Dapagliflozin versus empagliflozin in patients with chronic kidney disease

Background and Aim: Dapagliflozin and empagliflozin have demonstrated favorable clinical outcomes among patients with chronic kidney disease (CKD). However, their comparative monetary value for improving outcomes in CKD patients is unestablished. We examined the cost-per-outcome implications of utilizing dapagliflozin as compared to empagliflozin for prevention of renal and cardiovascular events in CKD patients.Methods: For calculation of preventable events we divided the allocated budget by the cost needed to treat (CNT) for preventing a single renal or cardiovascular event. CNT was derived by multiplying the annualized number needed to treat (aNNT) by the annual therapy cost. The aNNTs were determined based on data from the DAPA-CKD and EMPEROR-KIDNEY trials. The budget limit was defined based on the threshold recommended by the United States’ Institute for Clinical and Economic Review.Results: The aNNT was 42 both dapagliflozin (95% confidence interval [CI]: 34-59) and empagliflozin (CI: 33-66). The CNT estimates for the prevention of one primary event for dapagliflozin and empagliflozin were comparable at $201,911 (CI:$163,452-$283,636) and$209,664 (CI: $164,736-$329,472), respectively. However, diabetic patients had a higher CNT with dapagliflozin ($201,911 [CI:$153,837-$346,133]) than empagliflozin ($134,784 [CI: $109,824-$214,656]), whereas non-diabetic patients had lower CNT for dapagliflozin ($197,103 [CI:$149,029-$346,133]) than empagliflozin ($394,368 [CI: $219,648-$7,093,632]). The CNT for preventing CKD progression was higher for dapagliflozin ($427,858 [CI:$307,673-$855,717]) than empagliflozin ($224,640 [CI: $169,728-$344,448]). For preventing cardiovascular death (CVD), the CNT was lower for dapagliflozin ($1,634,515 [CI:$740,339-∞]) than empagliflozin ($2,990,208 [CI:$1,193,088-∞]).Conclusion: Among patients with CKD, empagliflozin provides a better monetary value for preventing the composite renal and cardiovascular events in diabetic patients while dapagliflozin has a better value for non-diabetic patients. Dapagliflozin provides a better monetary value for the prevention of CVD, whereas empagliflozin has a better value for the prevention of CKD progression

The Effect of Weight-Loss Interventions on Cervical and Chin Subcutaneous Fat Depots; the CENTRAL Randomized Controlled Trial

Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/− physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (−13.1% and −5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (−5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724

Wolffia globosa–Mankai Plant-Based Protein Contains Bioactive Vitamin B12 and Is Well Absorbed in Humans

Background: Rare plants that contain corrinoid compounds mostly comprise cobalamin analogues, which may compete with cobalamin (vitamin B12 (B12)) metabolism. We examined the presence of B12 in a cultivated strain of an aquatic plant: Wolffia globosa (Mankai), and predicted functional pathways using gut-bioreactor, and the effects of long-term Mankai consumption as a partial meat substitute, on serum B12 concentrations. Methods: We used microbiological assay, liquid-chromatography/electrospray-ionization-tandem-mass-spectrometry (LC-MS/MS), and anoxic bioreactors for the B12 experiments. We explored the effect of a green Mediterranean/low-meat diet, containing 100 g of frozen Mankai shake/day, on serum B12 levels during the 18-month DIRECT-PLUS (ID:NCT03020186) weight-loss trial, compared with control and Mediterranean diet groups. Results: The B12 content of Mankai was consistent at different seasons (p = 0.76). Several cobalamin congeners (Hydroxocobalamin(OH-B12); 5-deoxyadenosylcobalamin(Ado-B12); methylcobalamin(Me-B12); cyanocobalamin(CN-B12)) were identified in Mankai extracts, whereas no pseudo B12 was detected. A higher abundance of 16S-rRNA gene amplicon sequences associated with a genome containing a KEGG ortholog involved in microbial B12 metabolism were observed, compared with control bioreactors that lacked Mankai. Following the DIRECT-PLUS intervention (n = 294 participants; retention-rate = 89%; baseline B12 = 420.5 ± 187.8 pg/mL), serum B12 increased by 5.2% in control, 9.9% in Mediterranean, and 15.4% in Mankai-containing green Mediterranean/low-meat diets (p = 0.025 between extreme groups). Conclusions: Mankai plant contains bioactive B12 compounds and could serve as a B12 plant-based food source

