Contrast Volume-to-Estimated Glomerular Filtration Rate Ratio as a Predictor of Short-Term Outcomes Following Transcatheter Aortic Valve Implantation.

Background/Objectives: Contrast-induced acute kidney injury (AKI) is associated with early mortality and adverse events. However, in the setting of transcatheter aortic valve implantation (TAVI), previous literature has failed to establish a correlation between the absolute volume of contrast media administered and mortality. We aimed to investigate the impact of contrast volume administered normalised to estimated glomerular filtration rate (CV/eGFR) on the development of AKI and on 30-day all-cause mortality in TAVI patients. Methods: We retrospectively analysed a cohort of 1150 patients who underwent TAVI at our unit between 2015 and 2018. Results: Follow-up was complete for 1064 patients. There were 23 deaths within the follow-up period and 76 cases of AKI, 9 of which required new renal replacement therapy (RRT). Receiver-operating characteristic (ROC) curve analysis showed fair discrimination for 30-day all-cause mortality at a CV/eGFR ratio of 3.6 (area under the ROC curve (AUC) 0.671). Of patients in whom CV data were available, 86.0% (n = 757) had a CV/eGFR < 3.6 and 14.0% (n = 123) had a CV/eGFR ≥ 3.6. In multivariate logistic regression analysis, CV/eGFR ≥ 3.6 was the strongest predictor of 30-day all-cause mortality (odds ratio 5.06, 95% confidence interval [1.61-15.7], p = 0.004). Other independent predictors were procedural urgency (3.28 [1.04-10.3], p = 0.038) and being under general anaesthesia (4.81 [1.10-17.3], p = 0.023). CV/eGFR ≥ 3.6 was also independently associated with significantly increased odds of AKI (2.28 [1.20-4.17], p = 0.009) alongside significant non-left main stem coronary artery disease (2.56 [1.45-4.66], p = 0.001), and diabetes (1.82 [1.03-3.19], p = 0.037). In supplementary ROC curve analysis, a similar CV/eGFR cut point of 3.6 was found to be an excellent predictor for new RRT (AUC 0.833). Conclusions: In conclusion, a CV/eGFR ≥ 3.6 post-TAVI was found to be a strong predictor of 30-day mortality and AKI. The maximum contrast volume that can be safely administered in each patient without significantly increasing the risk of mortality and AKI can be calculated using this ratio.

Development and External Validation of Machine Learning Models for Diabetic Microvascular Complications: Cross-Sectional Study With Metabolites.

BACKGROUND: Diabetic kidney disease (DKD) and diabetic retinopathy (DR) are major diabetic microvascular complications, contributing significantly to morbidity, disability, and mortality worldwide. The kidney and the eye, having similar microvascular structures and physiological and pathogenic features, may experience similar metabolic changes in diabetes. OBJECTIVE: This study aimed to use machine learning (ML) methods integrated with metabolic data to identify biomarkers associated with DKD and DR in a multiethnic Asian population with diabetes, as well as to improve the performance of DKD and DR detection models beyond traditional risk factors. METHODS: We used ML algorithms (logistic regression [LR] with Least Absolute Shrinkage and Selection Operator and gradient-boosting decision tree) to analyze 2772 adults with diabetes from the Singapore Epidemiology of Eye Diseases study, a population-based cross-sectional study conducted in Singapore (2004-2011). From 220 circulating metabolites and 19 risk factors, we selected the most important variables associated with DKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2) and DR (defined as an Early Treatment Diabetic Retinopathy Study severity level ≥20). DKD and DR detection models were developed based on the variable selection results and externally validated on a sample of 5843 participants with diabetes from the UK biobank (2007-2010). Machine-learned model performance (area under the receiver operating characteristic curve [AUC] with 95% CI, sensitivity, and specificity) was compared to that of traditional LR adjusted for age, sex, diabetes duration, hemoglobin A1c, systolic blood pressure, and BMI. RESULTS: Singapore Epidemiology of Eye Diseases participants had a median age of 61.7 (IQR 53.5-69.4) years, with 49.1% (1361/2772) being women, 20.2% (555/2753) having DKD, and 25.4% (685/2693) having DR. UK biobank participants had a median age of 61.0 (IQR 55.0-65.0) years, with 35.8% (2090/5843) being women, 6.7% (374/5570) having DKD, and 6.1% (355/5843) having DR. The ML algorithms identified diabetes duration, insulin usage, age, and tyrosine as the most important factors of both DKD and DR. DKD was additionally associated with cardiovascular disease history, antihypertensive medication use, and 3 metabolites (lactate, citrate, and cholesterol esters to total lipids ratio in intermediate-density lipoprotein), while DR was additionally associated with hemoglobin A1c, blood glucose, pulse pressure, and alanine. Machine-learned models for DKD and DR detection outperformed traditional LR models in both internal (AUC 0.838 vs 0.743 for DKD and 0.790 vs 0.764 for DR) and external validation (AUC 0.791 vs 0.691 for DKD and 0.778 vs 0.760 for DR). CONCLUSIONS: This study highlighted diabetes duration, insulin usage, age, and circulating tyrosine as important factors in detecting DKD and DR. The integration of ML with biomedical big data enables biomarker discovery and improves disease detection beyond traditional risk factors.

