The effect of the collateral cerebrovascular circulation on tolerance to carotid artery cross-clamping and on early outcome after carotid endarterectomy.

OBJECTIVE: The Circle of Willis (CoW) serves as the primary source of contralateral blood supply in patients who undergo carotid artery cross-clamping (CC) for carotid endarterectomy (CEA). It has been suggested that the CoW's anatomy influences CEA outcomes. The aim of this study was to evaluate associations between the cerebral collateral circulation, a positive awake test for intraoperative neurologic deficit after carotid CC, and postoperative adverse neurologic events. METHODS: A systematic review was conducted searching MEDLINE, Cochrane, and Web of Science databases for studies that assessed the cerebral circulation, including CoW variations, using neuroimaging techniques in patients who underwent carotid CC. For the metanalytical incidence, the statistical technique used was weight averaging. Otherwise, descriptive analysis was used due to the excessive heterogeneity of the studies. RESULTS: Eight publications, seven cohort and one case-controlled study, involving 1313 patients who underwent carotid artery CC under loco-regional anesthesia, were included in the systematic review. The incidence of positive awake test in the cohort studies ranged from 4.4% to 19.7%. Carotid artery CC resulted in positive awake test in 5% to 91% of patients with alterations in the anterior portion and in 27% to 74% with alterations in the posterior portion of the CoW. A positive awake test in patients with contralateral carotid stenosis or occlusion ranged from 5.8% to 45.7%. Contralateral carotid stenosis >70% or occlusion were associated with a positive awake test (P < .001). Patients with incomplete CoW did not have statistically significant correlation with intraoperative neurological deficits after CC. Data were insufficient to evaluate the effect of the collateral circulation on early outcome after CEA. CONCLUSIONS: In this systematic review, contralateral carotid artery stenosis or occlusion, but not CoW abnormalities, were associated with a positive awake test after carotid artery CC. Further research is needed to evaluate which specific CoW anomaly predicts neurologic deficit after CC and to confirm association between a positive awake test and clinical outcome after CEA.

Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

Perspectives and awareness of endoscopy healthcare professionals on sustainable practices in gastrointestinal endoscopy: results of the LEAFGREEN survey.

BACKGROUND: Gastrointestinal (GI) endoscopy is one of healthcare's main contributors to climate change. We aimed to assess healthcare professionals' attitudes and the perceived barriers to implementation of sustainable GI endoscopy. METHODS: The LEAFGREEN web-based survey was a cross-sectional study conducted by the European Society of Gastrointestinal Endoscopy (ESGE) Green Endoscopy Working Group. The questionnaire comprised 39 questions divided into five sections (respondent demographics; climate change and sustainability beliefs; waste and resource management; single-use endoscopes and accessories; education and research). The survey was available via email to all active members of the ESGE and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) in March 2023. RESULTS: 407 respondents participated in the survey (11% response rate). Most participants (86%) agreed climate change is real and anthropogenic, but one-third did not consider GI endoscopy to be a significant contributor to climate change. Improvement in the appropriateness of endoscopic procedures (41%) and reduction in single-use accessories (34%) were considered the most important strategies to reduce the environmental impact of GI endoscopy. Respondents deemed lack of institutional support and knowledge from staff to be the main barriers to sustainable endoscopy. Strategies to reduce unnecessary GI endoscopic procedures and comparative studies of single-use versus reusable accessories were identified as research priorities. CONCLUSIONS: In this survey, ESGE and ESGENA members acknowledge climate change as a major threat to humanity. Further improvement in sustainability beliefs and professional attitudes, reduction in inappropriate GI endoscopy, and rational use of single-use accessories and endoscopes are critically required.

The environmental impact of small-bowel capsule endoscopy.

