Association of aortic valvular complex calcification burden with procedural and long-term clinical outcomes after transcatheter aortic valve replacement

Aims This study aimed to assess the impact of valvular/subvalvular calcium burden on procedural and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Methods and results In this prospective observational cohort study, we included patients with AS undergoing TAVR between March 2010 and December 2019. Calcium burden at baseline was quantified using multidetector computed tomography and the patients were classified into tertile groups according to the amount of calcium. Procedural outcomes [paravalvular leakage (PVL) or permanent pacemaker insertion (PPI)] and 12-month clinical outcomes (composite of death, stroke, or rehospitalization, and all-cause mortality) were assessed. A total of 676 patients (age, 79.8 ± 5.4 years) were analysed. The 30-day rates of moderate or severe PVL (P-for-trend = 0.03) and PPI (P-for-trend = 0.002) proportionally increased with the tertile levels of calcium volume. The 12-month rate of primary composite outcomes was 34.2% in low-tertile, 23.9% in middle-tertile, and 25.8% in high-tertile groups (log-rank P = 0.02). After multivariable adjustment, the risk for primary composite outcomes at 12 months was not significantly different between the tertile groups of calcium volume [reference = low-tertile; middle-tertile, hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.54–1.22; P = 0.31; high-tertile, HR 0.93; 95% CI 0.56–1.57; P = 0.80]. A similar pattern was observed for all-cause mortality. Conclusion The rates of PVL and PPI proportionally increased according to the levels of valvular/subvalvular calcium volume, while the adjusted risks for composite outcomes and mortality at 12 months were not significantly different.

Using food network analysis to understand meal patterns in pregnant women with high and low diet quality

Background Little is known about how meal-specific food intake contributes to overall diet quality during pregnancy, which is related to numerous maternal and child health outcomes. Food networks are probabilistic graphs using partial correlations to identify relationships among food groups in dietary intake data, and can be analyzed at the meal level. This study investigated food networks across meals in pregnant women and explored differences by overall diet quality classification. Methods Women were asked to complete three 24-h dietary recalls throughout pregnancy (n = 365) within a prospective cohort study in the US. Pregnancy diet quality was evaluated using the Healthy Eating Index-2015 (HEI, range 0-100), calculated across pregnancy. Networks from 40 food groups were derived for women in the highest and lowest HEI tertiles at each participant-labeled meal (i.e., breakfast, lunch, dinner, snacks) using Gaussian graphical models. Network composition was qualitatively compared across meals and between HEI tertiles. Results In both HEI tertiles, breakfast food combinations comprised ready-to-eat cereals with milk, quick breads with sweets (e.g., pancakes with syrup), and bread with cheese and meat. Vegetables were consumed at breakfast among women in the high HEI tertile only. Combinations at lunch and dinner were more varied, including vegetables with oils (e.g., salads) in the high tertile and sugary foods with nuts, fruits, and milk in the low tertile at lunch; and cooked grains with fats (e.g., pasta with oil) in the high tertile and potatoes with vegetables and meat in the low tertile at dinner. Fried potatoes, sugar-sweetened beverages, and sandwiches were consumed together at all main meals in the low tertile only. Foods were consumed individually at snacks in both tertiles; the most commonly consumed food were fruits in the high HEI tertile and cakes & cookies in the low tertile. Conclusions In this cohort of pregnant women, food network analysis indicated that food combinations differed by meal and between HEI tertiles. Meal-specific patterns that differed between diet quality tertiles suggest potential targets to improve food choices at meals; the impact of meal-based dietary modifications on intake of correlated foods and on overall diet quality should be investigated in simulations and intervention studies. Trial registration PEAS was registered with number NCT02217462 in Clinicaltrials.gov on August 13, 2014.

Association Between Alkaline Phosphatase and Muscle Mass, Strength, or Physical Performance in Patients on Maintenance Hemodialysis

