ATP-dependent citrate lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling of the Heart.

Background: Metabolic remodeling is a hallmark of the failing heart. Oncometabolic stress during cancer increases the activity and abundance of the ATP-dependent citrate lyase (ACL, Acly ), which promotes histone acetylation and cardiac adaptation. ACL is critical for the de novo synthesis of lipids, but how these metabolic alterations contribute to cardiac structural and functional changes remains unclear. Methods: We utilized human heart tissue samples from healthy donor hearts and patients with hypertrophic cardiomyopathy. Further, we used CRISPR/Cas9 gene editing to inactivate Acly in cardiomyocytes of MyH6-Cas9 mice. In vivo, positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to the loss of ACL. We conducted a multi-omics analysis using RNA-sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. Results: Here, we show that in mice, ACL drives metabolic adaptation in the heart to sustain contractile function, histone acetylation, and lipid modulation. Notably, we show that loss of ACL increases glucose oxidation while maintaining fatty acid oxidation. Ex vivo isotope tracing experiments revealed a reduced efflux of glucose-derived citrate from the mitochondria into the cytosol, confirming that citrate is required for reductive metabolism in the heart. We demonstrate that YAP inactivation facilitates ACL deficiency. Computational flux analysis and integrative multi-omics analysis indicate that loss of ACL induces alternative isocitrate dehydrogenase 1 flux to compensate. Conclusions: This study mechanistically delineates how cardiac metabolism compensates for suppressed citrate metabolism in response to ACL loss and uncovers metabolic vulnerabilities in the heart.

When birds of a feather flock together: Severe genomic erosion and the implications for genetic rescue in an endangered island passerine.

The Seychelles magpie-robin's (SMR) five island populations exhibit some of the lowest recorded levels of genetic diversity among endangered birds, and high levels of inbreeding. These populations collapsed during the 20th century, and the species was listed as Critically Endangered in the IUCN Red List in 1994. An assisted translocation-for-recovery program initiated in the 1990s increased the number of mature individuals, resulting in its downlisting to Endangered in 2005. Here, we explore the temporal genomic erosion of the SMR based on a dataset of 201 re-sequenced whole genomes that span the past ~150 years. Our sample set includes individuals that predate the bottleneck by up to 100 years, as well as individuals from contemporary populations established during the species recovery program. Despite the SMR's recent demographic recovery, our data reveal a marked increase in both the genetic load and realized load in the extant populations when compared to the historical samples. Conservation management may have reduced the intensity of selection by increasing juvenile survival and relaxing intraspecific competition between individuals, resulting in the accumulation of loss-of-function mutations (i.e. severely deleterious variants) in the rapidly recovering population. In addition, we found a 3-fold decrease in genetic diversity between temporal samples. While the low genetic diversity in modern populations may limit the species' adaptability to future environmental changes, future conservation efforts (including IUCN assessments) may also need to assess the threats posed by their high genetic load. Our computer simulations highlight the value of translocations for genetic rescue and show how this could halt genomic erosion in threatened species such as the SMR.

Effect of simulated extreme rainfall on the vegetative phenology of perennial and annual herbaceous plants from a Brazilian dry forest.

Detecting changes in the phenological responses of herbaceous species as a function of predicted climate change is important for forecasting future scenarios for the functioning of dry tropical forests, especially when predicting an increase in the frequency and intensity of extreme droughts. Because of the sensitivity of plants to water availability, our study hypothesizes that if years become drier or wetter, herbaceous plants will synchronously change the onset, duration, and intensity of their vegetative phenophases. We used a historical series of 60 years of precipitation observations for the Caatinga vegetation to define daily average of precipitation for rainy (Twet), median (Tcontrol), and dry (Tdry) years. We simulated past average daily rainfall (Twet, Tcontrol, and Tdry) while growing two herbaceous perennials and two herbaceous annuals. We monitored plant growth and measured the activity (absence or presence) and intensity of vegetative phenophases. We used circular statistical analysis to assess differences between treatments. Our results revealed that leaf production was seasonal but relatively uniform for perennial species and highly seasonal (wet season) for annual species. Simulated dry years induced lower leaf emergence concentrated over a few months in annual species, but this effect was more strongly significant in one of the two perennial species. Both annual and perennial species can experience delayed and less intense leaf abscission during the rainy season in years with below-average precipitation. In contrast, large voluminous rains in years with above-average precipitation can accelerate and intensify the process of leaf renewal. If future precipitation reductions occur, the changes in phenological response indicate that the cover of annual and perennial herbaceous species in this study will likely decrease, altering the landscape and functioning of dry tropical forests. However, the potential trade-offs observed may help populations of these species to persist during years of severe drought in the Caatinga.

