Utilization of Anti-obesity Medications After Bariatric Surgery: Analysis of a Large National Database.

PURPOSE: A significant proportion of patients experience insufficient weight loss or weight regain after bariatric surgery. There is a paucity of literature describing anti-obesity medication (AOM) use following bariatric surgery. We sought to identify prevalence and trends of AOM use following bariatric surgery. MATERIALS AND METHODS: We utilized the IBM Explorys® database to identify all adults with prior bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy). Those prescribed AOMs (semaglutide, liraglutide, topiramate, phentermine/topiramate, naltrexone/bupropion, orlistat) within 5 years of surgery were further identified. Data was analyzed to characterize AOM utilization among different age, demographic, and comorbid populations. RESULTS: A total of 59,160 adults with prior bariatric surgery were included. Among AOMs studies, prevalence of use was highest for topiramate (8%), followed by liraglutide (2.9%), phentermine/topiramate (1.03%), naltrexone/bupropion (0.95%) semaglutide (0.52%), and orlistat (0.17%). Age distribution varied, with the highest utilization among those age 35-39 years for topiramate, 40-44 years for phentermine/topiramate and naltrexone/bupropion, 45-49 years for semaglutide, and 65-69 years for liraglutide and orlistat. African American race was associated with higher utilization across all AOMs. Among comorbidities, hypertension, hyperlipidemia, and diabetes mellitus were most associated with AOM use. CONCLUSION: Despite a relatively high incidence of weight regain, AOMs are underutilized following bariatric surgery. It is imperative that barriers to their use be addressed and that AOMs be considered earlier and more frequently in patients with insufficient weight loss or weight regain after bariatric surgery.

Is open-capsule proton pump inhibitor associated with faster healing time for marginal ulceration after Roux-en-Y gastric bypass?

BACKGROUND: Marginal ulceration (MU) is a significant cause of morbidity after Roux-en-Y gastric bypass (RYGB). Proton pump inhibitors (PPIs) are the primary treatment. Prior limited data suggest that open-capsule PPIs (OC-PPIs) improve MU healing compared with intact-capsule PPIs (IC-PPIs), necessitating further validation. OBJECTIVES: We aimed to compare healing times of MU after RYGB when treated with OC-PPIs versus IC-PPIs. SETTING: Tertiary academic center, United States. METHODS: We retrospectively analyzed patients with prior RYGB diagnosed with MU from 2012 to 2022. Patients requiring mechanical closure without documented healing and without clear PPI prescriptions were excluded. The primary outcome was time to ulcer healing. Log-rank testing and Kaplan-Meier survival curve analyses were performed to compare MU healing times when treated with OC-PPIs versus IC-PPIs. Subgroup analyses further characterized ulcer healing times based on type and dosage of PPI used. RESULTS: A total of 108 patients were included for final analysis (38 received OC-PPIs and 70 received IC-PPIs). Treatment with OC-PPIs significantly decreased MU healing time compared with IC-PPIs (146.18 versus 226.14 d; p = .018). However, when stratified by PPI potency, the positive effect of opening the capsule lost significance. CONCLUSION: In this study, OC-PPIs significantly improved MU healing times compared with IC-PPIs in RYGB patients, consistent with prior data. However, on subgroup analysis comparing therapy with similar PPI potency, the MU healing time did not differ with respect to administration method. These results highlight the need for a prospective randomized trial to compare the true effect of administration method.

Association of Bariatric Surgery with Risk of Incident Obesity-Associated Malignancies: a Multi-center Population-Based Study.

INTRODUCTION: Obesity has a known association with certain types of malignancy, and we aimed to determine whether bariatric surgery has a protective effect against de novo obesity-associated cancer development in adult patients. METHODS: We performed a multi-center retrospective cohort studying utilizing TriNetX national database. Patients were identified utilizing ICD-10-CM coding, and propensity score matching was performed. We compared patients with obesity who underwent bariatric surgery to patients with obesity who did not undergo bariatric surgery. RESULTS: We initially identified 60,285 patients in the bariatric surgery group and 1,570,440 patients in nonsurgical control group. After propensity score matching, we included 55,789 patients in each patient cohort. The cumulative incidence of de novo obesity-associated cancers at 10 years was 4.0% (2206 patients) in the bariatric surgery group and 8.9% (4,960 patients) in the nonsurgical control group (HR 0.482 [95% CI 0.459-0.507]). The bariatric surgery group had lower incidence proportions for de novo breast cancer (HR 0.753 [CI 0.678-0.836]), colon cancer (HR 0.638 [CI 0.541-0.752]), liver cancer (HR 0.370 [CI 0.345-0.396]), ovarian cancer (HR 0.654 [CI 0.531-0.806]), and endometrial cancer (HR 0.448 [CI 0.362-0.556]) when compared to the nonsurgical control group. CONCLUSION: We noted that bariatric surgery is associated with a significantly lower cumulative incidence of de novo obesity-associated cancer compared to a nonsurgical matched control group. Incidence proportions of de novo breast, colon, liver, ovarian, and endometrial cancer were significantly lower in adult patients with obesity in the bariatric surgery group compared to the nonsurgical group.