Postoperative vasoplegia in lung transplantation: incidence and relation to outcome in a single-centre retrospective study.

BACKGROUND: The incidence and clinical importance of vasoplegia after lung transplantation remains poorly studied. We describe the incidence of vasoplegia and its association with complications after lung transplantation. METHODS: Perioperative data of 279 lung transplant recipients operated on from 2015 to 2020 in a UK hospital were analysed retrospectively. RESULTS: Vasoplegia occurred in 41.6% of patients after lung transplantation (mild, 31.0%; moderate, 55.2%; severe, 13.8%). Compared with non-vasoplegic patients, vasoplegic patients had a higher incidence of any acute kidney injury, defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria (78.5% vs 65%, P=0.015), renal replacement therapy (47.4% vs 24.5%, P<0.001), and delayed chest closure (18.4% vs 9.2%, P=0.025); were ventilated longer (70 [32-368] vs 34 [19-105] h, P<0.001); and stayed longer in the ICU (12.9 [5-30] vs 6.8 [3-20] days, P<0.001). Mortality at 30 days and 1 yr was higher in patients with vasoplegia (11.2% vs 5.5% and 20.7% vs 11.7%, P=0.039, respectively). Severe vasoplegia represented a predictor of longer-term mortality (hazard ratio=1.65, P=0.008). Underlying infectious disease, increased BMI, higher preoperative pulmonary artery systolic pressure and bilirubin levels, lower glomerular filtration rate, and increased fresh frozen plasma transfusion were predictors of vasoplegia severity. Neutrophilia, leucocytosis, and increased C-reactive protein were associated with vasoplegia, but release of the neutrophil activation markers myeloperoxidase and heparin-binding protein was similar between groups. CONCLUSIONS: Influenced by preoperative status as well as procedural factors and inflammatory response, vasoplegia is a common and critical condition after lung transplantation with worse short-term outcomes and long-term survival.

Perioperative group and save testing are not routinely indicated for emergency laparoscopic appendicectomy and laparoscopic hernia repairs: A North West London retrospective study.

INTRODUCTION: Two valid group and saves are commonly required for patients undergoing laparoscopic appendicectomy and laparoscopic hernia repairs preoperatively; however, perioperative blood transfusions are seldom required. This is financially burdensome and frequently leads to delays in theatre lists. We performed a retrospective analysis to investigate blood transfusions performed perioperatively and within 28 days of these procedures. METHOD: We used our electronic records to collect data of all laparoscopic appendectomies and laparoscopic hernia repairs between March 2017 and March 2021. Patients of any age undergoing these operations were included. Patients requiring concomitant intra-abdominal surgery or who had incomplete medical records were excluded. RESULTS: A total of 1891 patients were included, of which 1462 (77.3%) had a laparoscopic appendicectomy versus 429 (22.7%) who had a laparoscopic hernia repair. In all, 3507 group and saves were taken costing £47,398.50. One patient (0.068%) required emergency blood transfusion (4 units of red cells) secondary to major haemorrhage. CONCLUSION: Our findings demonstrate that the incidence of perioperative blood transfusions for laparoscopic appendicectomy and laparoscopic hernia repairs is low, challenging the indication for routine preoperative group and saves.