Worldwide distribution, symptoms and diagnosis of the coinfections between malaria and arboviral diseases: a systematic review.

The coinfection between malaria (ML) and arboviral diseases represents a major global public health problem, particularly in tropical and subtropical countries. Despite its relevance, this topic is still insufficiently discussed in the current literature. Here, we aimed to investigate the worldwide distribution, symptoms, and diagnosis during coinfection between ML and arboviral diseases. We conducted a systematic review following the Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and assessed the selection and eligibility criteria, created and diagrammed maps, and analysed major symptoms with 95% confidence intervals (CI) using prevalence ratio and effect size, also performing latent class analysis. A total of 85,485 studies were retrieved, of which 56 were included: 57.14% in Asia, 25% in Africa, 14.30% in South America, and 3.56% in Europe. A total of 746 individuals were reported to be coinfected with Plasmodium and arbovirus. Concurrent ML, Dengue (DEN), Chikungunya (CHIK), and Zika (ZIK) patients are more likely to present headache and skin rash. Regarding diagnosis, 58,253 were made, of which 38,176 were positive (ML and at least one arboviral disease). The magnitude of these pathogens' coexistence points out the pressing need for improvements in public health policies towards diagnosis and prevention of both diseases, especially in endemic areas.

Analysis during chest compressions in out-of-hospital cardiac arrest patients, a cross/sectional study: The DEFI 2022 study.

AIMS: During out-of-hospital cardiac arrest (OHCA), an automatic external defibrillator (AED) analyzes the cardiac rhythm every two minutes; however, 80% of refibrillations occur within the first minute post-shock. We have implemented an algorithm for Analyzing cardiac rhythm While performing chest Compression (AWC). When AWC detects a shockable rhythm, it shortens the time between analyses to one minute. We investigated the effect of AWC on cardiopulmonary resuscitation quality. METHOD: In this cross-sectional study, we compared patients treated in 2022 with AWC, to a historical cohort from 2017. Inclusion criteria were OHCA patients with a shockable rhythm at the first analysis. Primary endpoint was the chest compression fraction (CCF). Secondary endpoints were cardiac rhythm evolution and survival, including survival analysis of non-prespecified subgroups. RESULTS: In 2017 and 2022, 355 and 377 OHCAs met the inclusion criteria, from which we analyzed the 285 first consecutive cases in each cohort. CCF increased in 2022 compared to 2017 (77% [72-80] vs 72% [67-76]; P < 0.001) and VF recurrences were shocked more promptly (53 s [32-69] vs 117 s [90-132]). Survival did not differ between 2017 and 2022 (adjusted hazard-ratio 0.96 [95% CI, 0.78-1.18]), but was higher in 2022 within the sub-group of OHCAs that occurred in a public place and within a short time from call to AED switch-on (adjusted hazard ratio 0.85[0.76-0.96]). CONCLUSIONS: OHCA patients treated with AWC had higher CCF, shorter time spent in ventricular fibrillation, but no survival difference, except for OHCA that occurred in public places with short intervention time.

Automatic gait events detection with inertial measurement units: healthy subjects and moderate to severe impaired patients.

