multivariable linear regression analysis, age ( = 0.07, 95% CI 0.05 – 0.10, p < 0.01), body mass index ( = 0.02, 95% CI 0.01 – 0.03, p < 0.01), arterial hypertension ( = 0.15, 95% CI 0.08 – 0.23, p < 0.01), and LPA ( = −0.10, 95% CI −0.19 to −0.02, p=0.02) were independent associations of aSUVmax. Carotid [18F]fluoride uptake is significantly increased in patients with unfavorable cardiovascular and thromboembolic risk profiles. [18F]fluoride PET/CT could become a valuable tool to estimate subjects’ risk of future cardiovascular events although still major trials are needed to further evaluate the associations found in this study and their potential clinical usefulness. • Sodium fluoride ([ 18 F]fluoride) PET/CT imaging identifies patients with early-stage atherosclerosis. • Carotid [ 18 F]fluoride uptake is significantly higher in patients with increased risk of cardiovascular and thromboembolic events and inversely correlated with the level of physical activity. • Early detection of arterial mineralization at a molecular level could help guide clinical decisions in the context of cardiovascular risk assessment.

Background: Gastrointestinal dysfunction and related clinical symptoms are common in Parkinson’s disease (PD), but the underlying mechanisms are still poorly understood. Objective: In this study, we investigated how PD affects the postprandial vascular response in the splanchnic circulation. Methods: 23 patients with PD in the “ON-medication” state and 23 age- and sex-matched healthy control participants underwent serial phase-contrast magnetic resonance imaging (PC-MRI) to measure the postprandial blood flow response in the superior mesenteric artery (SMA). Participants ingested a standardized liquid test meal (∼400 kcal) and underwent four PC-MRI runs within the following hour. Each PC-MRI run consisted of six consecutive measurements of SMA blood flow. Results: In both groups, standardized food intake triggered an increase of blood flow in the SMA, but absolute and relative increases in blood flow were attenuated in patients compared to the control group (p

Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction that ranges in severity from subclinical alterations to coma. Patients with chronic liver disease are predisposed to HE due to metabolic failure and portosystemic shunting of toxins, of which ammonia is believed to be the main toxic chemical. Fecal microbiota transplantation (FMT) may reduce ammonia synthesis by altering the gut microbiota composition to a taxon low in urease, diminish uptake of ammonia by reestablishing the integrity of the intestinal barrier and increase ammonia clearance by improving liver function. In this systematic review, we summarize the insights of the current literature examining FMT as a treatment for HE. PubMed and EMBASE were searched on 08 February 2021 using the MeSH terms ‘fecal microbiota transplantation & hepatic encephalopathy’ and the abbreviations ‘FMT & HE’. Eight studies fulfilled our inclusion criteria, comprising two randomized clinical trials, three case reports and three rodent studies. Thirty-nine patients with HE were treated with FMT. Thirty-nine rodents received FMT in laboratory tests. FMT improved neurocognitive test results in four human studies and two rodent studies. Microbiota originating from donors was found in human recipients one year post-FMT. Readmission of patients was lower after treatment with FMT compared to standard of care. FMT may improve neurocognitive function and reduce serious adverse events in patients with HE, but the studies conducted so far have been small and their long-term follow-up is limited. Large-scale, randomized and controlled trials are needed to validate and help standardize the clinical application of FMT in cases of HE.

BACKGROUND: Enlargement of left atrium (LA) is a valuable marker of cardiovascular events, and LA size is readily available while performing non-contrast cardiac computed tomography (NCCT) for preventive purposes. We aimed to evaluate the predictive value of a single LA area from NCCT in a population-based cohort.METHOD: Mainly men aged 60-75 years from DANCAVAS were included. Traditional risk factors were recorded, and an NCCT scan performed at baseline. Coronary artery calcifications (CAC) score and the largest LA area were measured. LA was indexed to body surface area and categorised into four groups. Data on incident atrial fibrillation (AF), thromboembolic events, heart failure (HF) and death were obtained from Danish national registries.RESULTS: In total, 14,557 individuals were eligible, excluding those without LA measurement (N = 232) and with heart valve replacement (N = 197). Known AF or HF were respectively excluded from follow-up. Median follow-up time was 2.1 to 3.4 years. In total, 304 developed AF, 149 had thromboembolism, 129 developed HF and 482 died. In adjusted analysis, LA enlargement was associated with AF (HR (95% CI): large 1.99 (1.46-2.71) and very large LA 3.77 (2.31-6.14)) and HF (large 2.40 (1.50-3.85) and very large LA 6.54 (4.07-10.51)). A very large LA significantly increased mortality (HR: 2.01 (1.44-2.82)), and was associated with a two-fold increased risk of thromboembolism; however, not significantly in adjusted analysis (p = 0.09).CONCLUSION: We demonstrated that determination of LA area from NCCT was an important predictor of AF, HF and death. This knowledge could inform current risk assessment beyond CAC score.