The impact of complete versus partial preservation of the sub-valvular apparatus on left ventricular function in mitral valve replacement.

INTRODUCTION: In mitral valve replacement (MVR), sudden increases in afterload and disruption of the annular-chordal-papillary-left-ventricular wall causes left ventricular (LV) dysfunction in the early postoperative period. Preservation of the posterior mitral leaflet apparatus (MVR-P) has a favorable outcome on LV function. However, there is paucity of data on the impact of complete preservation of the sub-valvular apparatus (MVR-C). OBJECTIVE: We investigated the impact of MVR-P and MVR-C on baseline and 3-months postoperative LV ejection fraction (EF) and global longitudinal strain (GLS). METHODS: We retrospectively analyzed a cohort of 29 MVR-P and 19 MVR-C patients with complete echocardiography data at our unit, who were operated between 2008 and 2017. Between-group changes in LVEF and GLS were compared using independent sample T-test. RESULTS: Median age was 59 years (IQR 50-69 years). Baseline LVEF was 58% (51%- 60%). Baseline GLS was -18.4 (-21.2 to -15.5). There were no significant between-group differences between all baseline demographics and echocardiographic markers. There was significantly higher absolute postoperative LVEF in MVR-C patients (p = 0.029). There was also significant worsening in LVEF (p = 0.0121) and GLS (p < 0.0001) after MVR-P and not MVR-C, suggesting no reduction in LV function post-MVR-C but a reduction post-MVR-P. There was significantly less postoperative worsening of GLS per patient in MVR-C group as compared to the MVR-P group (p = 0.023), indicating better preservation of LV function. There was also a smaller decline in LVEF per patient in the MVR-C as compared to the MVR-P group, although not statistically significant (p = 0.23). CONCLUSION: MVR with complete preservation of the sub-valvular apparatus shows a favorable impact on the longitudinal function of the heart at 3 months. Further studies with larger patient numbers are indicated to investigate the long-term results of this surgical approach.

Should more patients be offered repair for mitral valve endocarditis? a single-centre 15-year experience.

OBJECTIVE: To describe the long-term outcomes of mitral valve repair (MVr) versus mitral valve replacement (MVR) in patients with native valve infective endocarditis (IE) at a centre with high-repair rates. METHODS: We conducted a retrospective single-centre cohort study. From 2005 to 2021, 183 patients with active or healed native valve IE were included. The primary outcome was long-term mortality. Patient status was last confirmed 31 March 2021. Secondary outcomes were post-operative MR, MV reoperation, length of post-operative intensive care stay and total hospital stay. RESULTS: 85 patients (46.4%) underwent MVr and 98 (53.6%) underwent MVR. Follow-up was 98.9% complete. Mean follow-up time was 5.3 years with 17% of patients reaching a follow-up time of over 10 years. There were 47 deaths (25.7%) within the follow-up period. MVR patients were more likely to have higher logistic EuroSCORE, active IE and were less likely to have elective surgery. In multivariate Cox proportional hazards analysis, there was no significant difference in long-term mortality between MVr and MVR groups (hazard ratio 1.09, 95% confidence interval [0.59-2.00]). In Kaplan-Meier analysis, MVR patients had a higher all-cause mortality although there was no significant difference at the endpoint. Propensity score matching analysis showed a significantly higher mortality in the replacement group instead (p = 0.002), Subgroup analysis revealed there remained no significant difference in mortality even in patients with active IE (P-interaction = 0.859) or non-elective surgery (P-interaction = 0.122). MV reoperation (odds ratio 1.00 [0.24-4.12]), post-operative intensive care stay (p = 0.9650) and total hospital stay (p = 0.9144) were comparable. CONCLUSIONS: Our data demonstrates repair was at least non-inferior to replacement in IE, supporting more aggressive use of repair. There is no reason the general principle of why repair is superior to replacement should not hold in IE, with enough operator expertise. Other experienced units should be encouraged to increase repair rates as feasible in line with current guidelines.

Lung cancer deaths (England 2001-2017)-comorbidities: a national population-based analysis.