Meta-Analysis Comparing Distal Radial Artery Approach Versus Traditional for Coronary Procedures.

Distal radial artery access (DRA) is recommended as the preferred approach over the traditional proximal radial artery access (TRA) for coronary procedures; however, there are limited randomized controlled trials (RCTs) that compared the 2. We conducted an updated meta-analysis of all RCTs from inception to July 26, 2021, that compared DRA versus TRA in patients who underwent coronary procedures. The statistical analysis was performed using a random effect model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). A total of 5 RCTs were included with a total of 1,005 patients. A pooled analysis of the data showed that the rate of successful cannulation was similar between the 2 arms (RR 0.85, 95% CI 0.68 to 1.07, p = 0.16, I2 = 94%). The rate of radial artery spasm significantly favored the DRA arm as compared with TRA (RR 0.51, 95% CI 0.34 to 0.75, p = 0.0007, I2 = 0%). Significantly more patients from the DRA arm required alternative arterial access. Moreover, the DRA group had an insignificantly decreased rates of radial artery occlusion (RR 0.24, 95% CI 0.05 to 1.20, p = 0.08, I2 = 46%) and early discharge after transradial stenting of coronary arteries access-site hematomas (RR 0.52, 95% CI 0.18 to 1.149, p = 0.22, I2 = 0%). The mean time for hemostasis was significantly shorter in the DRA arm (mean difference -6.64, 95% CI -10.37 to -2.90, p = 0.0005, I2 = 88%). In conclusion, DRA should be considered as a viable, effective, and safe arterial access method for patients who underwent coronary procedures.

NAD+ Repletion Reverses Heart Failure With Preserved Ejection Fraction.

[Figure: see text].

Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure and one for which no efficacious therapies exist. Obesity and lipid mishandling greatly contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are largely unknown. Here, we report that cardiomyocyte steatosis in HFpEF is coupled with increases in the activity of the transcription factor FoxO1 (Forkhead box protein O1). FoxO1 depletion, as well as over-expression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) in cardiomyocytes each ameliorates the HFpEF phenotype in mice and reduces myocardial lipid accumulation. Mechanistically, forced expression of Xbp1s in cardiomyocytes triggers ubiquitination and proteasomal degradation of FoxO1 which occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-box-containing protein 1) a novel and direct transcriptional target of Xbp1s. Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of cardiometabolic HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes.

Intravoxel incoherent motion (IVIM)-derived parameters in diffusion-weighted MRI: Associations with prognostic factors in invasive ductal carcinoma.

PURPOSE: To investigate relationships between intravoxel incoherent motion (IVIM) metrics of invasive ductal carcinoma of the breast and prognostic factors. MATERIALS AND METHODS: This retrospective study included a total of 82 masses from 72 patients who underwent 3T breast magnetic resonance imaging (MRI) and diffusion-weighted imaging. IVIM metrics of tissue diffusivity (Dslow ), pseudodiffusivity (Dfast ), and perfusion fraction (Dpf ) were measured using histogram analysis for whole lesion volumes. We evaluated relationships between IVIM metrics and prognostic factors or subtypes of invasive ductal carcinoma. RESULTS: The Dslow 50th , 75th , and 90th percentile metrics were reduced in the estrogen receptor (ER)-positive group compared with the ER-negative group (individually, P = 0.044, 0.024, 0.045). Additionally, the Dslow 75th percentile value was a significant differentiator of histologic grade, tumor subtype, and Ki-67 grouping (individually, P = 0.024, 0.049, 0.016). The Dpf mean, 75th , 90th percentile, skewness, and kurtosis metrics were correlated with the size of ductal carcinoma in situ (DCIS) component (individually, P = 0.034, 0.032, 0.027, 0.013, 0.013). CONCLUSION: The Dslow metrics differentiated between ER-positive and -negative groups, and the Dpf metrics were associated with the size of the DCIS component. LEVEL OF EVIDENCE: 4 J. MAGN. RESON. IMAGING 2017;45:1394-1406.

Dual function of a living polymerization initiator through the formation of a chain-end-protecting cluster: density functional theory calculation.