BACKGROUND: Recently, the use of inertial measurement units (IMUs) in quantitative gait analysis has been widely developed in clinical practice. Numerous methods have been developed for the automatic detection of gait events (GEs). While many of them have achieved high levels of efficiency in healthy subjects, detecting GEs in highly degraded gait from moderate to severely impaired patients remains a challenge. In this paper, we aim to present a method for improving GE detection from IMU recordings in such cases. METHODS: We recorded 10-meter gait IMU signals from 13 healthy subjects, 29 patients with multiple sclerosis, and 21 patients with post-stroke equino varus foot. An instrumented mat was used as the gold standard. Our method detects GEs from filtered acceleration free from gravity and gyration signals. Firstly, we use autocorrelation and pattern detection techniques to identify a reference stride pattern. Next, we apply multiparametric Dynamic Time Warping to annotate this pattern from a model stride, in order to detect all GEs in the signal. RESULTS: We analyzed 16,819 GEs recorded from healthy subjects and achieved an F1-score of 100%, with a median absolute error of 8 ms (IQR [3-13] ms). In multiple sclerosis and equino varus foot cohorts, we analyzed 6067 and 8951 GEs, respectively, with F1-scores of 99.4% and 96.3%, and median absolute errors of 18 ms (IQR [8-39] ms) and 26 ms (IQR [12-50] ms). CONCLUSIONS: Our results are consistent with the state of the art for healthy subjects and demonstrate a good accuracy in GEs detection for pathological patients. Therefore, our proposed method provides an efficient way to detect GEs from IMU signals, even in degraded gaits. However, it should be evaluated in each cohort before being used to ensure its reliability.

Comparative Leaf Anatomy under Sun and Shade Conditions and Pollen Morphology of Chrysophyllum rufum Mart. (Sapotaceae).

Chrysophyllum rufum leaves collected under different light conditions provide information on how this fact can influence the morphology of the species. The anatomy techniques applied to the samples showed that there were discreet differences in the characters considered diagnostic. This indicates that the plant is capable of adapting, despite its prevalence in both dry and humid environments. The pollen grains were acetolyzed, measured, described qualitatively, analyzed quantitatively, and illustrated using light microscopy (LM).

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later.

UNASSIGNED: Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6).

In vitro toxicity of latex, its terpenoidal fractions and isolated phorbol esters from Euphorbia umbellata (Pax) Bruyns on monocytic and melanoma cells.

In Brazil, latex from Euphorbia umbellata (African milk tree) has been increasingly used in folk medicine to treat several types of cancer, including melanoma. The effect of lyophilized latex (LL), its hydroethanolic extract (E80), triterpene (F-TRI)- and diterpene (F-DIT)-enriched fractions, along with six isolated phorbol esters from LL and phorbol 12-myristate 13-acetate (PMA) on J774A.1, THP-1, SK-MEL-28, and B16-F10 cell line viability were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The compounds were identified by 2D-NMR and HRESIMS. The effect of the LL, extract and fractions on cell viability was also assessed through a resazurin reduction assay. At 100 µg/ml, LL, and its fractions moderately inhibited J774A.1 (37.5-59.5%) and THP-1 (12.6-43.6%) metabolism. LL (IC50 70 µg/ml) and F-TRI (IC50 68 µg/ml) were barely more effective against B16-F10 cells, and only F-TRI exerted an inhibitory effect on SK-MEL-28 cells (IC50 66-75 µg/ml). The samples did not effectively inhibit THP-1 growth (IC50 69-87 µg/ml, assessed by MTT). B16-F10 was susceptible to PMA (IC50 53 µM) and two 12-phenylacetate esters (IC50 56-60 µM), while SK-MEL-28 growth was inhibited (IC50 58 µM) by one of these kinds of esters with an additional 4ß-deoxy structure. Synagrantol A (IC50 39 µM) was as effective as PMA (IC50 47 µM) in inhibiting J774A.1 growth in a dose-dependent manner. Furthermore, an in silico study with target receptors indicated a high interaction of the compounds with the PKC proteins. These results provide useful knowledge on the effect of tigliane-type diterpenes on tumor cell from the perspective of medicinal chemistry.

