Bioavailability of three novel oral, sustained-release pellets, relative to an immediate-release tablet containing 500 mg flucytosine: A randomized, open-label, crossover study in healthy volunteers.

The opportunistic fungal infection cryptococcal meningoencephalitis is a major cause of death among people living with HIV in sub-Saharan Africa. We report pharmacokinetic (PK) and safety data from a randomized, four-period crossover phase I trial of three sustained-release (SR) oral pellet formulations of 5-flucytosine conducted in South Africa. These formulations were developed to require less frequent administration, to provide a convenient alternative to the current immediate release (IR) formulation, A. Formulations B, C, and D were designed to release 5-flucytosine as a percentage of the nominal dose in vitro. We assessed their safety and PK profiles in a single dose (1 × 3000 mg at 0 h), relative to commercial IR tablets (Ancotil 500 mg tablets; 3 × 500 mg at 0 h and 3 × 500 mg at 6 h) in healthy, fasted participants. Forty-two healthy participants were included. All treatments were well-tolerated. The primary PK parameters, maximum observed plasma concentration (Cmax ) and area under the concentration-time profiles, were significantly lower for the SR formulations than for the IR tablets, and the geometric mean ratios fell outside the conventional bioequivalence limits. The median maximum time to Cmax was delayed for the SR pellets. Physiologically-based PK modeling indicated a twice-daily 6400 mg dose of SR formulation D in fasted condition would be optimal for further clinical development. This regimen is predicted to result in a rapid steady-state plasma exposure with effective and safe trough plasma concentration and Cmax values, within the therapeutic boundaries relative to plasma exposure after four times per day administration of IR tablets (PACTR202201760181404).

Development and Validation Process of the Intensive Care Unit Omitted Nursing Care (ICU-ONC) Instrument Among French Canadian Nurses.

Background and Purpose: The purpose of this article is to document the development and validation process of an instrument adapted for French-speaking nurses and to measure the occurrence of omitted nursing care (ONC) in the intensive care unit (ICU). Methods: An electronic Delphi panel, involving ICU nursing experts from the province of Quebec (Canada), was used to develop the intensive care unit omitted nursing care (ICU-ONC) instrument. For the validation process, an electronic cross-sectional survey was conducted. Results: A total of 564 nurses participated in the validation study. Exploratory factor analysis performed on 478 complete observations supports the presence of a single-factor structure for the 22-item ICU-ONC instrument. Coefficient alpha for the scale was .93, 95% confidence interval (CI) was [0.92, 0.94], item-partial total correlations ranged from .49 and .68, and the mean/median interitem correlations were .38 and .37, respectively. Moderate negative correlations were found between the ICU-ONC instrument overall score and two related constructs: nurses' perception of the quality as well as the safety of care. Conclusions: Our current understanding of ONC in the ICU is based on the results drawn from the administration of generic instruments to ICU nurses. The novel 22-item ICU-ONC instrument can help better estimate the occurrence of the phenomena in the ICU.

Hemiarch versus extended arch repair for acute type A dissection: Results from a multicenter national registry.