INTRODUCTION: The environmental impact of endoscopy, including small-bowel capsule endoscopy (SBCE), is a topic of growing attention and concern. This study aimed to evaluate the greenhouse gas (GHG) emissions (kgCO2) generated by an SBCE procedure. METHODS: Life cycle assessment methodology (ISO 14040) was used to evaluate three brands of SBCE device and included emissions generated by patient travel, bowel preparation, capsule examination, and video recording. A survey of 87 physicians and 120 patients was conducted to obtain data on travel, activities undertaken during the procedure, and awareness of environmental impacts. RESULTS: The capsule itself (4 g) accounted for < 6 % of the total product weight. Packaging (43-119 g) accounted for 9 %-97 % of total weight, and included deactivation magnets (5 g [4 %-6 %]) and paper instructions (11-50 g [up to 40 %]). A full SBCE procedure generated approximately 20 kgCO2, with 0.04 kgCO2 (0.2 %) attributable to the capsule itself and 18 kgCO2 (94.7 %) generated by patient travel. Capsule retrieval using a dedicated device would add 0.98 kgCO2 to the carbon footprint. Capsule deconstruction revealed materials (e. g. neodymium) that are prohibited from environmental disposal; 76 % of patients were not aware of the illegal nature of capsule disposal via wastewater, and 63 % would have been willing to retrieve it. The carbon impact of data storage and capsule reading was negligible. CONCLUSION: The carbon footprint of SBCE is mainly determined by patient travel. The capsule device itself has a relatively low carbon footprint. Given that disposal of capsule components via wastewater is illegal, retrieval of the capsule is necessary but would likely be associated with an increase in device-related emissions.

Prediabetes remission after bariatric surgery: a 4-years follow-up study.

BACKGROUND: Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. METHODS: Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. RESULTS: A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. CONCLUSION: We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.

Polyvascular Disease Influences Long-Term Cardiovascular Morbidity in Carotid Endarterectomy.

INTRODUCTION/OBJECTIVE: Carotid stenosis (CS) is an important cause of ischemic stroke. Secondary prevention lies in performing a carotid endarterectomy (CEA) procedure, the recommended treatment in most cases. When 2 or more vascular regions are simultaneously affected by atherosclerosis, mainly the carotid arteries, coronary arteries, or limb arteries, a multivessel disease polyvascular disease (PVD) is present. This study aims to assess the potential role of PVD as a long-term predictor of major adverse cardiovascular events (MACE) and all-cause mortality in patients submitted to CEA. METHODS: From January 2012 to December 2021, patients submitted to CEA for carotid stenosis in a tertiary care and referral center were eligible from a prospective database. A posthoc survival analysis was performed using the Kaplan-Meier survival curve method. The primary outcome was the incidence of long-term MACE and all-cause mortality. Secondary outcomes included acute myocardial infarction (AMI), major adverse limb events (MALE), stroke, and acute heart failure (AHF). RESULTS: A total of 207 patients were enrolled, with a median follow-up of 63 months. The mean age was 70.4 ± 8.9, and 163 (78.7%) were male. There were 65 (31.4%) patients that had 2 arterial vascular territories affected, and 29 (14.0%) patients had PVD in 3 arterial beds. On multivariable analysis, both MACE and all-cause mortality had as independent risk factors age (aHR 1.039, P = 0.003; aHR 1.041, P = 0.019), chronic kidney disease (aHR 2.524, P = 0.003; aHR 3.377, P < 0.001) and PVD2 (aHR 3.381, P < 0.001; aHR 2.665, P = 0.013). PVD1 was only associated with MACE as a statistically significant risk factor (aHR 2.531, 1.439-4.450, P < 0.001). CONCLUSIONS: PVD in patients with cerebrovascular disease (CVD) was revealed to carry a 2-fold increased risk for all-cause mortality and MACE during long-term follow-up. PVD may be a simple yet valuable tool in predicting all-cause mortality, MACE, AMI, and MALE after CEA.

Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest Score is a Long-Term Cardiovascular Risk Predictor After Aortoiliac Revascularization.