BACKGROUND: The presence of comorbidities in people with lung cancer is common. Despite this, large-scale contemporary reports describing patterns and trends in comorbidities are limited. DESIGN AND METHODS: Population-based patterns and trends analysis using Office for National Statistics Mortality Data. Our cohort included all adults who died from lung cancer (ICD-10 codes C33-C34) in England between 2001 and 2017. We describe decedents with 0, 1 or ≥2 comorbidities and explore changes overtime for the six most common comorbidities identified: chronic respiratory disease; diabetes; cardiovascular disease; dementia; cerebrovascular disease and chronic kidney disease. To determine future trends, the mean annual percentage change between 2001 and 2017 was calculated and projected forwards, while accounting for anticipated increases in lung cancer mortality. RESULTS: There were 472 259 deaths from lung cancer (56.9% men; mean age 72.9 years, SD: 10.7). Overall, 19.0% of lung cancer decedents had 1 comorbidity at time of death and 8.8% had ≥2. The proportion of patients with comorbidities increased over time-between 2001 and 2017 decedents with 1 comorbidity increased 54.7%, while those with ≥2 increased 294.7%. The most common comorbidities were chronic respiratory disease and cardiovascular disease, contributing to 18.5% (95% CI: 18.0 to 18.9) and 11.4% (11.0 to 11.7) of deaths in 2017. Dementia and chronic kidney disease had the greatest increase in prevalence, increasing 311% and 289% respectively. CONCLUSION: To deliver high-quality outcomes for the growing proportion of lung cancer patients with comorbidities, oncology teams need to work across traditional boundaries of care. Novel areas for development include integration with dementia and chronic kidney disease services.

Visual Impairment, Major Eye Diseases, and Mortality in a Multi-Ethnic Asian Population and a Meta-analysis of Prospective Studies.

PURPOSE: Vision impairment (VI) is associated with poor quality of life and increased risk of falls. Few prospective data are available on Asians. This study investigates the longitudinal impact of VI and the major eye diseases on mortality risk in Asians. DESIGN: Prospective cohort study with meta-analysis. METHODS: We conducted a multi-ethnic prospective study of adults (40-80 years old) in the Singapore Epidemiology of Eye Diseases Study (baseline: 2004-2011). All-cause mortality was obtained from the National Death Registry until May 2017. VI was defined by best-corrected visual acuity (BCVA) <20/40 in the better eye. Major eye diseases were assessed using standard protocols. We examined associations using multivariate-adjusted Cox proportional hazards regression models. Finally, we conducted a meta-analysis of the associations between VI and mortality. RESULTS: Of 9,986 participants, 1,210 deaths occurred (12.1%) over a median follow-up of 8.8 years. Compared to participants with normal vision, persons with VI had increased risk of mortality (hazards ratio [HR]: 1.53; 95% confidence interval [CI:] 1.30-1.81) in multivariate models. In ethnicity-specific analyses, this association was significant across Chinese (HR: 1.63; 95% CI: 1.08-2.48); Malays (HR: 1.31; 95% CI: 1.06-1.62); and Indians (HR: 2.25; 95% CI: 1.61-3.15). Cataract, under-corrected refractive errors (URE), and diabetic retinopathy (DR) were significantly associated with mortality (HRs: 1.30, 1.22, and 1.54, respectively). In a meta-analysis of 12 studies including 58,034 persons, VI was associated with 30% increased risk of mortality (HR: 1.3; 95% CI: 1.2-1.5). CONCLUSIONS: In this multi-ethnic Asian population, VI and preventable eye conditions (cataract, URE, and DR) were associated with mortality, emphasizing the need for early detection and intervention to prevent and treat VI and major eye diseases.

Obesity and risk of age-related eye diseases: a systematic review of prospective population-based studies.

BACKGROUND: Obesity is a public health challenge worldwide. The relationship between obesity and age-related eye diseases including cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR) have remained elusive. DESIGN AND METHODS: We conducted a systematic review of three electronic databases for longitudinal population-based studies that described associations between measures of obesity including body mass index (BMI), waist-circumference (WC), and waist-to-hip ratio (WHR), and age-related eye diseases. RESULTS: Our search yielded 1731 articles, of which 14, 10, 16 and 8 articles met our eligibility criteria for cataract, glaucoma, AMD and DR, respectively. BMI-defined obesity was positively associated with incident cataract, incident AMD and incident DR in Western populations, but in Asian populations associations for incident AMD were not significant and associations for incident DR were inverse. WC-defined obesity was associated with incident glaucoma in non-Western populations. WHR-defined obesity but not BMI-defined obesity was associated with the incidence or progression of AMD in two Western studies. CONCLUSIONS: Overall, we found strong evidence supporting associations between obesity and age-related eye diseases. Further research on the association of abdominal obesity and effect of weight loss and physical activity on age-related eye diseases is warranted to support clinical and public health recommendations.