OBJECTIVE: We compared perioperative outcomes of patients with acute type A aortic dissection undergoing hemiarch (HA) versus extended arch (EA) repair with or without descending aortic intervention. METHODS: Nine hundred twenty-nine patients underwent acute type A aortic dissection repair (2002-2021, 9 centers) including open distal repair (HA) with or without additional EA repair. EA with intervention on the descending aorta (EAD) included elephant trunk, antegrade thoracic endovascular aortic replacement, or uncovered dissection stent. EA with no descending intervention (EAND), included unstented suture-only methods. Primary outcomes were in-hospital mortality, permanent neurologic deficit, computed tomography malperfusion resolution, and a composite. Multivariable logistic regression was also performed. RESULTS: Mean age was 66 ± 18 years, 30% (278 out of 929) were women, and HA was performed more frequently (75% [n = 695]) than EA (25% [n = 234]). EAD techniques included: dissection stent (39 out of 234 [17%]), thoracic endovascular aortic replacement (18 out of 234 [7.7%]), and elephant trunk (87 out of 234 [37%]). In-hospital mortality (EA: n = 49 [21%] and HA: n = 129 [19%]; P = .42), and neurological deficit (EA: n = 43 [18%] and HA: n = 121 [17%]; P = .74) were similar. EA was not independently associated with death (EA vs HA odds ratio, 1.09; 95% CI, 0.77-1.54; P = .63) or neurologic deficit (EA vs HA odds ratio, 0.85; 95% CI, 0.47-1.55; P = .59). Composite adverse events differed significantly (EA vs HA odds ratio, 1.47; 95% CI, 1.16-1.87; P = .001). Malperfusion resolved more frequently after EAD (EAD: n = 32 [80%], EAND: n = 18 [56%], HA: n = 71 [50%]; P = .004), although multivariable analysis was not significant (EAD vs HA odds ratio, 2.17; 95% CI, 0.83-5.66; P = .10). CONCLUSIONS: Extended arch interventions pose similar perioperative mortality and neurologic risks as Hemiarch. Descending aortic reinforcement may promote malperfusion restoration. Extended techniques should be approached with caution in acute dissection due to increased risk of adverse events.

Trends in sex-specific differences following aortic arch repair: results from the Canadian Thoracic Aortic Collaborative.

Background: Previous data have shown that sex-related differences exist in aortic arch surgery, with female patients experiencing worse outcomes. Over time, as surgical techniques and strategies have improved, these improvements have benefitted female patients. Using a multicenter national aortic registry from the Canadian Thoracic Aortic Collaborative (CTAC), we aimed to determine the relationship between sex and outcomes following aortic arch repair and to examine how these have changed over time. Methods: The multicenter prospective CTAC database of all aortic procedures performed under circulatory arrest from participating centers across Canada (n=9) was used. Patients were included who underwent elective or urgent/emergency arch reconstruction under circulatory arrest from 2002 to 2021. The primary composite endpoint was defined as the occurrence of one of the following endpoints: in-hospital mortality, stroke, dialysis-dependent renal failure, deep sternal wound infection, reoperation, or prolonged ventilation of >40 hours. Secondary endpoints included in-hospital mortality, in-hospital stroke, and a modified version of the Society of Thoracic Surgeons-defined composite endpoint for mortality and major morbidity (MMOM). Results: A total of 2,592 patients who underwent aortic arch repair between 2002 and 2021 (31.4% female and 68.6% male patients). Operative mortality decreased through the study period for female patients. No change in operative mortality was observed in male patients or following elective repair. The composite endpoint improved for female patients over time in both elective and urgent surgery, while for male patients, rates improved for elective surgery and remained stable for urgent. Ultimately, female sex was not an independent predictor of adverse outcomes following aortic arch repair. Conclusions: Our results are congruent with existing data and are highly encouraging. It shows that multilevel improvements in our approach to aortic arch surgery have helped to serve female patients who were previously disadvantaged.

Correlation between measured and predicted mismatch with valve hemodynamics in transcatheter aortic valve replacement: A sex-based analysis.

BACKGROUND: Data regarding the reliability of predicted effective orifice area indexed (pEOAi) is scarce in transcatheter aortic valve replacement (TAVR). AIMS: To assess the validity of the pEOAi in TAVR by correlating its value with echocardiography-derived hemodynamic data. METHODS: A single-center retrospective cohort study of TAVR patients from 2012 to 2021 with available echocardiograms was conducted. Patient-prosthesis mismatch (PPM) was defined based on the Valve Academic Research Consortium 3 criteria. The main endpoints were the congruence of measured effective orifice area indexed (EOAi) and pEOAi with the hemodynamic data obtained by echocardiography. The secondary endpoint included a correlation of predicted PPM (pPPM) and measured PPM (mPPM) with postoperative New York Heart Association (NYHA) status. RESULTS: A total of 318 patients were included. pPPM was more frequent than mPPM (54 [17%]; all moderate PPM vs. 39 [12.3%]: 32 moderate and 7 severe PPM). Predicted and measured EOAi were statistically correlated with postprocedural transvalvular mean gradient and Doppler velocity index (all p < 0.001), including in both sex-based subgroups. The positive predictive value and negative predictive value (NPV) of pPPM for postprocedural transvalvular mean gradient ≥ 20 mmHg were 16% and 97%, respectively. Only pPPM was significantly more prevalent in the group in which NYHA failed to improve than in those with symptom improvement (30.1% vs. 16%, p = 0.027). CONCLUSION: Predicted PPM has an excellent NPV for postprocedural transvalvular mean gradient ≥ 20 mmHg and seems to be a good predictor of NYHA status evolution as opposed to measured PPM. Predicted EOAi can be used in procedural planning to reduce the risk of PPM in both TAVR male and female patients.