BACKGROUND: Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest (MICA) is a validated self-explanatory score applied in cardiac or noncardiac surgeries. This study aims to assess the predictive value of the MICA score for cardiovascular events after aortoiliac revascularization. METHODS: This prospective cohort underwent elective aortoiliac revascularization between 2013 and 2021. Patients' demographic, clinical characteristics, and outcomes were registered. The patients were divided into 2 groups according to the MICA score using optimal binning. Survival analysis to test for time-dependent variables and multivariate Cox regression analysis for independent predictors were performed. RESULTS: This study included 130 patients with a median follow-up of 55 months. Preoperative MICA score was ≥6.5 in 41 patients. MICA ≥6.5 presented a statistically significant association, with long-term occurrence of acute heart failure (HR = 1.695, 95% CI 1.208-2.379, P = 0.002), major adverse cardiovascular events (HR = 1.222, 95% CI 1.086-1.376, P < 0.001), and all-cause mortality (HR = 1.256, 95% CI 1.107-1.425, P < 0.001). Multivariable Cox regression confirmed MICA as a significant independent predictor of long-term major adverse cardiovascular events (aHR = 1.145 95% CI 1.010-1.298, P = 0.034) and all-cause mortality (aHR = 1.172 95% CI 1.026-1.339, P = 0.020). CONCLUSIONS: The MICA score is a quick, easy-to-obtain, predictive tool in identifying patients with a higher risk of postaortoiliac revascularization cardiovascular events, such as acute heart failure, major adverse cardiovascular events, and all-cause mortality. Additional research for the validation of the MICA score in the context of aortoiliac revascularization and specific interventions is necessary.

Incidence of myocardial injury in patients submitted to carotid endarterectomy.

Myocardial injury following noncardiac surgery (MINS) is associated with higher mortality and major adverse cardiovascular event rates in the short- and long-term in patients undergoing carotid endarterectomy (CEA). However, its incidence is still unclear in this subset of patients. Therefore, this systematic review with meta-analysis aims to determine the incidence of MINS in patients undergoing CEA. Three electronic databases MEDLINE, Scopus, and Web of Science were used to search for studies assessing the occurrence of MINS in the postoperative setting of patients undergoing CEA. The incidence of MINS was pooled by random-effects meta-analysis, with sources of heterogeneity being explored by meta-regression and subgroup analysis (general anesthesia vs. regional anesthesia). Assessment of studies' quality was performed using National Heart, Lung, and Blood Institute Study Quality Assessment Tool, and Risk of Bias 2 tools. Twenty studies were included, with a total of 117,933 participants. Four of them were RCTs, while the remaining were cohort studies. All observational cohorts had an overall high risk of bias, except for Pereira Macedo et al. Three of them had repeated population, thus only data from the most recent one was considered. On the other hand, all RCT had an overall low risk of bias. In patients under regional anesthesia, the incidence of MINS in primary studies ranged between 2% and 15.3%, compared to 0-42.5% for general anesthesia. The meta-analytical incidence of MINS after CEA was of 6.3% [95% CI 2.0-10.6%], but severe heterogeneity was observed (I2=99.1%). MINS appears to be relatively common among patients undergoing CEA. The observed severe heterogeneity points to the need for further larger studies adopting consistent definitions of MINS and equivalent cut-off values.

Hyperfunctioning papillary thyroid carcinoma - a case report and literature review.

BACKGROUND: Malignant hyperfunctioning thyroid nodules are rare and more likely to occur in follicular cancer types rather than papillary variants. The authors present a case of a papillary thyroid carcinoma associated with a hyperfunctioning nodule. METHODS: A single adult patient submitted to total thyroidectomy with the presence of thyroid carcinoma within hyperfunctioning nodules was selected. Additionally, brief literature was conducted. RESULTS: An asymptomatic 58-year-old male was subjected to routine blood analysis and a TSH level of <0.003 mIU/L was found. Ultrasonography revealed a 21 mm solid, hypoechoic, and heterogenous nodule with microcalcifications in the right lobe. A fine needle aspiration guided by ultrasound resulted in a follicular lesion of undetermined significance. A 99mTc thyroid scintigram was followed and identified a right-sided hyperfunctioning nodule. Another cytology was performed and a papillary thyroid carcinoma was derived as a result. The patient underwent a total thyroidectomy. Postoperative histology confirmed the diagnosis and a tumor-free margin with no vascular or capsular invasions. CONCLUSION: Hyperfunctioning malignant nodules are a rare association, although a careful approach should be led since major clinical implications arise. Selective fine needle aspiration in all suspicious ≥1 cm nodules should be considered.