Introduction: Alkaline phosphatase (ALP) is an indicator for checking liver or bone disorders, but recent studies have shown the possibility of an additive indicator beyond the simple mineral-bone status in dialysis patients. The aim of the study was to evaluate the ALP level and various indicators for malnutrition, physical performance, or hospitalization in patients on hemodialysis (HD).Methods: This study was an observational study (n = 84). We included all patients undergoing HD with the following criteria: age ≥ 20 years, duration of dialysis ≥ 6 months, ability to ambulate without an assistive device, ability to communicate with the interviewer, and no hospitalization within the last 3 months before enrollment. Furthermore, none of the patients had liver disease. We recommended abstinence of alcohol for ≥ 1 month for the duration of the study. The patients were divided into tertiles based on the ALP level. Muscle mass [appendicular muscle mass index using dual-energy X-ray absorptiometry (ASM/Ht2), thigh muscle area index using computed tomography (TMA/Ht2)], strength [handgrip strength (HGS)], and physical performance [gait speed (GS), sit-to-stand for 30-s test (STS30), 6-min walk test (6-MWT), or Short Physical Performance Battery test (SPPB)] were evaluated. The number of hospitalizations was also evaluated.Results: The ALP level in the low, middle, and high tertiles was 50.5 ± 7.5, 69.8 ± 5.4, and 113.3 ± 47.3 IU/l, respectively. The high tertile group showed the poorest trends in ASM/Ht2, TMA/Ht2, HGS, GS, STS30, and 6-MWT compared to the other tertile groups. Logistic regression analysis showed that the high tertile group for low HGS, low GS, or low SPPB had a higher odds ratio compared to the other tertiles. Subgroup analyses according to age, sex and diabetes mellitus showed similar trends as in the total cohort. Hospitalization-free survival rates after 300 days in the high tertile and the other tertiles were 53.8 and 77.2%, respectively (P = 0.105).Conclusion: The present study demonstrated that ALP is associated with muscle mass, strength, and physical performance in patients on maintenance HD. In addition, the trend showed better hospitalization-free survival in the low or middle tertiles than in the high tertile. ALP can be considered as a simple and useful indicator to detect malnutrition, physical performance, or hospitalization in patients on HD.

Abstract 14823: Comparison of a Novel Computed Tomography-Based Assessment of Mitral Annular Calcification to Transthoracic Echocardiogram

Introduction: Mitral annular calcification (MAC) is associated with increased stroke and death. The typical assessment by transthoracic echocardiography (TTE) is qualitative visual rating (VR), but this technique is user-dependent and lacks a gold standard for grading. Computed tomography (CT) has high sensitivity for calcium and can quantify MAC. The purpose of this study is to standardize grading of MAC and compare TTE-based assessment of MAC with CT. Methods: The analysis included 60 patients with non-contrast CT and TTE prior to aortic valve replacement or mitral valve (MV) repair. MAC was assessed on TTE by VR (none, mild, moderate, severe), a previously described echo calcium score (ECS), and systematic MAC grading (SMAC). TTE-based MV parameters were recorded. CT data were measured for calcium volume (MACV) via proprietary software (Visage Imaging) by an independent rater with 3D regions of interest in the MV area. Results: Mean age was 77 ± 11; 42% of patients were female. MACV for tertile-based groups (lowest, middle, highest) are shown in the Table. CT detected MAC in a notable portion of patients without MAC by TTE-derived methods: in 16 of 29 patients (55%) by VR, in 5 out of 15 (33%) by ECS, and in 5 out of 16 (31%) by SMAC. Fifteen of 22 patients (68%) with mild MAC by VR had middle or high-tertile MAC on CT. MACV-derived categories reclassified 65%, 60%, and 54% of patients compared with VR, ECS, and SMAC grading by TTE, respectively. Differences were also found across MACV categories for MV velocity, transmitral gradient, and E/e’. Except E/e’, trends were independent of TTE-based MAC analysis and significant after adjusting for mitral regurgitation or stenosis. Conclusions: TTE has limited ability to detect mild MAC compared with CT. This novel CT-based volumetric MAC assessment is feasible and can improve standardized quantification and sensitivity to detect MAC at lower values. Higher MACV by CT was associated with increasingly abnormal MV flow and diastology.

Relationship between the Length of Sperm Tail Mitochondrial Sheath and Fertility Traits in Boars Used for Artificial Insemination

The length of sperm tail midpiece, occupied by the mitochondrial sheath (MS), has been correlated with reproductive traits of mice, fish, and birds; however, it is not known whether such a correlation exists in higher order species such as domestic pigs. As the mitochondria provide for sperm motility and generate the fertility-affecting reactive oxygen species (ROS), we hypothesized that MS length correlates with boar semen parameters and artificial insemination (AI) fertility. Sperm samples collected from 57 boars and used for single sire AI were labeled with ProteoStat Aggresome probe (AGG; Enzo Life Sciences) for MS imaging by epifluorescence microscopy and image-based flow cytometry (IBFC). The mean boar MS length was 7.26 ± 0.2 µm, ranging from 6.94 ± 0.18 µm to 7.65 ± 0.31 µm. The absolute longest MS measured was 9.19 µm and the shortest was 5.83 µm. Boars in the high tertile of MS length had significantly higher conception rate (CR; p = 0.05) and sperm parameters. Boars within the high tertile of average number piglets born per litter had significantly shorter MS and more varied MS length than boars in the low tertile (p = 0.04). MS length data correlated with conventional sperm parameters including percent viable and intact acrosomes (p = 0.03), basal:induced oxidation ratio (measure of intracellular ROS levels; p = 0.02) and Comp DNA (chromatin integrity; p = 0.06) along with many flow cytometric AGG parameters in IBFC. Sperm head AGG intensity median absolute deviation had a negative correlation with total born (r = −0.423 p = 0.004). These data reveal a complex relationship between sperm MS length and aggresome abundance to sperm parameters and boar reproductive success in AI service.