Sodium benzanilide (Na(+)BA(-)) initiators have opened a new route to living anionic polymerization of n-hexylisocyanate (HIC) with 100% yield and controlled molecular weight. The NaBA initiators not only provide initiation points for polymerization by attacking HIC monomers but also successfully prevent back-biting side reactions without any help from additives. Our hypothesis on this dual function of the NaBA initiators is that they self-assemble to form protection shields around the chain ends. Indeed, our density functional theory calculations performed under experimental conditions on the free energy of formation of (NaBA)n clusters of various sizes and conformations searched by Monte Carlo simulations show that the BA(-) moiety forms a stable complex with Na(+) in a fan-like circular-sector shape owing to its double binding sites (N(-)-C=O ↔ N=C-O(-)) and that the tightly-bound NaBA units spontaneously self-assemble to form small (NaBA)n clusters (n = 2 and 4). The growing end of the polymer chain [(BA)(HIC)n(-)], which resembles BA(-), would also assemble with n - 1 NaBA units to form an n-mer cluster. We expect that the chain end in this cluster would be more available to attack small HIC monomers coming into the cluster (leading to chain growth) rather than folding back to attack the middle of the chain (leading to cyclotrimerization to isocyanurates and depolymerization).

Association of polymorphisms modulating low-density lipoprotein cholesterol with susceptibility, severity, and progression of rheumatoid arthritis.

OBJECTIVE: Dyslipidemia, a risk factor for cardiovascular diseases, is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. We investigated whether single-nucleotide polymorphisms (SNP) modulating low-density lipoprotein (LDL) cholesterol affect susceptibility, severity, and progression of RA. METHODS: We enrolled 302 patients with RA and 1636 healthy controls, and investigated the SNP modulating LDL cholesterol. Clinical characteristics of RA, serum adipocytokine concentrations, and radiographic severity were analyzed according to genotype score based on the number of unfavorable alleles. The influence of genotype score on radiographic progression was also investigated using multivariable logistic models. RESULTS: We identified 3 SNP (rs688, rs693, and rs4420638) modulating LDL cholesterol in Koreans, which correlated well with LDL cholesterol levels in both patients with RA and controls. Among them, 2 SNP, rs688 and rs4420638, were more prevalent in patients with RA than in controls. In patients with RA carrying more unfavorable alleles (genotype score ≥ 3), disease activity measures, serum adipocytokine levels, and radiographic severity were all increased. The genotype score was an independent risk factor for radiographic progression of RA over 2 years, and its effect was greater than the influence of conventional risk factors. CONCLUSION: SNP modulating LDL cholesterol influence the risk, activity, and severity of RA. These results provide the first evidence that genetic mechanisms linked to dyslipidemia may directly contribute to the susceptibility and prognosis of RA, a representative of chronic inflammatory diseases, explaining the high incidence of dyslipidemia in RA.

A general approach to controlling the surface composition of poly(ethylene oxide)-based block copolymers for antifouling coatings.

To control the surface properties of a polystyrene-block-poly(ethylene oxide) diblock copolymer, perfluorinated chemical moieties were specifically incorporated into the block copolymer backbone. A polystyrene-block-poly[(ethylene oxide)-stat-(allyl glycidyl ether)] [PS-b-P(EO-stat-AGE)] statistical diblock terpolymer was synthesized with varying incorporations of allyl glycidyl ether (AGE) in the poly(ethylene oxide) block from 0 to 17 mol %. The pendant alkenes of the AGE repeat units were subsequently functionalized by thiol-ene chemistry with 1H,1H,2H,2H-perfluorooctanethiol, yielding fluorocarbon-functionalized AGE (fAGE) repeat units. (1)H NMR spectroscopy and size-exclusion chromatography indicated well-defined structures with complete functionalization of the pendant alkenes. The surfaces of the polymer films were characterized after spray coating by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure spectroscopy (NEXAFS), showing that the P(EO-stat-fAGE) block starts to compete with polystyrene to populate the surface after only 1 mol % incorporation of fAGE. Increasing the incorporation of fAGE led to an increased amount of perfluorocarbons on the surface and a decrease in the concentration of PS. At a fAGE incorporation of 8 mol %, PS was not detected at the surface, as measured by NEXAFS spectroscopy. Water contact angles measured by the captive-air-bubble technique showed the underwater surfaces to be dynamic, with advancing and receding contact angles varying by >20°. Protein adsorption studies demonstrated that the fluorinated surfaces effectively prevent nonspecific binding of proteins relative to an unmodified PS-b-PEO diblock copolymer. In biological systems, settlement of spores of the green macroalga Ulva was significantly lower for the fAGE-incorporated polymers compared to the unmodified diblock and a polydimethylsiloxane elastomer standard. Furthermore, the attachment strength of sporelings (young plants) of Ulva was also reduced for the fAGE-containing polymers, affirming their potential as fouling-release coatings.

Combining living anionic polymerization with branching reactions in an iterative fashion to design branched polymers.

This paper reviews the precise synthesis of many-armed and multi-compositional star-branched polymers, exact graft (co)polymers, and structurally well-defined dendrimer-like star-branched polymers, which are synthetically difficult, by a commonly-featured iterative methodology combining living anionic polymerization with branched reactions to design branched polymers. The methodology basically involves only two synthetic steps; (a) preparation of a polymeric building block corresponding to each branched polymer and (b) connection of the resulting building unit to another unit. The synthetic steps were repeated in a stepwise fashion several times to successively synthesize a series of well-defined target branched polymers.