Bichectomy Surgery and EMG Masticatory Muscles Function in Adult Women: A Longitudinal Study.

AIM: This longitudinal study aimed to evaluate the electromyographic activity of the masseter and temporal muscles in adult women who underwent buccal fat removal. MATERIALS AND METHODS: The sample consisted of 20 healthy adult women with no temporomandibular dysfunction and normal occlusion, who were assessed before, 30, and 60 days after the surgery. The electromyographic signal of the masseter and temporal muscles was captured through mandibular tasks including rest, protrusion, right and left laterality, and maximum voluntary contraction with and without parafilm. The results obtained were tabulated and the Shapiro-Wilk normality test was performed, which indicated a normal distribution. Statistical analysis was performed using the repeated measures test (p < 0.05). RESULTS: Significant differences were observed between time periods in maximum voluntary contraction for the left masseter muscle (p = 0.006) and in maximum voluntary contraction with parafilm for the right temporal (p = 0.03) and left temporal (p = 0.03) muscles. CONCLUSION: Bichectomy surgery did not modify the electromyographic activity of the masseter and temporal muscles during the rest task but may have influenced variations in the electromyographic signal during different mandibular tasks after 60 days of surgery, suggesting compensatory adaptations and functional recovery. CLINICAL SIGNIFICANCE: Understanding the impact of buccal fat removal surgery on the stomatognathic system function provides insights into postoperative functional recovery and potential compensatory adaptations, guiding clinical management and rehabilitation strategies for patients undergoing such procedures. How to cite this article: Cardoso AHDLS, Palinkas M, Bettiol NB, et al. Bichectomy Surgery and EMG Masticatory Muscles Function in Adult Women: A Longitudinal Study. J Contemp Dent Pract 2024;25(3):207-212.

Chitosan Coating with Rosemary Extract Increases Shelf Life and Reduces Water Losses from Beef.

This study aimed to evaluate the influence of films based on chitosan and rosemary extract on the physicochemical, microbiological, and oxidative characteristics of beef. Refrigerated steaks of Longissimus dorsi were distributed in a factorial arrangement (4 × 4) into four treatments consisting of four edible films (control; chitosan; chitosan + 4% rosemary extract; and chitosan + 8% rosemary extract) and four days of aging (0, 2, 4, and 8 days). Incorporating 4% or 8% rosemary extract into the chitosan film improved the characteristics of the films in terms of moisture absorption and elasticity. The edible coatings with chitosan and rosemary extract and the different days of aging increased the tenderness and decreased the lipid oxidation of beef. In addition, the chitosan films containing rosemary extract increased the water-holding capacity and decreased the cooking losses of beef. The films containing 4% and 8% rosemary extract decreased the development of mesophilic and psychrotrophic bacteria and Staphylococcus ssp. in beef. We recommend incorporating 4% rosemary extract into chitosan-based coatings to preserve the quality of refrigerated beef.

Public parks in the city of Rio de Janeiro, southeast Brazil, and the risk of parasitosis transmission by freshwater gastropods.

Urban parks are not only important for the wellbeing of the human population, but are also widely considered to be potentially important sites for the conservation of biodiversity. However, they may offer risk parasitic infections, such as schistosomiasis and fascioliasis, which are both transmitted by freshwater snails. The present study investigated the occurrence of freshwater gastropods in urban parks of the Brazilian city of Rio de Janeiro, and their possible infection by helminths of medical-veterinary importance. Gastropods were collected from six parks (2021 - 2022) and examined for the presence of larval helminths. In all, 12 gastropod species from different families were collected: Ampullariidae, Assimineidae, Burnupidae, Lymnaeidae, Physidae, Planorbidae, Succineidae, and Thiaridae. The parasitological examination revealed cercaria of three types in five snail species, with the Pleurolophocerca cercariae type in Melanoides tuberculata (the most abundant species), Echinostoma cercariae in Physella acuta and Pomacea maculata, and Virgulate cercariae, in Pomacea sp. and Pomacea maculata. None of the Biomphalaria tenagophila and Pseudosuccinea columella (the most frequent species) specimens were parasitized by Schistosoma mansoni or Fasciola hepatica, respectively. Even so, some parks may represent a considerable potential risk for transmission of both Schistosoma mansoni and Fasciola hepatica, given the presence of these gastropod vectors and the frequent contact of visitors with the waterbodies.