Impact of Improvement in Walking Speed on Hospitalization and Mortality in Females with Cardiovascular Disease

Cardiovascular disease (CVD) is the principal cause of death in women. Walking speed (WS) is strongly related with mortality and CVD. The rate of all-cause hospitalization or death was assessed in 290 female outpatients with CVD after participation in a cardiac rehabilitation/secondary prevention program (CR/SP) and associated with the WS maintained during a moderate 1 km treadmill-walk. Three-year mortality rates were 57%, 44%, and 29% for the slow (2.1 ± 0.4 km/h), moderate (3.1 ± 0.3 km/h), and fast (4.3 ± 0.6 km/h) walkers, respectively, with adjusted hazard ratios (HRs) of 0.78 (p = 0.24) and 0.55 (p = 0.03) for moderate and fast walkers compared to the slow walkers. In addition, hospitalization or death was examined four to six years after enrollment as a function of the change in the WS of 176 patients re-assessed during the third year after baseline. The rates of hospitalization or death were higher across tertiles of reduced WS, with 35%, 50%, and 53% for the high (1.5 ± 0.3 km/h), intermediate (0.7 ± 0.2 km/h), and low tertiles (0.2 ± 0.2 km/h). Adjusted HRs were 0.79 (p = 0.38) for the intermediate and 0.47 (p = 0.02) for the high tertile compared to the low improvement tertile. Improved walking speed was associated with a graded decrease in hospitalization or death from any cause in women undergoing CR/SP.

Prognostic role of T3/T4 ratio in metastatic renal cell carcinoma (mRCC): Preliminary results of the threeFOUR multicenter study (Meet-Uro 14).

e17093 Background: Thyroid hormones metabolism can be altered in patients (pts) with chronic diseases and/or undergoing cancer treatments. The prognostic role of T3/T4 ratio has been investigated in metastatic colorectal cancer pts in whom a high T3/T4 ratio predicted longer survival. No data are available in mRCC. Methods: We retrospectively reviewed the clinical charts of pts with mRCC treated in first line for metastatic disease at 8 Italian Oncology Units before March 2017, having at least one response assessment and baseline complete thyroid panel data available. T3/T4 was calculated as the ratio of the two value of hormones and categorized in tertiles. Results: We identified 96 pts, median age 62 years (range 27-82), 72% males. Sunitinib wad administered in 56% of pts, pazopanib in 38%, nivolumab and ipilimumab in 6%. According to Heng Score, 33% of the pts were at favorable risk, 58% at intermediate risk, 9% at poor risk. With a median follow-up time of 42.8 months, median PFS was 24.8 months, estimated median OS was 71.6 months. Tertile distribution of patients was 36.4% in the high, 29.1% in the medium and 34.5% in the low subgroup. A baseline high tertile value (≥ 0.35) predicted longer PFS (39.4 vs 21.8 1vs 4.5 months, p = 0.01), while median OS has not been reached in the three tertiles, with survival at 24 months being 69.7%, 82.1% and 91.4%, respectively in the low, medium, high group (p = ns). The high T3/T4 ratio is also strongly associated with the chance to achieve a partial or complete response (42.8% vs 39.9% vs 21%, X squared test, p < 0.001). Heng prognostic model retained its prognostic role in this cohort (median OS was 77.1 vs 48.4 vs 22.3 months, p < 0.001, respectively for favorable, intermediate or poor risk group) and also predicted PFS (median PFS 38.2 vs 17.2 vs 8.4 months, p = 0.004). Baseline NLR ≥ 3 predicted shorter OS (46.5 vs 77.1 months, p = 0.02) in the whole group. Conclusions: In our retrospective multicenter experience, a high T3/T4 ratio was associated with longer PFS and a higher probability to respond to the treatment. Median OS had not been reached for all the subgroups, probably due to a favorable patients selection. A longer follow-up is needed to validate the prognostic value of T3/T4 ratio in this cohort.

Development of a risk calculator of recurrence in inguinal lymph node metastatic (ILNM) patients with surgically resected penile squamous cell carcinoma (PSCC).