It has been documented that aging increases the risk of cardiovascular disease including myocardial ischemia/reperfusion (IR) injury and acute myocardial infarction. In this study, we aimed to investigate the individual or combined effects of nicotinamide mononucleotide (NMN) and melatonin (Mel) treatment on apoptotic markers, expression of SIRT3, and FOXO1, and infarct size of the aged myocardium subjected to IR injury. Sixty aged Wistar rats (22–24 months) were assigned to five groups including sham, IR, NMN+IR, Mel+IR, and NMN+Mel+IR (combination therapy). Isolated hearts were exposed to 30-min regional ischemia followed by 60-min reperfusion. NMN (100 mg/kg/day/i.p.) was injected every second day starting on day 28 before IR injury. Melatonin was added to the perfusion solution five minutes prior to and until 15 min after the start of reperfusion. The infarct size was assessed by computerized planimetry. The mRNA levels of SIRT3, FOXO1, and apoptotic genes Bax, Bcl-2, and Caspase-3 were estimated by real-time PCR. All treatments reduced infarct size as compared with the IR group. Melatonin and NMN upregulated the gene expression of Bcl‐2, SIRT3, and FOXO1 and downregulated the gene expression of Bax, and Caspase‐3, in comparison to the IR group. Also, the protein levels of SIRT3, quantified by Western blotting, were upregulated by the interventions. The effects of combination therapy were significantly greater than those of melatonin or NMN alone. These findings indicate that the combined administration of NMN and melatonin can protect the aged heart against IR injury by decreasing apoptosis and activating the SIRT3/FOXO1 pathway.

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.

The aim of this study was to evaluate layer-specific global longitudinal strain (GLS), obtained by speckle tracking, in predicting outcomes following ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Echocardiography, including layer-specific GLS, was performed at median two days after the STEMI in a prospective study of STEMI patients treated with pPCI between September 2006 and December 2008. The outcome was the composite of heart failure hospitalization and/or cardiovascular death (HF/CVD). A total of 349 patients were included. Mean age was 62.2 ± 11.5 years, 76% were male, and mean ejection fraction (LVEF) was 46 ± 9. Seventy-seven (22%) patients developed HF/CVD during median follow-up 5.4 years. Patients with HF/CVD had lower absolute values for all GLS-layers: endocardial (GLSEndo) 11.4%vs 14.5% (p

Soil-transmissible helminthes (STH) infections are among the most common sanitation-related public health problems in poor periurban settlements of tropical regions of low- and middle-income countries. In Ghana, research studies documenting the incidence rate, intensity, and occupational risk factors of STH infections among adults are scanty. A prospective cohort study of 261 waste handlers was conducted to investigate this. Stool samples were collected after 90 and 180 days of treatment with albendazole (400 mg per dose). The geometric mean intensity of STH among waste handlers after 180 days of treatment was 2.8 eggs/gram (light intensity), with an incidence rate of 1.5%. The proportion of waste handlers with light intensity STH infections was 4.8%. The odds of STH infection among female waste handlers were 80% lower when compared with male waste handlers (aOR = 0.2; 95% CI: 0.0–0.8). Waste handlers who used rubber gloves when working were 80% (aOR = 0.2: 95% CI: 0.2–1.9) protected from STH infections compared with those who did not use gloves. Infections with STH among the 261 waste handlers significantly correlated with the type of waste handling activities (LR χ2 = 15.3; p = 0.033 ) with the highest proportion of infection found among transporters, 2 (40%). Waste handlers should receive periodic antihelminthic treatment, at least once every six months, practice adequate hand hygiene, and use suitable personal protective equipment during work.