CSDE1 promotes miR-451 biogenesis.

MicroRNAs are sequentially processed by RNase III enzymes Drosha and Dicer. miR-451 is a highly conserved miRNA in vertebrates which bypasses Dicer processing and instead relies on AGO2 for its maturation. miR-451 is highly expressed in erythrocytes and regulates the differentiation of erythroblasts into mature red blood cells. However, the mechanistic details underlying miR-451 biogenesis in erythrocytes remains obscure. Here, we report that the RNA binding protein CSDE1 which is required for the development of erythroblasts into erythrocytes, controls the expression of miR-451 in erythroleukemia cells. CSDE1 binds miR-451 and regulates AGO2 processing of pre-miR-451 through its N-terminal domains. CSDE1 further interacts with PARN and promotes the trimming of intermediate miR-451 to the mature length. Together, our results demonstrate that CSDE1 promotes biogenesis of miR-451 in erythroid progenitors.

Five-Year Hospital Readmission After Coronary Artery Bypass Surgery and the Association With Off-Pump Surgery and Sex.

Background Limited data exist on long-term readmission and its association with patient and procedural characteristics after coronary artery bypass grafting. We aimed to investigate 5-year readmission after coronary artery bypass grafting and specifically focus on the role of sex and off-pump surgery. Methods and Results We performed a post hoc analysis of the CORONARY (Coronary Artery Bypass Grafting [CABG] Off or On Pump Revascularization) trial, involving 4623 patients. The primary outcome was all-cause readmission, and the secondary outcome was cardiac readmission. Cox models were used to investigate the association of outcomes with sex and off-pump surgery. Hazard function for sex was studied over time using a flexible, fully parametric model, and time-segmented analyses were performed accordingly. Rho coefficient was calculated for the correlation between readmission and long-term mortality. Median follow-up was 4.4 years (interquartile range, 2.9-5.4 years). The cumulative incidence rates of all-cause and cardiac readmission were 29.4% and 8.2% at 5 years, respectively. Off-pump surgery was not associated with either all-cause or cardiac readmission. The hazard for all-cause readmission in women over time was constantly higher than the hazard for men (hazard ratio [HR], 1.21 [95% CI, 1.04-1.40]; P=0.011). Time-segmented analyses confirmed the higher risk for all-cause (HR, 1.21 [95% CI, 1.05-1.40]; P<0.001) and cardiac (HR, 1.26 [95% CI, 1.03-1.69]; P=0.033) readmission in women after the first 3 years of follow-up. All-cause readmission was strongly correlated with long-term all-cause mortality (Rho, 0.60 [95% CI, 0.48-0.66]), whereas cardiac readmission was strongly correlated with long-term cardiovascular mortality (Rho, 0.60 [95% CI, 0.13-0.86]). Conclusions Readmission rates are substantial at 5 years after coronary artery bypass grafting and are higher in women but not with off-pump surgery. Registration URL: http://www.clinicaltrials.gov/; Unique identifier: NCT00463294.

Anterolateral territory coronary artery bypass grafting strategies: a non-inferiority randomized clinical trial: the AMI-PONT trial.