Blood group is a long-term cardiovascular risk factor after carotid endarterectomy.

BACKGROUND: ABO blood group system has been clinically related to an increased incidence of cardiovascular diseases. Preliminary data relating Rhesus (Rh) factor and these outcomes also have been published. Our aim was to analyse the impact of blood group on the short and long-term outcomes after carotid endarterectomy (CEA). MATERIALS AND METHODS: From 2012 to 2019, patients from a referral centre who underwent CEA for atherosclerotic carotid stenosis were prospectively followed. Our primary outcomes were long-term major adverse cardiovascular events (MACEs) and all-cause mortality. Secondary outcomes were perioperative complications and myocardial injury after non-cardiac surgery (MINS). Median follow-up was 50 months (interquartile range 21-69). Time-to-event analysis was used to determine the effect of ABO and Rh groups in long-term outcomes. RESULTS: One hundred and eighty-four patients were included, with a mean age of 70.1 ± 9.1 years. Eighteen (25.7%) patients with O type and 48 (42.1%) patients with non-O type presented coronary artery disease (odds ratio [OR]: 2.313, 5-95% confidence interval (CI) 1.245-4.297, p = .008). Patients Rh+ presented significantly more congestive heart failure, 23 (14.7%), p = .03. The incidence of MACE in the long-term was higher in non-O patients (adjusted hazard ratio: 2.034; CI: 1.032-4.010, p = .040). Rh- patients, presented a higher incidence of perioperative MINS. However, there was no statistically significant association with long-term risk of MACE. CONCLUSION: The incidence of MACE in long-term analysis was higher in non-O blood type and 30-day MINS was significantly more common amongst Rh- patients. The benefit from a more complete preoperative cardiac study in these patients should be performed.

Brain natriuretic peptide is a long-term cardiovascular predictor in carotid endarterectomy.

BACKGROUND: In noncardiac surgery, several biomarkers are known to play a role in predicting long-term complications, such as major adverse cardiovascular events (MACE), myocardial infarction, or death. Carotid endarterectomy (CEA) is considered a low to medium-risk surgery for carotid stenosis aimed at preventing stroke events. Brain natriuretic peptide (BNP) is a biomarker with potential prognostic value regarding MACE. Since its role in patients undergoing CEA is unknown, this study aims to assess the potential role of BNP as a short and long-term predictor of all-cause mortality and MACE in patients undergoing CEA. METHODS: From a prospective database, patients who underwent CEA under regional anesthesia (RA) at a tertiary hospital center were enrolled, and a post hoc analysis was conducted. Patients on which BNP levels were measured up to fifteen days before surgery, and two groups based on the BNP threshold (200 pg/mL) were defined and compared. Kaplan Meier survival curves and adjusted hazard ratios (aHR) were assessed by multivariable Cox regression. The primary outcome was the incidence of long-term MACE and all-cause mortality. Secondary outcomes included the incidence of AMI and AHF. RESULTS: A total of 89 patients were evaluated. The mean age of the cohort was 71.2 ± 8.7 years, with 71 (79.8%) males, and presented a median follow-up of 30 [13.5-46.4] months. BNP > 200 pg/mL has demonstrated positive predictive value for MACE (aHR: 5.569, confidence interval (CI): 2.441-12.7, p < 0.001) and all-cause mortality (aHR: 3.469, CI: 1.315-9.150, p = 0.018). CONCLUSION: BNP has been demonstrated to independently predict long-term all-cause mortality, MACE and AMI following CEA. It serves as a low-cost, ready-to-use biomarker, although further studies are necessary.

Targeted intervention to achieve waste reduction in gastrointestinal endoscopy.