The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols

Background: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of Wolffia globosa ‘Mankai’, a novel cultivated strain of a polyphenol-rich aquatic plant, on the metabolomic-gut clinical axis in vitro, in-vivo and in a clinical trial. Methods: We used mass-spectrometry-based metabolomics methods from three laboratories to detect Mankai phenolic metabolites and examined predicted functional pathways in a Mankai artificial-gut bioreactor. Plasma and urine polyphenols were assessed among the 294 DIRECT-PLUS 18-month trial participants, comparing the effect of a polyphenol-rich green-Mediterranean diet (+1240 mg/polyphenols/day, provided by Mankai, green tea and walnuts) to a walnuts-enriched (+440 mg/polyphenols/day) Mediterranean diet and a healthy controlled diet. Results: Approximately 200 different phenolic compounds were specifically detected in the Mankai plant. The Mankai-supplemented bioreactor artificial gut displayed a significantly higher relative-abundance of 16S-rRNA bacterial gene sequences encoding for enzymes involved in phenolic compound degradation. In humans, several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups (p < 0.05) after six and 18 months of intervention (e.g., urine hydroxy-phenyl-acetic-acid and urolithin-A; plasma Naringenin and 2,5-diOH-benzoic-acid). Specific polyphenols, such as urolithin-A and 4-ethylphenol, were directly involved with clinical weight-related changes. Conclusions: The Mankai new plant is rich in various unique potent polyphenols, potentially affecting the metabolomic-gut-clinical axis

Dietary Strategies to Reduce Obesity Burden&mdash;Polyphenols as a Game-Changer?

The obesity epidemic has nearly tripled worldwide over the past five decades and has become a significant risk factor for noncommunicable diseases [...

The Safety and Impact of Raising the Urine Culture Reporting Threshold in Hospitalized Patients

Objective: To assess the impact of changing the reporting threshold policy of positive urine cultures in hospitalized non-pregnant adults from 104 CFU/mL to 105 CFU/mL on the unwarranted use of antibiotics and patient safety. Setting: A 1100-bed tertiary-care hospital in southern Israel. Methods: As an intervention, we changed urine culture reporting policy for patients admitted to general medical wards. If culture grew ≥105 CFU/mL, it was reported with pathogen and antibiotic susceptibility data, if it grew ≤104 CFU/mL, it was reported as “low growth". The withheld information was available upon request. We retrospectively collected data on all patients in a four-month period following the intervention and report using STROBE guidelines. Results: 7808 patients were admitted, in whom 3523 urine cultures were obtained. A total of 496 grew a pathogen, 51 were excluded (candida spp. positive, history of urinary surgery, obtained from catheter). A total of 300 were reported as positive and 145 were reported as low-growth. A higher rate of patients in the low-growth group were not treated with antibiotics 45/145(31%) vs. 56/300(18.7%) in the positive group p = 0.015 and the antibiotic duration of treatment was shorter by day 5 (IQR 0.9) vs. 6 (IQR 0.9) p = 0.015. No between-group difference was observed in recurrent admission rates, pyelonephritis within 30 days, bacteremia or all-cause mortality. Conclusions: Changing the reporting threshold of positive urine culture results from 104 CFU/mL to 105 CFU/mL in hospitalized patients reduced the number of patients who were unnecessarily treated for asymptomatic bacteriuria without negatively impacting patient safety. We urge microbiological laboratories to consider this change in threshold as part of an antimicrobial stewardship program

Artificial Intelligence (AI) versus POCUS Expert: A Validation Study of Three Automatic AI-Based, Real-Time, Hemodynamic Echocardiographic Assessment Tools