OBJECTIVES: The main objective was to assess whether a composite coronary artery bypass grafting strategy including a saphenous vein graft bridge to distribute left internal mammary artery outflow provides non-inferior patency rates compared to conventional grafting surgery with separated left internal mammary artery to left anterior descending coronary graft and aorto-coronary saphenous vein grafts to other anterolateral targets. METHODS: All patients underwent isolated grafting surgery with cardiopulmonary bypass and received ≥2 grafts/patients on the anterolateral territory. The graft patency (i.e. non-occluded) was assessed using multislice spiral computed tomography at 1 year. RESULTS: From 2012 to 2021, 208 patients were randomized to a bridge (n = 105) or conventional grafting strategy (n = 103). Patient characteristics were comparable between groups. The anterolateral graft patency was non-inferior in the composite bridge compared to conventional grafting strategy at 1 year [risk difference 0.7% (90% confidence interval -4.8 to 6.2%)]. The graft patency to the left anterior descending coronary was no different between groups (P = 0.175). Intraoperatively, the bridge group required shorter vein length for anterolateral targets (P < 0.001) and exhibited greater Doppler flow in the mammary artery pedicle (P = 0.004). The composite outcome of death, myocardial infarction or target vessel reintervention at 30 days was no different (P = 0.164). CONCLUSIONS: Anterolateral graft patency of the composite bridge grafting strategy is non-inferior to the conventional grafting strategy at 1 year. This novel grafting strategy is safe, efficient, associated with several advantages including better mammary artery flow and shorter vein requirement, and could be a valuable alternative to conventional grafting strategies. Ten-year clinical follow-up is underway. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585285.

Conduit selection and early graft failure in coronary artery bypass surgery: A post hoc analysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) coronary artery bypass grafting study.

OBJECTIVES: Relative rates of early graft failure and conduit selection in coronary artery bypass grafting (CABG) surgery remain controversial. Therefore, we sought to determine the incidence and determinants of graft failure of the left internal mammary artery (LIMA), radial artery, saphenous vein, and right internal mammary artery (RIMA) 1 year after CABG surgery. METHODS: A post hoc analysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) CABG study, involving patients from 83 centers in 22 countries. We completed an analysis of 3480 grafts from 1068 patients who underwent CABG surgery with complete computed tomography angiography data. The primary outcome was graft failure as diagnosed by computed tomography angiography 1 year after surgery. RESULTS: Graft failure occurred in 6.4% (68/1068) for LIMA, 9.9% (9/91) for radial artery, 10.4% (232/2239) for saphenous vein, and 26.8% (22/82) for RIMA grafts. The RIMA had a greater rate of graft failure (26.8%) than radial artery (9.9%) and veins (10.4%) (adjusted odds ratio, 2.69; 95% confidence interval, 1.30-5.57; P = .008 and adjusted odds ratio, 2.07; 95% confidence interval, 1.33-3.21; P = .001, respectively). CONCLUSIONS: In this international trial dataset, LIMA and radial artery performed as expected, whereas vein grafts performed better. However, high rates of RIMA failure are worrisome and highlight the need for a thorough evaluation of the patency and safety of the RIMA in CABG surgery.

The characteristics and factors associated with omitted nursing care in the intensive care unit: A cross-sectional study.

INTRODUCTION: Prior research showed that work environment features in acute care settings influence nurses' capacity to provide care and impacts patient outcomes (e.g., falls). However, little is known about this phenomenon in the intensive care unit. The objectives of this study were to describe the characteristics of omitted nursing care, and to examine the associations between work environment features, omitted nursing care and nurse-reported outcomes in the intensive care unit. METHODS: An electronic cross-sectional correlational study was conducted in the province of Quebec, Canada. Over September 2021, nurses were asked to complete the Healthy Work Environment Assessment Tool (HWEAT), the Intensive Care Unit Omitted Nursing Care instrument (ICU-ONC) and to report their perceptions of nurse-reported outcomes (e.g., quality of care). The associations between these variables were estimated using multivariable cluster-robust regression models, adjusted for nurse and hospital characteristics. RESULTS: A total of 493 nurses from 42 distinct hospitals participated to this study. On average, nurses felt that their work environment was acceptable, and that the quality and safety of patient care was good. Basic care activities (e.g., mobilisation) were most frequently reported as omitted as opposed to those related to surveillance and medical interventions. In multivariable analyses, higher work environment scores were associated with reduced omitted nursing care scores (p < 0.001) and better ratings for nurse-reported outcomes (p < 0.001). Also, higher omitted nursing care scores were associated with more negative perceptions about the quality and safety of care (p < 0.001). CONCLUSION: Our study portrays the characteristics and some factors associated with omitted nursing care in the intensive care unit. Further research should determine whether intensive care nurses' reports of organisational features and omitted nursing care are associated with objectively captured patient outcomes.

Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation.

Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis). NETs are composed of DNA filaments decorated with granular proteins contributing to vascular occlusion associated with PGD. The main objective was to correlate NETosis in PGD3 (n = 9) versus non-PGD3 (n = 27) recipients in an exploratory study. Clinical data and blood samples were collected from donors and recipients pre-, intra- and postoperatively (up to 72 h). Inflammatory inducers of NETs' release (IL-8, IL-6 and C-reactive protein [CRP]) and components (myeloperoxidase [MPO], MPO-DNA complexes and cell-free DNA [cfDNA]) were quantified by ELISA. When available, histology, immunohistochemistry and immunofluorescence techniques were performed on lung biopsies from donor grafts collected during the surgery to evaluate the presence of activated neutrophils and NETs. Lung biopsies from donor grafts collected during transplantation presented various degrees of vascular occlusion including neutrophils undergoing NETosis. Additionally, in recipients intra- and postoperatively, circulating inflammatory (IL-6, IL-8) and NETosis biomarkers (MPO-DNA, MPO, cfDNA) were up to 4-fold higher in PGD3 recipients compared to non-PGD3 (p = 0.041 to 0.001). In summary, perioperative elevation of NETosis biomarkers is associated with PGD3 following human lung transplantation and these biomarkers might serve to identify recipients at risk of PGD3 and initiate preventive therapies.

Coronary bioresorbable stents: Non-invasive quantitative evaluation of intra- and juxta-stent plaque composition-A computed tomography longitudinal study.

PURPOSE: Coronary bioresorbable stents (BRS) do not produce blooming artifacts on computed tomography (CT), in contrast to metallic stents, as they are made of a bioresorbable polymer and are radiolucent. They allow to evaluate the coronary plaque beneath. The low-attenuation plaque (LAP) suggests plaque vulnerability and is CT assessable. The aim of our study was to show the possibility of a non-invasive CT evaluation of the volume and the LAP composition of the intra- and juxta-stent plaque. METHODOLOGY: In our prospective longitudinal study, we recruited 27 consecutive patients (35 BRS stents total; mean age 60 +/- 9 years) with bioresorbable stents for a 256-slice ECG-synchronized CT evaluation at 1- and 12-months post stent implantation. Total plaque volume (mm3), absolute and relative (%) LAP volume per block in the pre- intra- and post-stent zones were analyzed; comparison 1- and 12-months post-implantation of BRS. Changes in the previously mentioned variables were assessed by the mixed effects models with and without spline, which also accounted for the correlation between repeated measurements. RESULTS: Our block or spline model analysis has shown no significant difference in plaque or absolute LAP volumes in pre- intra- and post-stent zones between 1 and 12 months. Interestingly, % LAP volume increases near-significantly in the distal block of the intrastent at 12-mo follow-up (from 23.38 ± 1.80% to 26.90 ± 2.22% (increase of 15%), p = 0.052). CONCLUSION: Our study demonstrates the feasibility of the repeated non-invasive quantitative analysis of the intrastent coronary plaque and of the in-stent lumen by CT scan.

Risk score for arch reconstruction under circulatory arrest with hypothermia: The ARCH score.