OBJECTIVE: Endoscopy is healthcare's third largest generator of medical waste in hospitals. This prospective study aimed to measure a single unit's waste carbon footprint and perform a pioneer intervention towards a more sustainable endoscopy practice. The relation of regulated medical waste (RMW; material fully contaminated with blood or body fluids or containing infectious agents) versus landfill waste (non-recyclable material not fully contaminated) may play a critical role. DESIGN: In a four-stage prospective study, following a 4-week observational audit with daily weighing of both waste types (stage 1), stage 2 consisted of a 1-week intervention with team education of waste handling. Recycling bins were placed in endoscopy rooms, landfill and RMW bins were relocated. During stages 3 (1 month after intervention) and 4 (4 months after intervention), daily endoscopic waste was weighed. Equivalence of 1 kg of landfill waste to 1 kg carbon dioxide equivalent (CO2e) and 1 kg of RMW to 3kgCO2e was assumed. Paired samples t-tests for comparisons. RESULTS: From stage 1 to stage 3, mean total waste and RMW were reduced by 12.9% (p=0.155) and 41.4% (p=0.010), respectively, whereas landfill (p=0.059) and recycling waste increased (paper: p=0.001; plastic: p=0.007). While mean endoscopy load was similar (46.2 vs 44.5, p=0.275), a total decrease of CO2e by 31.6% (138.8kgCO2e) was found (mean kgCO2e109.7 vs 74.9, p=0.018). The annual reduction was calculated at 1665.6kgCO2e. All these effects were sustained 4 months after the intervention (stage 4) without objections by responsible endoscopy personnel. CONCLUSION: In this interventional study, applying sustainability measures to a real-world scenario, RMW reduction and daily recycling were achieved and sustained over time, without compromising endoscopy productivity.

The GAIN Registry - a New Prospective Study for Patients with Multi-organ Autoimmunity and Autoinflammation.

Patient registries are a very important and essential tool for investigating rare diseases, as most physicians only see a limited number of cases during their career. Diseases of multi-organ autoimmunity and autoinflammation are especially challenging, as they are characterized by diverse clinical phenotypes and highly variable expressivity. The GAIN consortium (German multi-organ Auto Immunity Network) developed a dataset addressing these challenges. ICD-11, HPO, and ATC codes were incorporated to document various clinical manifestations and medications with a defined terminology. The GAIN dataset comprises detailed information on genetics, phenotypes, medication, and laboratory values. Between November 2019 and July 2022, twelve centers from Europe have registered 419 patients with multi-organ autoimmunity or autoinflammation. The median age at onset of symptoms was 13 years (IQR 3-28) and the median delay from onset to diagnosis was 5 years (IQR 1-14). Of 354 (84.5%) patients who were genetically tested, 248 (59.2%) had a defined monogenetic cause. For 87 (20.8%) patients, no mutation was found and for 19 (4.5%), the result was pending. The most common gene affected was NFkB1 (48, 11.5%), and the second common was CTLA4 (40, 9.5%), both genetic patient groups being fostered by specific research projects within GAIN. The GAIN registry may serve as a valuable resource for research in the inborn error of immunity community by providing a platform for etiological and diagnostic research projects, as well as observational trials on treatment options.

A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study.

INTRODUCTION: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. METHODS: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. RESULTS: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. CONCLUSION: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes with and without chronic heart failure: A meta-analysis of randomized placebo-controlled outcome trials.

AIM: Glucagon-like peptide 1 receptor agonists (GLP1-RA) reduce atherosclerotic events in patients with type 2 diabetes (T2D) and a high cardiovascular risk. The effect of GLP1-RA to reduce heart failure (HF) has been inconsistent across T2D trials, and individual trials were underpowered to assess the effect of GLP1-RA according to HF history. In this meta-analysis we aim to assess the effect of GLP1-RA in patients with and without HF history in stable ambulatory patients with T2D. METHODS: Random-effects meta-analysis of placebo-controlled trials. The hazard ratio (HR) and 95% confidence intervals (95% CI) were extracted from the treatment effect estimates of HF subgroup analyses reported in each individual study. The primary outcome was a composite of HF hospitalization or cardiovascular death. RESULTS: In total, 54 092 patients with T2D from seven randomized controlled trials were included, of whom 8460 (16%) had HF history. Compared with placebo, GLP1-RA did not reduce the composite of HF hospitalization or cardiovascular death in patients with HF history: HR 0.96, 95% CI: 0.84-1.08, but reduced this outcome in patients without HF history: HR 0.84, 95% CI: 0.76-0.92. GLP1-RA did not reduce all-cause death in patients with HF history: HR 0.98, 95% CI: 0.86-1.11, but reduced mortality in patients without HF history: HR 0.85, 95% CI: 0.79-0.92. GLP1-RA reduced atherosclerotic events regardless of HF history: HR 0.85, 95% CI: 0.75-0.97 with HF, and HR 0.88, 95% CI: 0.83-0.93 without HF. CONCLUSIONS: Treatment with GLP1-RA did not reduce HF hospitalizations and mortality in patients with concomitant T2D and HF, but may prevent new-onset HF and mortality in patients with T2D without HF. The reduction of atherosclerotic events with GLP1-RA was not influenced by HF history status.

Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial.

AIM: To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF). MATERIALS AND METHODS: FIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression. RESULTS: Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047). CONCLUSIONS: In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions.

Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort.

BACKGROUND: Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of free T4 (FT4) into free T3 (FT3) is thought to occur in these patients, decreasing the availability of FT3 and contributing to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (THs) are associated with clinical status and outcomes. OBJECTIVES: The objective of this study was to evaluate the association of FT3/FT4 ratio and TH with clinical, analytical, and echocardiographic parameters, as well as their prognostic impact in individuals with stable HFpEF. METHODS: We evaluated 74 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modeling to study the associations of TH and FT3/FT4 ratio with clinical, anthropometric, analytical, and echocardiographic parameters, and survival analysis to evaluate associations with the composite of diuretic intensification, urgent HF visit, HF hospitalization, or cardiovascular death over a median follow-up of 2.8 years. RESULTS: The mean age was 73.7 years and 62% were men. The mean FT3/FT4 ratio was 2.63 (standard deviation: 0.43). Subjects with lower FT3/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3/FT4 ratio was associated with higher body fat (ß = -5.60 kg per FT3/FT4 unit, p = 0.034), higher pulmonary arterial systolic pressure (PASP) (ß = -10.26 mm Hg per FT3/FT4 unit, p = 0.002), and lower left ventricular ejection fraction (LVEF) (ß = 3.60% per FT3/FT4 unit, p = 0.008). Lower FT3/FT4 ratio was associated with higher risk for the composite HF outcome (HR = 2.50, 95% CI: 1.04-5.88, per 1-unit decrease in FT3/FT4, p = 0.041). CONCLUSIONS: In patients with HFpEF, lower FT3/FT4 ratio was associated with higher body fat, higher PASP, and lower LVEF. Lower FT3/FT4 predicted a higher risk of diuretic intensification, urgent HF visits, HF hospitalization, or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion might be a mechanism associated with HFpEF progression.

R2CHA2DS2-VA Predictsthe Cardiovascular Risk after Carotid Endarterectomy.

BACKGROUND: R2CHA2DS2-VA score has been used to predict short and long-term outcomes in many cardiovascular diseases. This study aims to validate the R2CHA2DS2-VA score as a long-term major adverse cardiovascular events (MACE) predictor after carotid endarterectomy (CEA). Secondary outcomes were also assessed regarding the incidence of all-cause mortality, acute myocardial infarction (AMI), major adverse limb events (MALE), and acute heart failure (AHF). METHODS: From January 2012 to December 2021, patients (n = 205) from a Portuguese tertiary care and referral center that underwent CEA with regional anesthesia (RA) for carotid stenosis (CS) were selected from a previously collected prospective database, and a posthoc analysis was performed. Demographics and comorbidities were registered. Clinical adverse events were assessed 30 days after the procedure and in the subsequent long-term surveillance period. Statistical analysis was performed by the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: Of the patients enrolled, 78.5% were males with a mean age of 70.44 ± 8.9 years. Higher scores of R2CHA2DS2-VA were associated with long-term MACE (adjusted hazard ratio (aHR) 1.390; 95% confidence interval (CI) 1.173-1.647); and mortality (aHR 1.295; 95% CI 1.08-1.545). CONCLUSIONS: This study demonstrated the potential of the R2CHA2DS2-VA score to predict long-term outcomes, such as AMI, AHF, MACE, and all-cause mortality, in a population of patients submitted to carotid endarterectomy.