To explore the association between E-wave propagation index (EPI) as a marker of apical washout and the risk of left ventricular thrombus (LVT) formation in patients with ST-elevation myocardial infarction (STEMI).We performed a post-hoc analysis on 364 prospectively enrolled STEMI patients from a single-center. Non-contrast transthoracic echocardiographic examinations were performed a median of 2 days (IQR:1-3 days) after PCI. The endpoint was LVT formation, identified retrospectively. Univariable and multivariable logistic regression was applied to assess the association between EPI and LVT formation. Multivariable adjustments included LVEF, LAD culprit, prior myocardial infarction, heart rate, and early myocardial relaxation velocity. Area under receiver operating characteristic curves (AUC) was used to assess the diagnostic ability.Among 364 patients, 31 (8.5%) developed LVT. The mean age was 62 years, 75% were men, and mean LVEF was 46%. Patients developing LVT had increased heart rate, lower LVEF, impaired GLS, and more frequently had prior myocardial infarction. Variables associated with low values of EPI included, among others, LVEF, LV aneurysm, and GLS. EPI and LVT formation were significantly associated in the univariable model (OR = 1.87 (1.53-2.28), p 0.001), and EPI showed an AUC of 0.90. After multivariable adjustments, EPI and LVT formation remained significantly associated (OR = 1.79 (1.42-2.27), p 0.001). Patients with an EPI 1.0 had a 23 times higher likelihood of LVT formation (OR = 23.41 (10.06-54.49), p 0.001). EPI and LVT formation are strongly associated in patients with STEMI, with low values of EPI indicating a markedly increased probability of LVT formation.

The purpose of this study was to evaluate pain after mandibular ramus block harvesting and lateral ridge augmentation. Autogenous bone block grafts were covered with platelet-rich fibrin (PRF) membranes (test group) or deproteinized bovine bone and a resorbable collagen membrane (control group). This study included 27 partially edentulous patients (test = 14, control = 13) with an indication for bone block augmentation before staged implant placement. Postoperative methylprednisolone (32 mg, day 1) and analgesics comprising ibuprofen (400 mg, four times daily) and paracetamol (1 g, four times daily) were prescribed for 1 week. Pain was recorded by the patient on a 100-mm visual analogue scale (VAS), hourly on the day of surgery and daily for the following 7 days. The average (mean ± standard deviation) maximum pain score over the whole observation period was similar in the test (13.6 ± 13.5) and control (21.0 ± 19.9) groups (P = 0.17). In conclusion, harvesting of a mandibular ramus block and lateral ridge augmentation, in conjunction with the pharmacological protocol described, is characterized by low postoperative pain. Adding PRF membranes to the surgical site generally resulted in slightly lower pain perception, although a statistically significant difference between the test and control groups was only identified on day 1 postoperative.

Aims Technical advancements in 2D-speckle tracking echocardiography (2DSTE) have allowed for quantification of layer-specific global longitudinal strain (GLS) and circumferential strain (GCS) of the left ventricle (LV). The aim of this study was to establish age- and sex-based reference ranges of peak systolic layer-specific GLS and GCS and to assess normal values of regional strain. Methods and results We performed 2DSTE analysis of 1997 members of the general population from the fifth round of the Copenhagen City Heart Study, who were free of cardiovascular disease and risk factors. The mean age was 46 ± 16 years (range 21–97) and 62% were female. Mean values for peak systolic whole wall GLS (GLSWW.Sys), endomycardial (GLSEndo.Sys), and epimyocardial (GLSEpi.Sys) were 19.9 ± 2.1% (prediction interval [PI]: 15.8–24.0%), 23.5 ± 2.5% (PI: 18.6–28.4%), and 17.3 ± 1.9% (PI: 13.6–21.1%), respectively. Mean peak systolic whole wall GCS (GCSWW.Sys), was 21.6 ± 3.7% (PI: 14.3–28.9%), endomyocardial (GCSEndo.Sys) was 31.9 ± 4.7% (PI: 22.7–41.1%), and epimyocardial (GCSEpi.Sys) was 14.3 ± 3.8% (PI: 6.8–21.8%). A significant discrepancy in normal strain values between males and females was observed. Men had lower mean values and lower reference limits for all strain parameters. Furthermore, GLS and GCS changed differently with age in males and females. Finally, regional LS decreased from the apical to the basal LV region in both sexes, and regional CS varied significantly by LV segment. Conclusion In this study, we reported age- and sex-based reference ranges of layer-specific GLS and GCS. These reference ranges varied significantly with sex and age.