Secondary mitral regurgitation: pathophysiology, proportionality and prognosis.

Secondary mitral regurgitation (SMR) occurs as a result of multifactorial left atrioventricular dysfunction and maleficent remodelling. It is the most common and undertreated form of mitral regurgitation (MR) and is associated with a very poor prognosis. Whether SMR is a bystander reflecting the severity of the cardiomyopathy disease process has long been the subject of debate. Studies suggest that SMR is an independent driver of prognosis in patients with an intermediate heart failure (HF) phenotype and not those with advanced HF. There is also no universal agreement regarding the quantitative thresholds defining severe SMR and indeed there are challenges with echocardiographic quantification. Until recently, no surgical or transcatheter intervention for SMR had demonstrated prognostic benefit, in contrast with HF medical therapy and cardiac resynchronisation therapy. In 2018, the first two randomised controlled trials (RCTs) of edge-to-edge transcatheter mitral valve repair versus guideline-directed medical therapy in HF (Percutaneous Repair with the MitraClip Device for Severe (MITRA-FR), Transcather mitral valve repair in patients with heart failure (COAPT)) reported contrasting yet complimentary results. Unlike in MITRA-FR, COAPT demonstrated significant prognostic benefit, largely attributed to the selection of patients with disproportionately severe MR relative to their HF phenotype. Consequently, quantifying the degree of SMR in relation to left ventricular volume may be a useful discriminator in predicting the success of transcatheter intervention. The challenge going forward is the identification and validation of such parameters while in parallel maintaining a heart-team guided holistic approach.

Population-Based Quality Indicators for End-of-Life Cancer Care: A Systematic Review.

IMPORTANCE: Improving the quality of cancer care is an international priority. Population-based quality indicators (QIs) are key to this process yet remain almost exclusively used for evaluating care during the early, often curative, stages of disease. OBJECTIVES: To identify all existing QIs for the care of patients with cancer who have advanced disease and/or are at the end of life and to evaluate each indicator's measurement properties and appropriateness for use. EVIDENCE REVIEW: For this systematic review, 5 electronic databases (MEDLINE, Embase, CINAHL, PsycINFO, and the Cochrane Library) were searched from inception through February 4, 2019, for studies describing the development, review, and/or testing of QIs for the care of patients with cancer who have advanced disease and/or are at the end of life. For each QI identified, descriptive information was extracted and 6 measurement properties (acceptability, evidence base, definition, feasibility, reliability, and validity) were assessed using previously established criteria, with 4 possible ratings: positive, intermediate, negative, and unknown. Ratings were collated and each QI classified as appropriate for use, inappropriate for use, or of limited testing. Among the QIs determined as appropriate for use, a recommended shortlist was generated by excluding those that were specific to patient subgroups and/or care settings; related QIs were identified, and the indicator with the highest rating was retained. FINDINGS: The search yielded 7231 references, 35 of which (from 28 individual studies) met the eligibility criteria. Of 288 QIs extracted (260 unique), 103 (35.8%) evaluated physical aspects of care and 109 (37.8%) evaluated processes of care. Quality indicators relevant to psychosocial (18 [6.3%]) or spiritual and cultural (3 [1.0%]) care domains were limited. Eighty QIs (27.8%) were determined to be appropriate for use, 116 (40.3%) inappropriate for use, and 92 (31.9%) of limited testing. The measurement properties with the fewest positive assessments were acceptability (38 [13.2%]) and validity (63 [21.9%]). Benchmarking data were reported for only 16 QIs (5.6%). The final 15 recommended QIs came from 6 studies. CONCLUSIONS AND RELEVANCE: The findings suggest that only a small proportion of QIs developed for the care of patients with cancer who have advanced disease and/or are at the end of life have received adequate testing and/or are appropriate for use. Further testing may be needed, as is research to establish benchmarking data and to expand QIs relevant to psychosocial, cultural, and spiritual care domains.