OBJECTIVE: Currently, there is no risk scores built to predict risk in thoracic aortic surgery. This study aims to develop and internally validate a risk prediction score for patients who require arch reconstruction with hypothermic circulatory arrest. METHODS: From 2002 to 2018, data for 2270 patients who underwent aortic arch surgery in 12 institutions in Canada were retrospectively collected. The outcomes modeled included in-hospital mortality and a modified Society of Thoracic Surgeons-defined composite for mortality or major morbidity. Multivariable logistic regression using least absolute shrinkage and selection operator selection method and mixed-effect regression model was used to select the predictors. Internal calibration of the final models is presented with an observed-versus-predicted plot. RESULTS: There were 182 in-hospital deaths (8.0%), and the incidence of Society of Thoracic Surgeons-defined composite for mortality or major morbidity was 27.9%. Variables that increased risk of mortality are age, chronic obstructive pulmonary disease, atrial fibrillation, peripheral vascular disease, New York Heart Association class ≥III symptoms, acute aortic dissection or rupture, use of elephant trunk, concomitant surgery, and increased cardiopulmonary bypass time, with median c-statistics of 0.85 on internal validation. The c-statistics was 0.77 for the model predicting Society of Thoracic Surgeons-defined composite. Internal assessment shows good overall calibration for both models. CONCLUSIONS: We developed and internally validated a risk score for patients undergoing arch surgery requiring hypothermic circulatory arrest using a multicenter database. Once externally validated, the ARCH (Arch Reconstruction under Circulatory arrest with Hypothermia) score would allow for better patient risk-stratification and aid in the decision-making process for surgeons and patient prior to surgery.

Novel heat shock protein 90 inhibitor improves cardiac recovery in a rodent model of donation after circulatory death.

OBJECTIVE: Organ donation after circulatory death (DCD) is a potential solution for the shortage of suitable organs for transplant. Heart transplantation using DCD donors is not frequently performed due to the potential myocardial damage following warm ischemia. Heat shock protein (HSP) 90 has recently been investigated as a novel target to reduce ischemia/reperfusion injury. The objective of this study is to evaluate an innovative HSP90 inhibitor (HSP90i) as a cardioprotective agent in a model of DCD heart. METHODS: A DCD protocol was initiated in anesthetized Lewis rats by discontinuation of ventilation and confirmation of circulatory death by invasive monitoring. Following 15 minutes of warm ischemia, cardioplegia was perfused for 5 minutes at physiological pressure. DCD hearts were mounted on a Langendorff ex vivo heart perfusion system for reconditioning and functional assessment (60 minutes). HSP90i (0.01 µmol/L) or vehicle was perfused in the cardioplegia and during the first 10 minutes of ex vivo heart perfusion reperfusion. Following assessment, pro-survival pathway signaling was evaluated by western blot or polymerase chain reaction. RESULTS: Treatment with HSP90i preserved left ventricular contractility (maximum + dP/dt, 2385 ± 249 vs 1745 ± 150 mm Hg/s), relaxation (minimum -dP/dt, -1437 ± 97 vs 1125 ± 85 mm Hg/s), and developed pressure (60.7 ± 5.6 vs 43.9 ± 4.0 mm Hg), when compared with control DCD hearts (All P = .001). Treatment abrogates ischemic injury as demonstrated by a significant reduction of infarct size (2,3,5-triphenyl-tetrazolium chloride staining) of 7 ± 3% versus 19 ± 4% (P = .03), troponin T release, and mRNA expression of Bax/Bcl-2 (P < .05). CONCLUSIONS: The cardioprotective effects of HSP90i when used following circulatory death might improve transplant organ availability by expanding the use of DCD hearts.

Elements not Graded in the Cardiac Enhanced Recovery After Surgery Guidelines Might Improve Postoperative Outcome: A Comprehensive Narrative Review.

Enhanced Recovery Programs (ERPs) are protocols involving the whole patient surgical journey. These protocols are based on multimodal, multidisciplinary, evidence-based, and patient-centered approaches aimed at improving patient recovery after a surgical intervention. Such programs have shown striking positive results in different surgical specialties. However, only a few research groups have incorporated preoperative, intraoperative, and postoperative evidence-based interventions in bundles used to standardize care and build cardiac surgery ERPs. The Enhanced Recovery After Surgery Society recently published evidence-based recommendations for perioperative care in cardiac surgery. Their recommendations included 22 perioperative interventions that may be part of any cardiac ERP. However, various components integrated in already-published cardiac ERPs were neither graded nor reported in these recommendations. The goals of the current review are to present published cardiac ERPs and their effects on patient outcomes and reported components incorporated into these ERPs and to discuss the objectives and scope of cardiac ERPs.

Does "Obesity Paradox" Apply for Patients Undergoing Transcatheter Aortic Valve Replacement?