Background: Point Of Care Ultra-Sound (POCUS) is an operator dependent modality. POCUS examinations usually include ‘Eyeballing’ the inspected anatomical structure without conducting accurate measurements due to complexity and insufficient time. Automatic real time measuring tools can make accurate measurements fast and simple and dramatically increase examination reliability while saving the operator much time and effort. In this study we aim to assess three automatic tools which are integrated into the Venue™ device by GE: the automatic ejection fraction, velocity time integral, and inferior vena cava tools in comparison to the gold standard—an examination by a POCUS expert. Methods: A separate study was conducted for each of the three automatic tools. In each study, cardiac views were acquired by a POCUS expert. Relevant measurements were taken by both an auto tool and a POCUS expert who was blinded to the auto tool’s measurement. The agreement between the POCUS expert and the auto tool was measured for both the measurements and the image quality using a Cohen’s Kappa test. Results: All three tools have shown good agreement with the POCUS expert for high quality views: auto LVEF (0.498; p p = 0.009), and the auto VTI (0.655; p = 0.024). Auto VTI has also shown a good agreement for medium quality clips (0.914; p < 0.001). Image quality agreement was significant for the auto EF and auto IVC tools. Conclusions: The Venue™ show a high agreement with a POCUS expert for high quality views. This shows that auto tools can provide reliable real time assistance in performing accurate measurements, but do not reduce the need of a good image acquisition technique

Comparison of Transcatheter Aortic Valve Implantation Devices in Aortic Stenosis: A Network Meta-Analysis of 42,105 Patients

Background: In recent years, trans-catheter aortic valve implantation (TAVI) has emerged as an excellent alternative to surgical aortic valve replacement (SAVR). Currently, there are several approved devices on the market, yet comparisons among them are scarce. We aimed to compare the various devices via a network meta-analysis. Methods: We performed a network meta-analysis including randomized controlled trials (RCTs) and propensity-matched studies that provide comparisons of either a single TAVI with SAVR or two different TAVI devices and report clinical outcomes. Results: We included 12 RCT and 13 propensity-matched studies comprising 42,105 patients, among whom 27,134 underwent TAVI using various valve systems (Sapien &amp; Sapien XT, Sapien 3, Corvalve, Evolut &amp; Evolut Pro, Acurate Neo, Portico). The mean follow-up time was 23.4 months. Sapien 3 was superior over SAVR in the reduction of all-cause mortality (OR = 0.53; 95%CrI 0.31&ndash;0.91), while no significant difference existed between other devices and SAVR. Aortic regurgitation was more frequent among TAVI devices compared to SAVR. There was no significant difference between the various THVs and SAVR in cardiovascular mortality, myocardial infarction, NYHA class III-IV, and endocarditis. Conclusions: Newer generation TAVI devices, especially Sapien 3 and Evolut R/Pro are associated with improved outcomes compared to SAVR and other devices of the older generation

Effect of Dietary Strategies on Respiratory Quotient and Its Association with Clinical Parameters and Organ Fat Loss: A Randomized Controlled Trial

The relation between changes in respiratory quotient (RQ) following dietary interventions and clinical parameters and body fat pools remains unknown. In this randomized controlled trial, participants with moderate abdominal obesity or/and dyslipidemia (n = 159) were randomly assigned to a Mediterranean/low carbohydrate (MED/LC, n = 80) or a low fat (LF, n = 79) isocaloric weight loss diet and completed a metabolic assessment. Changes in RQ (measured by indirect calorimeter), adipose-tissue pools (MRI), and clinical measurements were assessed at baseline and after 6 months of intervention. An elevated RQ at baseline was significantly associated with increased visceral adipose tissue, hepatic fat, higher levels of insulin and homeostatic insulin resistance. After 6 months, body weight had decreased similarly between the diet groups (−6 ± 6 kg). However, the MED/LC diet, which greatly improved metabolic health, decreased RQ significantly more than the LF diet (−0.022 ± 0.007 vs. −0.002 ± 0.008, p = 0.005). Total cholesterol and diastolic blood pressure were independently associated with RQ changes (p = 0.045). RQ was positively associated with increased superficial subcutaneous-adipose-tissue but decreased renal sinus, pancreatic, and intramuscular fats after adjusting for confounders. Fasting RQ may reflect differences in metabolic characteristics between subjects affecting their potential individual response to the diet