Effect of Water Absorption and Stacking Sequences on the Tensile Properties and Damage Mechanisms of Hybrid Polyester/Glass/Jute Composites.

The aim of this work is to analyze the effect of water absorption on the mechanical properties and damage mechanisms of polyester/glass fiber/jute fiber hybrid composites obtained using the compression molding and vacuum-assisted resin transfer molding (VARTM) techniques with different stacking sequences. For this purpose, the mechanical behavior under tensile stress of the samples was evaluated before and after hygrothermal aging at different temperatures: TA, 50 °C, and 70 °C for a period of 696 h. The damage mechanism after the mechanical tests was evaluated using SEM analysis. The results showed a tendency for the mechanical properties of the composites to decrease with exposure to an aqueous ambient, regardless of the molding technique used to conform the composites. It was also observed that the stacking sequence had no significant influence on the dry composites. However, exposure to the aqueous ambient led to a reduction in mechanical properties, both for the molding technique and the stacking sequence. Damage such as delamination, fiber pull-out, fiber/matrix detachment, voids, and matrix removal were observed in the composites in the SEM analyses.

Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Influence of Lemongrass Essential Oil (Cymbopogon flexuosus) Supplementation on Diabetes in Rat Model.

(1) Background: Species of the genus Cymbopogon and its essential oil are known for their antioxidant and hypoglycemic effects. This study aimed to investigate the impact of the essential oil of Cymbopogon flexuosus (EOCF), and its major component, citral, on glycemic, lipid, antioxidant parameters, and oxidative stress in a type 1 diabetes (DM1) rat model. (2) Methods: Initially, EOCF was analyzed by Gas chromatography-mass spectrometry (GC-MS) and the antioxidant activity of EOCF and citral was evaluated. Next, male Wistar rats (3 months old, 200-250 g) induced with DM1 using Streptozotocin (STZ) were divided into four groups: negative control supplemented with an 80% Tween solution, two groups of animals supplemented with EOCF (32 mg/kg and 64 mg/kg) and with citral (32 mg/kg), and treated for 14 days. Measurements of blood glucose levels and body weight were taken; after euthanasia, biochemical markers, including lipid profile, uric acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated. (3) Results: The predominant compounds in EOCF were α-citral (53.21%) and neral (19.42%), constituting 72.63% citral. EOCF showed good antioxidant activity, significantly greater than citral. EOCF supplementation demonstrated a mitigating effect on glycemic, lipid, and hepatic abnormalities induced by DM1. (4) Conclusions: EOCF emerges as a promising therapeutic option for the management of DM1.

Preoperative antibiotics reduce early surgical site infections after orthopaedic implant removal: a propensity-matched cohort study.

BACKGROUND: Implant removal in orthopaedics after fracture consolidation is a very common procedure but is still associated with a high rate of surgical site infection (SSI). Antibiotic prophylaxis is not recommended but advocated by some. AIM: To assess the efficacy of antibiotic prophylaxis in the prevention of early SSI following orthopaedic implant removal. METHODS: A monocentric retrospective cohort study was conducted. Patients who underwent orthopaedic implant removal procedures performed from 2016 to 2021 were included. A 1:1 propensity score matching function was used to create a cohort with matched baseline characteristics and associated risk factors for SSI. Inter-cohort comparison of the occurrence of SSI (superficial or deep) and revision surgery for SSI, after propensity score matching, was performed using the odds ratio to determine the effect of preoperative antibiotic prophylaxis. FINDINGS: In total, 965 distinct surgical procedures were included. Of these, 69 (7.15%) had an SSI, 24 (35.7%) of which required surgical revision; 214 procedures (22.18%) were performed under preoperative antibiotic prophylaxis. The propensity-matched cohort consisted of 396 procedures (198 with and without antibiotic prophylaxis). The SSI rates were 11.11% and 3.03%, respectively, in the control and antibiotic prophylaxis groups (odds ratio: 0.25; 95% confidence interval: 0.099; 0.63; P = 0.011). No difference was found for revision surgery. CONCLUSION: Preoperative administration of antibiotic prophylaxis considerably reduces the risk of SSI during the removal of an orthopaedic implant without increasing the risk of side-effects.