Temporal validation of the MMCD score to predict kidney replacement therapy and in-hospital mortality in COVID-19 patients.

BACKGROUND: Acute kidney injury has been described as a common complication in patients hospitalized with COVID-19, which may lead to the need for kidney replacement therapy (KRT) in its most severe forms. Our group developed and validated the MMCD score in Brazilian COVID-19 patients to predict KRT, which showed excellent performance using data from 2020. This study aimed to validate the MMCD score in a large cohort of patients hospitalized with COVID-19 in a different pandemic phase and assess its performance to predict in-hospital mortality. METHODS: This study is part of the "Brazilian COVID-19 Registry", a retrospective observational cohort of consecutive patients hospitalized for laboratory-confirmed COVID-19 in 25 Brazilian hospitals between March 2021 and August 2022. The primary outcome was KRT during hospitalization and the secondary was in-hospital mortality. We also searched literature for other prediction models for KRT, to assess the results in our database. Performance was assessed using area under the receiving operator characteristic curve (AUROC) and the Brier score. RESULTS: A total of 9422 patients were included, 53.8% were men, with a median age of 59 (IQR 48-70) years old. The incidence of KRT was 8.8% and in-hospital mortality was 18.1%. The MMCD score had excellent discrimination and overall performance to predict KRT (AUROC: 0.916 [95% CI 0.909-0.924]; Brier score = 0.057). Despite the excellent discrimination and overall performance (AUROC: 0.922 [95% CI 0.914-0.929]; Brier score = 0.100), the calibration was not satisfactory concerning in-hospital mortality. A random forest model was applied in the database, with inferior performance to predict KRT requirement (AUROC: 0.71 [95% CI 0.69-0.73]). CONCLUSION: The MMCD score is not appropriate for in-hospital mortality but demonstrates an excellent predictive ability to predict KRT in COVID-19 patients. The instrument is low cost, objective, fast and accurate, and can contribute to supporting clinical decisions in the efficient allocation of assistance resources in patients with COVID-19.

The importance of inflammatory biomarkers in non-specific acute and chronic low back pain: a systematic review.

OBJECTIVE: The purpose of this study was to systematically review the evidence on inflammatory biomarkers as analytic predictors of non-specific low back pain (NsLBP). Low back pain (LBP) is the number one cause of disability globally, posing a major health problem that causes an enormous social and economic burden, and there is an increasing interest on the importance of biomarkers in quantifying and even emerge as potential therapeutic tools to LBP. METHODS: A systematic search was conducted on July 2022 in Cochrane Library, MEDLINE and Web of Science for all the available literature. Cross-sectional, longitudinal cohort or case-control studies that evaluated the relationship between inflammatory biomarkers collected from blood samples and low back pain in humans were considered eligible for inclusion, as well as prospective and retrospective studies. RESULTS: The systematic database search resulted in a total of 4016 records, of which 15 articles were included for synthesis. Sample size comprised a total of 14,555 patients with LBP (acute LBP (n = 2073); chronic LBP (n = 12482)) and 494 controls. Most studies found a positive correlation between classic pro-inflammatory biomarkers and NsLBP, namely C-reactive protein (CRP), interleukin 1 (IL-1) and IL-1ß, interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). On the other hand, anti-inflammatory biomarker interleukin 10 (IL-10) demonstrated a negative association with NsLBP. Four studies have made direct comparisons between ALBP and CLBP groups regarding their inflammatory biomarkers profile. CONCLUSIONS: This systematic review found evidence of increased levels of pro-inflammatory biomarkers CRP, IL-6 and TNF-α and decreased levels of anti-inflammatory biomarker IL-10 in patients with LBP. Hs-CRP was not correlated with LBP. There is insufficient evidence to associate these findings with the degree of pain severity or the activity status of the lumbar pain over time.