Coronavirus disease 2019 (COVID-19) is an ongoing major health emergency, but its occurrence and clinical impact on patients withliver cirrhosis is unknown. Therefore, we conducted a population-based study of 2.6 million Danish citizens investigating the occurrence and impact of COVID-19 in patients with liver cirrhosis.A prospective population-based cohort study was conducted in the Capital Region of Denmark and Region Zealand in the study period between 1 March 2020 up until 31 May 2020, with the only eligibility criteria being a reverse-transcriptase polymerase chain reaction for presence of viral genomic material confirming COVID-19. The patients were subsequently stratified according to presence of pre-existing liver cirrhosis.Among 575,935 individuals tested, 1713 patients had a diagnosis of cirrhosis. COVID-19 occurredsignificantly lessamongpatients with cirrhosis (In conclusion, patientswith cirrhosis may have a lower risk of COVID-19; but a higher risk of complications hereto and mortality.

Aims: Due to new evidence on fluoride neurotoxicity during early life, this study examined maternal exposure to fluoride through tea consumption in a low-fluoride region and measured fluoride releases from commercially available teas (tea bags and loose teas) to determine the need to limit fluoride exposure. Methods: Maternal urine fluoride (MUF) concentrations were measured in spot urine samples ( N=118) from first-trimester pregnant women and in prepared tea infusions made with deionised water from 33 brand teas and 57 loose-tea products, as determined by the direct method of using a fluoride-selective electrode. Results: The fluoride concentration in the local drinking water supplies ranged from 0.10 to 0.18 mg/L, and the creatinine-adjusted MUF ranged from 0.09 to 1.57 mg/L. Seventeen per cent of the women were daily tea drinkers, and their MUFs were higher than those with no consumption ( p=0.002). The fluoride concentration from tea bags ranged from 0.34 to 2.67 mg/L, while loose teas showed 0.72–4.50 mg/L (black), 0.56–1.58 mg/L (oolong), 1.28–1.50 mg/L (green), and 0.33–1.17 mg/L (white tea). Conclusions: Fluoride exposure among pregnant women increases with tea consumption, with likely risks of developmental neurotoxicity to their children. As the fluoride release from tea varies widely, the fluoride concentration should be indicated on tea packages in order to allow consumers to make informed decisions on minimising their fluoride exposure.

ObjectiveTo determine the prognostic value of global longitudinal strain (GLS) after coronary artery bypass grafting (CABG).MethodsWe performed a retrospective cohort study on patients undergoing CABG between 2006 and 2011 who had an echocardiogram available for strain analysis. The patients were followed up through nationwide registries for development of all-cause mortality, cardiovascular death (CVD) and major adverse cardiovascular events (MACEs) defined as heart failure hospitalisation and/or CVD. Multivariable Cox regression was applied to adjust for the European System for Cardiac Operative Risk Evaluation II (EuroSCORE-II). Additive value was assessed by Net Reclassification Index (NRI) improvement.ResultsOf the 709 patients included, 80 died during a median follow-up of 3.8 years. Of these, 45 had CVD, and 72 patients experienced MACE. Mean age was 68 years and 85% were men. Left ventricular ejection fraction (LVEF) was 50% and GLS was −13%.GLS was an independent predictor when adjusted for the EuroSCORE-II (all-cause mortality: HR=1.07 (1.01–1.13), p=0.018; CVD: HR=1.11 (1.03–1.20), p=0.007; MACE: HR=1.12 (1.06–1.19), pLVEF modified the association between GLS and outcomes (p for interactionConclusionGLS is an independent predictor of long-term outcomes after CABG. The predictive value appears strongest among patients with preserved LVEF.

BACKGROUND: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. PURPOSE: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. RESULTS: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). CONCLUSION: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020