BACKGROUND: Data is controversial regarding the existence of an "obesity paradox" in patients undergoing Transcatheter Aortic Valve Replacement (TAVR). We sought to investigate the prognostic value of the body mass index (BMI) on outcomes following TAVR. METHODS: This is an observational, single-center study involving all patients who underwent TAVR from 2009 to 2019. BMI was calculated in all patients before TAVR. The cohort was subdivided into four groups: underweight (<20 kg/m2), normal weight (≥20 to <25 kg/m2), overweight (≥25 to <30 kg/m2) and obese (≥30 kg/m2). The main endpoint was all-cause 30-day and one-year mortality. RESULTS: A total of 412 patients (mean age 79.6 ± 7.8 years, mean STS score 5.3 ± 3.6) were included. Patients were grouped as follows: underweight (n = 35, 8.5%), normal weight (n = 121, 29.4%), overweight (n = 140, 34%) and obese (n = 116, 28.1%). Obese patients were younger, included more females and had lower STS score than the rest of the cohort whereas underweight patients were older, had higher STS score, more chronic kidney disease, more left ventricular dysfunction and more often underwent non-transfemoral TAVR. BMI predicted 30-day survival (AUC:0.692 [95%CI 0.522-0.862]; p = 0.030) with an optimal cut-off of 24.4 (sensitivity = 66.6%, specificity = 63.6%). On multivariate analysis, higher BMI trended toward lower 30-day mortality (HR = 0.87 [95%CI 0.75-1.01]; p = 0.071). Thirty-day mortality was higher in the underweight group (8.3%) in comparison with other BMI subgroups (normal weight 2.5%, overweight 1.4%, obese 0.9%; p = 0.045). However, no significant difference was found after adjustment of confounders (all p = NS). BMI did not predict one-year mortality. No significant difference in one-year survival was observed between the four BMI subgroups (log rank p = 0.925). CONCLUSION: BMI could represent an interesting prognostic tool for short-term mortality in patients undergoing TAVR. BMI < 20 kg/m2 was associated with higher 30-day mortality. Symptoms improved similarly in obese patients compared to lower BMI patients. For 30-day survivors, no evidence of the existence of an obesity paradox was observed in this cohort.

Impact of early quantitative morbidity on 1-year outcomes in coronary artery bypass graft surgery.

OBJECTIVES: We applied the Clavien-Dindo Complications Classification (CDCC) and the Comprehensive Complication Index (CCI) to the CORONARY trial to assess whether quantitative early morbidity affects outcomes at 1 year. METHODS: All postoperative hospitalization and 30-day follow-up complications were assigned a CDCC grade. CCI were calculated for all patients (n = 4752). Kaplan-Meier analysis examined 1-year mortality and 1-year co-primary outcome (i.e. death, non-fatal stroke, non-fatal myocardial infarction, new-onset renal failure requiring dialysis or repeat coronary revascularization) by CDCC grade. Multivariable logistic regression evaluated the predictive value of CCI for both outcomes. RESULTS: For off-pump and on-pump coronary artery bypass graft surgery, median CDCC were 1 [interquartile range: 0, 2] and 2 [1, 2] (P < 0.001), while median CCI were 8.7 [0, 22.6] and 20.9 [8.7, 29.6], respectively (P < 0.001). In on-pump, there were more grade I and grade II complications, particularly grade I and II transfusions (P < 0.001) and grade I acute kidney injury (P = 0.039), and more grade IVa respiratory failures (P = 0.047). Patients with ≥IIIa complications had greater cumulative 1-year mortality (P < 0.001). The median CCI was 8.7 [0, 22.6] in patients who survived and 22.6 [8.7, 44.3] in patients who died at 1 year (P < 0.001). The CCI remained an independent risk factor for 1-year mortality and 1-year co-primary outcome after multivariable adjustment (P < 0.001). CONCLUSIONS: On-pump coronary artery bypass graft surgery had a greater number of complications in the early postoperative period, likely driven by transfusions, respiratory outcomes and acute kidney injury. This affects 1-year outcomes. Similar analyses have not yet been used to compare both techniques and could prove useful to quantify procedural morbidity. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT00463294; Unique Identifier: NCT00463294.