1 Background: ILNM PSCC patients (pts) have heterogeneous outcomes. We aimed to identify risk factors of early recurrence in order to optimize the selection of pts for adjuvant (adj) therapies (tx). Methods: In a multicenter database of 924 pts who underwent ILN dissection, we identified 311 ILNM pts. Pts treated with neoadj chemo (CT) and/or radiotherapy (RT) were excluded. Multivariable Cox regression analyses (MVA) tested for predictors of recurrence, after adjusting for adj tx, age, type of surgery of the primary and smoking status. As primary endpoint, a risk calculator predicting early (24-month) risk of recurrence was developed. As secondary endpoint, the overall survival (OS) benefit of adj tx was examined according to the risk calculator-derived tertiles using Kaplan-Meier analysis. Results: Overall, 159 pts (51.1%) had pN1-2 and 203 (65.3%) pT2-4 disease. Overall, 195 (62.7%) and 78 (25.1%) received partial or total penectomy, whereas 6 (1.9%) local excision and 32 (10.3%) other procedures. Median number of removed and positive ILN were 15 (IQR 9-21) and 2 (IQR 1-3). Pelvic LND was performed in 154 (49.5%) pts, and 39% of them had pelvic LNM. In MVA, ILN ratio (HR: 1.01, p= 0.04), pN3 (HR: 2.53, p=0.002) and positive proximal margin of the primary (HR: 2.13, p=0.02) were significantly associated with recurrence. The c-index of our 3-variable risk calculator was 68%, with a net benefit higher that treat-all option from 20% to 90% threshold-probabilities. Within the cohort of adj CT and/or RT (N=127) pts, intermediate-high tertile had similar median OS (NR vs 107m) compared to pts in the low tertile (p=0.1). Conversely, intermediate-high tertile pts who received observation alone had shorter OS (NR vs 40m) compared to the same pts in the lower tertile (p<0.001). Similar results were obtained for CT and RT separately analyzed. Conclusions: We developed and internally validated a risk calculator to predict early recurrence in ILNM surgically-resected PSCC pts. According to our risk-calculator, pts with intermediate/higher risk of early recurrence may benefit from adj tx. Our risk calculator can be used for counseling and enrolment in ongoing studies.

High Relative Abundance of Lactobacillus reuteri and Fructose Intake are Associated with Adiposity and Cardiometabolic Risk Factors in Children from Mexico City

In Mexico, 3 of 10 children are overweight. Fructose intake and relative abundance (RA) of Lactobacillus reuteri (L. reuteri) in the intestinal microbiota are associated with obesity and diabetes in adults, but studies in children are limited. This study evaluates the association between fructose intake and L. reuteri RA with adiposity and cardiometabolic risk markers in Mexican children dietary information, microbiota profiles, adiposity indicators (Body Mass Index, BMI and Waste Circumference, WC), and cardiometabolic markers were analyzed in 1087 children aged 6–12 years. Linear regression and path analysis models were used. High-tertile fructose intake and L. reuteri RA were positively associated with BMI (βTertil 3 vs. Tertil 1 = 0.24 (95% CI, 0.04; 0.44) and βT3 vs. T1 = 0.52 (95% CI, 0.32; 0.72)) and WC (βT3 vs. T1 = 2.40 (95% CI, 0.93; 3.83) and βT3 vs. T1 = 3.40 (95% CI, 1.95; 4.90)), respectively. Also, these factors mediated by adiposity were positively correlated with high triglycerides and insulin concentrations and HOMA-IR (p ≤ 0.03) and negatively associated with HDL-C concentration (p < 0.01). High-tertile fructose intake and L. reuteri RA were directly associated with adiposity and indirectly associated though adiposity with metabolic disorders in children. In conclusion, fructose intake and L. reuteri RA were directly associated with adiposity and indirectly associated with metabolic disorders in children, mediated by adiposity.

Serum ZAG Levels Were Associated with eGFR Mild Decrease in T2DM Patients with Diabetic Nephropathy

Objective.To investigate the changes of serum zinc-α2-glycoprotein (ZAG) in type 2 diabetes mellitus (T2DM) with eGFR mild decrease.Subjects and Methods.A total of 438 T2DM patients (61.3 ± 4.0 y) were recruited and the demographic, anthropometric, and biochemical parameters were all collected. Serum ZAG levels were determined by commercially available ELISA kits.Results. The proportion of T2DM patients with the high tertile ZAG levels was 11.9% higher in patients with mildly decreased estimated glomerular filtration rate (eGFR) (<90 mL/min/1.73 m2) than those with the low tertile ZAG levelsP=0.038. The probability of theeGFR<90 mL/min/1.73 m2in patients with the high ZAG levels was 94% higher than those with the low serum ZAG levels after adjusting for age, gender, and education [OR = 1.94, 95% CI (1.17–3.23),P=0.0094]. This phenomenon was more likely to be observed in the condition of uACR ≥ 2.7 mg/mmol, WC ≥ 90 cm for men, or WC ≥ 85 cm for women.Conclusion. Serum ZAG levels were firstly found to be related with eGFR in T2DM patients. The patients with the high tertile ZAG levels were more likely to have mildly eGFR decrease, especially for female patients with higher uACR and bigger WC.