Development of Biocompatible Cu(I)-Microdevices for Bioorthogonal Uncaging and Click Reactions.

Transition-metal-catalyzed bioorthogonal reactions emerged a decade ago as a novel strategy to implement spatiotemporal control over enzymatic functions and pharmacological interventions. The use of this methodology in experimental therapy is driven by the ambition of improving the tolerability and PK properties of clinically-used therapeutic agents. The preclinical potential of bioorthogonal catalysis has been validated in vitro and in vivo with the in situ generation of a broad range of drugs, including cytotoxic agents, anti-inflammatory drugs and anxiolytics. In this article, we report our investigations towards the preparation of solid-supported Cu(I)-microdevices and their application in bioorthogonal uncaging and click reactions. A range of ligand-functionalized polymeric devices and off-on Cu(I)-sensitive sensors were developed and tested under conditions compatible with life. Last, we present a preliminary exploration of their use for the synthesis of PROTACs through CuAAC assembly of two heterofunctional mating units.

Randomized trial of effect of bariatric surgery on blood pressure after 5 years

BACKGROUND: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. OBJECTIVES: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. METHODS: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. RESULTS: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m2). At 5 years, body mass index was 36.40 kg/m2 (95% CI: 35.28-37.52 kg/m2) for MT and 28.01 kg/m2 (95% CI: 26.95-29.08 kg/m2) for RYGB (P < 0.001). Compared with MT, RYGB promoted a significantly higher rate of number of medications reduction (80.7% vs 13.7%; relative risk: 5.91; 95% CI: 2.58-13.52; P < 0.001) and the mean number of antihypertensive medications was 2.97 (95% CI: 2.33-3.60) for MT and 0.80 (95% CI: 0.51-1.09) for RYGB (P < 0.001). The rates of hypertension remission were 2.4% vs 46.9% (relative risk: 19.66; 95% CI: 2.74-141.09; P < 0.001). Sensitivity analysis considering only completed cases revealed consistent results. Interestingly, the rate of apparent resistant hypertension was lower after RYGB (0% vs 15.2%). CONCLUSIONS: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).

Randomized Trial of Effect of Bariatric Surgery on Blood Pressure After 5 Years.

BACKGROUND: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. OBJECTIVES: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. METHODS: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. RESULTS: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m2). At 5 years, body mass index was 36.40 kg/m2 (95% CI: 35.28-37.52 kg/m2) for MT and 28.01 kg/m2 (95% CI: 26.95-29.08 kg/m2) for RYGB (P < 0.001). Compared with MT, RYGB promoted a significantly higher rate of number of medications reduction (80.7% vs 13.7%; relative risk: 5.91; 95% CI: 2.58-13.52; P < 0.001) and the mean number of antihypertensive medications was 2.97 (95% CI: 2.33-3.60) for MT and 0.80 (95% CI: 0.51-1.09) for RYGB (P < 0.001). The rates of hypertension remission were 2.4% vs 46.9% (relative risk: 19.66; 95% CI: 2.74-141.09; P < 0.001). Sensitivity analysis considering only completed cases revealed consistent results. Interestingly, the rate of apparent resistant hypertension was lower after RYGB (0% vs 15.2%). CONCLUSIONS: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).